HSPB3
Chr 5ADheat shock protein family B (small) member 3
Also known as: DHMN2C, HMN2C, HMND4, HSPL27
This gene encodes a muscle-specific small heat shock protein that inhibits actin polymerization. Mutations cause autosomal dominant distal hereditary motor neuropathy type 2C, a condition affecting the peripheral motor neurons and resulting in distal muscle weakness. The gene is not highly constrained against loss-of-function variants, and inheritance follows an autosomal dominant pattern.
Some data sources returned errors (1)
gnomad: Error: gnomAD API error: 502
Population Genetics & Constraint
Constraint data not available from gnomAD.
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
100 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 8 | 0 | 8 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 4 | 38 | 17 | 2 | 61 |
Likely Benign | 0 | 3 | 3 | 12 | 18 |
Benign | 0 | 1 | 4 | 2 | 7 |
Conflicting | — | 5 | |||
| Total | 4 | 42 | 33 | 16 | 100 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
HSPB3 · 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