HSPA5
Chr 9heat shock protein family A (Hsp70) member 5
Also known as: BIP, GRP78, HEL-S-89n
The protein functions as an endoplasmic reticulum chaperone that facilitates protein folding and quality control, and serves as a key repressor of the unfolded protein response by binding and inactivating stress sensors PERK and IRE1 under normal conditions. Pathogenic variants in HSPA5 have not been definitively established as a cause of human genetic disease based on the available information. The protein's role in cellular stress response and ER homeostasis suggests potential involvement in neurodevelopmental disorders if mutations were to occur, though specific disease associations and inheritance patterns require further clinical characterization.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Highly missense-constrained (top ~0.1%)
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative 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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
HSPA5 · 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
External Resources
Links to major genomics databases and tools