NPHP1
Chr 2ARnephrocystin 1
Also known as: JBTS4, NPH1, SLSN1
The NPHP1 protein controls epithelial cell polarity and organizes apical junctions in kidney cells, while also regulating intraflagellar transport during cilia assembly and retinal development. Mutations cause autosomal recessive disorders including juvenile nephronophthisis (kidney disease), Senior-Loken syndrome (kidney and eye disease), and Joubert syndrome type 4 (cerebellar ataxia, oculomotor apraxia, psychomotor delay, and neonatal breathing abnormalities). This gene is extremely intolerant to loss-of-function variants, reflecting the critical nature of these ciliopathy syndromes.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
ClinVar Variant Classifications
700 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 28 | 0 | 38 | 0 | 66 |
Likely Pathogenic | 47 | 2 | 20 | 0 | 69 |
VUS | 3 | 176 | 39 | 3 | 221 |
Likely Benign | 0 | 7 | 155 | 156 | 318 |
Benign | 0 | 0 | 8 | 1 | 9 |
Conflicting | — | 5 | |||
| Total | 78 | 185 | 260 | 160 | 688 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NPHP1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools