HDAC1
histone deacetylase 1, the group of MiDAC complex subunits|SIN3 histone deacetylase complex subunits|Histone deacetylases, class I|NuRD complex subunits|EMSY complex
Basic information
Region (hg38): 1:32292083-32333635
Previous symbols: [ "RPD3L1" ]
Links
Phenotypes
GenCC
Source:
- congenital heart disease (Disputed Evidence), mode of inheritance: AD
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 HDAC1 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 | 14 | 15 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 0 | |||||
| Total | 0 | 1 | 14 | 0 | 2 |
Variants in HDAC1
This is a list of pathogenic ClinVar variants found in the HDAC1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-32327044-A-G | Inborn genetic diseases | Likely pathogenic (Apr 02, 2013) | ||
| 1-32327052-G-A | not specified | Uncertain significance (Nov 25, 2024) | ||
| 1-32327536-G-A | not specified | Likely benign (Mar 25, 2024) | ||
| 1-32327580-G-A | not specified | Uncertain significance (May 04, 2023) | ||
| 1-32327605-C-T | HDAC1-related disorder | Benign (Dec 31, 2019) | ||
| 1-32327646-G-C | not specified | Uncertain significance (Dec 25, 2024) | ||
| 1-32329133-C-T | HDAC1-related disorder | Benign (Dec 19, 2017) | ||
| 1-32329141-A-G | not specified | Uncertain significance (Oct 14, 2023) | ||
| 1-32330614-G-A | not specified | Uncertain significance (Jul 17, 2024) | ||
| 1-32330797-A-T | not specified | Uncertain significance (Mar 31, 2022) | ||
| 1-32330858-G-A | not specified | Uncertain significance (Jun 03, 2024) | ||
| 1-32331749-G-A | not specified | Uncertain significance (Oct 16, 2024) | ||
| 1-32331756-C-A | not specified | Uncertain significance (Oct 01, 2024) | ||
| 1-32331770-G-A | not specified | Uncertain significance (Jan 21, 2025) | ||
| 1-32331776-G-A | not specified | Uncertain significance (Oct 13, 2023) | ||
| 1-32332108-G-A | not specified | Uncertain significance (Dec 07, 2023) | ||
| 1-32332133-C-T | HDAC1-related disorder | Likely benign (Jun 13, 2019) | ||
| 1-32332134-G-A | not specified | Uncertain significance (Jan 02, 2025) | ||
| 1-32332197-G-C | not specified | Uncertain significance (Dec 12, 2023) | ||
| 1-32332709-G-A | not specified | Uncertain significance (Mar 20, 2024) | ||
| 1-32332746-A-G | not specified | Uncertain significance (Aug 17, 2021) | ||
| 1-32333028-A-T | not specified | Uncertain significance (Oct 25, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| HDAC1 | protein_coding | protein_coding | ENST00000373548 | 14 | 41550 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.614 | 0.386 | 125732 | 0 | 16 | 125748 | 0.0000636 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.04 | 147 | 293 | 0.501 | 0.0000173 | 3206 |
| Missense in Polyphen | 28 | 77.811 | 0.35985 | 949 | ||
| Synonymous | 1.76 | 92 | 116 | 0.792 | 0.00000774 | 854 |
| Loss of Function | 3.98 | 6 | 29.3 | 0.205 | 0.00000158 | 347 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000580 | 0.0000580 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000797 | 0.0000791 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.000131 | 0.000131 |
| 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. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST- mediated transcription in resting neurons. Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B. Deacetylates NR1D2 and abrogates the effect of KAT5-mediated relieving of NR1D2 transcription repression 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. Involved in CIART-mediated transcriptional repression of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex or CRY1 through histone deacetylation. {ECO:0000269|PubMed:12837748, ECO:0000269|PubMed:16478997, ECO:0000269|PubMed:17000776, ECO:0000269|PubMed:17704056, ECO:0000269|PubMed:17996965, ECO:0000269|PubMed:19081374, ECO:0000269|PubMed:19343227}.;
- 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);Amphetamine addiction - Homo sapiens (human);MicroRNAs in cancer - 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);Valproic Acid Pathway, Pharmacodynamics;Pathway_PA165964473;Cell Cycle;Androgen receptor signaling pathway;Energy Metabolism;Integrated Breast Cancer Pathway;TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway;Neural Crest Differentiation;Retinoblastoma (RB) in Cancer;Notch Signaling Pathway;Apoptosis-related network due to altered Notch3 in ovarian cancer;Initiation of transcription and translation elongation at the HIV-1 LTR;MECP2 and Associated Rett Syndrome;IL-6 signaling pathway;TGF-beta Signaling Pathway;Valproic acid pathway;VEGFA-VEGFR2 Signaling Pathway;Ethanol effects on histone modifications;Notch Signaling Pathway;Notch Signaling Pathway;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;TWEAK;Degradation of beta-catenin by the destruction complex;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;Signaling by WNT;Signal Transduction;Epigenetic regulation of gene expression;Gene expression (Transcription);wnt signaling pathway;the prc2 complex sets long-term gene silencing through modification of histone tails;sumoylation by ranbp2 regulates transcriptional repression;downregulated of mta-3 in er-negative breast tumors;cell cycle: g1/s check point;role of mef2d in t-cell apoptosis;multi-step regulation of transcription by pitx2;overview of telomerase protein component gene htert transcriptional regulation;Generic Transcription Pathway;Repression of WNT target genes;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;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;Chromatin modifying enzymes;Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1;G0 and Early G1;RNA Polymerase I Transcription;RNA Polymerase I Transcription Initiation;Downregulation of SMAD2/3:SMAD4 transcriptional activity;Signaling by NOTCH1;Mitotic G1-G1/S phases;Signaling by NOTCH;AndrogenReceptor;TGF-beta super family signaling pathway canonical;SUMOylation;TGF_beta_Receptor;Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer;EGFR1;Glucocorticoid receptor regulatory network;Regulation of PTEN gene transcription;Hemostasis;PTEN Regulation;PIP3 activates AKT signaling;Signaling by Nuclear Receptors;Death Receptor Signalling;Chromatin organization;p75 NTR receptor-mediated signalling;Regulation of TP53 Activity through Acetylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Notch signaling pathway;Estrogen-dependent gene expression;Cell Cycle;IL6;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;Signaling by TGF-beta Receptor Complex;Signaling by TGF-beta family members;Cell Cycle, Mitotic;ESR-mediated signaling;Intracellular signaling by second messengers;Regulation of nuclear beta catenin signaling and target gene transcription;Notch-mediated HES/HEY network;Transcriptional regulation by RUNX1;Diseases of signal transduction;Validated nuclear estrogen receptor alpha network;Validated targets of C-MYC transcriptional repression;Regulation of Telomerase;Retinoic acid receptors-mediated signaling;Formation of the beta-catenin:TCF transactivating complex;TCF dependent signaling in response to WNT;Regulation of Androgen receptor activity;Sumoylation by RanBP2 regulates transcriptional repression;NOTCH1 Intracellular Domain Regulates Transcription;Regulation of retinoblastoma protein;Signaling events mediated by HDAC Class I;Hedgehog signaling events mediated by Gli proteins;Regulation of nuclear SMAD2/3 signaling;Presenilin action in Notch and Wnt signaling;E2F transcription factor network;IL3-mediated signaling events;p75NTR negatively regulates cell cycle via SC1
(Consensus)
Recessive Scores
- pRec
- 0.919
Intolerance Scores
- loftool
- 0.449
- rvis_EVS
- -0.69
- rvis_percentile_EVS
- 14.97
Haploinsufficiency Scores
- pHI
- 0.999
- hipred
- Y
- hipred_score
- 0.756
- ghis
- 0.631
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- K
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.811
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Hdac1
- 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; muscle phenotype; craniofacial phenotype; cellular phenotype; embryo phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); hematopoietic 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; limbs/digits/tail phenotype; vision/eye phenotype; immune system phenotype;
Zebrafish Information Network
- Gene name
- hdac1
- Affected structure
- endodermal cell
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;chromatin organization;chromatin remodeling;methylation-dependent chromatin silencing;protein deacetylation;endoderm development;blood coagulation;positive regulation of cell population proliferation;epidermal cell differentiation;negative regulation of gene expression;negative regulation of myotube differentiation;positive regulation of receptor biosynthetic process;histone deacetylation;hippocampus development;neuron differentiation;circadian regulation of gene expression;odontogenesis of dentin-containing tooth;embryonic digit morphogenesis;ATP-dependent chromatin remodeling;negative regulation of apoptotic process;negative regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation by host of viral transcription;regulation of megakaryocyte differentiation;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;positive regulation of oligodendrocyte differentiation;negative regulation of androgen receptor signaling pathway;hair follicle placode formation;eyelid development in camera-type eye;fungiform papilla formation;histone H3 deacetylation;histone H4 deacetylation;negative regulation of canonical Wnt signaling pathway;beta-catenin-TCF complex assembly;negative regulation of intrinsic apoptotic signaling pathway
- Cellular component
- histone deacetylase complex;chromatin;nuclear chromatin;heterochromatin;nucleus;nucleoplasm;transcription factor complex;cytoplasm;cytosol;Sin3 complex;NuRD complex;protein-containing complex;neuronal cell body;Sin3-type complex
- Molecular function
- transcription regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;core promoter sequence-specific DNA binding;RNA polymerase II transcription factor binding;RNA polymerase II repressing transcription factor binding;p53 binding;DNA-binding transcription factor activity;transcription corepressor activity;histone deacetylase activity;protein binding;transcription factor binding;deacetylase activity;enzyme binding;nucleosomal DNA binding;NAD-dependent histone deacetylase activity (H3-K14 specific);protein deacetylase activity;activating transcription factor binding;Krueppel-associated box domain binding;histone deacetylase binding;transcription regulatory region DNA binding;protein N-terminus binding;NF-kappaB binding;repressing transcription factor binding;E-box binding;promoter-specific chromatin binding