NPHP3

Chr 3AR

nephrocystin 3

Also known as: CFAP31, MKS7, NPH3, RHPD, RHPD1, SLSN3

This gene encodes a protein containing a coiled-coil (CC) domain, a tubulin-tyrosine ligase (TTL) domain, and a tetratrico peptide repeat (TPR) domain. The encoded protein interacts with nephrocystin, it is required for normal ciliary development, and it functions in renal tubular development. Mutations in this gene are associated with nephronophthisis type 3, and also with renal-hepatic-pancreatic dysplasia, and Meckel syndrome type 7. Naturally occurring read-through transcripts exist between this gene and the downstream ACAD11 (acyl-CoA dehydrogenase family, member 11) gene. [provided by RefSeq, Feb 2011]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 0.654 OMIM phenotypes
Clinical SummaryNPHP3
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Gene-Disease Validity (ClinGen)
nephronophthisis · 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.
📖
GeneReview available — NPHP3
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?
0.65LOEUF
pLI 0.000
Z-score 4.10
OE 0.50 (0.380.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.86Z-score
OE missense 0.91 (0.850.97)
627 obs / 690.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.50 (0.380.65)
00.351.4
Missense OE?0.91 (0.850.97)
00.61.4
Synonymous OE?0.89
01.21.6
LoF obs/exp: 38 / 76.7Missense obs/exp: 627 / 690.9Syn Z: 1.41
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveNPHP3-related Senior-Loken syndromeOTHERAR
definitiveNPHP3-related nephronophthisisLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6161th %ile
GOF
0.6247th %ile
LOF
0.3356th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NPHP3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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