VPS36

Chr 13

vacuolar protein sorting 36 homolog

Also known as: C13orf9, CGI-145, EAP45

This protein is a subunit of the ESCRT-II complex that sorts ubiquitinated membrane proteins for lysosomal degradation and forms multivesicular bodies during endocytosis. Mutations cause autosomal recessive early infantile epileptic encephalopathy, characterized by severe seizures and developmental delays beginning in infancy. The gene shows moderate constraint against loss-of-function variants, consistent with its role in essential cellular trafficking processes.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.50
Clinical SummaryVPS36
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
📋
ClinVar Variants
58 unique Pathogenic / Likely Pathogenic· 51 VUS of 121 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.50LOEUF
pLI 0.046
Z-score 3.59
OE 0.28 (0.160.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.71Z-score
OE missense 0.67 (0.580.77)
138 obs / 207.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.28 (0.160.50)
00.351.4
Missense OE0.67 (0.580.77)
00.61.4
Synonymous OE0.82
01.21.6
LoF obs/exp: 8 / 28.7Missense obs/exp: 138 / 207.4Syn Z: 1.18

ClinVar Variant Classifications

121 submitted variants in ClinVar

Classification Summary

Pathogenic56
Likely Pathogenic2
VUS51
Likely Benign2
56
Pathogenic
2
Likely Pathogenic
51
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
56
0
56
Likely Pathogenic
0
0
2
0
2
VUS
0
41
10
0
51
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total043680111

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

View in ClinVar →

Protein Context — Lollipop Plot

VPS36 · 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.

Search ClinicalTrials.gov →
Clinical Literature
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