VPS37D

Chr 7

VPS37D subunit of ESCRT-I

Also known as: WBSCR24

The VPS37D protein is a component of the ESCRT-I complex that regulates vesicular trafficking and sorts ubiquitinated proteins into multivesicular bodies for degradation. Mutations cause autosomal recessive developmental and epileptic encephalopathy with movement abnormalities, typically presenting in infancy with seizures, developmental delay, and dystonia. The gene is highly constrained against loss-of-function variants, suggesting that complete loss of protein function is likely pathogenic.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.38
Clinical SummaryVPS37D
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
30 unique Pathogenic / Likely Pathogenic· 59 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.38LOEUF
pLI 0.916
Z-score 2.61
OE 0.00 (0.000.38)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.88Z-score
OE missense 0.78 (0.660.92)
96 obs / 123.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.38)
00.351.4
Missense OE0.78 (0.660.92)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 0 / 8.0Missense obs/exp: 96 / 123.5Syn Z: -0.55

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic1
VUS59
Likely Benign6
Benign1
29
Pathogenic
1
Likely Pathogenic
59
VUS
6
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
29
0
29
Likely Pathogenic
0
0
1
0
1
VUS
0
58
1
0
59
Likely Benign
0
1
1
4
6
Benign
0
0
0
1
1
Total05932596

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

View in ClinVar →

Protein Context — Lollipop Plot

VPS37D · 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
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found