HDAC9

histone deacetylase 9, the group of Histone deacetylases, class IIA

Basic information

Region (hg38): 7:18086948-19002416

Links

ENSG00000048052 ∙ NCBI:9734 ∙ OMIM:606543 ∙ HGNC:14065 ∙ Uniprot:Q9UKV0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Auriculocondylar syndrome 4	AD	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial	34750192

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HDAC9 gene.

• Inborn genetic diseases (25 variants)
• not provided (11 variants)
• not specified (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HDAC9 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	4	6
missense			26	1	2	29
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region					2	2
non coding					2	2
Total	0	0	27	3	8

Variants in HDAC9

This is a list of pathogenic ClinVar variants found in the HDAC9 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-18458861-A-G			Likely benign (Jun 01, 2022)
7-18496317-C-G		not specified	Uncertain significance (Aug 26, 2022)
7-18585364-G-A		not specified	Uncertain significance (Sep 06, 2022)
7-18590357-A-G		not specified	Uncertain significance (Oct 22, 2021)
7-18590386-G-C		not specified	Uncertain significance (Jan 26, 2022)
7-18590439-G-C		not specified	Uncertain significance (Aug 02, 2022)
7-18591587-A-G		not specified	Uncertain significance (Feb 07, 2023)
7-18591594-C-G			Likely benign (Apr 24, 2018)
7-18591652-G-A			Benign (Dec 31, 2019)
7-18629397-G-A		not specified	Uncertain significance (Oct 25, 2022)
7-18629459-G-C		not specified	Uncertain significance (Jan 08, 2024)
7-18634659-G-T		not specified	Uncertain significance (Aug 30, 2021)
7-18634723-C-T		not specified	Uncertain significance (Aug 10, 2021)
7-18634740-G-A		not specified	Uncertain significance (May 09, 2023)
7-18644713-A-G		not specified	Uncertain significance (May 16, 2023)
7-18644773-G-T		not specified	Uncertain significance (Feb 06, 2023)
7-18647822-C-T		not specified	Uncertain significance (Apr 17, 2023)
7-18647877-G-A			Likely benign (Dec 01, 2022)
7-18647893-C-G		not specified	Uncertain significance (Mar 04, 2024)
7-18647919-A-T		not specified	Benign (Mar 29, 2016)
7-18648516-T-G		not specified	Uncertain significance (Sep 14, 2022)
7-18648550-G-A		not specified	Uncertain significance (Dec 22, 2023)
7-18666259-T-C		not specified	Uncertain significance (Dec 28, 2023)
7-18666379-T-G		not specified	Uncertain significance (Aug 30, 2021)
7-18666418-A-T		not specified	Uncertain significance (Dec 06, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HDAC9	protein_coding	protein_coding	ENST00000441542	25	915468

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000268	124662	0	26	124688	0.000104

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.06	422	559	0.755	0.0000289	6906
Missense in Polyphen		121	239.67	0.50485		3034
Synonymous	-0.0164	211	211	1.00	0.0000112	2057
Loss of Function	6.32	9	63.2	0.142	0.00000354	702

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000187	0.000187
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.000160	0.000159
Middle Eastern	0.00	0.00
South Asian	0.0000981	0.0000980
Other	0.00	0.00

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). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Represses MEF2-dependent transcription.
• Disease: DISEASE: Note=A chromosomal aberration involving HDAC9 is found in a family with Peters anomaly. Translocation t(1;7)(q41;p21) with TGFB2 resulting in lack of HDAC9 protein. {ECO:0000269|PubMed:12706107}.
• Pathway: Viral carcinogenesis - Homo sapiens (human);Alcoholism - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Valproic Acid Pathway, Pharmacodynamics;Pathway_PA165964473;MicroRNAs in cardiomyocyte hypertrophy;Neural Crest Differentiation;Cardiac Hypertrophic Response;Initiation of transcription and translation elongation at the HIV-1 LTR;VEGFA-VEGFR2 Signaling Pathway;Ethanol effects on histone modifications;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Disease;Signal Transduction;sumoylation by ranbp2 regulates transcriptional repression;signal dependent regulation of myogenesis by corepressor mitr;nfat and hypertrophy of the heart ;Signaling by NOTCH1;Signaling by NOTCH;TGF-beta super family signaling pathway canonical;Signaling events mediated by HDAC Class II;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;Diseases of signal transduction;NOTCH1 Intracellular Domain Regulates Transcription (Consensus)

Recessive Scores

• pRec: 0.715

Intolerance Scores

• loftool: 0.306
• rvis_EVS: -1.06
• rvis_percentile_EVS: 7.52

Haploinsufficiency Scores

• pHI: 0.933
• hipred: Y
• hipred_score: 0.603
• ghis: 0.536

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.555

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hdac9
• Phenotype: muscle phenotype; growth/size/body region 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); 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)

Zebrafish Information Network

• Gene name: hdac9b
• Affected structure: vascular lymphangioblast
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;response to amphetamine;inflammatory response;heart development;histone deacetylation;neuron differentiation;B cell differentiation;cellular response to insulin stimulus;peptidyl-lysine deacetylation;B cell activation;negative regulation of transcription, DNA-templated;regulation of skeletal muscle fiber development;regulation of striated muscle cell differentiation;histone H3 deacetylation;histone H4 deacetylation;positive regulation of cell migration involved in sprouting angiogenesis
• Cellular component: histone deacetylase complex;nucleus;nucleoplasm;transcription factor complex;cytoplasm;histone methyltransferase complex
• Molecular function: transcription corepressor activity;histone deacetylase activity;protein kinase C binding;protein binding;transcription factor binding;NAD-dependent histone deacetylase activity (H3-K14 specific);protein deacetylase activity;histone deacetylase binding;metal ion binding;repressing transcription factor binding