NPHP1

Chr 2

nephrocystin 1

Also known as: JBTS4, NPH1, SLSN1

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]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNephronophthisis 1
UniProtSenior-Loken syndrome 1
UniProtJoubert syndrome 4

Clinical highlights

Gene-disease validity (ClinGen)
nephronophthisis 1 · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
24
Pubs (1 yr)
P/LP submissions
P/LP missense
0.97
LOEUF
LOF
Mechanism· G2P
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GeneReview available — NPHP1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.73 (0.550.97)
00.351.4
Missense OE?0.97 (0.891.05)
00.61.4
Synonymous OE?0.92
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.