HDAC4 Gene - Histone Deacetylase 4
A key epigenetic regulator in muscle development, neurological function, and cancer
Gene Information Card
| Symbol | HDAC4 |
|---|---|
| Full Name | Histone Deacetylase 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q37.3 |
| NCBI Gene ID | 9759 ncbi.nlm.nih.gov/gene/9759 |
| Ensembl ID | ENSG00000168036 |
| UniProt ID | P56524 |
| OMIM ID | 605314 |
| HGNC ID | 14063 |
| Aliases | HDAC4; HD4; HDAC-A; HDACA; KIAA0288 |
Description
HDAC4 (Histone Deacetylase 4) is a protein-coding gene that encodes a class II histone deacetylase. It regulates gene expression by deacetylating lysine residues on histone and non-histone proteins, playing critical roles in muscle differentiation, neuronal survival, and synaptic plasticity. Mutations in HDAC4 are associated with brachydactyly-mental retardation syndrome (BDMR) and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Brachydactyly-mental retardation syndrome (BDMR) | Haploinsufficiency of HDAC4 due to deletions or loss-of-function mutations disrupts transcriptional regulation during development. | OMIM #605314; ClinVar |
| Huntington disease | HDAC4 interacts with huntingtin protein; altered HDAC4 localization contributes to neuronal toxicity. | NCBI Gene; PubMed |
| Cancer (various) | HDAC4 overexpression or aberrant deacetylase activity promotes tumorigenesis by silencing tumor suppressor genes. | COSMIC; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 8.2 | Medium |
| Heart | 6.5 | Medium |
| Skeletal muscle | 12.1 | High |
| Liver | 3.4 | Low |
| Kidney | 5.0 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 7.8 | Cervical cancer cell line |
| HEK293 | 9.1 | Embryonic kidney cells |
| SH-SY5Y | 11.3 | Neuroblastoma cell line |
| MCF7 | 6.2 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2062C>T (p.Arg688Trp) | Missense | <0.1% | Loss of function; associated with BDMR |
| c.1057G>A (p.Gly353Arg) | Missense | <0.1% | Likely pathogenic; altered protein stability |
| Whole gene deletion | Copy number loss | Rare | Haploinsufficiency; BDMR phenotype |
Mutation functional classification
Loss of Function (LOF)
Missense and nonsense mutations that reduce HDAC4 deacetylase activity or protein stability, leading to haploinsufficiency in BDMR.
Gain of Function (GOF)
Not well documented; some cancer-associated overexpression may act as a gain-of-function by enhancing repression of tumor suppressors.
Dominant Negative (DN)
Truncating mutations that produce a protein interfering with wild-type HDAC4 function have been proposed in BDMR.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004407 - histone deacetylase activity | • GO:0005634 - nucleus |
| • GO:0005737 - cytoplasm | • GO:0006355 - regulation of transcription |
| • DNA-templated | • GO:0045944 - positive regulation of transcription by RNA polymerase II |
| • GO:0016575 - histone deacetylation |
Pathways
• Notch signaling pathway (Reactome: R-HSA-157118)
• Class I/II HDAC-mediated deacetylation (Reactome: R-HSA-3214847)
• Transcriptional regulation by MEF2 (Reactome: R-HSA-9616222)
Protein Summary
HDAC4 is a 1084-amino acid protein belonging to class IIa histone deacetylases. It contains a conserved deacetylase domain and an N-terminal MEF2-binding domain. HDAC4 shuttles between the nucleus and cytoplasm in response to cellular signals, regulating transcription by deacetylating histones and transcription factors such as MEF2. It is essential for proper muscle and neuronal development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HDAC4 Knockout HEK293 Cell Line | EDJ-KQ1457 | Human | 9759 | Details Get a Quote |
| HDAC4 Knockout A-549 Cell Line | EDJ-KQ21013 | Human | 9759 | Details Get a Quote |
| HDAC4 Knockout HCT 116 Cell Line | EDJ-KQ21014 | Human | 9759 | Details Get a Quote |
| HDAC4 Knockout HeLa Cell Line | EDJ-KQ21015 | Human | 9759 | Details Get a Quote |
| HDAC4 Knockout HAP1 Cell Line | EDC08020 | Human | 9759 | Details Get a Quote |
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