WDR37

Chr 10AD

WD repeat domain 37

Also known as: NOCGUS

NCBI Gene: 22884 ENSG00000047056 UniProt: Q9Y2I8 OMIM: 618586

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismADLOEUF 0.411 OMIM phenotype

Clinical Summary— WDR37

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Gene-Disease Validity (ClinGen)

neurooculocardiogenitourinary syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.57) — some intolerance to loss-of-function variants.

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ClinVar Variants

10 unique Pathogenic / Likely Pathogenic· 86 VUS of 161 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.41LOEUF

pLI 0.566

Z-score 3.93

OE 0.21 (0.11–0.41)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.31Z-score

OE missense 0.64 (0.57–0.71)

205 obs / 321.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.21 (0.11–0.41)

0≤0.351.4

Missense OE?0.64 (0.57–0.71)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 6 / 28.7Missense obs/exp: 205 / 321.7Syn Z: -0.11

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveWDR37-related syndromic intellectual disabilityOTHERAD

This gene — mechanism propensity

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.1

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

References

1.PMID 31327510 ↗

ClinVar Variant Classifications

161 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic10

VUS86

Likely Benign43

Benign3

Conflicting2

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	1	8	1	0	10
VUS	3	81	2	0	86
Likely Benign	0	19	6	18	43
Benign	0	1	2	0	3
Conflicting	—				2
Total	4	109	11	18	144

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

View in ClinVar →

31 pathogenic / likely-pathogenic (of 54) ClinVar copy-number / structural variants overlap WDR37 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →