NPHP1

Chr 2AR

nephrocystin 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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.974 OMIM phenotypes
Clinical SummaryNPHP1
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Gene-Disease Validity (ClinGen)
nephronophthisis 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — NPHP1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.97LOEUF
pLI 0.000
Z-score 1.69
OE 0.73 (0.550.97)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.23Z-score
OE missense 0.97 (0.891.05)
369 obs / 381.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.73 (0.550.97)
00.351.4
Missense OE0.97 (0.891.05)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 33 / 45.2Missense obs/exp: 369 / 381.4Syn Z: 0.78

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold
Clinical Literature
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