HSPB1
Chr 7ADheat shock protein family B (small) member 1
Also known as: CMT2F, HEL-S-102, HMN2B, HMND3, HS.76067, HSP27, HSP28, Hsp25
The protein functions as a molecular chaperone that maintains denatured proteins in a folding-competent state and regulates neurofilament protein phosphorylation and axonal transport. Mutations cause autosomal dominant Charcot-Marie-Tooth disease type 2F and distal hereditary motor neuropathy, affecting peripheral nerves. The gene is highly tolerant to loss-of-function variants (pLI near zero, LOEUF 1.87), suggesting the pathogenic variants likely affect protein function through other mechanisms.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
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
HSPB1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools