6o1q

Structural highlights

Disease

NPHP1_HUMAN Defects in NPHP1 are the cause of nephronophthisis type 1 (NPHP1) [MIM:256100; also known as familial juvenile nephronophthisis 1. NPHP1 is 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.^[1] Defects in NPHP1 are the cause of Senior-Loken syndrome type 1 (SLSN1) [MIM:266900; also known as juvenile nephronophthisis with Leber amaurosis. SLSN is a renal-retinal disorder characterized by progressive wasting of the filtering unit of the kidney, with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life.^[2] Defects in NPHP1 are the cause of Joubert syndrome type 4 (JBTS4) [MIM:609583. JBTS is an autosomal recessive 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. JBTS4 is a phenotypically mild form.^[3]

Function

NPHP1_HUMAN Together with BCAR1 it may play a role in the control of epithelial cell polarity. 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. May play a role in the regulation of intraflagellar transport (IFT) during cilia assembly. Required for normal retina development. In connecting photoreceptor cilia influences the movement of some IFT proteins such as IFT88 and WDR19. Involved in spermatogenesis (By similarity).

References

1. ↑ Betz R, Rensing C, Otto E, Mincheva A, Zehnder D, Lichter P, Hildebrandt F. Children with ocular motor apraxia type Cogan carry deletions in the gene (NPHP1) for juvenile nephronophthisis. J Pediatr. 2000 Jun;136(6):828-31. PMID:10839884
2. ↑ Caridi G, Murer L, Bellantuono R, Sorino P, Caringella DA, Gusmano R, Ghiggeri GM. Renal-retinal syndromes: association of retinal anomalies and recessive nephronophthisis in patients with homozygous deletion of the NPH1 locus. Am J Kidney Dis. 1998 Dec;32(6):1059-62. PMID:9856524
3. ↑ Parisi MA, Bennett CL, Eckert ML, Dobyns WB, Gleeson JG, Shaw DW, McDonald R, Eddy A, Chance PF, Glass IA. The NPHP1 gene deletion associated with juvenile nephronophthisis is present in a subset of individuals with Joubert syndrome. Am J Hum Genet. 2004 Jul;75(1):82-91. Epub 2004 May 11. PMID:15138899 doi:10.1086/421846