NPHP1

NPHP1 is a human gene that encodes nephrocystin-1, a protein associated with ciliary function in the kidney. Nephrocystin-1 localizes to the primary cilium and to cell junctions in renal tubular epithelium, where it is thought to participate in ciliary signaling and the maintenance of epithelial polarity.

Mutations in NPHP1 cause nephronophthisis type 1, a recessive kidney disease characterized by tubulointerstitial fibrosis, cystic changes in the kidneys, and progressive loss of kidney function, often presenting in childhood or adolescence. Some individuals with NPHP1 mutations have the retinal degeneration and kidney disease seen in Senior-Løken syndrome.

Inheritance is autosomal recessive; affected individuals typically have two pathogenic variants, one inherited from each parent, and carriers are usually asymptomatic.

Among nephronophthisis genes, NPHP1 is one of the most commonly mutated, and a frequent cause of disease in affected families; a large homozygous or compound heterozygous deletion of the NPHP1 locus is a well-described recurrent mutation found in diverse populations.

Diagnosis is confirmed by genetic testing, often using targeted NPHP1 panels or exome/genome sequencing; imaging and renal function tests support clinical assessment.

Management is supportive and multidisciplinary, focusing on monitoring kidney function, blood pressure, growth, and treating complications; renal replacement therapy may be required in end-stage disease, and kidney transplantation is an option.

Research ongoing to elucidate nephrocystin-1 interactions with other nephrocystins and ciliary pathways, which may reveal targets for therapy in ciliopathies.