HSPA6
<div class="infobox infobox-gene">
<div class="infobox-header">HSPA6</div>
Overview
```mermaid
flowchart TD
classDef gene fill:#0a1f0a,stroke:#4caf50
classDef protein fill:#0a1929,stroke:#2196f3
classDef disease fill:#2d0f0f,stroke:#e91e63
classDef pathway fill:#3e2200,stroke:#ff9800
classDef mechanism fill:#1a0a1f,stroke:#9c27b0
classDef therapeutic fill:#e0f2f1,stroke:#009688
HSPA6["HSPA6"] -->|"implicated_in"| neurodegeneration["neurodegeneration"]
HSPA6["HSPA6"] -->|"expressed_in"| DNAJB1["DNAJB1"]
HSPA6["HSPA6"] -->|"expressed_in"| IKBKB["IKBKB"]
HSPA6["HSPA6"] -->|"expressed_in"| HSPA1B["HSPA1B"]
HSPA6["HSPA6"] -->|"expressed_in"| HSPE1["HSPE1"]
HSPA6["HSPA6"] -->|"expressed_in"| HSP90AB1["HSP90AB1"]
HSPA6["HSPA6"] -->|"expressed_in"| HSP70["HSP70"]
HSPA6["HSPA6"] -->|"expressed_in"| PHAGOCYTOSIS["PHAGOCYTOSIS"]
HSPA6["HSPA6"] -->|"expressed_in"| HSPH1["HSPH1"]
HSPA6["HSPA6"] -->|"expressed_in"| HSPA1L["HSPA1L"]
HSPA6["HSPA6"] -->|"expressed_in"| HSPA1A["HSPA1A"]
HSPA6["HSPA6"] -->|"expressed_in"| DNAJC10["DNAJC10"]
HSPA6["HSPA6"] -->|"expressed_in"| Lymphoma["Lymphoma"]
HSPA6["HSPA6"] -->|"expressed_in"| Ms["Ms"]
HSPA6["HSPA6"] -->|"expressed_in"| Cancer["Cancer"]
HSPA6["HSPA6"] -->|"expressed_in"| Tumor["Tumor"]
HSPA6["HSPA6"] -->|"expressed_in"| Apoptosis["Apoptosis"]
HSPA6["HSPA6"] -->|"expressed_in"| Unfolded_Protein_Response["Unfolded Protein Response"]
HSPA6["HSPA6"] -->|"expressed_in"| Nf__b["Nf-Kb"]
HSPA6["HSPA6"] -->|"expressed_in"| Phagocyt
...HSPA6
<div class="infobox infobox-gene">
<div class="infobox-header">HSPA6</div>
Overview
Mermaid diagram (expand to render)
HSPA1A is a human gene whose product hSPA6** (Heat Shock Protein Family A (Hsp70) Member 6) is a member of the Hsp70 family of molecular chaperones. It functions as a molecular chaperone that assists in protein folding, refolding, and degradation. HSPA6 is induced by heat stress and other cellular stressors. Variants in HSPA1A have been implicated in Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration. [@heat2018]
<div class="infobox-row"> [@hspa2017]
<div class="infobox-label">Gene Symbol</div> [@targeting2021]
<div class="infobox-value">HSPA6</div> [@hsphsp2016]
</div>
<div class="infobox-row">
<div class="infobox-label">Full Name</div>
<div class="infobox-value">Heat Shock Protein Family A (Hsp70) Member 6</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Chromosomal Location</div>
<div class="infobox-value">1p36.33</div>
</div>
<div class="infobox-row">
<div class="infobox-label">NCBI Gene ID</div>
<div class="infobox-value">[3310](https://www.ncbi.nlm.nih.gov/gene/3310)</div>
</div>
<div class="infobox-row">
<div class="infobox-label">OMIM</div>
<div class="infobox-value">[604377](https://www.omim.org/entry/604377)</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Ensembl ID</div>
<div class="infobox-value">ENSG00000173110</div>
</div>
<div class="infobox-row">
<div class="infobox-label">UniProt ID</div>
<div class="infobox-value">[P17066](https://www.uniprot.org/uniprot/P17066)</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Protein</div>
<div class="infobox-value">[HSPA6-protein](/proteins/hspa6-protein)</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Associated Diseases</div>
<div class="infobox-value">[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis), Cancer</div>
</div>
</div>
Function
HSPA6 (Heat Shock Protein Family A (Hsp70) Member 6) is a member of the Hsp70 family of molecular chaperones. It functions as a molecular chaperone that assists in protein folding, refolding, and degradation. HSPA6 is induced by heat stress and other cellular stressors.
Molecular Function
HSPA6 exhibits ATP-dependent chaperone activity:
- Protein folding assistance: HSPA6 binds to nascent polypeptides and unfolded proteins to facilitate proper folding
- Protein refolding: Helps refold stress-denatured proteins
- Protein degradation: Partners with the [ubiquitin-proteasome system](/mechanisms/ubiquitin-proteasome-system) and [autophagy](/entities/autophagy) pathways to clear misfolded proteins
- Anti-aggregation: Prevents aggregation of misfolded proteins
- Cell protection: Confers protection against various cellular stresses including heat, oxidative stress, and proteotoxic insults
Interaction Network
HSPA6 interacts with:
- [HSPA1A](/genes/hspa1a) and [HSPA1B](/genes/hspa1b) (Hsp70 family members)
- [HSP90AA1](/genes/hsp90aa1) (Hsp90 chaperone system)
- [DNAJ heat shock proteins](/genes/dnaja1) (Hsp40 co-chaperones)
- [BAG family](/genes/bag1) co-chaperones (BAG1-BAG6)
- [SQSTM1](/genes/sqstm1) (p62) for selective autophagy
- [HSP90AB1](/genes/hsp90ab1) (Hsp90-beta)
Disease Associations
Alzheimer's Disease
HSPA6 is implicated in AD pathogenesis through its role in protein homeostasis:
-HSPA6 expression is altered in AD brain tissue
-The protein participates in clearance of [Aβ](/proteins/amyloid-beta) aggregates
-It helps refold [tau protein](/proteins/tau) and prevent tau pathology
-Studies show HSPA6 can protect against Aβ-induced neurotoxicity [1]
Parkinson's Disease
HSPA6 involvement in PD includes:
-Participation in [alpha-synuclein](/proteins/alpha-synuclein) ([SNCA](/genes/snca)) clearance
-Protection against dopaminergic neuron degeneration
-Association with LRRK2 ([LRRK2](/genes/lrrk2)) pathogenic variants
-Heat shock response is dysregulated in PD [2]
Amyotrophic Lateral Sclerosis
In ALS:
-HSPA6 may help clear [TDP-43](/mechanisms/tdp-43-proteinopathy) aggregates ([TARDBP](/genes/tardbp))
-Protects against SOD1 ([SOD1](/genes/sod1)) mutant toxicity
-Heat shock response is impaired in ALS motor [neurons](/entities/neurons)
-Compensation by HSPA6 may be protective [3]
Cancer
HSPA6 is frequently overexpressed in various cancers:
-Confers resistance to chemotherapeutic agents
-Promotes cell survival under stress
-Associated with poor prognosis in some tumor types
Expression
Brain Expression
HSPA6 is expressed in various brain regions:
- Cerebral [cortex](/brain-regions/cortex): Moderate expression, particularly in neurons
- [Hippocampus](/brain-regions/hippocampus): Expressed in CA1-CA3 regions and dentate gyrus
- Substantia nigra: Present in dopaminergic neurons
- Cerebellum: Detected in Purkinje cells and granule cells
- [Astrocytes](/entities/astrocytes) and [microglia](/cell-types/microglia-neuroinflammation): Inducible expression in glial cells
Regulation
HSPA6 expression is regulated by:
- Heat shock factor 1 (HSF1): Primary transcription factor
- Stress-responsive elements (HSE) in the promoter
- Age-related changes: Expression patterns shift with aging
- Disease states: Altered expression in neurodegeneration
Common Variants
| Variant | Type | Effect | Significance |
|---------|------|--------|--------------|
| rs2071499 | Promoter | Altered expression | Associated with cancer risk |
| rs2000998 | 3'UTR | miRNA binding | May affect mRNA stability |
| rs1043618 | Coding | Synonymous | Heat shock response modifier |
Therapeutic Implications
Pharmacological Targeting
- Hsp70 activators: 2-phenylethynesulfonamide (PES) and analogs
- HSF1 activators: Geldanamycin derivatives (17-AAG, 17-DMAG)
- Combination therapies: Hsp70 + Hsp90 inhibitors
Gene Therapy
- Viral vector-mediated HSPA6 overexpression for neuroprotection
- CRISPR-based approaches to enhance HSPA6 expression
See Also
- [HSP90AA1](/genes/hsp90aa1) - Hsp90 chaperone
- [HSPA1A](/genes/hspa1a) - Hsp70 member 1A
- [DNAJA1](/genes/dnaja1) - Hsp40 co-chaperone
- [BAG1](/genes/bag1) - BAG family co-chaperone
- [SQSTM1](/genes/sqstm1) - p62 autophagy adaptor
- [Protein homeostasis mechanisms](/mechanisms/protein-quality-control-network)
- [Heat shock response pathway](/mechanisms/heat-shock-response)
External Links
- [NCBI Gene: HSPA6](https://www.ncbi.nlm.nih.gov/gene/3310)
- [UniProt: HSPA6](https://www.uniprot.org/uniprot/P17066)
- [HGNC: HSPA6](https://www.genenames.org/data/hgnc-data/)
- [Ensembl: HSPA6](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000173110)
References
[Unknown, Heat shock protein 70 in Alzheimer's disease: Role and implications (Journal of Alzheimer's Disease, 2019) (2019)](https://doi.org/10.3233/JAD-190123)
[Unknown, The role of Hsp70 family members in Parkinson's disease (Molecular Neurobiology, 2020) (2020)](https://doi.org/10.1007/s12035-020-02042-8)
[Unknown, Heat shock proteins in amyotrophic lateral sclerosis (Neurobiology of Disease, 2018) (2018)](https://doi.org/10.1016/j.nbd.2018.01.012)
[Unknown, HSPA6: A redundant Hsp70 family? (Cell Stress and Chaperones, 2017) (2017)](https://doi.org/10.1007/s12192-017-0776-9)
[Unknown, Targeting Hsp70 for therapeutic intervention in neurodegeneration (Pharmacology & Therapeutics, 2021) (2021)](https://doi.org/10.1016/j.pharmthera.2021.107853)
[Unknown, Hsp70/Hsp40 networks in protein homeostasis (Trends in Biochemical Sciences, 2016) (2016)](https://doi.org/10.1016/j.tibs.2016.01.006)Pathway Diagram
The following diagram shows the key molecular relationships involving HSPA6 discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)