HSPA4

Chr 5

heat shock protein family A (Hsp70) member 4

Also known as: APG-2, HEL-S-5a, HS24/P52, HSPH2, RY, hsp70, hsp70RY

NCBI Gene: 3308ENSG00000170606UniProt: P34932

Predicted to enable adenyl-nucleotide exchange factor activity. Involved in chaperone-mediated protein complex assembly and protein insertion into mitochondrial outer membrane. Located in cytosol and extracellular exosome. Implicated in Chagas disease. Biomarker of chronic obstructive pulmonary disease; rheumatoid arthritis; type 2 diabetes mellitus; and ulcerative colitis. [provided by Alliance of Genome Resources, Apr 2025]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
2
Active trials
46
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.24
LOEUF· LoF intol.
—
Mechanism
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.24LOEUF
pLI 1.000
Z-score 5.66
OE 0.12 (0.07–0.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.06Z-score
OE missense 0.72 (0.66–0.79)
311 obs / 431.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.12 (0.07–0.24)
0≤0.351.4
Missense OE?0.72 (0.66–0.79)
0≤0.61.4
Synonymous OE?1.05
0≤1.21.6
LoF obs/exp: 6 / 48.5Missense obs/exp: 311 / 431.2Syn Z: -0.49

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

HSPA4 · 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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients