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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 0.411 OMIM phenotype
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.

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

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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