HDAC3

histone deacetylase 3, the group of Histone deacetylases, class I|NCoR/SMRT transcriptional repression complex subunits

Basic information

Region (hg38): 5:141620875-141636849

Links

ENSG00000171720 ∙ NCBI:8841 ∙ OMIM:605166 ∙ HGNC:4854 ∙ Uniprot:O15379 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HDAC3 gene.

• Inborn genetic diseases (5 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HDAC3 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					1	1
missense		2	5		1	8
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	2	5	0	2

Variants in HDAC3

This is a list of pathogenic ClinVar variants found in the HDAC3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-141621473-T-C		not specified	Uncertain significance (Aug 29, 2023)
5-141621523-T-C			Benign (Dec 31, 2019)
5-141625208-C-T			Uncertain significance (Jul 01, 2018)
5-141625708-T-G		not specified	Uncertain significance (Dec 28, 2022)
5-141626026-C-T			Benign (Dec 31, 2019)
5-141626042-T-C			Uncertain significance (Jul 01, 2018)
5-141626212-C-T		Inborn genetic diseases	Likely pathogenic (Jun 11, 2015)
5-141626221-T-C		Inborn genetic diseases	Likely pathogenic (Apr 07, 2017)
5-141626254-T-C		not specified	Uncertain significance (Aug 16, 2021)
5-141634814-T-C		not specified	Uncertain significance (Feb 27, 2024)
5-141636730-CCTCACCGTAGT-C		Ependymoma	Uncertain significance (Dec 29, 2017)
5-141636743-G-T		not specified	Uncertain significance (Feb 06, 2024)
5-141636782-C-A		not specified	Uncertain significance (Jan 30, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HDAC3	protein_coding	protein_coding	ENST00000305264	15	15995

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.567	0.433	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.72	92	261	0.353	0.0000150	2860
Missense in Polyphen		19	117.74	0.16137		1253
Synonymous	0.0170	102	102	0.998	0.00000633	784
Loss of Function	3.93	6	28.7	0.209	0.00000147	311

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates. 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. Participates in the BCL6 transcriptional repressor activity by deacetylating the H3 'Lys- 27' (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase activity and repressing proximal gene expression. Probably participates in the regulation of transcription through its binding to the zinc-finger transcription factor YY1; increases YY1 repression activity. Required to repress transcription of the POU1F1 transcription factor. Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML bodies for sumoylation (PubMed:21444723, PubMed:23911289). Contributes, together with XBP1 isoform 1, to the activation of NFE2L2-mediated HMOX1 transcription factor gene expression in a PI(3)K/mTORC2/Akt-dependent signaling pathway leading to endothelial cell (EC) survival under disturbed flow/oxidative stress (PubMed:25190803). {ECO:0000269|PubMed:21444723, ECO:0000269|PubMed:23911289, ECO:0000269|PubMed:25190803}.
• Pathway: Thyroid hormone signaling pathway - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Alcoholism - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Cell Cycle;Neural Crest Differentiation;Initiation of transcription and translation elongation at the HIV-1 LTR;HDAC6 interactions;Ethanol effects on histone modifications;Developmental Biology;RUNX2 regulates osteoblast differentiation;RUNX2 regulates bone development;Transcriptional regulation by RUNX2;Disease;Signal Transduction;Gene expression (Transcription);Circadian Clock;acetylation and deacetylation of rela in nucleus;nuclear receptors coordinate the activities of chromatin remodeling complexes and coactivators to facilitate initiation of transcription in carcinoma cells;Generic Transcription Pathway;Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);Metabolism of lipids;HDACs deacetylate histones;Metabolism of proteins;RNA Polymerase II Transcription;Chromatin modifying enzymes;Chaperonin-mediated protein folding;NR1D1 (REV-ERBA) represses gene expression;Metabolism;Association of TriC/CCT with target proteins during biosynthesis;Transcriptional regulation of white adipocyte differentiation;Signaling by NOTCH1;Signaling by NOTCH;TGF-beta super family signaling pathway canonical;Signaling events mediated by HDAC Class II;Regulation of PTEN gene transcription;PTEN Regulation;PIP3 activates AKT signaling;Protein folding;Death Receptor Signalling;Chromatin organization;p75 NTR receptor-mediated signalling;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;Diseases of signal transduction;Validated targets of C-MYC transcriptional repression;Retinoic acid receptors-mediated signaling;NOTCH1 Intracellular Domain Regulates Transcription;Regulation of retinoblastoma protein;Signaling events mediated by HDAC Class I;p75NTR negatively regulates cell cycle via SC1 (Consensus)

Recessive Scores

• pRec: 0.649

Intolerance Scores

• loftool: 0.329
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.4

Haploinsufficiency Scores

• pHI: 0.966
• hipred: Y
• hipred_score: 0.825
• ghis: 0.540

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.946

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hdac3
• 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; 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; embryo phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype

Zebrafish Information Network

• Gene name: hdac3
• Affected structure: neuromast hair cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;positive regulation of protein phosphorylation;chromatin organization;protein deacetylation;circadian rhythm;negative regulation of myotube differentiation;regulation of lipid metabolic process;regulation of protein stability;positive regulation of TOR signaling;positive regulation of protein import into nucleus;negative regulation of apoptotic process;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;negative regulation of JNK cascade;spindle assembly;histone H3 deacetylation;histone H4 deacetylation;cellular response to fluid shear stress;positive regulation of cold-induced thermogenesis
• Cellular component: histone deacetylase complex;nucleus;nucleoplasm;cytoplasm;Golgi apparatus;cytosol;plasma membrane;transcriptional repressor complex;mitotic spindle
• Molecular function: chromatin binding;transcription corepressor activity;histone deacetylase activity;protein binding;transcription factor binding;enzyme binding;cyclin binding;NAD-dependent histone deacetylase activity (H3-K14 specific);protein deacetylase activity;histone deacetylase binding;NF-kappaB binding