Limb disorders
Gene: VCPEnsemblGeneIds (GRCh38): ENSG00000165280
EnsemblGeneIds (GRCh37): ENSG00000165280
OMIM: 601023, Gene2Phenotype
VCP is in 15 panels
1 review
Arina Puzriakova (Genomics England Curator)
Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - 7 unrelated individuals with Adams-Oliver syndrome due to heterozygous hypermorphic variants in the NTD domain of VCP.Created: 26 Jun 2026, 11:02 a.m. | Last Modified: 26 Jun 2026, 11:02 a.m.
Panel Version: 8.16
Lehman et al 2026 (PMID: 41979051) report 7 unrelated families with Adams-Oliver syndrome characterised by aplasia cutis congenita and terminal limb reduction defects. Members of three families displayed features of multisystem proteinopathy, previously associated with this gene, including a parent (myopathy, lytic bone lesions and/or neuropathy in F1 and 2) or grandparent (frontotemporal dementia in F4). Pulmonary hypertension was found in 6/7 families.
Heterozygous rare missense variants in the VCP gene were identified by WGS or WES (4 de novo, 2 inherited and 1 presumed inherited). Variants clustered in the N-terminal domain (NTD), and the same amino acid residue, p.Arg89, was altered in 4/7 families. Variants were shown to exert a GoF effect, leading to overactive ATP hydrolysis and caused NTD hyperflexibility with loss of interdomain coupling.
Sources: LiteratureCreated: 26 Jun 2026, 10:59 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Adams-Oliver syndrome, MONDO:0007034
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
- Sources
-
- Expert Review Amber
- Literature
- Phenotypes
-
- Adams-Oliver syndrome, MONDO:0007034
- Tags
- OMIM
- 601023
- Clinvar variants
- Variants in VCP
- Penetrance
- None
- Publications
- Mode of Pathogenicity
- Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
- Panels with this gene
-
- Limb disorders
- Early onset dementia (encompassing fronto-temporal dementia and prion disease)
- DDG2P
- Hereditary neuropathy
- Distal myopathies
- Arthrogryposis
- Skeletal dysplasia
- Fetal anomalies
- Hereditary neuropathy or pain disorder
- Congenital myopathy
- Adult onset neurodegenerative disorder
- Pulmonary arterial hypertension
- Intellectual disability
- Amyotrophic lateral sclerosis/motor neuron disease
- Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies
History Filter Activity
Entity classified by Genomics England curator
Arina Puzriakova (Genomics England Curator)Gene: vcp has been classified as Amber List (Moderate Evidence).
Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes, Set mode of pathogenicity
Arina Puzriakova (Genomics England Curator)gene: VCP was added gene: VCP was added to Limb disorders. Sources: Literature Q2_26_promote_green tags were added to gene: VCP. Mode of inheritance for gene: VCP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: VCP were set to 41979051 Phenotypes for gene: VCP were set to Adams-Oliver syndrome, MONDO:0007034 Mode of pathogenicity for gene: VCP was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: VCP was set to GREEN