WDR37

Chr 10AD

WD repeat domain 37

Also known as: NOCGUS

This protein is required for normal endoplasmic reticulum calcium handling in lymphocytes and plays an essential role in stabilizing peripheral lymphocyte populations together with PACS1. Mutations cause neurooculocardiogenitourinary syndrome, a multisystem disorder affecting the nervous system, eyes, heart, and genitourinary tract, with autosomal dominant inheritance. The gene shows significant constraint against loss-of-function variants (LOEUF 0.412), indicating that such variants are likely pathogenic.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Neurooculocardiogenitourinary syndromeMIM #618652
AD
0
Active trials
2
Pubs (1 yr)
58
P/LP submissions
21%
P/LP missense
0.41
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryWDR37
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Gene-Disease Validity (ClinGen)
neurooculocardiogenitourinary syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.57) — some intolerance to loss-of-function variants.
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ClinVar Variants
39 unique Pathogenic / Likely Pathogenic· 103 VUS of 207 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.41LOEUF
pLI 0.566
Z-score 3.93
OE 0.21 (0.110.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.31Z-score
OE missense 0.64 (0.570.71)
205 obs / 321.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.21 (0.110.41)
00.351.4
Missense OE0.64 (0.570.71)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 6 / 28.7Missense obs/exp: 205 / 321.7Syn Z: -0.11
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveWDR37-related syndromic intellectual disabilityOTHERAD
DN
0.4983th %ile
GOF
0.3986th %ile
LOF
0.67top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · LOEUF 0.41
DN1 literature citation

Literature Evidence

DNZebrafish larvae carrying a heterozygous S129C wdr37 variant showed poor growth and died within 1 month, whereas zebrafish heterozygous for frameshift variants survived to adulthood, suggesting a dominant-negative effect of the missense allele.PMID:31327510

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

207 submitted variants in ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic10
VUS103
Likely Benign41
Benign3
Conflicting2
29
Pathogenic
10
Likely Pathogenic
103
VUS
41
Likely Benign
3
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
29
0
29
Likely Pathogenic
0
8
2
0
10
VUS
0
79
24
0
103
Likely Benign
0
19
5
17
41
Benign
0
1
2
0
3
Conflicting
2
Total01076217188

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

View in ClinVar →

Protein Context — Lollipop Plot

WDR37 · 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 →
Clinical Literature
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