Required for the assembly of axonemal inner and outer dynein arms. Involved in preassembly of dyneins into complexes before their transport into cilia

CytoplasmDynein axonemal particle

Ciliary dyskinesia, primary, 2

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.

Participates in the apoptotic response to DNA damage. Isoforms containing the transactivation domain are pro-apoptotic, isoforms lacking the domain are anti-apoptotic and block the function of p53 and transactivating p73 isoforms. May be a tumor suppressor protein. Is an activator of FOXJ1 expression (By similarity). It is an essential factor for the positive regulation of lung ciliated cell differentiation (PubMed:34077761)

NucleusCytoplasm

Ciliary dyskinesia, primary, 47, and lissencephaly

A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD47 is an autosomal recessive form characterized by onset soon after birth or in early childhood. Affected individuals also have neurologic features, such as impaired intellectual development and central hypotonia, associated with structural brain abnormalities, most notably lissencephaly and thin or absent corpus callosum. No situs abnormalities have been observed.

Required for assembly and function of cilia and flagella

Cytoplasm, cytoskeleton, cilium axoneme

Spermatogenic failure 98

An autosomal recessive, male infertility disorder characterized by abnormal sperm morphology, and reduced sperm concentration and motility.

Required for kinetochore function and chromosome segregation in mitosis. Required for kinetochore localization of dynein, LIS1, NDE1 and NDEL1. Regulates recycling of the plasma membrane by acting as a link between recycling vesicles and the microtubule network though its association with STX4 and SNAP25. Acts as a potential inhibitor of pocket protein-mediated cellular processes during development by regulating the activity of RB proteins during cell division and proliferation. May play a regul

Cytoplasm, perinuclear regionNucleus matrixChromosome, centromere, kinetochoreCytoplasm, cytoskeleton, spindle

Stromme syndrome

An autosomal recessive congenital disorder characterized by intestinal atresia, ocular anomalies, microcephaly, and renal and cardiac abnormalities in some patients. The disease has features of a ciliopathy, and lethality in early childhood is observed in severe cases.

Required for assembly of dynein regulatory complex (DRC) and inner dynein arm (IDA) complexes, which are responsible for ciliary beat regulation, thereby playing a central role in motility in cilia and flagella (PubMed:21131974). Probably acts together with CCDC39 to form a molecular ruler that determines the 96 nanometer (nm) repeat length and arrangements of components in cilia and flagella (By similarity). Not required for outer dynein arm complexes assembly. Required for axonemal recruitment

CytoplasmCell projection, cilium

Ciliary dyskinesia, primary, 15

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.

Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia

Cell projection, cilium, flagellum

Ciliary dyskinesia, primary, 34

A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD34 inheritance is autosomal recessive.

Specifically required for generation of multiciliated cells, possibly by promoting a cell cycle state compatible with centriole amplification and maturation. Acts downstream of MCIDAS to promote mother centriole amplification and maturation in preparation for apical docking

CytoplasmNucleus, nucleolus

Ciliary dyskinesia, primary, 29

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD29 patients do not exhibit situs inversus, a congenital abnormality in which visceral organs are opposite to their normal positions (situs solitus) due to lateral transposition.

Plays a role in the cellular response to UV irradiation. Mediates G2/M cell cycle arrest, MEK autoactivation and ERK1/2-signaling pathway activation in response to UV irradiation. In ciliated cells of airways, it is involved in the regulation of mucociliary transport (PubMed:31959991)

Ciliary dyskinesia, primary, 44

A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD44 inheritance is autosomal recessive.

Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule (PubMed:25192045). Involved in mediating assembly of both ODAs and their axonemal docking complex onto ciliary microtubules (PubMed:25192045)

Cytoplasm, cytoskeleton, cilium basal bodyCytoplasm, cytoskeleton, microtubule organizing center, centrosome, centrioleCytoplasm, cytoskeleton, cilium axoneme

Ciliary dyskinesia, primary, 30

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Patients may exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.

Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia (By similarity). Functions as a protein kinase A-anchoring protein that scaffolds the cAMP-dependent protein kinase holoenzyme. May serve as a point of convergence for MAPK and PKA signaling in cilia (PubMed:19684019)

Cytoplasm, cytoskeleton, cilium axonemeCytoplasm, cytoskeleton, flagellum axoneme

Ciliary dyskinesia, primary, 32

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia.

Required for assembly of dynein regulatory complex (DRC) and inner dynein arm (IDA) complexes, which are responsible for ciliary beat regulation, thereby playing a central role in motility in cilia and flagella (PubMed:21131972). Probably acts together with CCDC40 to form a molecular ruler that determines the 96 nanometer (nm) repeat length and arrangements of components in cilia and flagella (By similarity). Not required for outer dynein arm complexes assembly (PubMed:21131972)

Cytoplasm, cytoskeleton, cilium axoneme

Ciliary dyskinesia, primary, 14

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.

Involved in the cross-linking of microtubules and microfilaments (PubMed:12584248, PubMed:24706950). Regulates microtubule dynamics and stability by interacting with microtubule plus-end tracking proteins, such as MAPRE1, to regulate microtubule growth along actin stress fibers (PubMed:24706950). Enhances ADORA2-mediated adenylyl cyclase activation by acting as a scaffold to recruit trimeric G-protein complexes to ADORA2A (By similarity). Regulates ciliary orientation and performance in cells lo

Cytoplasm, cytoskeletonCell membraneCytoplasm, cytoskeleton, stress fiberCytoplasm, cytoskeleton, cilium basal body

Ciliary dyskinesia, primary, 41

A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD41 inheritance is autosomal recessive.

Plays a role in axonemal structure organization and motility (PubMed:23891469, PubMed:23891471). Involved in axonemal pre-assembly of inner and outer dynein arms (IDA and ODA, respectively) for proper axoneme building for cilia motility (By similarity). May act by indirectly regulating transcription of dynein proteins (By similarity)

CytoplasmCytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriolar satelliteApical cell membraneDynein axonemal particle

Ciliary dyskinesia, primary, 22

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Patients may exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.

Required for ciliary motility

Cell projection, ciliumCytoplasm, cytoskeleton, cilium axonemeCell projection, cilium, flagellum

Ciliary dyskinesia, primary, 5

An autosomal recessive form of primary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. CILD5 is characterized by early onset of a progressive decline in lung function due to an inability to clear mucus and particles from the airways. Affected individuals have recurrent infections of the sinuses, ears, airways, and lungs. Sperm motility is also decreased. Individuals with CILD5 do not have situs inversus.

Part of the multisubunit axonemal ATPase complexes that generate the force for cilia motility and govern beat frequency (By similarity). Component of the outer arm dynein (ODA). May be involved in a mechanosensory feedback mechanism controlling ODA activity based on external conformational cues by tethering the outer arm dynein heavy chain (DNAH5) to the microtubule within the axoneme (By similarity). Important for ciliary function in the airways and for the function of the cilia that produce th

Cytoplasm, cytoskeleton, cilium axoneme

Ciliary dyskinesia, primary, 16

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.

Required for cytoplasmic pre-assembly of axonemal dyneins, thereby playing a central role in motility in cilia and flagella. Involved in pre-assembly of dynein arm complexes in the cytoplasm before intraflagellar transport loads them for the ciliary compartment

CytoplasmDynein axonemal particle

Ciliary dyskinesia, primary, 10

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.

Serine/threonine protein kinase which plays an important role in the sonic hedgehog (Shh) pathway by regulating the activity of GLI transcription factors (PubMed:10806483). Controls the activity of the transcriptional regulators GLI1, GLI2 and GLI3 by opposing the effect of SUFU and promoting their nuclear localization (PubMed:10806483). GLI2 requires an additional function of STK36 to become transcriptionally active, but the enzyme does not need to possess an active kinase catalytic site for th

CytoplasmNucleusCytoplasm, cytoskeleton, cilium axoneme

Ciliary dyskinesia, primary, 46

A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD46 is an autosomal recessive form. No situs abnormalities have been observed.

Transcription regulator specifically required for multiciliate cell differentiation (PubMed:25048963). Acts in a multiprotein complex containing E2F4 and E2F5 that binds and activates genes required for centriole biogenesis. Required for the deuterosome-mediated acentriolar pathway (PubMed:25048963). Plays a role in mitotic cell cycle progression by promoting cell cycle exit. Modulates GMNN activity by reducing its affinity for CDT1 (PubMed:21543332, PubMed:24064211)

Nucleus

Ciliary dyskinesia, primary, 42

A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Other more variable features may include infertility and mild hydrocephalus. Patients with this form of the disorder do not have situs abnormalities. CILD42 inheritance is autosomal recessive.

Component of the centrioles controlling mother and daughter centrioles length. Recruits to the centriole IFT88 and centriole distal appendage-specific proteins including CEP164 (By similarity). Involved in the biogenesis of the cilium, a centriole-associated function. The cilium is a cell surface projection found in many vertebrate cells required to transduce signals important for development and tissue homeostasis (PubMed:33934390). Plays an important role in development by regulating Wnt signa

Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centrioleCytoplasm, cytoskeleton, cilium basal bodyNucleusCytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriolar satellite

Orofaciodigital syndrome 1

A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by abnormalities in the oral cavity, face, and digits and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD1 is X-linked dominant syndrome, lethal in males. Craniofacial findings consist of facial asymmetry, hypertelorism, median cleft, or pseudocleft of the upper lip, hypoplasia of the alae nasi, oral clefts and abnormal frenulea, tongue anomalies (clefting, cysts, hamartoma), and anomalous dentition involving missing or extra teeth. Asymmetric brachydactyly and/or syndactyly of the fingers and toes occur frequently. Approximately 50% of OFD1 females have some degree of intellectual disability. Some patients have structural central nervous system anomalies such as agenesis of the corpus callosum, cerebellar agenesis, or a Dandy-Walker malformation. Patients with OFD1 can develop fibrocystic disease of the liver and pancreas, in addition to polycystic kidneys.

Component of dynein, a family of motor proteins essential for movement along microtubules (By similarity). Required for structural and functional integrity of cilia (By similarity). Part of the dynein complex of respiratory cilia

Dynein axonemal particleCytoplasm, cytoskeleton, cilium axonemeCell projection, cilium, flagellumCytoplasm, cytoskeleton

Ciliary dyskinesia, primary, 1

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.

Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia (PubMed:19200523). Essential for both the radial spoke head assembly and the central pair microtubule stability in ependymal motile cilia (By similarity). Required for motility of olfactory and neural cilia and for the structural integrity of ciliary axonemes in both 9+0 and 9+2 motile cilia (By similarity)

Cytoplasm, cytoskeleton, cilium axonemeCytoplasm, cytoskeleton, flagellum axonemeCell projection, kinocilium

Ciliary dyskinesia, primary, 12

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit situs inversus, due to dysfunction of monocilia at the embryonic node and randomization of left-right body asymmetry. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.

Dynein-attachment factor required for cilia motility

CytoplasmCell projection, cilium, flagellum

Ciliary dyskinesia, primary, 17

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.

As part of the central apparatus of the cilium axoneme may play a role in cilium movement. May play an important role in sperm architecture and function

Cytoplasm, cytoskeleton, cilium axonemeCytoplasm, cytoskeleton, flagellum axoneme

Ciliary dyskinesia, primary, 49, without situs inversus

A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD49 is an autosomal recessive form without situs abnormalities. Affected males also show infertility due to defective flagellar morphology and function.

Cytoplasmic protein involved in the delivery of the dynein machinery to the motile cilium. It is required for the assembly of the axonemal dynein inner and outer arms, two structures attached to the peripheral outer doublet A microtubule of the axoneme, that play a crucial role in cilium motility

CytoplasmDynein axonemal particle

Ciliary dyskinesia, primary, 18

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.

Functions as part of axonemal radial spoke complexes, which play an important part in the motility of sperm and cilia (By similarity). In vitro, does not display nucleoside diphosphate kinase (NDPK) activity (Probable) (PubMed:16313181, PubMed:9742940). Exhibits a 3'-5'-DNA exonuclease activity that removes single nucleotides from the 3' terminus of single-stranded DNA substrates and digests overhanging mismatched 3' termini from double-stranded DNA substrates, possibly participating in DNA nucl

Cell projection, ciliumCytoplasm, cytoskeleton, flagellum axoneme

Ciliary dyskinesia, primary, 48, without situs inversus

A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD48 is an autosomal recessive form. No situs abnormalities have been observed.

Cytoplasmic protein that plays a role in the proper assembly of dynein arm complexes in motile cilia in both respiratory cells and sperm flagella

Cytoplasm

Ciliary dyskinesia, primary, 45

A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD45 is an autosomal recessive form characterized by onset of symptoms in infancy or early childhood. Male patients have infertility due to immotile sperm.

Component of the axonemal radial spoke head which plays an important role in ciliary motility (PubMed:19200523). Essential for triplet radial spokes (RS1, RS2 and RS3) head assembly in the motile cilia (By similarity)

Cytoplasm, cytoskeleton, cilium axonemeCell projection, cilium

Ciliary dyskinesia, primary, 11

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit situs inversus, due to dysfunction of monocilia at the embryonic node and randomization of left-right body asymmetry. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.

Force generating protein of respiratory cilia (By similarity). Produces force towards the minus ends of microtubules (By similarity). Key component of dynein, a family of motor proteins essential for movement along microtubules (By similarity). Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP (By similarity). Required for structural and functional integrity of the cilia of ependymal cells lining the brain ventricles (By similarity)

Cytoplasm, cytoskeleton, cilium axoneme

Ciliary dyskinesia, primary, 3

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.

Involved in dynein arm assembly, is important for expression and transporting outer dynein arm (ODA) proteins from the cytoplasm to the cilia (PubMed:23122589, PubMed:23527195, PubMed:33403504). Acts as a crucial component in the formation and motility of spermatozoal flagella (PubMed:33403504)

CytoplasmCell projection, ciliumDynein axonemal particleCell projection, cilium, flagellum

Ciliary dyskinesia, primary, 19

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.

Force generating protein of cilia required for sperm flagellum motility. Produces force towards the minus ends of microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Required in spermatozoa for the formation of the inner dynein arms and biogenesis of the axoneme (PubMed:24360805)

Cytoplasm, cytoskeleton, cilium axonemeCell projection, cilium, flagellum

Spermatogenic failure 18

An infertility disorder caused by spermatogenesis defects and characterized by abnormally shaped spermatozoa in the semen of affected individuals. SPGF18 patients present with primary infertility and multiple morphological abnormalities of sperm flagella that result in impaired sperm mobility. Abnormalities include absent, short, coiled, bent, and irregular flagella. SPGF18 inheritance is autosomal recessive.

Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule. Seems to regulate the assembly of both ODAs and their axonemal docking complex onto ciliary microtubules (By similarity). Regulates ciliary and flagellar motility and is required for cilia-driven determination of body laterality (By similarity)

Cytoplasm, cytoskeleton, cilium axonemeCell projection, ciliumCell projection, cilium, flagellum

Ciliary dyskinesia, primary, 53

A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Some patients exhibit randomization of left-right body asymmetry and situs inversus. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. CILD53 is an autosomal recessive form characterized by randomization of the left-right body asymmetry and respiratory symptoms.

Component of dynein, a family of motor proteins essential for movement along microtubules (By similarity). Required for structural and functional integrity of cilia (By similarity). Part of the dynein complex of respiratory cilia

Cytoplasm, cytoskeleton, cilium axonemeDynein axonemal particle

Ciliary dyskinesia, primary, 9

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.

Required for axonemal dynein assembly and ciliary motility in ciliated organs, including Kupffer's vesicle, during embryogenesis (PubMed:36074124). Facilitates the onset of robust cilia motility during development (PubMed:36074124)

Cytoplasm, cytoskeleton, flagellum basal bodyCytoplasm, cytoskeleton, flagellum axoneme

Ciliary dyskinesia, primary, 52

A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD52 is an autosomal recessive form characterized by laterality defects, and mild respiratory symptoms.

Required for correct axoneme development in spermatozoa. Important for normal development of the manchette and sperm head morphology. Essential for male fertility. Plays a role in localization of the intraflagellar transport protein IFT20 to the manchette, suggesting function as an adapter for dynein-mediated protein transport during spermatogenesis (PubMed:31048344, PubMed:31151990, PubMed:31278745). Also plays a role in bone growth where it seems to be required for normal osteoblast differenti

Cell projection, cilium, flagellumCytoplasmGolgi apparatus

Spermatogenic failure 43

An autosomal recessive infertility disorder characterized by asthenospermia due to multiple morphologic abnormalities of sperm flagella, including short, absent, coiled, and bent flagella.

Acts as a guanine-nucleotide releasing factor (GEF) for RAB8A and RAB37 by promoting the conversion of inactive RAB-GDP to the active form RAB-GTP (PubMed:20631154). GEF activity towards RAB8A may facilitate ciliary trafficking by modulating ciliary intracellular localization of RAB8A (PubMed:20631154). GEF activity towards RAB37 maintains autophagic homeostasis and retinal function (By similarity). Involved in photoreceptor integrity (By similarity). May control cilia formation by regulating ac

Cytoplasm, cytoskeleton, flagellum axonemeGolgi apparatusCell projection, ciliumCytoplasm, cytoskeleton, microtubule organizing center, centrosomeCytoplasm, cytoskeleton, cilium basal bodyCytoplasm, cytoskeleton, cilium axoneme

Retinitis pigmentosa 3

An X-linked retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. In RP3, affected males have a severe phenotype, and carrier females show a wide spectrum of clinical features ranging from completely asymptomatic to severe retinitis pigmentosa. Heterozygous women can manifest a form of choroidoretinal degeneration which is distinguished from other types by the absence of visual defects in the presence of a brilliant, scintillating, golden-hued, patchy appearance most striking around the macula, called a tapetal-like retinal reflex.

Plays a role in motile cilium function, possibly by acting on outer dynein arm assembly (PubMed:24094744). Seems to be important for initiation rather than maintenance of cilium motility (By similarity). Required for correct positioning of the cilium at the apical cell surface, suggesting an additional role in the planar cell polarity (PCP) pathway (By similarity). May suppress canonical Wnt signaling activity (By similarity)

CytoplasmCytoplasm, cytoskeleton, cilium basal body

Ciliary dyskinesia, primary, 26

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Patients may exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.

Required for the assembly of dynein arms

Cell projection, cilium

Ciliary dyskinesia, primary, 39

A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Some patients exhibit randomization of left-right body asymmetry and situs inversus. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. CILD39 inheritance is autosomal recessive.

Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes. Plays an important role in the assembly of the N-DRC linker (By similarity). Plays dual roles at both the primary (or non-motile) cilia to regulate hedgehog signaling and in motile cilia to coordinate cilia movement. Required for proper motile cilia functioning (PubMed:263875

CytoplasmCytoplasm, cytoskeletonCell projection, cilium, flagellumCytoplasm, cytoskeleton, cilium axonemeCytoplasm, cytoskeleton, cilium basal bodyGolgi apparatusCell projection, ciliumCytoplasm, cytoskeleton, flagellum axoneme

Ciliary dyskinesia, primary, 33

A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD33 inheritance is autosomal recessive.

Force generating protein that plays an important role in respiratory cilia and sperm flagella beating (PubMed:34476482). Produces force towards the minus ends of microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP (By similarity)

Cytoplasm, cytoskeleton, cilium axonemeCell projection, cilium, flagellum

Ciliary dyskinesia, primary, 50

A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD50 is an autosomal recessive form characterized by chronic sinusitis and bronchitis as well as male infertility. Patient sperm have markedly reduced progressive motility, and multiple morphologic abnormalities of the flagella.

Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule. Involved in mediating assembly of both ODAs and their axonemal docking complex onto ciliary microtubules (By similarity)

Cytoplasm, cytoskeleton, cilium axoneme

Ciliary dyskinesia, primary, 20

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Patients may exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. Unlike other forms of CILD characterized by reduced fertility, patients with CILD20 do not appear to be infertile.

Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule (PubMed:27486780). Involved in mediating assembly of both ODAs and their axonemal docking complex onto ciliary microtubules (PubMed:23849778)

Cytoplasm, cytoskeleton, cilium axonemeCytoplasm, cytoskeleton, cilium basal body

Ciliary dyskinesia, primary, 23

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Patients may exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.

Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes (By similarity). Plays a critical role in the assembly of N-DRC and also stabilizes the assembly of multiple inner dynein arms and radial spokes. Coassembles with DRC1 to form a central scaffold needed for assembly of the N-DRC and its attachment to the outer doublet microtubu

Cytoplasm, cytoskeleton, flagellum basal bodyCell projection, cilium, flagellumCytoplasm, cytoskeleton, flagellum axoneme

Ciliary dyskinesia, primary, 27

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Patients may exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.

May play a role in the cytoplasmic assembly of the ciliary dynein arms (By similarity). May play a role in fertilization. Binds GTP and has GTPase activity

CytoplasmDynein axonemal particle

Ciliary dyskinesia, primary, 28

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Patients may exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.

May be a transcriptional activator. May be involved in chromatin remodeling (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape

CytoplasmNucleusCell projection, cilium membraneCytoplasm, cytoskeleton, flagellum axoneme

Ciliary dyskinesia, primary, 51

A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. CILD51 is an autosomal recessive form characterized by male infertility due to multiple morphologic abnormalities of the sperm flagella, resulting in severely reduced progressive motility. Affected individuals have recurrent upper and lower respiratory infections, and some exhibit dextrocardia and/or situs inversus.

Axonemal dynein assembly factor required for ciliary motility. Involved in neuronal migration during development of the cerebral neocortex. May regulate the stability and proteasomal degradation of the estrogen receptors that play an important role in neuronal differentiation, survival and plasticity

NucleusCytoplasmDynein axonemal particleCell projection, neuron projection

Dyslexia 1

A relatively common, complex cognitive disorder characterized by an impairment of reading performance despite adequate motivational, educational and intellectual opportunities. It is a multifactorial trait, with evidence for familial clustering and heritability.

Force generating protein required for cilia beating in respiratory epithelia (By similarity). Produces force towards the minus ends of microtubules (By similarity). Key component of dynein, a family of motor proteins essential for movement along microtubules (By similarity). Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP (By similarity). Required for structural and functional integrity of cilia (By similarity)

Cytoplasm, cytoskeleton, cilium axoneme

Ciliary dyskinesia, primary, 7

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.

Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule. Plays an essential role for the assembly of ODA-DC and for the docking of ODA in ciliary axoneme

Cytoplasm, cytoskeleton, cilium axoneme

Ciliary dyskinesia, primary, 35

A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Some patients exhibit randomization of left-right body asymmetry and situs inversus. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. CILD35 inheritance is autosomal recessive.

Cilium-specific protein required for the stability of the ciliary architecture. Plays a role in cytoplasmic preassembly of dynein arms. Involved in regulation of microtubule-based cilia and actin-based brush border microvilli

Cell projection, ciliumCytoplasmCytoplasm, cytoskeleton, spindle pole

Ciliary dyskinesia, primary, 13

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. At ultrastructural level, CILD13 is characterized by a marked reduction or absence of both dynein arms from the patients cilia.

Force generating protein required for cilia beating in respiratory epithelia (PubMed:30471717, PubMed:30471718). Produces force towards the minus ends of microtubules (PubMed:30471717, PubMed:30471718). Key component of dynein, a family of motor proteins essential for movement along microtubules (By similarity). Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP (PubMed:30471717, PubMed:30471718). Required for structural and functional integrity of

Cytoplasm, cytoskeleton, cilium axonemeCell projection, cilium, flagellum

Ciliary dyskinesia, primary, 40

A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Some patients exhibit randomization of left-right body asymmetry and situs inversus. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. CILD40 inheritance is autosomal recessive.

Promotes cell proliferation, G1/S cell cycle progression and induces expression of the cell cycle regulator CCND1 (PubMed:30009832). Regulates proliferation induced by pro-inflammatory cytokine response via activation of NFKB1 and PI3K/AKT signaling pathways (PubMed:30009832)

Cytoplasm

Esophageal cancer

A malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage.

Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia

CytoplasmChromosomeCytoplasm, cytoskeleton, cilium axonemeCytoplasm, cytoskeleton, flagellum axoneme

Ciliary dyskinesia, primary, 24

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Situs inversus is not observed in CILD24 patients.

Cilium- and flagellum-specific protein that plays a role in axonemal structure organization and motility. May play a role in outer and inner dynein arm assembly

CytoplasmCytoplasm, cytoskeleton, cilium axoneme

Ciliary dyskinesia, primary, 38

A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Some patients exhibit randomization of left-right body asymmetry and situs inversus. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. CILD38 inheritance is autosomal recessive.

Plays a role in cytoplasmic pre-assembly of axonemal dynein

CytoplasmGolgi apparatus, trans-Golgi network

Ciliary dyskinesia, primary, 36, X-linked

A form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Some patients exhibit randomization of left-right body asymmetry and situs inversus. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. CILD36 inheritance is X-linked recessive. About half of CILD36 patients have laterality defects due to ciliary dysfunction at the embryonic node.

Transcription factor specifically required for the formation of motile cilia (PubMed:31630787). Acts by activating transcription of genes that mediate assembly of motile cilia, such as CFAP157. Binds the DNA consensus sequences 5'-HWDTGTTTGTTTA-3' or 5'-KTTTGTTGTTKTW-3' (where H is not G, W is A or T, D is not C, and K is G or T). Activates the transcription of a variety of ciliary proteins in the developing brain and lung

Nucleus

Allergic rhinitis

A common disease with complex inheritance characterized by mucosal inflammation caused by allergen exposure.

Possesses an intrinsic kinase activity (PubMed:16313181). In vitro, does not exhibit nucleoside diphosphate kinase (NDPK) activity or disulfide bond-reducing activity (PubMed:11737268, PubMed:16313181). Additionally, exhibits a 3'-5'-DNA exonuclease activity that removes single nucleotides from the 3' terminus of single-stranded DNA substrates and digests overhanging mismatched 3' termini from double-stranded DNA substrates, suggesting a role in DNA nucleolytic processing (PubMed:16313181). May

Cytoplasm

Ciliary dyskinesia, primary, 6

A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.

May play a role in cilium morphogenesis and ciliary function

Cytoplasm, cytoskeleton, cilium axonemeCytoplasmCytoplasm, cytoskeleton

Ciliary dyskinesia, primary, 55

An autosomal recessive form of primary ciliary dyskinesia, a disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia. Male infertility may result from reduced motility of spermatozoa. Some CILD55 affected individuals also exhibit obstructive azoospermia.