NPHP1

This gene encodes a protein with src homology domain 3 (SH3) patterns. This protein interacts with Crk-associated substrate, and it appears to function in the control of cell division, as well as in cell-cell and cell-matrix adhesion signaling, likely as part of a multifunctional complex localized in actin- and microtubule-based structures. Mutations in this gene cause familial juvenile nephronophthisis type 1, a kidney disorder involving both tubules and glomeruli. Defects in this gene are also associated with Senior-Loken syndrome type 1, also referred to as juvenile nephronophthisis with Leber amaurosis, which is characterized by kidney and eye disease, and with Joubert syndrome type 4, which is characterized by cerebellar ataxia, oculomotor apraxia, psychomotor delay and neonatal breathing abnormalities, sometimes including retinal dystrophy and renal disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Full Name

Nephrocystin 1

Function

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 intraflagellar transport (IFT) during cilia assembly. Required for normal retina development (By similarity).
In connecting photoreceptor cilia influences the movement of some IFT proteins such as IFT88 and WDR19. Involved in spermatogenesis (By similarity).

Biological Process

Actin cytoskeleton organization1 PublicationNAS:UniProtKB
Cell projection organizationISS:UniProtKB
Cell-cell adhesion1 PublicationNAS:UniProtKB
Positive regulation of bicellular tight junction assemblyManual Assertion Based On ExperimentIMP:UniProtKB
Protein localization involved in establishment of planar polarityManual Assertion Based On ExperimentIBA:GO_Central
Retina development in camera-type eyeISS:UniProtKB
Signal transduction1 PublicationNAS:UniProtKB
Spermatid differentiationISS:UniProtKB
Visual behavior1 PublicationNAS:UniProtKB

Cellular Location

Cell junction
Cell junction, adherens junction
Cell projection, cilium
Cytoplasm, cytoskeleton, cilium axoneme
Cell junction, tight junction
In the retinal photoreceptor cell layer, localizes at the connecting cilium (By similarity).
Colocalizes with E-cadherin and BCAR1 at or near the cell-cell adherens junctions (By similarity).
Localized to respiratory cilia axoneme (PubMed:16308564, PubMed:16885411).
Localized to the transition zone of respiratory cilia (PubMed:16885411).
Localized to the transition zone of photoreceptor-connecting cilia and renal monocilia (By similarity).
In cultured renal cells, it localizes diffusely in the cytoplasm but, as cells approach confluence, it accumulates at basolateral tight junctions (By similarity).

Involvement in disease

Nephronophthisis 1 (NPHP1):
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.
Senior-Loken syndrome 1 (SLSN1):
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.
Joubert syndrome 4 (JBTS4):
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 4 is a phenotypically mild form.

PTM

Phosphorylation by CK2 is required for the interaction with PACS1 and the targeting to the base region of cilia.