HSPA8
Chr 11heat shock protein family A (Hsp70) member 8
Also known as: HEL-33, HEL-S-72p, HSC54, HSC70, HSC71, HSP71, HSP73, HSPA10
The HSPA8 protein is a constitutively expressed heat shock cognate protein that functions as a molecular chaperone, facilitating protein folding, chaperone-mediated autophagy, and clathrin-coated vesicle uncoating. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and neurological features. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to cause severe developmental consequences.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
104 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 | 47 | 0 | 47 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 1 | 23 | 3 | 0 | 27 |
Likely Benign | 1 | 0 | 0 | 0 | 1 |
Benign | 0 | 0 | 0 | 4 | 4 |
| Total | 2 | 23 | 52 | 4 | 81 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
HSPA8 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools