VPS53

Chr 17

VPS53 subunit of GARP complex

Also known as: HCCS1, PCH2E, hVps53L, pp13624

NCBI Gene: 55275ENSG00000141252UniProt: Q5VIR6

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…

Primary Disease Associations & Inheritance

UniProtPontocerebellar hypoplasia 2E

Clinical highlights

Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
4
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.61
LOEUF
LOF
Mechanism· G2P
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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

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.61LOEUF
pLI 0.000
Z-score 3.70
OE 0.42 (0.29–0.61)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.58Z-score
OE missense 0.80 (0.73–0.87)
374 obs / 470.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.42 (0.29–0.61)
0≤0.351.4
Missense OE?0.80 (0.73–0.87)
0≤0.61.4
Synonymous OE?1.03
0≤1.21.6
LoF obs/exp: 20 / 47.5Missense obs/exp: 374 / 470.3Syn Z: -0.28

ClinVar Variant Classifications

0 submitted variants in ClinVar

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

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients