HDAC8

histone deacetylase 8, the group of Histone deacetylases, class I

Basic information

Region (hg38): X:72329515-72573101

Previous symbols: [ "HDACL1", "WTS", "MRXS6" ]

Links

ENSG00000147099 ∙ NCBI:55869 ∙ OMIM:300269 ∙ HGNC:13315 ∙ Uniprot:Q9BY41 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Cornelia de Lange syndrome 5 (Strong), mode of inheritance: XL
• Cornelia de Lange syndrome (Supportive), mode of inheritance: AD
• Wilson-Turner syndrome (Supportive), mode of inheritance: XL
• Cornelia de Lange syndrome (Definitive), mode of inheritance: XL
• Cornelia de Lange syndrome 5 (Strong), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cornelia de Lange syndrome 5	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Dental; Musculoskeletal; Neurologic	1746601; 22885700; 24403048; 25209348; 25644381

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HDAC8 gene.

• Cornelia de Lange syndrome 5 (169 variants)
• not provided (65 variants)
• Inborn genetic diseases (25 variants)
• not specified (7 variants)
• Intellectual disability (6 variants)
• Cornelia de Lange syndrome 1 (3 variants)
• 6 conditions (2 variants)
• HDAC8-related condition (1 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HDAC8 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	32	11	45
missense	5	23	41	9	5	83
nonsense	10	2	1			13
start loss						0
frameshift	10	2				12
inframe indel		2	1		1	4
splice donor/acceptor (+/-2bp)	6	4	1			11
splice region	1		6	4	1	12
non coding			6	30	16	52
Total	31	33	52	71	33

Variants in HDAC8

This is a list of pathogenic ClinVar variants found in the HDAC8 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-72330062-C-T		Cornelia de Lange syndrome 5 • Inborn genetic diseases	Uncertain significance (Oct 03, 2023)
X-72330071-G-T		Cornelia de Lange syndrome 5	Uncertain significance (Mar 17, 2023)
X-72330071-GATTCCCTGC-G		Cornelia de Lange syndrome 1	Pathogenic (-)
X-72330078-T-C		Cornelia de Lange syndrome 5	Uncertain significance (Jul 31, 2017)
X-72330081-A-C		Cornelia de Lange syndrome 5	Likely benign (Nov 23, 2022)
X-72330084-CAG-C		Cornelia de Lange syndrome 5	Likely benign (Mar 23, 2022)
X-72330087-G-C		Cornelia de Lange syndrome 5	Likely benign (Mar 18, 2022)
X-72330118-T-C			Benign (Sep 26, 2018)
X-72330675-A-G			Uncertain significance (Oct 01, 2023)
X-72330702-G-A			Likely benign (Sep 01, 2023)
X-72351602-G-T			Likely benign (Sep 01, 2022)
X-72351605-G-A			Likely benign (Jun 01, 2022)
X-72351715-TC-T		Cornelia de Lange syndrome 5	Likely benign (Feb 08, 2023)
X-72351717-G-A		Cornelia de Lange syndrome 5	Benign (Oct 13, 2023)
X-72351720-G-A		Cornelia de Lange syndrome 5	Likely benign (Aug 27, 2023)
X-72351723-C-A		Cornelia de Lange syndrome 5	Benign (Dec 11, 2023)
X-72351724-G-A		Cornelia de Lange syndrome 5	Benign (Dec 27, 2023)
X-72351733-C-T		Cornelia de Lange syndrome 5	Uncertain significance (Jan 11, 2024)
X-72351739-T-C		Inborn genetic diseases • Cornelia de Lange syndrome 5	Likely benign (May 23, 2022)
X-72351740-G-A		Cornelia de Lange syndrome 5	Likely benign (May 19, 2022)
X-72351759-A-G		Cornelia de Lange syndrome 5	Uncertain significance (Nov 18, 2023)
X-72351762-C-T		Cornelia de Lange syndrome 5	Benign (Dec 11, 2023)
X-72351763-G-A		Cornelia de Lange syndrome 5	Pathogenic (-)
X-72351776-G-T		Cornelia de Lange syndrome 5	Likely benign (Jan 23, 2024)
X-72351778-G-A		Cornelia de Lange syndrome 5	Likely benign (Dec 18, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HDAC8	protein_coding	protein_coding	ENST00000373573	11	243588

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.977	0.0229	121907	0	1	121908	0.00000410

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.82	51	147	0.346	0.0000111	2472
Missense in Polyphen		4	61.321	0.06523		1001
Synonymous	0.339	54	57.3	0.943	0.00000451	718
Loss of Function	3.47	1	16.0	0.0625	0.00000129	255

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000138	0.000104
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
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. Histone deacetylases act via the formation of large multiprotein complexes. Also involved in the deacetylation of cohesin complex protein SMC3 regulating release of cohesin complexes from chromatin. May play a role in smooth muscle cell contractility. {ECO:0000269|PubMed:10748112, ECO:0000269|PubMed:10922473, ECO:0000269|PubMed:10926844, ECO:0000269|PubMed:14701748, ECO:0000269|PubMed:22885700}.
• Disease: DISEASE: Cornelia de Lange syndrome 5 (CDLS5) [MIM:300882]: A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. It is characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. {ECO:0000269|PubMed:22885700}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Wilson-Turner X-linked mental retardation syndrome (WTS) [MIM:309585]: A neurologic disorder characterized by severe intellectual disability, dysmorphic facial features, hypogonadism, short stature, and truncal obesity. Affected females have a milder phenotype than affected males. {ECO:0000269|PubMed:22889856}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: 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;Ethanol effects on histone modifications;Disease;Signal Transduction;HDACs deacetylate histones;Chromatin modifying enzymes;Signaling by NOTCH1;Signaling by NOTCH;TGF-beta super family signaling pathway canonical;Chromatin organization;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Cell Cycle;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;Resolution of Sister Chromatid Cohesion;Cell Cycle, Mitotic;Diseases of signal transduction;NOTCH1 Intracellular Domain Regulates Transcription;Signaling events mediated by HDAC Class I (Consensus)

Recessive Scores

• pRec: 0.126

Intolerance Scores

• loftool: 0.487
• rvis_EVS: -0.27
• rvis_percentile_EVS: 33.97

Haploinsufficiency Scores

• pHI: 0.181
• hipred: Y
• hipred_score: 0.825
• ghis: 0.564

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.961

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hdac8
• Phenotype: craniofacial phenotype; cellular 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; growth/size/body region 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); 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); skeleton phenotype; embryo phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;chromatin organization;chromatin assembly or disassembly;sister chromatid cohesion;negative regulation of protein ubiquitination;regulation of protein stability;regulation of telomere maintenance;positive regulation of transcription by RNA polymerase II;histone H3 deacetylation;histone H4 deacetylation;regulation of cohesin loading
• Cellular component: histone deacetylase complex;nuclear chromosome;nucleus;nucleoplasm;cytoplasm;plasma membrane
• Molecular function: histone deacetylase activity;protein binding;transcription factor binding;Hsp70 protein binding;NAD-dependent histone deacetylase activity (H3-K14 specific);metal ion binding;Hsp90 protein binding