NPHP4

Chr 1AR

nephrocystin 4

Also known as: POC10, SLSN4

The protein organizes apical junctions and is required for building functional cilia, playing critical roles in renal tubular development and function. Mutations cause nephronophthisis type 4 (a renal cystic disease) and Senior-Loken syndrome type 4 (nephronophthisis combined with retinitis pigmentosa), affecting both kidney and retinal function. The condition follows autosomal recessive inheritance.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Nephronophthisis 4MIM #606966
AR
Senior-Loken syndrome 4MIM #606996
AR
Nephronophthisis 4MIM #606966
AR
1
Active trials
11
Pubs (1 yr)
61
P/LP submissions
2%
P/LP missense
0.98
LOEUF
LOF
Mechanism· G2P
Clinical SummaryNPHP4
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Gene-Disease Validity (ClinGen)
nephronophthisis 4 · 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.
📋
ClinVar Variants
55 unique Pathogenic / Likely Pathogenic· 191 VUS of 400 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
GeneReview available — NPHP4
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
0.98LOEUF
pLI 0.000
Z-score 1.67
OE 0.78 (0.630.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.24Z-score
OE missense 1.02 (0.971.08)
910 obs / 889.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.78 (0.630.98)
00.351.4
Missense OE1.02 (0.971.08)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 53 / 67.8Missense obs/exp: 910 / 889.6Syn Z: -1.57

ClinVar Variant Classifications

400 submitted variants in ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic36
VUS191
Likely Benign121
Benign5
Conflicting2
19
Pathogenic
36
Likely Pathogenic
191
VUS
121
Likely Benign
5
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
13
0
19
Likely Pathogenic
22
1
13
0
36
VUS
2
167
17
5
191
Likely Benign
0
4
49
68
121
Benign
0
0
5
0
5
Conflicting
2
Total301729773374

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

View in ClinVar →

Protein Context — Lollipop Plot

NPHP4 · protein map & ClinVar variants

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

Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC