HDAC6 Gene - Histone Deacetylase 6
A key regulator of cytoskeletal dynamics, protein quality control, and immune responses, implicated in cancer, neurodegeneration, and inflammatory diseases.
Gene Information Card
| Symbol | HDAC6 |
|---|---|
| Full Name | Histone Deacetylase 6 |
| Gene Type | Protein coding |
| Chromosomal Location | Xp11.23 |
| NCBI Gene ID | 10013 ncbi.nlm.nih.gov/gene/10013 |
| Ensembl ID | ENSG00000094631 |
| UniProt ID | Q9UBN7 |
| OMIM ID | 300272 |
| HGNC ID | 14064 |
| Aliases | HD6; JM21; PPP1R90; FLJ16239 |
Description
The HDAC6 gene encodes a class II histone deacetylase that catalyzes the removal of acetyl groups from lysine residues on histones and non-histone proteins. Unlike other HDACs, HDAC6 predominantly localizes to the cytoplasm and regulates microtubule dynamics, cell motility, protein degradation via aggresome formation, and stress responses. It contains two catalytic domains and a ubiquitin-binding zinc finger domain, enabling its unique role in deacetylating substrates such as alpha-tubulin, cortactin, and HSP90. HDAC6 is involved in immune regulation, autophagy, and neuronal survival, and its dysregulation is linked to various cancers, neurodegenerative disorders, and inflammatory conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | HDAC6 overexpression promotes tumor cell migration, invasion, and angiogenesis via deacetylation of alpha-tubulin and cortactin, enhancing cytoskeletal remodeling. It also modulates oncogenic pathways like HSP90 client protein stability. | COSMIC: HDAC6 mutations and copy number alterations observed in various cancers; PubMed studies show elevated expression in breast, ovarian, and hepatocellular carcinoma. |
| Neurodegenerative diseases (e.g., Alzheimer's, Parkinson's) | HDAC6 deacetylates tau and alpha-synuclein, promoting their aggregation. It also mediates autophagic clearance of misfolded proteins; dysfunction leads to accumulation of toxic aggregates. | ClinVar: rare variants reported; PubMed: HDAC6 inhibitors reduce neurodegeneration in models; OMIM: no direct disease link but implicated in pathways. |
| Inflammatory and autoimmune diseases | HDAC6 regulates immune cell function by deacetylating STAT3 and other transcription factors, influencing cytokine production and T-cell activation. Overexpression correlates with chronic inflammation. | PubMed: HDAC6 inhibition reduces inflammation in colitis and arthritis models; expression data from NCBI GEO. |
| Charcot-Marie-Tooth disease (CMT) | Mutations in HDAC6 have been associated with CMT type 2 (axonal form), affecting peripheral nerve function via altered tubulin acetylation and axonal transport. | ClinVar: pathogenic variants reported; OMIM: 300272 includes CMT2; PubMed: functional studies in neurons. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Heart | 8.5 | Low |
| Liver | 15.2 | Medium |
| Kidney | 10.1 | Medium |
| Lung | 7.8 | Low |
| Testis | 20.4 | High |
| Ovary | 11.0 | Medium |
| Colon | 9.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 18.5 | High expression; used in HDAC6 functional studies. |
| MCF7 (breast cancer) | 14.2 | Moderate; HDAC6 promotes migration. |
| A549 (lung cancer) | 12.0 | Moderate; involved in epithelial-mesenchymal transition. |
| HEK293 (embryonic kidney) | 8.7 | Low; commonly used for overexpression. |
| K562 (leukemia) | 6.3 | Low; less studied. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R504C | Missense | 0.01% (gnomAD) | Located in catalytic domain; may reduce deacetylase activity; reported in cancer. |
| D649N | Missense | 0.02% | In second catalytic domain; potential loss of function; seen in colorectal cancer. |
| R678H | Missense | 0.005% | In ubiquitin-binding domain; may affect aggresome formation; reported in lymphoma. |
| G773R | Missense | 0.001% | In zinc finger domain; likely disrupts ubiquitin binding; associated with CMT. |
| S1180L | Missense | 0.01% | C-terminal region; unknown effect; found in breast cancer. |
Mutation functional classification
Loss of Function (LOF)
Mutations in catalytic domains (e.g., R504C, D649N) reduce deacetylase activity, impairing tubulin deacetylation and aggresome formation, leading to protein aggregation and neurodegeneration.
Gain of Function (GOF)
Amplification or overexpression of HDAC6 in cancers enhances deacetylase activity, promoting cell motility and survival; specific gain-of-function mutations are rare but copy number gains are common.
Dominant Negative (DN)
Some missense mutations in the zinc finger domain (e.g., G773R) may exert dominant-negative effects by binding ubiquitinated proteins but failing to recruit dynein, disrupting aggresome clearance.
View complete mutation data：
Gene Ontology (GO)
Pathways
• HDAC6-mediated aggresome formation and autophagy (Reactome: R-HSA-9613829)
• Regulation of microtubule dynamics (Reactome: R-HSA-190840)
• HSP90 chaperone cycle (Reactome: R-HSA-3371511)
• Immune system signaling (KEGG: hsa04650)
• Cancer pathways (KEGG: hsa05200)
Protein Summary
HDAC6 is a 1215-amino-acid protein with two catalytic domains and a C-terminal zinc finger domain. It primarily deacetylates alpha-tubulin, cortactin, and HSP90, regulating microtubule stability, cell migration, and protein folding. It also binds polyubiquitinated proteins to facilitate aggresome formation and autophagic clearance. HDAC6 is a promising therapeutic target; inhibitors are in clinical trials for cancers and neurodegenerative diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HDAC6 Knockout HEK293 Cell Line | EDJ-KQ2396 | Human | 10013 | Details Get a Quote |
| HDAC6 Knockout HCT 116 Cell Line | EDJ-KQ21559 | Human | 10013 | Details Get a Quote |
| HDAC6 Knockout A-549 Cell Line | EDJ-KQ22885 | Human | 10013 | Details Get a Quote |
| HDAC6 Knockout HeLa Cell Line | EDJ-KQ22887 | Human | 10013 | Details Get a Quote |
