Activity
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| Limb disorders v8.16 | VCP | Arina Puzriakova Classified gene: VCP as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v8.16 | VCP | Arina Puzriakova Added comment: 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v8.16 | VCP | Arina Puzriakova Gene: vcp has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb disorders v8.15 | VCP |
Arina Puzriakova 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 Added comment: 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: Literature |
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