HDAC2
histone deacetylase 2, the group of EMSY complex|SIN3 histone deacetylase complex subunits|MiDAC complex subunits|Histone deacetylases, class I|NuRD complex subunits
Basic information
Region (hg38): 6:113933028-114011308
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the HDAC2 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | |||||
| missense | 9 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 2 | 1 | 3 | |||
| non coding | 2 | |||||
| Total | 0 | 0 | 9 | 2 | 2 |
Variants in HDAC2
This is a list of pathogenic ClinVar variants found in the HDAC2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 6-113941763-C-T | not specified | Uncertain significance (Oct 17, 2023) | ||
| 6-113943382-T-G | not specified | Uncertain significance (Dec 28, 2022) | ||
| 6-113943407-CCTTT-C | HDAC2-related disorder | Uncertain significance (May 25, 2024) | ||
| 6-113943462-C-T | not specified | Uncertain significance (Dec 20, 2023) | ||
| 6-113944273-A-G | HDAC2-related disorder | Likely benign (Sep 13, 2019) | ||
| 6-113944330-T-C | not specified | Uncertain significance (Dec 18, 2023) | ||
| 6-113946031-G-C | not specified | Uncertain significance (Jun 02, 2024) | ||
| 6-113946123-T-A | Benign (May 24, 2018) | |||
| 6-113948991-G-A | Likely benign (Dec 19, 2018) | |||
| 6-113949200-C-A | not specified | Uncertain significance (Jan 23, 2023) | ||
| 6-113953298-A-G | HDAC2-related disorder | Likely benign (May 02, 2019) | ||
| 6-113953359-T-G | HDAC2-related disorder | Uncertain significance (Dec 20, 2023) | ||
| 6-113956005-T-G | HDAC2-related disorder | Likely benign (May 02, 2023) | ||
| 6-113956160-T-C | HDAC2-related disorder | Likely benign (Sep 18, 2019) | ||
| 6-113956654-A-G | not specified | Uncertain significance (Dec 11, 2020) | ||
| 6-113956687-A-G | not specified | Uncertain significance (Dec 30, 2019) | ||
| 6-113956702-G-T | Benign (Dec 31, 2019) | |||
| 6-113958760-G-A | not specified | Uncertain significance (Jan 03, 2024) | ||
| 6-113959978-C-T | Inborn genetic diseases | Uncertain significance (May 03, 2017) | ||
| 6-113960025-T-C | Benign (Dec 31, 2019) | |||
| 6-113970880-T-C | not specified | Uncertain significance (May 14, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| HDAC2 | protein_coding | protein_coding | ENST00000519065 | 14 | 78281 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.0000268 | 123860 | 0 | 1 | 123861 | 0.00000404 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 4.05 | 79 | 264 | 0.299 | 0.0000131 | 3217 |
| Missense in Polyphen | 11 | 81.454 | 0.13504 | 996 | ||
| Synonymous | 1.28 | 70 | 85.0 | 0.824 | 0.00000404 | 837 |
| Loss of Function | 5.05 | 0 | 29.7 | 0.00 | 0.00000152 | 401 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000558 | 0.0000558 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.0000558 | 0.0000558 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
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. Forms transcriptional repressor complexes by associating with MAD, SIN3, YY1 and N-COR. Interacts in the late S-phase of DNA-replication with DNMT1 in the other transcriptional repressor complex composed of DNMT1, DMAP1, PCNA, CAF1. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. May be involved in the transcriptional repression of circadian target genes, such as PER1, mediated by CRY1 through histone deacetylation. Involved in MTA1-mediated transcriptional corepression of TFF1 and CDKN1A. {ECO:0000269|PubMed:19343227, ECO:0000269|PubMed:21965678}.;
- Pathway
- Chronic myeloid leukemia - Homo sapiens (human);Cell cycle - Homo sapiens (human);Longevity regulating pathway - multiple species - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Notch signaling pathway - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Alcoholism - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Cell Cycle;Neural Crest Differentiation;Notch Signaling Pathway;Initiation of transcription and translation elongation at the HIV-1 LTR;Ethanol effects on histone modifications;Notch Signaling Pathway;Notch Signaling Pathway;ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression;Positive epigenetic regulation of rRNA expression;Notch;Disease;NoRC negatively regulates rRNA expression;Negative epigenetic regulation of rRNA expression;Signal Transduction;Epigenetic regulation of gene expression;Gene expression (Transcription);the prc2 complex sets long-term gene silencing through modification of histone tails;role of mef2d in t-cell apoptosis;mets affect on macrophage differentiation;Generic Transcription Pathway;Factors involved in megakaryocyte development and platelet production;SUMOylation of chromatin organization proteins;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;HDACs deacetylate histones;Metabolism of proteins;RNA Polymerase I Promoter Clearance;RNA Polymerase II Transcription;Chromatin modifying enzymes;RNA Polymerase I Transcription;RNA Polymerase I Transcription Initiation;Signaling by NOTCH1;Signaling by NOTCH;TGF-beta super family signaling pathway canonical;SUMOylation;Glucocorticoid receptor regulatory network;Regulation of PTEN gene transcription;Hemostasis;PTEN Regulation;PIP3 activates AKT signaling;Death Receptor Signalling;Chromatin organization;p75 NTR receptor-mediated signalling;Regulation of TP53 Activity through Acetylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Direct p53 effectors;TNFalpha;Constitutive Signaling by NOTCH1 PEST Domain Mutants;Signaling by NOTCH1 PEST Domain Mutants in Cancer;Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants;Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer;Signaling by NOTCH1 in Cancer;Intracellular signaling by second messengers;Regulation of nuclear beta catenin signaling and target gene transcription;Diseases of signal transduction;Regulation of Telomerase;NOTCH1 Intracellular Domain Regulates Transcription;Signaling events mediated by HDAC Class I;Hedgehog signaling events mediated by Gli proteins;Regulation of nuclear SMAD2/3 signaling;p75NTR negatively regulates cell cycle via SC1
(Consensus)
Recessive Scores
- pRec
- 0.841
Intolerance Scores
- loftool
- rvis_EVS
- -0.12
- rvis_percentile_EVS
- 44.54
Haploinsufficiency Scores
- pHI
- 0.952
- hipred
- Y
- hipred_score
- 0.728
- ghis
- 0.686
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Hdac2
- Phenotype
- growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; limbs/digits/tail phenotype; vision/eye phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; pigmentation phenotype; neoplasm; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;response to amphetamine;cardiac muscle hypertrophy;chromatin remodeling;maintenance of chromatin silencing;blood coagulation;positive regulation of cell population proliferation;epidermal cell differentiation;positive regulation of epithelial to mesenchymal transition;positive regulation of receptor biosynthetic process;negative regulation of neuron projection development;dendrite development;histone deacetylation;response to caffeine;response to lipopolysaccharide;positive regulation of interleukin-1 production;positive regulation of tumor necrosis factor production;circadian regulation of gene expression;positive regulation of collagen biosynthetic process;cellular response to heat;response to nicotine;response to cocaine;odontogenesis of dentin-containing tooth;positive regulation of tyrosine phosphorylation of STAT protein;embryonic digit morphogenesis;ATP-dependent chromatin remodeling;negative regulation of apoptotic process;negative regulation of DNA binding;negative regulation of DNA-binding transcription factor activity;negative regulation of MHC class II biosynthetic process;positive regulation of proteolysis;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;behavioral response to ethanol;positive regulation of oligodendrocyte differentiation;response to hyperoxia;hair follicle placode formation;negative regulation of dendritic spine development;eyelid development in camera-type eye;fungiform papilla formation;cellular response to hydrogen peroxide;histone H3 deacetylation;histone H4 deacetylation;cellular response to retinoic acid;cellular response to transforming growth factor beta stimulus;cellular response to dopamine;negative regulation of peptidyl-lysine acetylation
- Cellular component
- histone deacetylase complex;nuclear chromatin;nucleus;nucleoplasm;cytoplasm;Sin3 complex;NuRD complex;protein-containing complex;ESC/E(Z) complex;Sin3-type complex
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;RNA polymerase II repressing transcription factor binding;chromatin binding;RNA binding;histone deacetylase activity;protein binding;transcription factor binding;deacetylase activity;enzyme binding;heat shock protein binding;nucleosomal DNA binding;NAD-dependent histone deacetylase activity (H3-K14 specific);protein deacetylase activity;histone deacetylase binding;sequence-specific DNA binding;NF-kappaB binding;promoter-specific chromatin binding