Muscle assembly regulating factor. Mediates the antiparallel assembly of titin (TTN) molecules at the sarcomeric Z-disk

Cytoplasm, myofibril, sarcomere

Cardiomyopathy, familial hypertrophic, 25

A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.

Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen (By similarity). Contributes to calcium sequestration involved in muscular excitation/contraction (PubMed:10914677)

Endoplasmic reticulum membraneSarcoplasmic reticulum membrane

Brody disease

An autosomal recessive muscular disorder characterized by exercise-induced muscle stiffness and cramps primarily affecting the arms, legs, and eyelids, although more generalized muscle involvement may also occur.

May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity. May also regulate voltage-gated potassium channels. Plays a role in the sarcolemma repair mechanism of both skeletal muscle and cardiomyocytes that permits rapid resealing of membranes disrupted by mechanical stress (By similarity). Mediates the recruitment of CAVIN2 and CAVIN3 proteins to the caveolae (PubMed:19262564)

Golgi apparatus membraneCell membraneMembrane, caveolaCell membrane, sarcolemma

HyperCKmia

Characterized by persistent elevated levels of serum creatine kinase without muscle weakness.

Muscle-specific filamin, which plays a central role in sarcomere assembly and organization (PubMed:34405687). Critical for normal myogenesis, it probably functions as a large actin-cross-linking protein with structural functions at the Z lines in muscle cells. May be involved in reorganizing the actin cytoskeleton in response to signaling events (By similarity)

CytoplasmMembraneCytoplasm, cytoskeletonCytoplasm, myofibril, sarcomere, Z line

Myopathy, myofibrillar, 5

A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM5 is characterized by onset in adulthood, clinical features of a limb-girdle myopathy, and focal myofibrillar destruction.

This giant muscle protein may be involved in maintaining the structural integrity of sarcomeres and the membrane system associated with the myofibrils. Binds and stabilize F-actin

Cytoplasm, myofibril, sarcomereCytoplasm, cytoskeleton

Nemaline myopathy 2

A form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination.

Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix

Cell membrane, sarcolemmaCytoplasm, cytoskeleton

Muscular dystrophy, limb-girdle, autosomal recessive 4

An autosomal recessive degenerative myopathy characterized by pelvic and shoulder muscle wasting, onset usually in childhood and variable progression rate.

Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. Coexpression of both POMT1 and POMT2 is necessary for enzyme activity, expression of either POMT1 or POMT2 alone is insufficient (PubMed:12369018, PubMed:14699049, PubMed:28512129). Essentially dedicated to O-mannosylation of alpha-DAG1 and few other proteins but not of cadherins and protocaherins (PubMed:28512129)

Endoplasmic reticulum membrane

Muscular dystrophy-dystroglycanopathy congenital with impaired intellectual development B1

An autosomal recessive disorder characterized by congenital muscular dystrophy associated with intellectual disability and mild structural brain abnormalities.

Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. Forms regular bipolar thick filaments that, together with actin thin filaments, constitute the fundamental contractile unit of skeletal and cardiac muscle

Cytoplasm, myofibrilCytoplasm, myofibril, sarcomere

Cardiomyopathy, familial hypertrophic, 1

A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.

Plays a role in plasma membrane repair in a process involving annexins (PubMed:33496727). Does not exhibit calcium-activated chloride channel (CaCC) activity

Endoplasmic reticulum membraneCell membrane

Gnathodiaphyseal dysplasia

Rare skeletal syndrome characterized by bone fragility, sclerosis of tubular bones, and cemento-osseous lesions of the jawbone. Patients experience frequent bone fractures caused by trivial accidents in childhood; however the fractures heal normally without bone deformity. The jaw lesions replace the tooth-bearing segments of the maxilla and mandible with fibrous connective tissues, including various amounts of cementum-like calcified mass, sometimes causing facial deformities. Patients also have a propensity for jaw infection and often suffer from purulent osteomyelitis-like symptoms, such as swelling of and pus discharge from the gums, mobility of the teeth, insufficient healing after tooth extraction and exposure of the lesions into the oral cavity.

Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix

Cell membrane, sarcolemmaCytoplasm, cytoskeleton

Muscular dystrophy, limb-girdle, autosomal recessive 3

An autosomal recessive degenerative myopathy characterized by progressive muscle wasting from early childhood with loss of independent ambulation by teenage years. Muscle biopsy shows necrosis, decreased immunostaining for alpha sarcoglycan, and adhalin deficiency.

E3 ubiquitin ligase that plays a role in various biological processes including neural stem cell differentiation, innate immunity, inflammatory resonse and autophagy (PubMed:19349376, PubMed:31123703). Plays a role in virus-triggered induction of IFN-beta and TNF by mediating the ubiquitination of STING1. Mechanistically, targets STING1 for 'Lys-63'-linked ubiquitination which promotes the interaction of STING1 with TBK1 (PubMed:22745133). Regulates bacterial clearance and promotes autophagy in

CytoplasmMitochondrionEndoplasmic reticulum

Muscular dystrophy, limb-girdle, autosomal recessive 8

An autosomal recessive degenerative myopathy characterized by pelvic girdle, shoulder girdle and quadriceps muscle weakness. Clinical phenotype and severity are highly variable. Disease progression is slow and most patients remain ambulatory into the sixth decade of life.

Component of the sarcomere that tethers together nebulin (skeletal muscle) and nebulette (cardiac muscle) to alpha-actinin, at the Z lines

CytoplasmNucleusCytoplasm, myofibril, sarcomereCytoplasm, myofibril, sarcomere, Z line

Congenital myopathy 24

An autosomal recessive muscular disorder characterized by slowly progressive muscle weakness and atrophy, mainly affecting the lower limbs and neck. Some patients may have mild cardiac or respiratory involvement, but they do not have respiratory failure. Muscle biopsy shows nemaline bodies.

Controls reversibly actin polymerization and depolymerization in a pH-sensitive manner. Its F-actin depolymerization activity is regulated by association with CSPR3 (PubMed:19752190). It has the ability to bind G- and F-actin in a 1:1 ratio of cofilin to actin. It is the major component of intranuclear and cytoplasmic actin rods. Required for muscle maintenance. May play a role during the exchange of alpha-actin forms during the early postnatal remodeling of the sarcomere (By similarity)

Nucleus matrixCytoplasm, cytoskeleton

Nemaline myopathy 7

A form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. Nemaline myopathy type 7 presents at birth with hypotonia and generalized weakness. Major motor milestones are delayed, but independent ambulation is achieved.

Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex

Cytoplasm

Nemaline myopathy 6

A form of nemaline myopathy characterized by childhood onset of slowly progressive proximal muscle weakness, exercise intolerance, and slow movements with stiff muscles. Patients are unable to run or correct themselves from falling over.

Isoform 3 may have a role in regulating the growth and differentiation of arterial smooth muscle cells

Nucleus

Myopathy, centronuclear, 5

A form of centronuclear myopathy, a congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers. CNM5 features include severe neonatal hypotonia with respiratory insufficiency, difficulty feeding, and delayed motor development. Some patients die in infancy, and some develop dilated cardiomyopathy.

Involved in skeletal muscle development and differentiation. Regulates proliferation and differentiation of myoblasts and plays a role in myofibril assembly by promoting lateral fusion of adjacent thin fibrils into mature, wide myofibrils. Required for pseudopod elongation in transformed cells

CytoplasmCytoplasm, cytoskeletonCell projection, pseudopodiumCell projection, ruffleCytoplasm, myofibril, sarcomere, M lineSarcoplasmic reticulum membraneEndoplasmic reticulum membrane

Nemaline myopathy 9

An autosomal recessive form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. NEM9 phenotype is highly variable, ranging from death in infancy due to lack of antigravity movements, to slowly progressive distal muscle weakness with preserved ambulation later in childhood.

Is a key player in the control of plasma membrane curvature, membrane shaping and membrane remodeling. Required in muscle cells for the formation of T-tubules, tubular invaginations of the plasma membrane that function in depolarization-contraction coupling (PubMed:24755653). Is a negative regulator of endocytosis (By similarity). Is also involved in the regulation of intracellular vesicles sorting, modulation of BACE1 trafficking and the control of amyloid-beta production (PubMed:27179792). In

NucleusCytoplasmEndosomeCell membrane, sarcolemma, T-tubule

Myopathy, centronuclear, 2

A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers.

Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes. Could also bind muscle proteins such as actin to membrane complexes in muscle. May be involved not only in the filaments network, but also in the regulation of their dynamics. Structural component of muscle. Isoform 9 plays a major role in the maintenance of myofiber integrity

Cytoplasm, cytoskeletonCell junction, hemidesmosomeCell projection, podosome

Epidermolysis bullosa simplex 5C, with pyloric atresia

A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. EBS5C is an autosomal recessive disorder characterized by severe skin blistering at birth and congenital pyloric atresia. Death usually occurs in infancy.

Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion. Plays a role in the sarcolemma repair mechanism of both skeletal muscle and cardiomyocytes that permits rapid resealing of membranes disrupted by mechanical stress (By similarity)

Cell membrane, sarcolemmaCytoplasmic vesicle membraneCell membraneLate endosome membrane

Muscular dystrophy, limb-girdle, autosomal recessive 2

An autosomal recessive degenerative myopathy characterized by weakness and atrophy starting in the proximal pelvifemoral muscles, with onset in the late teens or later, massive elevation of serum creatine kinase levels and slow progression. Scapular muscle involvement is minor and not present at onset. Upper limb girdle involvement follows some years after the onset in lower limbs.

Collagen VI acts as a cell-binding protein

Secreted, extracellular space, extracellular matrix

Bethlem myopathy 1A

A form of Bethlem myopathy, a slowly progressive muscular dystrophy characterized by joint contractures, most frequently affecting the elbows and ankles, and muscle weakness and wasting involving the proximal and extensor muscles more than the distal and flexor ones. The clinical onset more often occurs in childhood or adulthood, but it can be prenatal with decreased fetal movements or neonatal with hypotonia. The hallmark of Bethlem myopathy is long finger flexion contractures. Inheritance can be autosomal dominant or autosomal recessive.

Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells

Cytoplasm, cytoskeleton

Congenital myopathy 2A, typical, autosomal dominant

A muscular disorder characterized by generalized muscle weakness, delayed motor milestones, hypotonia, and muscle fiber abnormalities on histologic examination. Histologic findings include abnormal thread- or rod-like structures (nemaline rods), intranuclear rods, clumped filaments, cores, or fiber-type disproportion. The spectrum of clinical phenotypes ranges from severe neonatal presentations to onset of a milder disorder in childhood.

May function as an adapter in striated muscle to couple protein kinase C-mediated signaling via its LIM domains to the cytoskeleton

Cytoplasm, perinuclear regionCell projection, pseudopodiumCytoplasm, cytoskeletonCytoplasm, myofibril, sarcomere, Z line

Cardiomyopathy, dilated, 1C, with or without left ventricular non-compaction

A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. Cardiomyopathy dilated type 1C is associated with left ventricular non-compaction in some patients. Left ventricular non-compaction is characterized by numerous prominent trabeculations and deep intertrabecular recesses in hypertrophied and hypokinetic segments of the left ventricle.

Catalyzes the transfer of a ribitol-phosphate from CDP-ribitol to the distal N-acetylgalactosamine of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1) (PubMed:26923585, PubMed:27194101, PubMed:29477842). This constitutes the first step in the formation of the ribitol 5-phosphate tandem repeat which links the phosphorylated O-mannosyl trisaccharide to the ligan

Golgi apparatus membraneCytoplasmNucleus

Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A4

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.

Muscle-specific type III intermediate filament essential for proper muscular structure and function. Plays a crucial role in maintaining the structure of sarcomeres, inter-connecting the Z-disks and forming the myofibrils, linking them not only to the sarcolemmal cytoskeleton, but also to the nucleus and mitochondria, thus providing strength for the muscle fiber during activity (PubMed:25358400). In adult striated muscle they form a fibrous network connecting myofibrils to each other and to the

Cytoplasm, myofibril, sarcomere, Z lineCytoplasmCell membrane, sarcolemmaNucleusCell tipNucleus envelope

Myopathy, myofibrillar, 1

A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM1 is characterized by skeletal muscle weakness associated with cardiac conduction blocks, arrhythmias, restrictive heart failure, and accumulation of desmin-reactive deposits in cardiac and skeletal muscle cells.

Catalytic subunit of the GMPPA-GMPPB mannose-1-phosphate guanylyltransferase complex (PubMed:33986552). Catalyzes the formation of GDP-mannose, an essential precursor of glycan moieties of glycoproteins and glycolipids (PubMed:33986552). Can catalyze the reverse reaction in vitro (PubMed:33986552). Together with GMPPA regulates GDP-alpha-D-mannose levels (PubMed:33986552)

Cytoplasm

Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A14

An autosomal recessive disorder characterized by congenital muscular dystrophy associated with brain anomalies, eye malformations, and profound intellectual disability. The disorder includes a severe form designated as Walker-Warburg syndrome and a less severe phenotype known as muscle-eye-brain disease. MDDGA14 features include increased muscle tone, microcephaly, cleft palate, feeding difficulties, severe muscle weakness, sensorineural hearing loss, cerebellar hypoplasia, ataxia, and retinal dysfunction.

Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules (PubMed:11741831, PubMed:16163667, PubMed:18268335, PubMed:18650434, PubMed:26115329). Repeated very high-level exercise increases the open probability of the channel and leads to Ca(2+) leaking into the cytoplasm (PubMed:18268335). Can also mediate the release of Ca(2+)

Sarcoplasmic reticulum membrane

Malignant hyperthermia 1

Autosomal dominant pharmacogenetic disorder of skeletal muscle and is one of the main causes of death due to anesthesia. In susceptible people, an MH episode can be triggered by all commonly used inhalational anesthetics such as halothane and by depolarizing muscle relaxants such as succinylcholine. The clinical features of the myopathy are hyperthermia, accelerated muscle metabolism, contractures, metabolic acidosis, tachycardia and death, if not treated with the postsynaptic muscle relaxant, dantrolene. Susceptibility to MH can be determined with the 'in vitro' contracture test (IVCT): observing the magnitude of contractures induced in strips of muscle tissue by caffeine alone and halothane alone. Patients with normal response are MH normal (MHN), those with abnormal response to caffeine alone or halothane alone are MH equivocal (MHE(C) and MHE(H) respectively).

Plays an important role in cell protection against oxidative stress and in the regulation of redox-related calcium homeostasis. Regulates the calcium level of the ER by protecting the calcium pump ATP2A2 against the oxidoreductase ERO1A-mediated oxidative damage. Within the ER, ERO1A activity increases the concentration of H(2)O(2), which attacks the luminal thiols in ATP2A2 and thus leads to cysteinyl sulfenic acid formation (-SOH) and SEPN1 reduces the SOH back to free thiol (-SH), thus restor

Endoplasmic reticulum membrane

Congenital myopathy 3 with rigid spine

An autosomal recessive, slowly progressive muscular disorder apparent from birth or early childhood and characterized by hypotonia, proximal muscle weakness, poor axial muscle strength, scoliosis and neck weakness, and a variable degree of spinal rigidity. Most patients remain ambulatory. Early ventilatory insufficiency may lead to death by respiratory failure. Additional features may include facial muscle weakness, amyotrophy, joint contractures, distal hyperlaxity, pulmonary hypertension with secondary cardiac dysfunction, and insulin resistance in patients with a low BMI. Skeletal muscle biopsy typically shows multiminicores and other abnormal non-specific myopathic findings.

Cytidylyltransferase required for protein O-linked mannosylation (PubMed:22522420, PubMed:22522421, PubMed:26687144, PubMed:26923585, PubMed:27130732, PubMed:27601598). Catalyzes the formation of CDP-ribitol nucleotide sugar from D-ribitol 5-phosphate (PubMed:26687144, PubMed:26923585, PubMed:27130732). CDP-ribitol is a substrate of FKTN during the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carboh

Cytoplasm, cytosol

Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A7

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.

Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a key regulator of skeletal muscle development (PubMed:23746549). The BCR(KLHL40) complex acts by mediating ubiquitination and degradation of TFDP1, thereby regulating the activity of the E2F:DP transcription factor complex (By similarity). Promotes stabilization of LMOD3 by acting as a negative regulator of LMOD3 ubiquitination; the molecular process by which it negatively regulates ubiquitination of LM

CytoplasmCytoplasm, myofibril, sarcomere, A bandCytoplasm, myofibril, sarcomere, I band

Nemaline myopathy 8

A severe form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. NEM8 is characterized by fetal akinesia or hypokinesia, followed by contractures, fractures, respiratory failure, and swallowing difficulties apparent at birth. Most patients die in infancy. Skeletal muscle biopsy shows numerous small nemaline bodies, often with no normal myofibrils.

Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1) (PubMed:26923585, PubMed:27194101, PubMed:29477842, PubMed:31949166). This constitutes the second step in the formation of the ribose 5-phosphate tandem repeat which links the phos

Golgi apparatus membraneSecretedCell membrane, sarcolemmaRough endoplasmic reticulumCytoplasm

Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A5

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.

Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix

Cell membrane, sarcolemmaCytoplasm, cytoskeleton

Muscular dystrophy, limb-girdle, autosomal recessive 5

An autosomal recessive degenerative myopathy characterized by rapidly progressive muscle wasting from early childhood with loss of independent ambulation around age 12 years, dystrophic pattern on muscle biopsy, absence of gamma-sarcoglycan and normal dystrophin immunostaining.

Binds to actin filaments in muscle and non-muscle cells. Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction. Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments

Cytoplasm, cytoskeleton

Congenital myopathy 4A, autosomal dominant

A muscular disorder characterized by onset of muscle weakness in infancy or childhood. Most affected individuals show mildly delayed motor development, hypotonia, generalized muscle weakness, and weakness of the proximal limb muscles and neck muscles, resulting in difficulty running and easy fatigability. Many patients have respiratory insufficiency with reduced vital capacity. Skeletal muscle biopsy shows nemaline rod inclusions, subsarcolemmal 'cap' structures, and fiber-type disproportion.

Integral component of basement membranes. Component of the glomerular basement membrane (GBM), responsible for the fixed negative electrostatic membrane charge, and which provides a barrier which is both size- and charge-selective. It serves as an attachment substrate for cells. Plays essential roles in vascularization. Critical for normal heart development and for regulating the vascular response to injury. Also required for avascular cartilage development (PubMed:12435733, PubMed:15591058, Pub

Secreted, extracellular space, extracellular matrix, basement membraneSecreted

Schwartz-Jampel syndrome

Rare autosomal recessive disorder characterized by permanent myotonia (prolonged failure of muscle relaxation) and skeletal dysplasia, resulting in reduced stature, kyphoscoliosis, bowing of the diaphyses and irregular epiphyses.

Key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The size and extensibility of the cross-links are the main determinants of sarcomere extensibility properties of muscle. In non-muscle cells, seems to play a role in chromosome condensation and chromosome segregation during mitosis. Might link the lamina network to ch

CytoplasmNucleus

Myopathy, myofibrillar, 9, with early respiratory failure

An autosomal dominant myopathy characterized by adulthood onset of weakness in proximal, distal, axial and respiratory muscles. Pelvic girdle weakness, foot drop and neck weakness are the main symptoms at onset, but ultimately the weakness usually involves the proximal compartment of both upper and lower limbs. Additional features include variable degrees of Achilles tendon contractures, spinal rigidity and muscle hypertrophy. Respiratory involvement often leads to requirement for non-invasive ventilation support.

Essential for the organization of sarcomeric actin thin filaments in skeletal muscle (PubMed:25250574). Increases the rate of actin polymerization (PubMed:25250574)

CytoplasmCytoplasm, myofibril, sarcomere, M lineCytoplasm, myofibril, sarcomere, A bandCytoplasm, cytoskeleton

Nemaline myopathy 10

An autosomal recessive severe form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. NEM10 is characterized by early-onset generalized muscle weakness and hypotonia with respiratory insufficiency and feeding difficulties. Additional features include arthrogryposis or congenital contractures, ophthalmoplegia, a history of prematurity, reduced fetal movements, and polyhydramnios. Most patients die of respiratory failure in early infancy.

Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. Coexpression of both POMT1 and POMT2 is necessary for enzyme activity, expression of either POMT1 or POMT2 alone is insufficient (PubMed:14699049, PubMed:28512129). Essentially dedicated to O-mannosylation of alpha-DAG1 and few other proteins but not of cadherins and protocaherins (PubMed:28512129)

Endoplasmic reticulum membrane

Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A2

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.

The dystroglycan complex is involved in a number of signaling events and processes including laminin deposition and extracellular matrix assembly, acetylcholine receptor clustering, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cell migration, epithelial polarization, and epithelium branching morphogenesis (By similarity). Required for the formation of photoreceptor ribbon synapses, and long-term maintenance of inhibitory synapses in cerebellar Purkinje cel

Secreted, extracellular spaceSecreted, extracellular space, extracellular matrix, basement membraneSynapseCell membraneCytoplasm, cytoskeletonNucleus, nucleoplasmCell membrane, sarcolemmaPostsynaptic cell membrane

Muscular dystrophy-dystroglycanopathy limb-girdle C9

An autosomal recessive muscular dystrophy showing onset in early childhood, and associated with intellectual disability without structural brain anomalies.

Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix

Cell membrane, sarcolemmaCytoplasm, cytoskeleton

Muscular dystrophy, limb-girdle, autosomal recessive 6

An autosomal recessive degenerative myopathy initially affecting the proximal limb girdle musculature. Muscle from patients shows a complete loss of delta-sarcoglycan as well as of the others components of the sarcoglycan complex.

Binds to actin filaments in muscle and non-muscle cells. Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction. Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments. The non-muscle isoform may have a role in agonist-mediated receptor internalization

Cytoplasm, cytoskeleton

Congenital myopathy 23

An autosomal dominant muscular disorder characterized clinically by hypotonia and muscle weakness, and a static or slowly progressive clinical course. Disease onset ranges from birth to childhood. Histologic examination of muscle fibers shows various anomalies including fiber type disproportion, an irregular myofibrillar network, abnormal thread-like or rod-shaped structures, and cap-like structures which are well demarcated and peripherally located under the sarcolemma with abnormal accumulation of sarcomeric proteins.

Protein O-mannose kinase that specifically mediates phosphorylation at the 6-position of an O-mannose of the trisaccharide (N-acetylgalactosamine (GalNAc)-beta-1,3-N-acetylglucosamine (GlcNAc)-beta-1,4-mannose) to generate phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-1,3-N-acetylglucosamine-beta-1,4-(phosphate-6-)mannose). Phosphorylated O-mannosyl trisaccharide is a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like d

Endoplasmic reticulum membrane

Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A12

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.