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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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HSPA2
heat shock protein family A (Hsp70) member 2
Chromosome 14 · 14q23.3
NCBI Gene: 3306Ensembl: ENSG00000126803.10HGNC: HGNC:5235UniProt: P54652
229PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingenzyme bindingunfolded protein bindingprotein refoldingopen-angle glaucomaglaucomaneoplasmnon-small cell lung carcinoma
✦AI Summary

HSPA2 is a specialized heat shock protein family member that functions as a molecular chaperone with distinct tissue-specific roles. Unlike other HSP70 family members, HSPA2 is not heat shock-inducible but exhibits constitutive expression in specific cell types including testis, brain, and stratified epithelia 1. The protein plays a crucial role in male fertility, being highly expressed in pachytene spermatocytes, and its deficiency is associated with impaired spermatogenesis 12. In somatic tissues, HSPA2 regulates keratinocyte differentiation, with knockout leading to impaired granular layer development and increased pro-inflammatory cytokine secretion 3. The protein interacts with HIF-1α in epidermal keratinocytes, though HIF-1α stability depends on collective HSPA family activity rather than HSPA2 specifically 4. HSPA2 demonstrates significant clinical relevance as a biomarker, with elevated expression correlating with poor prognosis in hepatocellular carcinoma and association with tumor size and stage 5. Additionally, circulating HSPA2 levels are linked to cardiovascular outcomes, with higher levels associated with left ventricular dysfunction and increased heart failure risk 6. The protein's tissue-specific expression pattern and involvement in both reproductive and somatic cell functions distinguish it from other HSPA family members.

Sources cited
1
HSPA2 is testis-enriched, not heat shock-inducible, and crucial for male fertility
PMID: 25344376
2
HSPA2 knockout impairs keratinocyte differentiation and increases inflammatory mediator secretion
PMID: 40287440
3
HSPA2 interacts with HIF-1α in keratinocytes but HIF-1α stability depends on collective HSPA activity
PMID: 38641179
4
Elevated HSPA2 expression correlates with poor prognosis in hepatocellular carcinoma
PMID: 25117073
5
Higher circulating HSPA2 levels associated with left ventricular dysfunction and heart failure risk
PMID: 39180332
6
HSPA2 serves as a biomarker for sperm selection and quality assessment
PMID: 30463455
Disease Associationsⓘ20
open-angle glaucomaOpen Targets
0.21Weak
glaucomaOpen Targets
0.20Weak
neoplasmOpen Targets
0.10Suggestive
non-small cell lung carcinomaOpen Targets
0.10Suggestive
azoospermiaOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
esophageal squamous cell carcinomaOpen Targets
0.07Suggestive
partial chromosome Y deletionOpen Targets
0.07Suggestive
cancerOpen Targets
0.07Suggestive
spermatogenic failure 57Open Targets
0.06Suggestive
spermatogenic failure 50Open Targets
0.06Suggestive
ovarian neoplasmOpen Targets
0.06Suggestive
spermatogenic failure, X-linked, 2Open Targets
0.06Suggestive
spermatogenic failure 25Open Targets
0.06Suggestive
spermatogenic failure 59Open Targets
0.06Suggestive
spermatogenic failure 60Open Targets
0.06Suggestive
spermatogenic failure 73Open Targets
0.06Suggestive
spermatogenic failure 74Open Targets
0.06Suggestive
spermatogenic failure 62Open Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
HSP90AB1Protein interaction100%HSP90AA1Protein interaction100%BAG3Protein interaction100%CATSPER1Protein interaction100%HSPA4Protein interaction100%CATSPER4Protein interaction99%
Tissue Expression6 tissues
Brain
100%
Heart
35%
Lung
8%
Ovary
3%
Liver
3%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
HSPA2HSP90AB1HSP90AA1BAG3CATSPER1HSPA4CATSPER4
PROTEIN STRUCTURE
Preparing viewer…
PDB3I33 · 1.30 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.52Moderately Constrained
pLIⓘ
0.97Intolerant
Observed/Expected LoF0.31 [0.20–0.52]
RankingsWhere HSPA2 stands among ~20K protein-coding genes
  • #1,762of 20,598
    Most Researched229 · top 10%
  • #3,187of 17,882
    Most Constrained (LOEUF)0.52 · top quartile
Genes detectedHSPA2
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
HSPA2 influences the differentiation and production of immunomodulatory mediators in human immortalized epidermal keratinocyte lines.
PMID: 40287440
Cell Death Dis · 2025
1.00
2
The diabetic myocardial transcriptome reveals Erbb3 and Hspa2 as a novel biomarkers of incident heart failure.
PMID: 39180332
Cardiovasc Res · 2024
0.90
3
Expression, function, and regulation of the testis-enriched heat shock HSPA2 gene in rodents and humans.
PMID: 25344376
Cell Stress Chaperones · 2015
0.80
4
The human testis-enriched HSPA2 interacts with HIF-1α in epidermal keratinocytes, yet HIF-1α stability and HIF-1-dependent gene expression rely on the HSPA (HSP70) activity.
PMID: 38641179
Biochim Biophys Acta Mol Cell Res · 2024
0.70
5
Paternal factors in recurrent pregnancy loss: an insight through analysis of non-synonymous single-nucleotide polymorphism in human testis-specific chaperone HSPA2 gene.
PMID: 34845642
Environ Sci Pollut Res Int · 2022
0.64