VPS37D

Chr 7

VPS37D subunit of ESCRT-I

Also known as: WBSCR24

NCBI Gene: 155382 ENSG00000176428 UniProt: Q86XT2 OMIM: 610039

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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in protein targeting to membrane; protein targeting to vacuole; and ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. Located in extracellular exosome. Part of ESCRT I complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.38

Clinical Summary— VPS37D

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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.

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ClinVar Variants

58 VUS of 69 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.38LOEUF

pLI 0.916

Z-score 2.61

OE 0.00 (0.00–0.38)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.88Z-score

OE missense 0.78 (0.66–0.92)

96 obs / 123.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.38)

0≤0.351.4

Missense OE?0.78 (0.66–0.92)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 0 / 8.0Missense obs/exp: 96 / 123.5Syn Z: -0.55

ClinVar Variant Classifications

69 submitted variants in ClinVar

ClinVar

Classification Summary

VUS58

Likely Benign6

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	58	0	0	58
Likely Benign	1	1	4	6
Benign	0	0	1	1
Total	59	1	5	65

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

View in ClinVar →

164 pathogenic / likely-pathogenic (of 168) ClinVar copy-number / structural variants overlap VPS37D — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →