HDAC5
protein-codinghistone deacetylase 5, the group of Histone deacetylases, class IIA
Gene summary
Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to the class II histone deacetylase/acuc/apha family. It possesses histone deacetylase activity and represses transcription when tethered to a promoter. It coimmunoprecipitates only with HDAC3 family member and might form multicomplex proteins. It also interacts with myocyte enhancer factor-2 (MEF2) proteins, resulting in repression of MEF2-dependent genes. This gene is thought to be associated with colon cancer. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~47.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0007661
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HDAC5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005474.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 3 | 1 | 7 | ||
| missense | 135 | 3 | 3 | 141 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 144 | 6 | 4 | 154 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005465.2 | 26 | MANE Select | |
| Ensembl | ENSP00000507606.1 | 26 | MANE Select | |
| RefSeq | NP_001015053.1 | 26 | Standard | |
| RefSeq | NP_001369322.1 | 26 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Apelin signaling pathway - Homo sapiens (human)
- Viral carcinogenesis - Homo sapiens (human)
- Epstein-Barr virus infection - Homo sapiens (human)
- Alcoholism - Homo sapiens (human)
- Human papillomavirus infection - Homo sapiens (human)
Biological Process
- negative regulation of transcription by RNA polymerase II
- chromatin organization
- chromatin remodeling
- chromatin silencing
- protein deacetylation
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- RNA polymerase II transcription factor binding
- chromatin binding
- histone deacetylase activity
- protein kinase C binding
Cellular Component
- histone deacetylase complex
- nucleus
- nucleoplasm
- cytoplasm
- Golgi apparatus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000225983
- Coding exons
- 26
- Length
- 46957
- Individuals with no LoFs
- 125720
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 27
- Defined
- 125747
- p
- 0.000107
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.32 | 402 | 638 | 0.630 | 0.0000389 | 7215 |
| Missense (PolyPhen) | 183 | 330.45 | 0.5538 | 3757 | ||
| Synonymous | 0.176 | 276 | 280 | 0.987 | 0.0000185 | 2316 |
| Loss of Function | 6.49 | 3 | 54.9 | 0.0547 | 0.00000258 | 639 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000063 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00012 | 0.00011 | rare |
| South Asian | 0.00023 | 0.00023 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Involved in muscle maturation by repressing transcription of myocyte enhancer MEF2C. During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. {ECO:0000269|PubMed:24413532}.;
Recessive Scores
- pRec
- 0.287
Intolerance Scores
- LoFtool
- 0.426
- RVIS EVS
- -1.28
- RVIS percentile EVS
- 5.17
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.804
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |