VPS53

Chr 17

VPS53 subunit of GARP complex

Also known as: HCCS1, PCH2E, hVps53L, pp13624

Involved in endocytic recycling and retrograde transport, endosome to Golgi. Acts upstream of or within lysosomal transport. Located in several cellular components, including Golgi apparatus; perinuclear region of cytoplasm; and recycling endosome. Part of EARP complex and GARP complex. Implicated in pontocerebellar hypoplasia type 2E. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviewsResearchGenerating clinical summary…
LOFmechanismLOEUF 0.61
Clinical SummaryVPS53
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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GeneReview available — VPS53
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.61LOEUF
pLI 0.000
Z-score 3.70
OE 0.42 (0.290.61)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.58Z-score
OE missense 0.80 (0.730.87)
374 obs / 470.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.42 (0.290.61)
00.351.4
Missense OE?0.80 (0.730.87)
00.61.4
Synonymous OE?1.03
01.21.6
LoF obs/exp: 20 / 47.5Missense obs/exp: 374 / 470.3Syn Z: -0.28
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveVPS53-related progressive cerebello-cerebral atrophyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.74top 25%
GOF
0.6932th %ile
LOF
0.2970th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

VPS53 · 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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