HSPA1A (HSP70-1): A Central Chaperone in Protein Homeostasis and Stress Response
Explore the genomic context, expression patterns, disease associations, and functional roles of the human HSPA1A gene, encoding the major heat shock protein 70 (HSP70-1).
Gene Information Card
| Symbol | HSPA1A |
|---|---|
| Full Name | Heat Shock Protein Family A (Hsp70) Member 1A |
| Gene Type | protein-coding |
| Chromosomal Location | 6p21.33 (GRCh38: chr6:31,815,464-31,817,951) |
| NCBI Gene ID | 3303 ncbi.nlm.nih.gov/gene/3303 |
| Ensembl ID | ENSG00000204389 |
| UniProt ID | P0DMV8 |
| OMIM ID | 140550 |
| HGNC ID | 5232 |
| Aliases | HSP70-1, HSP70-1A, HSP70I, HSP72, HSPA1, HSP70A, HSP70-2 (historical) |
Description
HSPA1A encodes the 70 kDa heat shock protein 1A (HSP70-1), a major inducible heat shock protein that functions as a molecular chaperone. It is rapidly upregulated in response to cellular stress (e.g., heat, oxidative stress, toxins) and plays critical roles in protein folding, assembly, transport, and degradation. HSP70-1 also participates in immune responses, apoptosis regulation, and protection against protein aggregation. The gene is located in the major histocompatibility complex (MHC) class III region on chromosome 6, a region associated with numerous immune-related diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer's Disease | HSP70-1 is involved in clearance of tau and amyloid-beta aggregates; reduced expression or function may impair proteostasis, contributing to neurodegeneration. | ClinVar: Variants in HSPA1A are not directly curated for Alzheimer's, but literature (PMID: 19061868) shows altered HSP70 levels in AD brains. OMIM: 104300 (Alzheimer's) lists HSPA1A as a candidate modifier gene. |
| Parkinson's Disease | HSP70-1 assists in refolding of alpha-synuclein and prevents its aggregation; loss of function may exacerbate dopaminergic neuron loss. | ClinVar: No direct pathogenic variants; functional studies (PMID: 15548617) demonstrate neuroprotective role. OMIM: 168600 (Parkinson's) mentions HSP70 as a modifier. |
| Huntington's Disease | HSP70-1 binds to mutant huntingtin and reduces its toxicity; overexpression is protective in models. | ClinVar: No direct variants; experimental evidence (PMID: 10611394) shows HSP70 suppresses polyglutamine aggregation. OMIM: 143100 (Huntington's) lists HSPA1A as a potential therapeutic target. |
| Cancer (Multiple Types) | HSP70-1 is overexpressed in many tumors, promoting cell survival by inhibiting apoptosis and stabilizing oncoproteins; also involved in drug resistance. | COSMIC: HSPA1A is not a known cancer gene, but expression is elevated in various cancers (e.g., breast, colon, lung). ClinVar: No germline pathogenic variants; somatic mutations are rare. |
| Heat Stroke / Heat Stress | HSP70-1 is essential for thermotolerance; deficiency or impaired induction increases susceptibility to heat-induced cell death. | ClinVar: No direct variants; functional studies (PMID: 11278762) show HSP70 knockout mice are more sensitive to heat stress. OMIM: 140550 (HSPA1A) notes role in stress response. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 10.2 | Low |
| Adrenal gland | 8.5 | Low |
| Appendix | 12.4 | Low |
| Bone marrow | 15.3 | Low |
| Brain (cerebral cortex) | 9.8 | Low |
| Breast | 11.2 | Low |
| Colon | 13.5 | Low |
| Esophagus | 12.1 | Low |
| Fallopian tube | 10.9 | Low |
| Gallbladder | 14.2 | Low |
| Heart muscle | 8.7 | Low |
| Kidney | 12.8 | Low |
| Liver | 9.5 | Low |
| Lung | 11.6 | Low |
| Lymph node | 10.4 | Low |
| Ovary | 12.0 | Low |
| Pancreas | 9.9 | Low |
| Prostate | 11.3 | Low |
| Salivary gland | 10.1 | Low |
| Skeletal muscle | 7.8 | Low |
| Skin | 13.0 | Low |
| Small intestine | 12.6 | Low |
| Spleen | 11.8 | Low |
| Stomach | 12.2 | Low |
| Testis | 14.5 | Low |
| Thyroid | 10.6 | Low |
| Urinary bladder | 12.3 | Low |
| Uterus | 11.9 | Low |
| Vagina | 11.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung carcinoma) | 18.5 | Moderate expression; inducible by stress |
| HeLa (cervical carcinoma) | 22.3 | High basal expression; heat shock increases levels |
| HepG2 (hepatocellular carcinoma) | 15.7 | Moderate expression; responsive to stress |
| MCF7 (breast adenocarcinoma) | 14.2 | Moderate expression; estrogen-regulated |
| SH-SY5Y (neuroblastoma) | 12.8 | Low expression; inducible by oxidative stress |
| K562 (chronic myelogenous leukemia) | 20.1 | High expression; constitutively active |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1043618 (5' UTR) | SNP | Allele frequency: G=0.35, C=0.65 (global) | Associated with altered HSP70-1 expression; linked to susceptibility to various diseases (e.g., inflammatory conditions). |
| rs1061581 (coding synonymous) | SNP | Allele frequency: A=0.40, G=0.60 | No known functional effect; used as a genetic marker. |
| rs2227956 (coding missense, p.Met493Thr) | SNP | Allele frequency: T=0.05 | May affect chaperone function; associated with increased risk of certain cancers (e.g., breast cancer) in some studies. |
| rs539689 (intronic) | SNP | Allele frequency: C=0.70, T=0.30 | Potential regulatory effect on splicing; not well characterized. |
Mutation functional classification
Loss of Function (LOF)
Complete loss-of-function mutations are rare and not well documented in human populations. Knockout models in mice show impaired thermotolerance and increased apoptosis under stress, but no major developmental defects.
Gain of Function (GOF)
Overexpression of HSP70-1 is observed in many cancers and is considered a gain-of-function event that promotes tumor cell survival and drug resistance. No activating mutations have been identified.
Dominant Negative (DN)
No dominant-negative mutations have been reported for HSPA1A. However, overexpression of mutant forms with impaired ATPase activity could theoretically interfere with chaperone function, but this is speculative.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • ATP hydrolysis activity |
| • chaperone binding | • protein folding |
| • protein refolding | • response to heat |
| • response to unfolded protein | • cellular response to stress |
| • negative regulation of apoptotic process | • positive regulation of NF-kappaB transcription factor activity |
Pathways
• Protein processing in endoplasmic reticulum (KEGG: hsa04141)
• Antigen processing and presentation (KEGG: hsa04612)
• MAPK signaling pathway (KEGG: hsa04010)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• Apoptosis (KEGG: hsa04210)
• Endocytosis (KEGG: hsa04144)
Protein Summary
HSP70-1 is a 70 kDa protein consisting of an N-terminal ATPase domain, a substrate-binding domain, and a C-terminal lid domain. It binds to exposed hydrophobic patches of unfolded proteins, facilitating their proper folding or targeting for degradation. ATP hydrolysis drives conformational changes that regulate substrate binding and release. HSP70-1 interacts with co-chaperones such as HSP40 (DNAJ) and nucleotide exchange factors (e.g., BAG1, HSP110). It is localized in the cytoplasm and nucleus, and upon stress, translocates to the nucleus to protect proteins from aggregation. HSP70-1 also plays a role in antigen presentation by chaperoning peptides for MHC class I loading.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HSPA1A Knockout HEK293 Cell Line | EDJ-KQ50366 | Human | 3303 | Details Get a Quote |
| HSPA1A Knockout HeLa Cell Line | EDJ-KQ53579 | Human | 3303 | Details Get a Quote |
| HSPA1A Knockout A-549 Cell Line | EDJ-KQ62046 | Human | 3303 | Details Get a Quote |
| HSPA1A Knockout HCT 116 Cell Line | EDJ-KQ70527 | Human | 3303 | Details Get a Quote |
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