ArticleAmerican journal of human genetics2023
An autosomal-dominant childhood-onset disorder associated with pathogenic variants in VCP.
Article in American journal of human genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
8 citing papers in PubMed, 8 citations in OpenAlex.
- Genetic frontotemporal degeneration across the lifespan? A critical appraisal of the neurodevelopmental hypothesis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Impaired Activity-Regulated Proteostasis: A Shared Mechanism in Neurodevelopmental Disorders.Biological psychiatry · 2026Review
- Shared and divergent alteration of whole-brain connectivity and sensory deficits in multiple autism mouse models.Molecular psychiatry · 2026Article
- 2024 VCP International Conference: Exploring multi-disciplinary approaches from basic science of valosin containing protein, an AAA+ ATPase protein, to the therapeutic advancement for VCP-associated multisystem proteinopathy.Neurobiology of disease · 2025Review
- Elevated VCP ATPase Activity Correlates With Disease Onset in Multisystem Proteinopathy-1.Neurology. Genetics · 2024Article
- Dominantly inherited muscle disorders: understanding their complexity and exploring therapeutic approaches.Disease models & mechanisms · 2024Review
- Valosin-Containing Protein (VCP): A Review of Its Diverse Molecular Functions and Clinical Phenotypes.International journal of molecular sciences · 2024Review
- HNRNPA1 de novo Variant Associated with Early Childhood Onset, Rapidly Progressive Generalized Myopathy.Journal of neuromuscular diseases · 2024Article
Corrections and comments
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Authors and funding
35 authors at 18 institutions in 5 countries.
Funding
Abstract
Valosin-containing protein (VCP) is an AAA+ ATPase that plays critical roles in multiple ubiquitin-dependent cellular processes. Dominant pathogenic variants in VCP are associated with adult-onset multisystem proteinopathy (MSP), which manifests as myopathy, bone disease, dementia, and/or motor neuron disease. Through GeneMatcher, we identified 13 unrelated individuals who harbor heterozygous VCP variants (12 de novo and 1 inherited) associated with a childhood-onset disorder characterized by developmental delay, intellectual disability, hypotonia, and macrocephaly. Trio exome sequencing or a multigene panel identified nine missense variants, two in-frame deletions, one frameshift, and one splicing variant. We performed in vitro functional studies and in silico modeling to investigate the impact of these variants on protein function. In contrast to MSP variants, most missense variants had decreased ATPase activity, and one caused hyperactivation. Other variants were predicted to cause haploinsufficiency, suggesting a loss-of-function mechanism. This cohort expands the spectrum of VCP-related disease to include neurodevelopmental disease presenting in childhood.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.