KAT5

lysine acetyltransferase 5, the group of Zinc fingers C2HC-type|MYST type domain containing lysine acetyltransferases|Tip60/Nua4 histone acetyltransferase complex subunits

Basic information

Region (hg38): 11:65711995-65719604

Previous symbols: [ "HTATIP" ]

Links

ENSG00000172977 ∙ NCBI:10524 ∙ OMIM:601409 ∙ HGNC:5275 ∙ Uniprot:Q92993 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities	AD	Renal	Among other features, indivbiduals have been described with renal anomalies that may result in recurrent urinary tract infections, and awareness may allow early diagnosis and management, which may help preserve renal function	Craniofacial; Genitourinary; Neurologic; Renal	32822602

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KAT5 gene.

• Aicardi-Goutieres syndrome 3 (43 variants)
• Inborn genetic diseases (17 variants)
• not provided (13 variants)
• Neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities (6 variants)
• KAT5-related condition (2 variants)
• Aicardi Goutieres syndrome (1 variants)
• not specified (1 variants)
• Familial colorectal cancer (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 KAT5 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	2	1	5
missense			25	1		26
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			2			2
non coding			28	8	7	43
Total	0	0	57	11	8

Variants in KAT5

This is a list of pathogenic ClinVar variants found in the KAT5 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-65712286-C-G		not specified	Uncertain significance (Oct 27, 2022)
11-65712316-G-T		not specified	Uncertain significance (Feb 28, 2023)
11-65712346-G-A		not specified	Uncertain significance (Dec 27, 2023)
11-65712362-T-A		KAT5-related disorder • not specified	Uncertain significance (Dec 16, 2023)
11-65712395-G-C			Uncertain significance (Jul 19, 2022)
11-65712396-C-T			Likely benign (Sep 01, 2023)
11-65712759-C-T			Likely benign (Jan 01, 2023)
11-65712785-C-T			Benign (Dec 31, 2019)
11-65712792-G-A		not specified	Uncertain significance (May 11, 2022)
11-65712795-A-T		not specified	Uncertain significance (Jun 21, 2023)
11-65712931-G-A		Neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities	Pathogenic (Dec 04, 2020)
11-65712952-A-T		not specified	Uncertain significance (Oct 06, 2022)
11-65712984-C-G		not specified	Uncertain significance (Oct 29, 2021)
11-65713355-C-T		not specified	Uncertain significance (Jun 24, 2022)
11-65713367-G-T		not specified	Uncertain significance (Jun 28, 2023)
11-65713388-C-T		not specified	Uncertain significance (Mar 13, 2024)
11-65713412-A-C		not specified	Uncertain significance (Oct 18, 2021)
11-65713441-G-C		not specified	Uncertain significance (Jan 24, 2024)
11-65713447-G-A			Likely benign (Feb 01, 2022)
11-65713469-C-G		not specified	Uncertain significance (Jun 27, 2022)
11-65713484-AGCCCAACCACC-A		Neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities	Uncertain significance (Sep 20, 2022)
11-65713501-A-G		not specified	Uncertain significance (Nov 29, 2023)
11-65713503-G-A		Neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities	Uncertain significance (Dec 01, 2023)
11-65713618-C-T		not specified	Uncertain significance (Aug 02, 2021)
11-65713638-G-A		not specified	Uncertain significance (Nov 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KAT5	protein_coding	protein_coding	ENST00000341318	13	7609

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0882	0.912	125730	0	18	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.61	146	331	0.441	0.0000214	3518
Missense in Polyphen		25	123.17	0.20298		1393
Synonymous	-1.78	164	137	1.19	0.00000895	1110
Loss of Function	3.78	8	30.6	0.262	0.00000164	340

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000156	0.000156
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000792	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalytic subunit of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome-DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Directly acetylates and activates ATM. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AFZ from the nucleosome. Relieves NR1D2-mediated inhibition of APOC3 expression by acetylating NR1D2. Promotes FOXP3 acetylation and positively regulates its transcriptional repressor activity (PubMed:17360565). Acetylates RAN at 'Lys-134' (PubMed:29040603). {ECO:0000269|PubMed:12776177, ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:15042092, ECO:0000269|PubMed:15121871, ECO:0000269|PubMed:15310756, ECO:0000269|PubMed:16141325, ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:17360565, ECO:0000269|PubMed:17996965, ECO:0000269|PubMed:19909775, ECO:0000269|PubMed:24463511, ECO:0000303|PubMed:15196461}.
• Pathway: HTLV-I infection - Homo sapiens (human);Androgen receptor signaling pathway;ATM Signaling Network in Development and Disease;HDR through Single Strand Annealing (SSA);HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;Signaling by WNT;Signal Transduction;Gene expression (Transcription);Nonhomologous End-Joining (NHEJ);DNA Double-Strand Break Repair;multi-step regulation of transcription by pitx2;Generic Transcription Pathway;DNA Damage/Telomere Stress Induced Senescence;Cellular Senescence;Homology Directed Repair;Cellular responses to stress;RNA Polymerase II Transcription;G2/M DNA damage checkpoint;Chromatin modifying enzymes;G2/M Checkpoints;Cell Cycle Checkpoints;p73 transcription factor network;ATF-2 transcription factor network;AndrogenReceptor;HATs acetylate histones;Cellular responses to external stimuli;Regulation of TP53 Activity through Phosphorylation;Signaling by Nuclear Receptors;Chromatin organization;C-MYC pathway;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Estrogen-dependent gene expression;Sensing of DNA Double Strand Breaks;Cell Cycle;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response;ESR-mediated signaling;IL9;Validated targets of C-MYC transcriptional activation;Processing of DNA double-strand break ends;Formation of the beta-catenin:TCF transactivating complex;TCF dependent signaling in response to WNT;Regulation of Androgen receptor activity;ATM pathway;p53 pathway;Presynaptic phase of homologous DNA pairing and strand exchange;Homologous DNA Pairing and Strand Exchange;Resolution of D-loop Structures through Holliday Junction Intermediates;Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA);Resolution of D-Loop Structures;HDR through Homologous Recombination (HRR) (Consensus)

Recessive Scores

• pRec: 0.635

Intolerance Scores

• loftool: 0.590
• rvis_EVS: -0.78
• rvis_percentile_EVS: 12.77

Haploinsufficiency Scores

• pHI: 0.971
• hipred: Y
• hipred_score: 0.809
• ghis: 0.622

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.985

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kat5
• Phenotype: cellular phenotype; homeostasis/metabolism 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); hematopoietic system phenotype; immune system phenotype; neoplasm

Zebrafish Information Network

• Gene name: kat5a
• Affected structure: primitive hemopoiesis
• Phenotype tag: abnormal
• Phenotype quality: increased occurrence

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;DNA double-strand break processing;DNA replication;double-strand break repair;double-strand break repair via nonhomologous end joining;DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator;response to ionizing radiation;viral process;histone acetylation;androgen receptor signaling pathway;negative regulation of interleukin-2 production;regulation of growth;proteasome-mediated ubiquitin-dependent protein catabolic process;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 estradiol stimulus;positive regulation of protein acetylation;beta-catenin-TCF complex assembly
• Cellular component: histone acetyltransferase complex;nuclear chromatin;Swr1 complex;nucleus;nucleoplasm;transcription factor complex;nucleolus;Piccolo NuA4 histone acetyltransferase complex;NuA4 histone acetyltransferase complex;perinuclear region of cytoplasm
• Molecular function: transcription coactivator activity;histone acetyltransferase activity;protein binding;H4 histone acetyltransferase activity;acetyltransferase activity;histone binding;metal ion binding;androgen receptor binding;repressing transcription factor binding