VPS54

Chr 2

VPS54 subunit of GARP complex

Also known as: HCC8, PPP1R164, SLP-8p, VPS54L, WR, hVps54L

NCBI Gene: 51542ENSG00000143952UniProt: Q9P1Q0

This gene encodes for a protein that in yeast forms part of a trimeric vacuolar-protein-sorting complex that is required for retrograde transport of proteins from prevacuoles to the late Golgi compartment. As in yeast, mammalian Vps54 proteins contain a coiled-coil region and dileucine motifs. Alternative splicing results in multiple transcript variants encoding different isoforms [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
0
Active trials
5
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.25
LOEUF· LoF intol.
LOF
Mechanism· predicted
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.25LOEUF
pLI 0.999
Z-score 5.77
OE 0.14 (0.08–0.25)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
0.95Z-score
OE missense 0.88 (0.81–0.95)
425 obs / 483.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.14 (0.08–0.25)
0≤0.351.4
Missense OE?0.88 (0.81–0.95)
0≤0.61.4
Synonymous OE?1.04
0≤1.21.6
LoF obs/exp: 7 / 51.8Missense obs/exp: 425 / 483.8Syn Z: -0.37

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

VPS54 · 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.

Search ClinicalTrials.gov →

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