VPS28

Chr 8

VPS28 subunit of ESCRT-I

Also known as: CIIA

This gene encodes a protein subunit of the ESCRT-I complex that functions in transport and sorting of proteins into subcellular vesicles. Mutations cause autosomal recessive microcephaly, seizures, and developmental delay. The gene shows moderate constraint against loss-of-function variants, suggesting some intolerance to complete protein loss.

Summary from RefSeq, UniProt
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0
Active trials
11
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.74
LOEUF
DN
Mechanism· predicted
Clinical SummaryVPS28
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.74LOEUF
pLI 0.069
Z-score 2.19
OE 0.33 (0.160.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.87Z-score
OE missense 0.80 (0.700.93)
127 obs / 157.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.33 (0.160.74)
00.351.4
Missense OE0.80 (0.700.93)
00.61.4
Synonymous OE1.19
01.21.6
LoF obs/exp: 4 / 12.3Missense obs/exp: 127 / 157.8Syn Z: -1.21
DN
0.7034th %ile
GOF
0.5954th %ile
LOF
0.2777th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

VPS28 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

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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