SQSTM1
Chr 5ADARsequestosome 1
Also known as: A170, DMRV, EBIAP, FTDALS3, NADGP, OSIL, PDB3, ZIP3
This gene encodes a multifunctional scaffolding protein that binds ubiquitin, regulates NF-kB signaling pathway activation, and functions in autophagy. Mutations cause autosomal dominant frontotemporal dementia and/or amyotrophic lateral sclerosis, distal myopathy with rimmed vacuoles, and Paget disease of bone, as well as autosomal recessive childhood-onset neurodegeneration with ataxia, dystonia, and gaze palsy. The pathogenic mechanism involves disrupted protein aggregation clearance and impaired autophagy processes.
Primary Disease Associations & Inheritance
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and loss-of-function). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports gain-of-function. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SQSTM1 · 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
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools