HDAC8 Gene: Histone Deacetylase 8
A key epigenetic regulator involved in Cornelia de Lange syndrome and cancer
Gene Information Card
| Symbol | HDAC8 |
|---|---|
| Full Name | Histone Deacetylase 8 |
| Gene Type | Protein-coding |
| Chromosomal Location | Xq13.1 |
| NCBI Gene ID | 55869 ncbi.nlm.nih.gov/gene/55869 |
| Ensembl ID | ENSG00000147099 |
| UniProt ID | Q9BY41 |
| OMIM ID | 300269 |
| HGNC ID | 13315 |
| Aliases | HDAC8; RPD3; KDAC8; FLJ13941 |
Description
The HDAC8 gene encodes a class I histone deacetylase enzyme that removes acetyl groups from lysine residues on histone and non-histone proteins, thereby regulating chromatin structure and gene expression. It plays critical roles in cell cycle control, smooth muscle differentiation, and neuronal development. Mutations in HDAC8 are associated with Cornelia de Lange syndrome (CdLS) and have been implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cornelia de Lange syndrome (CdLS) | Loss-of-function mutations reduce deacetylase activity, leading to aberrant acetylation of histones and non-histone proteins, disrupting gene expression and development. | ClinVar, OMIM |
| Colorectal cancer | Overexpression of HDAC8 promotes tumor cell proliferation and invasion; inhibition reduces tumor growth. | COSMIC, PubMed |
| Neuroblastoma | HDAC8 is overexpressed and contributes to cell survival; knockdown induces apoptosis. | COSMIC, PubMed |
| T-cell acute lymphoblastic leukemia (T-ALL) | HDAC8 is required for T-ALL cell survival; inhibition induces apoptosis. | PubMed |
| X-linked intellectual disability | Mutations in HDAC8 can cause intellectual disability with or without CdLS features. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.2 | Medium |
| Heart | 8.5 | Low |
| Liver | 6.3 | Low |
| Kidney | 7.8 | Low |
| Testis | 15.4 | Medium |
| Skeletal muscle | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 18.5 | Cervical cancer cell line |
| A549 | 12.3 | Lung carcinoma |
| MCF7 | 9.8 | Breast cancer |
| HepG2 | 7.2 | Liver cancer |
| K562 | 14.6 | Leukemia |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg316Trp | Missense | Rare (found in CdLS patients) | Reduced catalytic activity |
| p.Gly319Ser | Missense | Rare (found in CdLS patients) | Reduced catalytic activity |
| p.Pro409Ala | Missense | Rare (found in CdLS patients) | Reduced catalytic activity |
| p.Arg97Cys | Missense | Rare (found in CdLS patients) | Reduced catalytic activity |
| p.Gln112* | Nonsense | Rare (found in CdLS patients) | Truncated protein, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most CdLS-associated mutations are loss-of-function, reducing deacetylase activity and leading to hyperacetylation of substrates.
Gain of Function (GOF)
In some cancers, HDAC8 overexpression or amplification may act as an oncogenic gain-of-function, promoting cell proliferation.
Dominant Negative (DN)
Some missense mutations may exert a dominant-negative effect by dimerizing with wild-type HDAC8 and impairing its function.
View complete mutation data：
Gene Ontology (GO)
| • histone deacetylase activity | • protein deacetylase activity |
| • zinc ion binding | • chromatin binding |
| • nucleus | • cytoplasm |
| • regulation of transcription by RNA polymerase II | • chromatin remodeling |
| • cell cycle | • smooth muscle cell differentiation |
Pathways
• Chromatin organization
• Epigenetic regulation of gene expression
• Notch signaling pathway (in T-ALL)
• p53 pathway (via deacetylation of p53)
Protein Summary
HDAC8 is a 377-amino acid protein that belongs to the class I histone deacetylase family. It catalyzes the removal of acetyl groups from lysine residues of histone H3 and H4, as well as non-histone proteins such as p53, SMC3, and estrogen-related receptor alpha. HDAC8 is predominantly nuclear but can also be cytoplasmic. It forms homodimers and interacts with various co-repressor complexes. Its activity is regulated by phosphorylation and by binding to inositol phosphates. HDAC8 is essential for proper chromosome cohesion and gene expression during development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HDAC8 Knockout HEK293 Cell Line | EDJ-KQ51478 | Human | 55869 | Details Get a Quote |
| HDAC8 Knockout HeLa Cell Line | EDJ-KQ56646 | Human | 55869 | Details Get a Quote |
| HDAC8 Knockout A-549 Cell Line | EDJ-KQ65151 | Human | 55869 | Details Get a Quote |
| HDAC8 Knockout HCT 116 Cell Line | EDJ-KQ73587 | Human | 55869 | Details Get a Quote |
