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.
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ClinVar Variants
168 unique Pathogenic / Likely Pathogenic· 682 VUS of 1444 total submissions
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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

1444 submitted variants in ClinVar

Classification Summary

Pathogenic91
Likely Pathogenic77
VUS682
Likely Benign424
Benign61
Conflicting105
91
Pathogenic
77
Likely Pathogenic
682
VUS
424
Likely Benign
61
Benign
105
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
82
2
7
0
91
Likely Pathogenic
66
8
2
1
77
VUS
6
597
68
11
682
Likely Benign
0
7
214
203
424
Benign
0
0
58
3
61
Conflicting
105
Total1546143492181,440

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

13 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap NPHP3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

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.

Search ClinicalTrials.gov →