CytoplasmCytoplasm, cytoskeleton

Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defe

CytoplasmNucleus, nucleolusNucleus

Pontocerebellar hypoplasia 1B

A severe autosomal recessive neurologic disorder characterized by a combination of cerebellar and spinal motor neuron degeneration beginning at birth. There is diffuse muscle weakness, progressive microcephaly, global developmental delay, and brainstem involvement.

RNA-binding protein involved in the biogenesis of circular RNAs (circRNAs), which are produced by back-splicing circularization of pre-mRNAs (PubMed:39461343). Acts by binding to both exon-intron boundary and 3'-UTR of pre-mRNAs to promote circRNA biogenesis through dimerization and the association with the spliceosome (PubMed:39461343). Required for spermatogenesis via involvement in circRNA biogenesis (PubMed:39461343). Regulates the pre-mRNA processing of ATP5MC1; preventing its degradation (

Nucleus speckleCytoplasm

Intellectual developmental disorder, autosomal recessive 56

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.

Serine/threonine kinase involved in the regulation of key cellular processes including the cell cycle, nuclear condensation, transcription regulation, and DNA damage response (PubMed:14645249, PubMed:18617507, PubMed:19103756, PubMed:33076429). Controls chromatin organization and remodeling by mediating phosphorylation of histone H3 on 'Thr-4' and histone H2AX (H2aXT4ph) (PubMed:31527692, PubMed:37179361). It also phosphorylates KAT5 in response to DNA damage, promoting KAT5 association with chr

NucleusCytoplasmNucleus, Cajal body

Pontocerebellar hypoplasia 1A

A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH1A is an autosomal recessive form characterized by an abnormally small cerebellum and brainstem, central and peripheral motor dysfunction from birth, gliosis and spinal cord anterior horn cells degeneration resembling infantile spinal muscular atrophy. Additional features include muscle hypotonia, congenital contractures and respiratory insufficiency that is evident at birth.

Plays an important role in the final stage of carbohydrate digestion. Isomaltase activity is specific for both alpha-1,4- and alpha-1,6-oligosaccharides

Apical cell membrane

Congenital sucrase-isomaltase deficiency

Autosomal recessive intestinal disorder that is clinically characterized by fermentative diarrhea, abdominal pain, and cramps upon ingestion of sugar. The symptoms are the consequence of absent or drastically reduced enzymatic activities of sucrase and isomaltase. The prevalence of CSID is 0.02 % in individuals of European descent and appears to be much higher in Greenland, Alaskan, and Canadian native people. CSID arises due to post-translational perturbations in the intracellular transport, polarized sorting, aberrant processing, and defective function of SI.

Non-catalytic component of the multisynthase complex. Stimulates the catalytic activity of cytoplasmic arginyl-tRNA synthase (PubMed:10358004). Binds tRNA. Possesses inflammatory cytokine activity (PubMed:11306575). Negatively regulates TGF-beta signaling through stabilization of SMURF2 by binding to SMURF2 and inhibiting its SMAD7-mediated degradation (By similarity). Involved in glucose homeostasis through induction of glucagon secretion at low glucose levels (By similarity). Promotes dermal f

NucleusCytoplasm, cytosolSecretedEndoplasmic reticulumGolgi apparatus

Leukodystrophy, hypomyelinating, 3

A severe autosomal recessive hypomyelinating leukodystrophy characterized by early infantile onset of global developmental delay, lack of development, lack of speech acquisition, and peripheral spasticity associated with decreased myelination in the central nervous system.

Catalyzes the formation of the NeuAc-alpha-2,3-Gal-beta-1,4-GlcNAc-, NeuAc-alpha-2,3-Gal-beta-1,3-GlcNAc- and NeuAc-alpha-2,3-Gal-beta-1,3-GalNAc- sequences found in terminal carbohydrate groups of glycoproteins and glycolipids. The highest activity is toward Gal-beta-1,3-GlcNAc and the lowest toward Gal-beta-1,3-GalNAc

Golgi apparatus, Golgi stack membraneSecreted

Intellectual developmental disorder, autosomal recessive 12

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.

RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs) (PubMed:17071714, PubMed:22995836, PubMed:31199786, PubMed:31358969). Involved in various processes, such as epidermal stem cell differentiation, testis differentiation and maternal to zygotic transition during early development: acts by increasing protein synthesis; cytosine C(5)-methylation promoting tRNA stability and preventing m

Nucleus, nucleolusCytoplasmMitochondrionCytoplasm, cytoskeleton, spindleSecreted, extracellular exosome

Intellectual developmental disorder, autosomal recessive 5

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.

Binds single-stranded RNA. Involved in the process of mRNA degradation and in the positive regulation of mRNA decapping. May play a role in spermiogenesis and oogenesis

Cytoplasm, P-body

Intellectual developmental disorder, autosomal recessive 50

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT50 patients show mild intellectual disability and microcephaly.

Acts as accessory component of the N-oligosaccharyl transferase (OST) complex which catalyzes the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide donor to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains. Involved in N-glycosylation of STT3B-dependent substrates. Specifically required for the glycosylation of a subset of acceptor sites that are near cysteine residues; in this function seems to act redundantly with MAGT1. I

Endoplasmic reticulum membrane

Intellectual developmental disorder, autosomal recessive 7

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.

Serine/threonine kinase that acts as an essential activator of the Wnt signaling pathway. Recruited to promoters of Wnt target genes and required to activate their expression. May act by phosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N-terminal pathway. May play a role in the response to environmental stress. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it may play a

NucleusCytoplasmRecycling endosomeCytoplasm, cytoskeleton

Intellectual developmental disorder, autosomal recessive 54

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT54 patients manifest intellectual disability, delayed speech and hyperactivity.

Catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its methyltransferase domain (PubMed:20123966, PubMed:20308323, PubMed:31079898). Catalyzes the last step in the formation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA (PubMed:20123966, PubMed:20308323). Has a preference for tRNA(Arg) and tRNA(Glu), and does not bind tRNA(Lys) (PubMed:20308323). Binds tRNA a

CytoplasmNucleus

Intellectual developmental disorder, autosomal recessive 71

A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT71 features include impaired intellectual development, global developmental delay, mildly delayed walking, poor language, seizures in the first years of life, and behavioral abnormalities.

Binds to the plus end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes microtubule growth and microtubule bundling. Links cytoplasmic vesicles to microtubules and thereby plays an important role in intracellular vesicle trafficking. Plays a role macropinocytosis and endosome trafficking

CytoplasmCytoplasm, cytoskeletonCytoplasmic vesicle membraneCell projection, ruffle

Acyltransferase which catalyzes the transfer of an acyl group from an acyl-CoA to a lysophosphatidylinositol (1-acylglycerophosphatidylinositol or LPI) leading to the production of a phosphatidylinositol (1,2-diacyl-sn-glycero-3-phosphoinositol or PI) and participates in the reacylation step of the phospholipid remodeling pathway also known as the Lands cycle (PubMed:18094042, PubMed:18772128). Prefers arachidonoyl-CoA as the acyl donor, thus contributing to the regulation of free levels arachid

Endoplasmic reticulum membrane

Intellectual developmental disorder, autosomal recessive 57

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT57 patients have moderate to severe intellectual disability, and delayed psychomotor development with poor or absent speech. Some patients manifest seizures and autistic features.

Actin-binding protein that is involved in actin cytoskeleton assembly and reorganization (PubMed:21730168, PubMed:22330775). Acts as an actin nucleation factor and promotes assembly of actin filaments together with SPIRE1 and SPIRE2 (PubMed:21730168, PubMed:22330775). Involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport (By similarity). Required for asymmetric spindle positioning, asymmetric oocyte

Cytoplasm, cytoskeletonCytoplasm, cytosolCytoplasm, perinuclear regionNucleusNucleus, nucleolusCell membraneCytoplasmic vesicle membraneCytoplasm, cell cortex

Intellectual developmental disorder, autosomal recessive 47

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT47 patients show delayed development, with cognition and speech more affected than motor skills.

Inactivates histamine by N-methylation. Plays an important role in degrading histamine and in regulating the airway response to histamine

Cytoplasm

Intellectual developmental disorder, autosomal recessive 51

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.

Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid, and kainic acid (PubMed:1311100, PubMed:20805473, PubMed:21172611, PubMed:28628100, PubMed:35675825). L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation chan

Cell membraneEndoplasmic reticulum membranePostsynaptic cell membranePostsynaptic density membraneCell projection, dendriteCell projection, dendritic spineEarly endosome membraneRecycling endosome membranePresynapseSynapse

Intellectual developmental disorder, autosomal dominant 67

An autosomal dominant disorder characterized by global development delay and impaired intellectual development apparent from infancy or early childhood. Additional features may include behavioral abnormalities, and language and sleeping difficulties.

Involved in both the production of very long-chain fatty acids for sphingolipid synthesis and the degradation of the sphingosine moiety in sphingolipids through the sphingosine 1-phosphate metabolic pathway (PubMed:25049234). Catalyzes the last of the four reactions of the long-chain fatty acids elongation cycle (PubMed:12482854). This endoplasmic reticulum-bound enzymatic process, allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle (PubMed:124

Endoplasmic reticulum membrane

Intellectual developmental disorder, autosomal recessive 14

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.

Required for ciliogenesis and for structural integrity at the ciliary tip

Cell projection, ciliumCytoplasm, cytoskeleton, microtubule organizing center, centrosome, centrioleCytoplasm, cytoskeleton, microtubule organizing center, centrosomeCytoplasm, cytoskeleton, spindle pole

Joubert syndrome 25

A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS25 clinical manifestations appear to be confined to the neurologic system. JBTS25 inheritance is autosomal recessive.

Functions as an activator of NF-kappa-B through increased phosphorylation of the IKK complex. May function in neuronal cells differentiation. May play a role in vesicular transport from endoplasmic reticulum to Golgi

Golgi apparatus, cis-Golgi networkEndoplasmic reticulumCytoplasm

Intellectual developmental disorder, autosomal recessive 13

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Brain magnetic resonance imaging of MRT13 patients indicates the presence of mild cerebral white matter hypoplasia. Microcephaly is present in some but not all affected individuals.

Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1. Transporter activity is driven by a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump (PubMed:20980548, PubMed:34880492, PubMed:35077764, PubMed:8563765, PubMed:37217492). Has a primary role in the transport of dietary monosaccharides from enterocytes to blood. Responsible for the absorption of D-glucose or D-galac

Apical cell membrane

Congenital glucose/galactose malabsorption

Intestinal monosaccharide transporter deficiency. It is an autosomal recessive disorder manifesting itself within the first weeks of life. It is characterized by severe diarrhea and dehydration which are usually fatal unless glucose and galactose are eliminated from the diet.

Probably involved in signal transduction in the nervous system, via increasing cell surface localization of GRM5/mGluR5 and positively regulating its signaling (PubMed:33711248). Required for the spatial learning process. Acts as a negative regulator of Ca(2+)-calmodulin-dependent protein kinase 2 (CaMK2) phosphorylation. May play a role in modulating melanin-concentrating hormone-mediated functions via its interaction with MCHR1 that interferes with G protein-coupled signal transduction. May be

Cytoplasm, cytosolEndosome membraneCell projection, dendritePostsynapse

Neurodevelopmental disorder with infantile epileptic spasms

An autosomal dominant neurodevelopmental disorder characterized by onset of severe and frequent epileptic spasms within the first year of life. Affected individuals have global developmental delay with delayed walking and poor or absent speech. More variable features may include poor overall growth, high-arched palate, and delayed myelination on brain imaging.

Adenosine kinase that mediates the phosphorylation of the purine nucleoside adenosine at the 5' position in an ATP-dependent manner: catalyzes phosphorylation of both unmodified and modified adenosines (PubMed:21963049, PubMed:40840445, PubMed:6246102, PubMed:8577746, PubMed:9070863). Plays a key role in the detoxification of modified adenosines containing N(6)-methylated adenine (m6A) post-transcriptional modification (PubMed:40840445). Modified nucleosides are derived from the degradation of R

Cytoplasm, cytosolNucleusCytoplasm

Hypermethioninemia due to adenosine kinase deficiency

A metabolic disorder characterized by global developmental delay, early-onset seizures, mild dysmorphic features, and characteristic biochemical anomalies, including persistent hypermethioninemia with increased levels of S-adenosylmethionine and S-adenosylhomocysteine. Homocysteine levels are typically normal.

Catalytic subunit of the NatB complex which catalyzes acetylation of the N-terminal methionine residues of peptides beginning with Met-Asp, Met-Glu, Met-Asn and Met-Gln (PubMed:34230638). Proteins with cell cycle functions are overrepresented in the pool of NatB substrates. Required for maintaining the structure and function of actomyosin fibers and for proper cellular migration

CytoplasmNucleus

Intellectual developmental disorder, autosomal recessive 73

A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT73 patients manifest global developmental delay with hypotonia and mildly delayed walking, impaired intellectual development with poor or absent speech, and mildly dysmorphic features.

Broad specificity glycosidase of the intestinal brush border membrane that hydrolyzes lactose, the main sugar in mammalian milk, to produce D-glucose and D-galactose (PubMed:12594539, PubMed:16400612, PubMed:3929764, PubMed:9762914). The mature protein is composed of two domains that catalyze the hydrolysis of beta-glucopyranosides and beta-galactopyranosides, with a preference for hydrophilic aglycones (in lactose and cellobiose) for one domain and hydrophobic aglycones (in phlorizin and glycos

Apical cell membrane

Congenital lactase deficiency

Autosomal recessive, rare and severe gastrointestinal disorder. It is characterized by watery diarrhea in infants fed with breast milk or other lactose-containing formulas. An almost total lack of LCT activity is found in jejunal biopsy material of patients with congenital lactase deficiency. Opposite to congenital lactase deficiency, also known as lactose intolerance, is the most common enzyme deficiency worldwide. It is caused by developmental down-regulation of lactase activity during childhood or early adulthood. The decline of lactase activity is a normal physiological phenomenon; however, the majority of Northern Europeans have the ability to maintain lactase activity and digest lactose throughout life (lactase persistence). The down-regulation of lactase activity operates at the transcriptional level and it is associated with a noncoding variation in the MCM6 gene, located in the upstream vicinity of LCT.

Plays a role in neuronal plasticity and the proteolytic action may subserve structural reorganizations associated with learning and memory operations

Secreted

Intellectual developmental disorder, autosomal recessive 1

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.

ATPase involved both in DNA repair and rescue of stalled ribosomes (PubMed:22055184, PubMed:28757607, PubMed:32099016, PubMed:32579943, PubMed:36302773). 3'-5' DNA helicase involved in repair of alkylated DNA: promotes DNA unwinding to generate single-stranded substrate needed for ALKBH3, enabling ALKBH3 to process alkylated N3-methylcytosine (3mC) within double-stranded regions (PubMed:22055184). Also involved in activation of the ribosome quality control (RQC) pathway, a pathway that degrades

NucleusNucleus speckleCytoplasm, cytosol

Intellectual developmental disorder, autosomal recessive 81

An autosomal recessive disorder characterized by variable features including mild to severe developmental delay, hypotonia, feeding difficulties, extreme fatigue, and neurobehavioral abnormalities.

Intellectual developmental disorder, autosomal recessive 27

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.

Metallocarboxypeptidase that mediates protein deglutamylation of tubulin and non-tubulin target proteins (PubMed:22170066, PubMed:24022482, PubMed:30420557). Catalyzes the removal of polyglutamate side chains present on the gamma-carboxyl group of glutamate residues within the C-terminal tail of alpha- and beta-tubulin (PubMed:22170066, PubMed:24022482, PubMed:30420557). Specifically cleaves tubulin long-side-chains, while it is not able to remove the branching point glutamate (PubMed:24022482).

CytoplasmCytoplasm, cytosolNucleusMitochondrion

Neurodegeneration, childhood-onset, with cerebellar atrophy

An autosomal recessive disorder characterized by early onset of progressive neurodegeneration affecting the central and peripheral nervous systems. Clinical features include global developmental delay, impaired intellectual development, poor or absent speech, and motor abnormalities. Brain imaging shows cerebellar atrophy. Death in childhood may occur.

As part of the KICSTOR complex functions in the amino acid-sensing branch of the TORC1 signaling pathway. Recruits, in an amino acid-independent manner, the GATOR1 complex to the lysosomal membranes and allows its interaction with GATOR2 and the RAG GTPases. Functions upstream of the RAG GTPases and is required to negatively regulate mTORC1 signaling in absence of amino acids. In absence of the KICSTOR complex mTORC1 is constitutively localized to the lysosome and activated. The KICSTOR complex

Lysosome membrane

Intellectual developmental disorder, autosomal recessive 83

An autosomal recessive disorder characterized by developmental delay, mild to moderate intellectual disability, and poor or absent speech. Additional variable features include seizures, hearing impairment, hypotonia, and non-specific facial dysmorphism.

Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defe

CytoplasmNucleusNucleus, nucleolusNucleus, nucleoplasm

Pontocerebellar hypoplasia 1D

An autosomal recessive neurologic disorder with onset at birth or in infancy, and characterized by progressive axonal motor neuronopathy, severe generalized hypotonia, respiratory insufficiency, and cerebellar atrophy. Death in childhood may occur.

Required for transcriptional activation subsequent to the assembly of the pre-initiation complex (By similarity). Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a s

Nucleus

Intellectual developmental disorder, autosomal recessive 18, with or without epilepsy

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.

Probably involved in connections of major cytoskeletal structures to the plasma membrane. In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along with PLEKHG6, required for normal macropinocytosis

Apical cell membraneCell projectionCell projection, microvillus membraneCell projection, ruffle membraneCytoplasm, cell cortexCytoplasm, cytoskeletonCell projection, microvillus

May be involved in transcriptional regulation

Nucleus, nucleolus

Neurodevelopmental disorder with progressive movement abnormalities, cognitive decline, and brain abnormalities

An autosomal recessive disorder characterized by global developmental delay, developmental regression, variably impaired intellectual development with poor or absent speech, difficulty walking or inability to walk, and various movement abnormalities, including spasticity, hypertonia, dystonia, tremor, and myoclonus. Affected individuals usually show poor overall growth, often with microcephaly, hypotonia, limb contractures, and cataracts.

S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates the C5 position of cytosine 72 in tRNA(Thr)(TGT) and tRNA(Cys)(GCA) (PubMed:26160102, PubMed:27703015, PubMed:28531330). In vitro also methylates tRNA(Thr)(AGT) (PubMed:26160102, PubMed:27703015). Methylation requires, in the acceptor stem region, the presence of the 3'-CCA terminus, the target site C72, the discriminator base U73, and the second and third base pairs (2:71 and 3:70) in the tRNA substrates (PubMed:26

Cytoplasm

Intellectual developmental disorder, autosomal recessive 82

An autosomal recessive disorder characterized by developmental delay, motor and speech delay, intellectual disability, and behavioral anomalies.

Catalytic subunit of a heterodimer with TRMT112, which specifically methylates the 6th position of adenine in position 1832 of 18S rRNA (PubMed:31328227, PubMed:32217665, PubMed:33357433, PubMed:33428944, PubMed:35033535). N6-methylation of adenine(1832) in 18S rRNA resides in the decoding center of 18S rRNA and is required for translation and embryonic stem cells (ESCs) pluripotency and differentiation (PubMed:33357433)

NucleusPresynapsePostsynapse

Intellectual developmental disorder, autosomal recessive 72

A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT72 patients manifest moderate to severe intellectual disability, microcephaly, and dysmorphic facial features.

The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (PubMed:33795473, PubMed:9695952). TFIID recognizes and binds promoters via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC) (PubMed:33795473). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (Pu

Nucleus

Intellectual developmental disorder, autosomal recessive 60

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT60 patients display mild intellectual disability, delayed psychomotor development, learning difficulties, and poor overall growth with variable microcephaly.

Histone demethylase that demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code (PubMed:24952722, PubMed:27214403, PubMed:28262558). Does not demethylate histone H3 'Lys-9' or H3 'Lys-27'. Demethylates trimethylated, dimethylated and monomethylated H3 'Lys-4'. Acts as a transcriptional corepressor for FOXG1B and PAX9. Favors the proliferation of breast cancer cells by repressing tumor suppressor genes such as BRCA1 and HOXA5 (PubMed:24952722). In contrast, may act as

Nucleus

Intellectual developmental disorder, autosomal recessive 65

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT65 patients have moderate to severe intellectual disability, developmental delay, and facial dysmorphism. Camptodactyly is present in some patients.

Has a role in alternative splicing and transcription regulation (PubMed:29522154). Involved in both constitutive and alternative pre-mRNA splicing. May have a role in the recognition of the 3' splice site during the second step of splicing

NucleusNucleus speckleCytoplasm

Intellectual developmental disorder, autosomal recessive 70

A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT70 patients manifest impaired intellectual development, mild facial dysmorphism, febrile seizures, and behavioral abnormalities.

Beta-1,3-N-acetylgalactosaminyltransferase that synthesizes a unique carbohydrate structure, GalNAc-beta-1-3GlcNAc, on N- and O-glycans. Has no galactose nor galactosaminyl transferase activity toward any acceptor substrate. Involved in alpha-dystroglycan (DAG1) glycosylation: acts coordinately with GTDC2/POMGnT2 to synthesize a GalNAc-beta3-GlcNAc-beta-terminus at the 4-position of protein O-mannose in the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3

Golgi apparatus membraneEndoplasmic reticulum

Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A11

An autosomal recessive disorder characterized by congenital muscular dystrophy associated with cobblestone lissencephaly and other brain anomalies, eye malformations, profound intellectual disability, and death usually in the first years of life. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle-eye-brain disease.

Transmembrane protein of the mitochondrial outer membrane that controls mitochondrial organization (PubMed:26168012, PubMed:27390132, PubMed:27543974). May regulate the assembly of the MICOS (mitochondrial contact site and cristae organizing system) complex which is essential to the biogenesis and dynamics of mitochondrial cristae, the inwards folds of the inner mitochondrial membrane (PubMed:27390132). Through its interaction with the EMC (endoplasmic reticulum membrane protein complex), could

Mitochondrion outer membrane

Neuropathy, hereditary motor and sensory, 6B, with optic atrophy

An autosomal recessive neurologic disorder characterized by early-onset optic atrophy, progressive visual loss, and peripheral sensorimotor neuropathy manifesting as axonal Charcot-Marie-Tooth disease, with variable age at onset and severity. Charcot-Marie-Tooth disease is a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. It is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies and primary peripheral axonal neuropathies. Peripheral axonal neuropathies are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, and normal or slightly reduced nerve conduction velocities.

Involved in the Hedgehog (Hh) signaling pathway, is essential for normal ciliogenesis (PubMed:29263200). Regulates the proteolytic processing of GLI3 and cooperates with the transcription factor EMX1 in the induction of downstream Hh pathway gene expression and gonadotropin-releasing hormone production (PubMed:29263200). WDR11 complex facilitates the tethering of Adaptor protein-1 complex (AP-1)-derived vesicles. WDR11 complex acts together with TBC1D23 to facilitate the golgin-mediated capture

Cytoplasm, cytoskeleton, cilium basal bodyCytoplasmNucleusCytoplasm, cytoskeleton, cilium axonemeCytoplasmic vesicleGolgi apparatus, trans-Golgi network

Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defe

CytoplasmNucleusNucleus, nucleolus

Pontocerebellar hypoplasia 1C

A severe autosomal recessive neurodegenerative disease characterized by cerebellar and corpus callosum hypoplasia, abnormal myelination of the central nervous system, and spinal motor neuron disease. Affected individuals manifest failure to thrive, severe muscle weakness, spasticity and psychomotor retardation. Vision and hearing are impaired.

Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as MEIS2, ILF2 or GLUL (PubMed:26990986, PubMed:33009960). Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8 (PubMed:20223979, PubMed:24328678, PubMed:25043012, PubMed:25108355). Maintains presynaptic glutamate release and consequen

CytoplasmNucleusMembrane

Intellectual developmental disorder, autosomal recessive 2

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT2 patients display mild intellectual disability with a standard IQ ranged from 50 to 70. IQ scores are lower in males than females. Developmental milestones are mildly delayed. There are no dysmorphic or autistic features.

Part of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI biosynthesis

Endoplasmic reticulum membrane

Glycosylphosphatidylinositol biosynthesis defect 16

An autosomal recessive disorder characterized by delayed psychomotor development, intellectual disability, and seizures.

G-protein coupled receptor activated by glutamate that regulates axon outgrowth through the MAPK-cAMP-PKA signaling pathway during neuronal development (PubMed:33500274). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase that it inhibits (PubMed:9473604)

Cell membrane

Neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities

An autosomal recessive neurodevelopmental disorder characterized by global developmental delay, hypotonia, severe to profound intellectual disability, early-onset epilepsy, and microcephaly. Neuroimaging shows cerebral atrophy, thin corpus callosum and hypomyelination in a majority of cases. Death in childhood may occur.

Adapter protein that associates with PIDD1 and the caspase CASP2 to form the PIDDosome, a complex that activates CASP2 and triggers apoptosis (PubMed:15073321, PubMed:16652156, PubMed:17159900, PubMed:17289572, PubMed:9044836). Also recruits CASP2 to the TNFR-1 signaling complex through its interaction with RIPK1 and TRADD and may play a role in the tumor necrosis factor-mediated signaling pathway (PubMed:8985253)

CytoplasmNucleus

Intellectual developmental disorder, autosomal recessive 34, with variant lissencephaly

A disorder characterized by mild to moderate intellectual disability, megalencephaly or enlarged head circumference, and a mild variant of lissencephaly with anterior-predominant pachygyria with shallow and unusually wide sulci and mildly thickened cortex. Some patients may have seizures.

Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcriptio

Nucleus

Histone methyltransferase that dimethylates histone H3 at 'Arg-17', forming asymmetric dimethylarginine (H3R17me2a), leading to activate transcription via chromatin remodeling (By similarity). Maternal factor involved in epigenetic chromatin reprogramming of the paternal genome in the zygote: mediates H3R17me2a, promoting histone H3.3 incorporation in the male pronucleus, leading to TET3 recruitment and subsequent DNA demethylation (By similarity)

NucleusCytoplasm

Intellectual developmental disorder, autosomal recessive 44

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT44 manifestations include mild to severe cognitive impairment, delayed psychomotor development, seizures in some patients, and dysmorphic features.

Phosphatase involved in the dephosphorylation of myo-inositol monophosphates to generate myo-inositol (PubMed:17068342, PubMed:8718889, PubMed:9462881). Is also able to dephosphorylate scyllo-inositol-phosphate, myo-inositol 1,4-diphosphate, scyllo-inositol-1,3-diphosphate and scyllo-inositol-1,4-diphosphate (PubMed:17068342). Also dephosphorylates in vitro other sugar-phosphates including D-galactose-1-phosphate, glucose-1-phosphate, glucose-6-phosphate, fructose-1-phosphate, beta-glycerophosph

Cytoplasm

Intellectual developmental disorder, autosomal recessive 59

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.

Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773, PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. T

Cytoplasm

Intellectual developmental disorder, autosomal recessive 67

A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Some MRT67 patients manifest seizures and sensorineural hearing loss.

Decapping scavenger enzyme that catalyzes the cleavage of a residual cap structure following the degradation of mRNAs by the 3'->5' exosome-mediated mRNA decay pathway. Hydrolyzes cap analog structures like 7-methylguanosine nucleoside triphosphate (m7GpppG) with up to 10 nucleotide substrates (small capped oligoribonucleotides) and specifically releases 5'-phosphorylated RNA fragments and 7-methylguanosine monophosphate (m7GMP). Cleaves cap analog structures like tri-methyl guanosine nucleoside

CytoplasmNucleus

Al-Raqad syndrome

A syndrome characterized by delayed psychomotor development, moderate to severe intellectual disability, poor or absent speech, microcephaly, congenital hypotonia, and severe growth delay.

Component of chylomicrons, very low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL) in plasma. Plays an important role in lipoprotein metabolism as an activator of lipoprotein lipase. Both proapolipoprotein C-II and apolipoprotein C-II can activate lipoprotein lipase. In normolipidemic individuals, it is mainly distributed in the HDL, whereas in hypertriglyceridemic individuals, predominantly found in the VLDL and LDL

Secreted

Hyperlipoproteinemia 1B

Autosomal recessive trait characterized by hypertriglyceridemia, xanthomas, and increased risk of pancreatitis and early atherosclerosis.

Component of the FERRY complex (Five-subunit Endosomal Rab5 and RNA/ribosome intermediary) (PubMed:37267905). The FERRY complex directly interacts with mRNAs and RAB5A, and functions as a RAB5A effector involved in the localization and the distribution of specific mRNAs most likely by mediating their endosomal transport. The complex recruits mRNAs and ribosomes to early endosomes through direct mRNA-interaction (PubMed:37267905). Plays a role in mast cell degranulation

CytoplasmEarly endosome

Intellectual developmental disorder, autosomal recessive 66

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT66 patients have intellectual disability, delayed speech development, neuropsychiatric symptoms, and relatively normal life span.

GPI inositol-deacylase that catalyzes the remove of the acyl chain linked to the 2-OH position of inositol ring from the GPI-anchored protein (GPI-AP) in the endoplasmic reticulum (PubMed:24784135, PubMed:38167496). Initiates the post-attachment remodeling phase of GPI-AP biogenesis and participates in endoplasmic reticulum (ER)-to-Golgi transport of GPI-anchored protein (PubMed:24784135, PubMed:38167496)

Endoplasmic reticulum membrane

Neurodevelopmental disorder with dysmorphic features, spasticity, and brain abnormalities

An autosomal recessive disorder characterized by severely delayed global development, with hypotonia, impaired intellectual development, and poor or absent speech. Most patients have spasticity with limb hypertonia and brisk tendon reflexes. Additional features include non-specific dysmorphic facial features, structural brain abnormalities, and cortical visual impairment.

Guanine nucleotide exchange factor for ARF1 and ARF6 (PubMed:11226253, PubMed:24058294). Guanine nucleotide exchange factor activity is enhanced by lipid binding (PubMed:24058294). Accelerates GTP binding by ARFs of all three classes. Guanine nucleotide exchange protein for ARF6, mediating internalization of beta-1 integrin (PubMed:16461286). Involved in neuronal development (Probable). In neurons, plays a role in the control of vesicle formation by endocytoc cargo. Upon long term depression, in

CytoplasmNucleusPostsynaptic densityCytoplasmic vesicle, secretory vesicle, synaptic vesicle

Intellectual developmental disorder with short stature and behavioral abnormalities

An autosomal recessive disorder with onset in infancy and characterized by intellectual disability, developmental delay, short stature, aphasia, and hypotonia. Additional features include seizures and behavioral abnormalities, such as inattention, hyperactivity and aggression.

Ionotropic glutamate receptor that functions as a cation-permeable ligand-gated ion channel, gated by L-glutamate and the glutamatergic agonist kainic acid (PubMed:7536611, PubMed:8730589, PubMed:14511640). L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system (By similarity). Binding of the excitatory neurotransmitter L-glutamate induces a conformational change leading to the opening of the cation channel, converting the chemical signal to an electric

Cell membranePostsynaptic cell membrane

Intellectual developmental disorder, autosomal recessive 6

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT6 patients display mild to severe intellectual disability and psychomotor development delay in early childhood. Patients do not have neurologic problems, congenital malformations, or facial dysmorphism. Body height, weight, and head circumference are normal.

Associates with the adapter-like complex 4 (AP-4) and may therefore play a role in vesicular trafficking of proteins at the trans-Golgi network

Cytoplasm, cytosolCell membrane

Intellectual developmental disorder, autosomal recessive 61

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT61 patients manifest delayed psychomotor development, moderate to severe intellectual disability, and variable dysmorphic facial features. Refractory seizures and brain abnormalities are present in severely affected patients.

Multifunctional anion transporter that operates via two distinct transport mechanisms, namely proton-coupled anion cotransport and membrane potential-dependent anion transport (PubMed:15510212, PubMed:21781115, PubMed:22778404, PubMed:23889254). Electroneutral proton-coupled acidic monosaccharide symporter, with a sugar to proton stoichiometry of 1:1. Exports glucuronic acid and free sialic acid derived from sialoglycoconjugate degradation out of lysosomes, driven by outwardly directed lysosomal

Basolateral cell membraneCytoplasmic vesicle, secretory vesicle, synaptic vesicle membraneLysosome membrane

Salla disease

Sialic acid storage disease (SASD). SASDs are autosomal recessive neurodegenerative disorders characterized by hypotonia, cerebellar ataxia and intellectual disability. They are caused by a defect in the metabolism of sialic acid which results in increased urinary excretion of unconjugated sialic acid, specifically N-acetylneuraminic acid. Enlarged lysosomes are seen on electron microscopic studies. Clinical symptoms of SD present usually at age less than 1 year and progression is slow.

Intestinal trehalase is probably involved in the hydrolysis of ingested trehalose

Cell membrane

Trehalase deficiency

An autosomal recessive condition characterized by the inability to digest trehalose, a disaccharide found in mushrooms, products containing baker's yeast, and dried food. Individuals with trehalase deficiency suffer from abdominal pain, increased rectal flatulence, and diarrhea due to osmotic water flow into the colon.

Functions as a transporter for creatine and as well for its precursor guanidinoacetate. Transport of creatine and GAA is independent of resting membrane potential and extracellular Na(+), Cl(-), or pH. Contributes to the process of creatine biosynthesis and distribution

Cell membraneBasolateral cell membrane

Cataract 47

A form of cataract, an opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT47 is characterized by the association of cataract with microcornea and renal glucosuria. Microcornea is defined by a corneal diameter inferior to 10 mm in both meridians in an otherwise normal eye. Renal glucosuria is defined by elevated glucose level in the urine without hyperglycemia and without evidence of morphological renal anomalies.

Ubiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases. May also function as an E4 ligase mediating the assembly of polyubiquitin chains on substrates ubiquitinated by another E3 ubiquitin ligase. Mediates 'Lys-48'-linked polyubiquitination of substrates

Cytoplasm

Neurodevelopmental disorder with hypotonia and gross motor and speech delay

An autosomal recessive disorder characterized by severe global developmental delay apparent from infancy, axial hypotonia, limited or absent ability to walk, impaired intellectual development, and poor or absent speech. Additional features may include seizures, behavioral problems, distal skeletal anomalies, and facial dysmorphism.

Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose at the plasma membrane, with a Na(+) to sugar coupling ratio of 1:1 (PubMed:20980548, PubMed:28592437, PubMed:34880493, PubMed:37217492, PubMed:38057552). Transporter activity is driven by a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump (PubMed:20980548, PubMed:28592437, PubMed:34880493). Unlike SLC5A1/SGLT1, requires the auxiliary protein PDZK1IP1/MAP17 for full transporter activity (PubMed:3

Apical cell membrane

Renal glucosuria

A disorder characterized by persistent isolated glucosuria, normal fasting serum glucose concentration, decreased renal tubular resorption of glucose from the urine, and absence of any other signs of tubular dysfunction.

Dimethylates a single guanine residue at position 26 of most nuclear- and mitochondrial-encoded tRNAs using S-adenosyl-L-methionine as donor of the methyl groups (PubMed:10982862, PubMed:28784718, PubMed:37204604, PubMed:39786990). tRNA guanine(26)-dimethylation is required for redox homeostasis and ensure proper cellular proliferation and oxidative stress survival (PubMed:28784718)

MitochondrionNucleusCytoplasm

Intellectual developmental disorder, autosomal recessive 68

A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.

Functional component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors (PubMed:14966521, PubMed:15694321). Is also an important negative regulator of oligodentrocyte differentiation and axonal myelination (PubMed:15895088). Acts in conjunction with RTN4 and RTN4R in regulating neuronal precursor cell motility during cortical development (By similarity)

Cell membrane

Intellectual developmental disorder, autosomal recessive 64

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT64 patients have moderate to severe intellectual disability, delayed motor development, aggressive behavior, and slurred or absent speech.

Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc(2), but at high enzyme concentrations, as found in the ER quality control compartment (ERQC), it further trims the carbohydrates to Man(5-6)GlcNAc(2)

Endoplasmic reticulum membrane

Rafiq syndrome

An autosomal recessive disorder characterized by variably impaired intellectual and motor development, a characteristic facial dysmorphism, truncal obesity, and hypotonia. The facial dysmorphism comprises prominent eyebrows with lateral thinning, downward-slanting palpebral fissures, bulbous tip of the nose, large ears, and a thin upper lip. Behavioral problems, including overeating, verbal and physical aggression, have been reported in some cases. Serum transferrin isoelectric focusing shows a type 2 pattern.

Acts as a component of the WASH core complex that functions as a nucleation-promoting factor (NPF) at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerization, playing a key role in the fission of tubules that serve as transport intermediates during endosome sorting

Early endosome

Intellectual developmental disorder, autosomal recessive 43

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.

Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs, plays a role in the establishment of nuclear-peripheral chromatin compartmentalization in interphase, and in the mitotic spindle checkpoint signaling during mitosis. Involved in the quality control and retention of unspliced mRNAs in the nucleus; i

NucleusNucleus membraneNucleus envelopeNucleus, nuclear pore complexCytoplasmCytoplasm, cytoskeleton, spindleChromosome, centromere, kinetochore

Essential bifunctional enzyme that catalyzes both the N-deacetylation and the N-sulfation of glucosamine (GlcNAc) of the glycosaminoglycan in heparan sulfate (PubMed:35137078, PubMed:9230113, PubMed:9744796). Modifies the GlcNAc-GlcA disaccharide repeating sugar backbone to make N-sulfated heparosan, a prerequisite substrate for later modifications in heparin biosynthesis (PubMed:9230113). Plays a role in determining the extent and pattern of sulfation of heparan sulfate. Participates in biosynt

Golgi apparatus, trans-Golgi network membraneGolgi apparatus, cis-Golgi network membrane

Intellectual developmental disorder, autosomal recessive 46

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT46 manifestations include delayed psychomotor development apparent from infancy or early childhood, delayed or absent expressive speech, hypotonia, and therapy-responsive seizures in some patients. Behavioral abnormalities are variable and include aggression, self-injurious behavior, and sleep disturbances.

Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, PubMed:32860739). Has a very broad substrate specificity; can transport a wide range of aldoses including both pentoses and hexoses (PubMed:18245775, PubMed:19449892). Most important energy carrier of the brain: present at the blood-brain barrier and assures the energy-independent, facilitative trans

Cell membraneMelanosomePhotoreceptor inner segment

GLUT1 deficiency syndrome 1

A neurologic disorder showing wide phenotypic variability. The most severe 'classic' phenotype comprises infantile-onset epileptic encephalopathy associated with delayed development, acquired microcephaly, motor incoordination, and spasticity. Onset of seizures, usually characterized by apneic episodes, staring spells, and episodic eye movements, occurs within the first 4 months of life. Other paroxysmal findings include intermittent ataxia, confusion, lethargy, sleep disturbance, and headache. Varying degrees of cognitive impairment can occur, ranging from learning disabilities to severe intellectual disability.

Plays a key role in phospholipid biosynthesis by catalyzing the phosphorylation of free choline to phosphocholine, the first step in phosphatidylcholine biosynthesis (PubMed:17007874, PubMed:19915674, PubMed:23416529, PubMed:34077757). Also phosphorylates ethanolamine, thereby contributing to phosphatidylethanolamine biosynthesis (PubMed:17007874, PubMed:19915674). Has higher activity with choline (PubMed:17007874, PubMed:19915674). May contribute to tumor cell growth (PubMed:19915674) This isof

Cytoplasm, cytosolLipid droplet

Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures

An autosomal recessive neurodevelopmental disorder characterized by severe global developmental delay, impaired intellectual development, microcephaly, early-onset seizures, and movement abnormalities.

Transcription factor that binds specifically to the DRE (dual repressor element) and represses HTR1A gene transcription in neuronal cells. The combination of calcium and ATP specifically inactivates the binding with FRE. May play a role in the altered regulation of HTR1A associated with anxiety and major depression. Mediates HDAC-independent repression of HTR1A promoter in neuronal cell. Performs essential function in controlling functional maturation of synapses (By similarity). Plays distinct

CytoplasmNucleusCytoplasm, cytoskeleton, microtubule organizing center, centrosome

Intellectual developmental disorder, autosomal recessive 3

A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.