VCP

Chr 9

valosin containing protein

Also known as: CDC48, FTDALS6, TERA, p97

NCBI Gene: 7415ENSG00000165280UniProt: P55072

This gene encodes a member of the AAA ATPase family of proteins. The encoded protein plays a role in protein degradation, intracellular membrane fusion, DNA repair and replication, regulation of the cell cycle, and activation of the NF-kappa B pathway. This protein forms a homohexameric complex that interacts with a variety of cofactors and extracts ubiquitinated proteins from lipid membranes or protein complexes. Mutations in this gene cause IBMPFD (inclusion body myopathy with paget disease of bone and frontotemporal dementia), ALS (amyotrophic lateral sclerosis) and Charcot-Marie-Tooth disease in human patients. [provided by RefSeq, Aug 2017]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtInclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 1
UniProtFrontotemporal dementia and/or amyotrophic lateral sclerosis 6
UniProtCharcot-Marie-Tooth disease, axonal, type 2Y

Clinical highlights

Gene-disease validity (ClinGen)
inclusion body myopathy with Paget disease of bone and frontotemporal dementia · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
5
Active trials
323
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.13
LOEUF· LoF intol.
LOF
Mechanism· G2P
📖
GeneReview available — VCP
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.13LOEUF
pLI 1.000
Z-score 5.52
OE 0.03 (0.01–0.13)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
5.41Z-score
OE missense 0.28 (0.24–0.33)
126 obs / 448.0 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios?
LoF OE?0.03 (0.01–0.13)
0≤0.351.4
Missense OE?0.28 (0.24–0.33)
0≤0.61.4
Synonymous OE?1.12
0≤1.21.6
LoF obs/exp: 1 / 37.5Missense obs/exp: 126 / 448.0Syn Z: -1.16

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

VCP · protein map & ClinVar variants

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

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