Involved in early and late steps in cilia formation. Its association with CCP110 is required for inhibition of primary cilia formation by CCP110 (PubMed:18694559). May play a role in early ciliogenesis in the disappearance of centriolar satellites and in the transition of primary ciliar vesicles (PCVs) to capped ciliary vesicles (CCVs). Required for the centrosomal recruitment of RAB8A and for the targeting of centriole satellite proteins to centrosomes such as of PCM1 (PubMed:24421332). Require

Cytoplasm, cytoskeleton, microtubule organizing center, centrosomeCytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriolar satelliteNucleusCell projection, ciliumCytoplasm, cytoskeleton, cilium basal bodyCytoplasm, cytoskeleton, microtubule organizing center, centrosome, centrioleCytoplasmic vesicle

Joubert syndrome 5

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 and renal disease. Joubert syndrome type 5 shares the neurologic and neuroradiologic features of Joubert syndrome together with severe retinal dystrophy and/or progressive renal failure characterized by nephronophthisis.

Required for normal ciliary development and function. Inhibits disheveled-1-induced canonical Wnt-signaling activity and may also play a role in the control of non-canonical Wnt signaling which regulates planar cell polarity. Probably acts as a molecular switch between different Wnt signaling pathways. Required for proper convergent extension cell movements

Cell projection, cilium

Nephronophthisis 3

An autosomal recessive disorder resulting in end-stage renal disease. It is characterized by polyuria, polydipsia, anemia. Onset of terminal renal failure occurr significantly later (median age, 19 years) than in juvenile nephronophthisis. Renal pathology is characterized by alterations of tubular basement membranes, tubular atrophy and dilation, sclerosing tubulointerstitial nephropathy, and renal cyst development predominantly at the corticomedullary junction.

Plays a role in microtubule organization and/or maintenance for the formation of primary cilia (PC), a microtubule-based structure that protrudes from the surface of epithelial cells. Plays a critical role in G2/M checkpoint and nuclear divisions. A key player in the DNA damage-activated ATR/ATM signaling cascade since it is required for the proper phosphorylation of H2AX, RPA, CHEK2 and CHEK1. Plays a critical role in chromosome segregation, acting as a mediator required for the maintenance of

Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centrioleNucleus

Nephronophthisis 15

An autosomal recessive disorder characterized by the association of nephronophthisis with Leber congenital amaurosis and retinal degeneration, often resulting in blindness during childhood. Additional features include seizures, cerebellar vermis hypoplasia, facial dysmorphism, bronchiectasis and liver failure. Nephronophthisis is a chronic tubulo-interstitial nephritis that progresses to end-stage renal failure.

Required for normal renal development and establishment of left-right axis. Probably acts as a molecular switch between different Wnt signaling pathways. Inhibits the canonical Wnt pathway by targeting cytoplasmic disheveled (DVL1) for degradation by the ubiquitin-proteasome. This suggests that it is required in renal development to oppose the repression of terminal differentiation of tubular epithelial cells by Wnt signaling. Involved in the organization of apical junctions in kidney cells toge

CytoplasmCytoplasm, cytoskeletonCytoplasm, cytoskeleton, spindleMembraneNucleusCell projection, cilium

Nephronophthisis 2

An autosomal recessive disorder resulting in end-stage renal disease. It is characterized by early onset and rapid progression. Phenotypic manifestations include enlarged kidneys, chronic tubulo-interstitial nephritis, anemia, hyperkalemic metabolic acidosis. Some patients also display situs inversus. Pathologically, it differs from later-onset nephronophthisis by the absence of medullary cysts and thickened tubular basement membranes, and by the presence of cortical microcysts.

As component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is involved in cilia function and/or assembly (PubMed:20889716). Essential for functional IFT-A assembly and ciliary entry of GPCRs (PubMed:20889716). Associates with the BBSome complex to mediate ciliary transport (By similarity)

Cell projection, ciliumCytoplasm, cytoskeleton, cilium basal bodyCell projection, cilium, photoreceptor outer segmentCell projection, cilium, flagellum

Cranioectodermal dysplasia 4

A disorder primarily characterized by craniofacial, skeletal and ectodermal abnormalities. Clinical features include craniosynostosis, narrow rib cage, short limbs, brachydactyly, hypoplastic and widely spaced teeth, sparse hair, skin laxity and abnormal nails. Nephronophthisis leading to progressive renal failure, hepatic fibrosis, heart defects, and retinitis pigmentosa have also been described.

Involved in ciliogenesis. The function in an early step in cilia formation depends on its association with CEP290/NPHP6 (PubMed:21565611, PubMed:23446637). Involved in regulation of the BBSome complex integrity, specifically for presence of BBS2 and BBS5 in the complex, and in ciliary targeting of selected BBSome cargos. May play a role in controlling entry of the BBSome complex to cilia possibly implicating CEP290/NPHP6 (PubMed:25552655)

Cytoplasm, cytoskeleton, microtubule organizing center, centrosomeCytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole

Senior-Loken syndrome 5

A renal-retinal disorder characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life.

Together with BCAR1 it may play a role in the control of epithelial cell polarity (By similarity). Involved in the organization of apical junctions in kidney cells together with NPHP4 and RPGRIP1L/NPHP8 (By similarity). Does not seem to be strictly required for ciliogenesis (By similarity). Seems to help to recruit PTK2B/PYK2 to cell matrix adhesions, thereby initiating phosphorylation of PTK2B/PYK2 and PTK2B/PYK2-dependent signaling (By similarity). May play a role in the regulation of intrafla

Cell junctionCell junction, adherens junctionCell projection, ciliumCytoplasm, cytoskeleton, cilium axonemeCell junction, tight junction

Nephronophthisis 1

An autosomal recessive inherited disease characterized by anemia, polyuria, polydipsia, isosthenuria and death in uremia. Symmetrical destruction of the kidneys involving both tubules and glomeruli occurs. The underlying pathology is a chronic tubulo-interstitial nephropathy with characteristic tubular basement membrane thickening and medullary cyst formation. Associations with extrarenal symptoms, especially ocular lesions, are frequent. The age at death ranges from about 4 to 15 years.

Plays an inhibitory role on IL13 signaling by binding to IL13RA1. Involved in suppression of IL13-induced STAT6 phosphorylation, transcriptional activity and DNA-binding. Recruits TRAF3 and DISC1 to the microtubules. Involved in kidney development and epithelial morphogenesis. Involved in the regulation of microtubule cytoskeleton organization. Is a negative regulator of microtubule stability, acting through the control of MAP4 levels (PubMed:26487268). Involved in ciliogenesis (By similarity)

Cytoplasm, cytoskeletonCell projection, ciliumCytoplasm, cytoskeleton, cilium axonemeCytoplasm, cytoskeleton, cilium basal body

Senior-Loken syndrome 9

A renal-retinal disorder characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life.

Plays a role in the establishment of cell polarity and epithelial lumen formation (By similarity). Also plays an essential role in ciliogenesis and subsequent Hedgehog signaling pathway that requires the presence of intact primary cilia for pathway activation. Mechanistically, interacts with and mediates RABEP2 centrosomal localization which is critical for ciliogenesis (PubMed:27224062)

Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centrioleCytoplasm, cytoskeleton, microtubule organizing center, centrosomeCytoplasm, cytoskeleton, cilium basal bodyCell junctionCytoplasm

Senior-Loken syndrome 7

A renal-retinal disorder characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life.

Involved in the organization of apical junctions; the function is proposed to implicate a NPHP1-4-8 module (PubMed:19755384, PubMed:21565611). Does not seem to be strictly required for ciliogenesis (PubMed:21565611). Required for building functional cilia. Involved in the organization of the subapical actin network in multiciliated epithelial cells. Seems to recruit INT to basal bodies of motile cilia which subsequently interacts with actin-modifying proteins such as DAAM1 (By similarity). In co

Cytoplasm, cytoskeleton, cilium basal bodyCytoplasm, cytoskeleton, microtubule organizing center, centrosomeCell junction, tight junctionNucleus

Nephronophthisis 4

An autosomal recessive inherited disease resulting in end-stage renal disease at age ranging between 6 and 35 years. It is a progressive tubulo-interstitial kidney disorder characterized by polydipsia, polyuria, anemia and growth retardation. The most prominent histological features are modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts.