KAT5
protein-codinglysine acetyltransferase 5, the group of Zinc fingers C2HC-type|MYST type domain containing lysine acetyltransferases|Tip60/Nua4 histone acetyltransferase complex subunits
Gene summary
The protein encoded by this gene belongs to the MYST family of histone acetyl transferases (HATs) and was originally isolated as an HIV-1 TAT-interactive protein. HATs play important roles in regulating chromatin remodeling, transcription and other nuclear processes by acetylating histone and nonhistone proteins. This protein is a histone acetylase that has a role in DNA repair and apoptosis and is thought to play an important role in signal transduction. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]
- HTATIP
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0030852
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0030852
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0030852
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Genitourinary; Neurologic; Renal
Intervention: Renal
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KAT5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_182710.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | 12 | 1 | 18 | ||
| missense | 3 | 1 | 91 | 4 | 99 | |
| nonsense | 2 | 1 | 3 | |||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 3 | 1 | 104 | 17 | 1 | 126 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_874369.1 | 13 | MANE Select | |
| Ensembl | ENSP00000340330.4 | 13 | MANE Select | |
| RefSeq | NP_001193762.1 | 12 | Standard | |
| RefSeq | NP_006379.2 | 14 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| kat5a | Danio rerio | Structure: primitive hemopoiesis Quality: increased occurrence abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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)
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
Molecular Function
- transcription coactivator activity
- histone acetyltransferase activity
- protein binding
- H4 histone acetyltransferase activity
- acetyltransferase activity
Cellular Component
- histone acetyltransferase complex
- nuclear chromatin
- Swr1 complex
- nucleus
- nucleoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000341318
- Coding exons
- 13
- Length
- 7609
- Individuals with no LoFs
- 125730
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 18
- Defined
- 125748
- p
- 0.0000716
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.61 | 146 | 331 | 0.441 | 0.0000214 | 3518 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00016 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000079 | 0.000079 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.635
Intolerance Scores
- LoFtool
- 0.590
- RVIS EVS
- -0.78
- RVIS percentile EVS
- 12.77
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.985
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |