KAT6A

lysine acetyltransferase 6A, the group of PHD finger proteins|Zinc fingers C2HC-type|MYST type domain containing lysine acetyltransferases

Basic information

Region (hg38): 8:41929479-42051994

Previous symbols: [ "ZNF220", "RUNXBP2", "MYST3" ]

Links

ENSG00000083168 ∙ NCBI:7994 ∙ OMIM:601408 ∙ HGNC:13013 ∙ Uniprot:Q92794 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome (Definitive), mode of inheritance: AD
• autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome (Strong), mode of inheritance: AD
• autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome (Strong), mode of inheritance: AD
• autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome (Supportive), mode of inheritance: AD
• autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome (Definitive), mode of inheritance: AD
• syndromic intellectual disability (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Arboleda-Tham syndrome	AD	Cardiovascular; Gastrointestinal	Due to the risk of cardiovascular involvement, screening (with ECG and echocardiogram) has been recommended to ascertain and enable management of cardiovascular sequelae (which may require surgical intervention); Individuals have been described as having increased risk of intestinal malrotation and bowel obstruction, and awareness may allow prompt interventions if these sequelae occur	Cardiovascular; Craniofacial; Dental; Gastrointestinal; Neurologic; Ophthalmologic; Pulmonary	25728775; 25728777; 27133397; 30245513

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KAT6A gene.

• not provided (43 variants)
• Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome (32 variants)
• Inborn genetic diseases (13 variants)
• Intellectual disability (4 variants)
• Syndromic intellectual disability (1 variants)
• KAT6A-related disorder (1 variants)
• Global developmental delay (1 variants)
• Neurodevelopmental disorder (1 variants)
• Craniosynostosis syndrome (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KAT6A 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			3	212	100	315
missense		6	419	225	44	694
nonsense	28	12	1			41
start loss						0
frameshift	50	17	2	1		70
inframe indel			26	15		41
splice donor/acceptor (+/-2bp)	3	6				9
splice region		1	15	24	4	44
non coding			3	77	35	115
Total	81	41	454	530	179

Variants in KAT6A

This is a list of pathogenic ClinVar variants found in the KAT6A region.

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

Position	Type	Phenotype	Significance	ClinVar
8-41932020-G-C			Benign (Jul 17, 2018)
8-41932207-A-T			Uncertain significance (Apr 25, 2022)
8-41932209-C-G			Uncertain significance (Feb 22, 2023)
8-41932212-C-A			Uncertain significance (Aug 14, 2023)
8-41932216-T-C		Inborn genetic diseases • KAT6A-related disorder	Likely benign (Sep 09, 2023)
8-41932220-A-C			Likely benign (Aug 19, 2022)
8-41932223-T-A			Likely benign (Aug 19, 2022)
8-41932225-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Oct 05, 2023)
8-41932226-G-A		Inborn genetic diseases	Benign/Likely benign (Feb 01, 2024)
8-41932227-T-C			Uncertain significance (Jan 05, 2024)
8-41932232-T-C			Likely benign (Aug 11, 2023)
8-41932236-T-C		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
8-41932241-G-A			Likely benign (Aug 04, 2023)
8-41932242-G-C			Uncertain significance (Mar 07, 2024)
8-41932246-C-G			Uncertain significance (Apr 20, 2018)
8-41932246-C-T		Inborn genetic diseases	Likely benign (Jul 05, 2024)
8-41932247-G-A			Benign (Jul 17, 2023)
8-41932248-C-A			Likely benign (Oct 05, 2023)
8-41932252-C-T			Uncertain significance (Nov 07, 2023)
8-41932253-A-G		Inborn genetic diseases	Benign/Likely benign (Jan 29, 2024)
8-41932254-G-C			Uncertain significance (Jun 26, 2019)
8-41932256-G-A			Benign (Apr 18, 2023)
8-41932257-T-C			Uncertain significance (Nov 08, 2022)
8-41932259-C-T		Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome	Uncertain significance (Aug 08, 2023)
8-41932261-T-C			Uncertain significance (Jul 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KAT6A	protein_coding	protein_coding	ENST00000396930	16	122512

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	6.47e-14	125672	0	74	125746	0.000294

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.07	925	1.12e+3	0.826	0.0000642	13287
Missense in Polyphen		130	244.05	0.53269		2702
Synonymous	0.0397	408	409	0.998	0.0000244	3748
Loss of Function	8.67	2	91.6	0.0218	0.00000570	1034

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000940	0.000940
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000343	0.000343
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Histone acetyltransferase that acetylates lysine residues in histone H3 and histone H4 (in vitro). Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. May act as a transcriptional coactivator for RUNX1 and RUNX2. Acetylates p53/TP53 at 'Lys-120' and 'Lys-382' and controls its transcriptional activity via association with PML. {ECO:0000269|PubMed:11742995, ECO:0000269|PubMed:11965546, ECO:0000269|PubMed:12771199, ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:17925393, ECO:0000269|PubMed:23431171}.
• Disease: DISEASE: Note=Chromosomal aberrations involving KAT6A may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with CREBBP (PubMed:8782817). Translocation t(8;22)(p11;q13) with EP300 (PubMed:10824998). KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription (PubMed:11742995). Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation (PubMed:12676584). {ECO:0000269|PubMed:10824998, ECO:0000269|PubMed:11742995, ECO:0000269|PubMed:12676584, ECO:0000269|PubMed:8782817}.; DISEASE: Note=A chromosomal aberration involving KAT6A is a cause of therapy-related myelodysplastic syndrome. Translocation t(2;8)(p23;p11.2) with ASXL2 generates a KAT6A-ASXL2 fusion protein. {ECO:0000269|Ref.3}.; DISEASE: Mental retardation, autosomal dominant 32 (MRD32) [MIM:616268]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD32 patients manifest intellectual disability, dysmorphic facial features, delayed psychomotor development, and lack of speech. {ECO:0000269|PubMed:25728775, ECO:0000269|PubMed:25728777}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Pathways Affected in Adenoid Cystic Carcinoma;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Chromatin modifying enzymes;HATs acetylate histones;Chromatin organization;Regulation of TP53 Activity through Acetylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53 (Consensus)

Recessive Scores

• pRec: 0.136

Intolerance Scores

• rvis_EVS: -3.09
• rvis_percentile_EVS: 0.48

Haploinsufficiency Scores

• pHI: 0.918
• hipred: Y
• hipred_score: 0.783
• ghis: 0.592

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: N
• gene_indispensability_score: 0.340

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kat6a
• Phenotype: endocrine/exocrine gland 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); growth/size/body region phenotype; craniofacial phenotype; cellular phenotype; immune system phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; embryo 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); reproductive system 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); limbs/digits/tail 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); digestive/alimentary phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: kat6a
• Affected structure: pharyngeal arch 2
• Phenotype tag: abnormal
• Phenotype quality: physical object quality

Gene ontology

• Biological process: DNA packaging;nucleosome assembly;protein acetylation;histone acetylation;myeloid cell differentiation;histone H3 acetylation;histone H4 acetylation;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;cellular senescence;regulation of signal transduction by p53 class mediator
• Cellular component: histone acetyltransferase complex;nucleosome;nuclear chromatin;nucleus;nucleoplasm;nucleolus;cytosol;PML body;nuclear speck;MOZ/MORF histone acetyltransferase complex
• Molecular function: DNA binding;transcription coactivator activity;histone acetyltransferase activity;protein binding;transcription factor binding;zinc ion binding;H4 histone acetyltransferase activity;acetyltransferase activity;histone binding