KAT6B

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

Basic information

Region (hg38): 10:74824926-75032624

Previous symbols: [ "MYST4" ]

Links

ENSG00000156650 ∙ NCBI:23522 ∙ OMIM:605880 ∙ HGNC:17582 ∙ Uniprot:Q8WYB5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• blepharophimosis - intellectual disability syndrome, SBBYS type (Definitive), mode of inheritance: AD
• genitopatellar syndrome (Definitive), mode of inheritance: AD
• blepharophimosis - intellectual disability syndrome, SBBYS type (Supportive), mode of inheritance: AD
• genitopatellar syndrome (Supportive), mode of inheritance: AD
• genitopatellar syndrome (Strong), mode of inheritance: AD
• blepharophimosis - intellectual disability syndrome, SBBYS type (Strong), mode of inheritance: AD
• KAT6B-related multiple congenital anomalies syndrome (Definitive), mode of inheritance: AD
• RASopathy (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ohdo syndrome, SBBYS variant; Genitopatellar syndrome	AD	Audiologic/Otolaryngologic; Endocrine	Among other manifestations, individuals may demonstrate early-onset hypothyroidism, and appropriate management may be beneficial; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Dental; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal	12210329; 12210330; 12949978; 16761293; 21412151; 22077973; 22265014; 23236640; 23436491

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KAT6B gene.

• Genitopatellar syndrome (733 variants)
• not provided (317 variants)
• Inborn genetic diseases (66 variants)
• Genitopatellar syndrome;Blepharophimosis - intellectual disability syndrome, SBBYS type (57 variants)
• not specified (49 variants)
• Blepharophimosis - intellectual disability syndrome, SBBYS type (43 variants)
• Blepharophimosis - intellectual disability syndrome, SBBYS type;Genitopatellar syndrome (34 variants)
• KAT6B-related condition (13 variants)
• Intellectual disability (9 variants)
• KAT6B-Related Spectrum Disorders (6 variants)
• Neurodevelopmental disorder (2 variants)
• See cases (2 variants)
• Autosomal dominant KAT6B-related disorders (2 variants)
• KAT6B-related disorders (2 variants)
• Hypospadias (1 variants)
• Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome;Retinal arterial tortuosity;Microangiopathy and leukoencephalopathy, pontine, autosomal dominant;Brain small vessel disease 1 with or without ocular anomalies;Intracerebral hemorrhage (1 variants)
• Macrocephaly;Generalized joint hypermobility;Joint laxity;Delayed speech and language development;Seizure (1 variants)
• KAT6B-realted disoder (1 variants)
• KBG syndrome (1 variants)
• KAT6B-related disorder (1 variants)
• Genitopatellar syndrome;Epilepsy, familial temporal lobe, 1 (1 variants)
• 9 conditions (1 variants)
• Nephronophthisis (1 variants)
• 10 conditions (1 variants)
• Congenital anomaly of kidney and urinary tract (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KAT6B 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		5	229	6	242
missense		6	371	66	29	472
nonsense	23	7	2			32
start loss		1				1
frameshift	50	19	4			73
inframe indel			24	22		46
splice donor/acceptor (+/-2bp)	6	2	2			10
splice region			8	9	3	20
non coding			10	50	22	82
Total	81	35	418	367	57

Variants in KAT6B

This is a list of pathogenic ClinVar variants found in the KAT6B region.

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

Position	Type	Phenotype	Significance	ClinVar
10-74826685-A-AGCGGTG		KAT6B-Related Spectrum Disorders	Uncertain significance (Jun 14, 2016)
10-74838733-C-T		not specified	Likely benign (Nov 09, 2017)
10-74842497-CT-C			Benign (Oct 22, 2019)
10-74842856-C-T			Uncertain significance (Apr 29, 2022)
10-74842858-A-G		Blepharophimosis - intellectual disability syndrome, SBBYS type	Likely pathogenic (Jul 12, 2022)
10-74842884-T-C		Genitopatellar syndrome	Likely benign (Jun 28, 2022)
10-74842905-T-C		Genitopatellar syndrome	Likely benign (Nov 03, 2023)
10-74842911-G-A		Genitopatellar syndrome	Likely benign (Sep 10, 2023)
10-74842923-G-A		Genitopatellar syndrome	Likely benign (Jun 20, 2022)
10-74842943-A-T		Genitopatellar syndrome	Uncertain significance (Jul 04, 2022)
10-74842959-T-G			Uncertain significance (Mar 11, 2021)
10-74842961-C-T		Genitopatellar syndrome	Benign (Oct 03, 2023)
10-74842966-A-G		Genitopatellar syndrome	Uncertain significance (Dec 02, 2023)
10-74842969-A-G		Genitopatellar syndrome	Uncertain significance (Sep 01, 2021)
10-74842976-A-G		Genitopatellar syndrome	Conflicting classifications of pathogenicity (Jan 07, 2022)
10-74842978-G-A		Genitopatellar syndrome	Likely benign (Jun 06, 2020)
10-74842987-A-T		Blepharophimosis - intellectual disability syndrome, SBBYS type	Likely pathogenic (Sep 01, 2022)
10-74843004-A-G		Genitopatellar syndrome • Blepharophimosis - intellectual disability syndrome, SBBYS type;Genitopatellar syndrome	Likely benign (Nov 19, 2022)
10-74843017-A-G		Genitopatellar syndrome	Uncertain significance (Apr 24, 2023)
10-74843055-A-G		Genitopatellar syndrome	Likely benign (Jul 25, 2023)
10-74843079-A-G		Genitopatellar syndrome	Likely benign (Dec 01, 2023)
10-74843084-AC-A		Genitopatellar syndrome	Uncertain significance (Aug 09, 2022)
10-74843085-C-T		Genitopatellar syndrome	Likely benign (May 27, 2022)
10-74843112-AG-A			Pathogenic (Aug 23, 2016)
10-74843135-AG-A			Pathogenic (Oct 18, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KAT6B	protein_coding	protein_coding	ENST00000287239	16	207041

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	3.04e-10	125736	0	11	125747	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.89	834	1.10e+3	0.755	0.0000629	13793
Missense in Polyphen		259	444.47	0.58271		5468
Synonymous	0.264	410	417	0.984	0.0000262	3888
Loss of Function	7.89	5	82.2	0.0608	0.00000454	1046

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000220	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000924	0.0000462
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000656	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Histone acetyltransferase which may be involved in both positive and negative regulation of transcription. Required for RUNX2-dependent transcriptional activation. May be involved in cerebral cortex development. Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. {ECO:0000269|PubMed:10497217, ECO:0000269|PubMed:11965546, ECO:0000269|PubMed:16387653}.
• Disease: DISEASE: Note=A chromosomal aberration involving KAT6B may be a cause acute myeloid leukemias. Translocation t(10;16)(q22;p13) with CREBBP. {ECO:0000269|PubMed:11157802}.; DISEASE: Ohdo syndrome, SBBYS variant (SBBYSS) [MIM:603736]: A syndrome characterized by distinctive facial appearance with severe blepharophimosis, an immobile mask-like face, a bulbous nasal tip, and a small mouth with a thin upper lip. The condition presents in infancy with severe hypotonia and feeding problems. Associated skeletal problems include joint laxity, abnormally long thumbs and great toes, and dislocated or hypoplastic patellae. Structural cardiac defects are present in around 50% of cases, and dental anomalies, including small and pointed teeth, are common. Optic atrophy and conductive or sensorineural deafness are repeatedly reported. Many affected individuals have abnormalities of thyroid structure or function. SBBYSS is usually associated with severe mental retardation, delayed motor milestones, and significantly impaired speech. {ECO:0000269|PubMed:22077973}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Genitopatellar syndrome (GTPTS) [MIM:606170]: A rare disorder consisting of microcephaly, severe psychomotor retardation, and characteristic coarse facial features, including broad nose and small or retracted chin, associated with congenital flexion contractures of the lower extremities, abnormal or missing patellae, and urogenital anomalies. {ECO:0000269|PubMed:22265014}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Chromatin modifying enzymes;HATs acetylate histones;Chromatin organization (Consensus)

Recessive Scores

• pRec: 0.194

Intolerance Scores

• rvis_EVS: -2.38
• rvis_percentile_EVS: 1.11

Haploinsufficiency Scores

• pHI: 0.812
• hipred: Y
• hipred_score: 0.825
• ghis: 0.625

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• 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: Kat6b
• Phenotype: vision/eye phenotype; 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); hearing/vestibular/ear phenotype; skeleton phenotype; normal 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); growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; cellular phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: nucleosome assembly;regulation of transcription, DNA-templated;histone acetylation;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 response to leukemia inhibitory factor
• Cellular component: histone acetyltransferase complex;nucleosome;nuclear chromatin;nucleus;nucleoplasm;MOZ/MORF histone acetyltransferase complex
• Molecular function: DNA binding;histone acetyltransferase activity;protein binding;transcription factor binding;H4 histone acetyltransferase activity;acetyltransferase activity;histone binding;metal ion binding