KAT2A

Summary

KAT2A (lysine acetyltransferase 2A, HGNC:4201) is a protein-coding gene on chromosome 17q21.2, encoding Histone acetyltransferase KAT2A (Q92830). Protein lysine acyltransferase that can act as a acetyltransferase, glutaryltransferase, succinyltransferase or malonyltransferase, depending on the context.

KAT2A, or GCN5, is a histone acetyltransferase (HAT) that functions primarily as a transcriptional activator. It also functions as a repressor of NF-kappa-B (see MIM 164011) by promoting ubiquitination of the NF-kappa-B subunit RELA (MIM 164014) in a HAT-independent manner (Mao et al., 2009 [PubMed 19339690]).

Source: NCBI Gene 2648 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 108 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_021078

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4201
Approved symbol	KAT2A
Name	lysine acetyltransferase 2A
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	GCN5, PCAF-b
Ensembl gene	ENSG00000108773
Ensembl biotype	protein_coding
OMIM	602301
Entrez	2648

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 13 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000225916, ENST00000465682, ENST00000586972, ENST00000588759, ENST00000592310, ENST00000873169, ENST00000873170, ENST00000873171, ENST00000873172, ENST00000873173, ENST00000873174, ENST00000873175, ENST00000873176, ENST00000873177, ENST00000915289, ENST00000963387, ENST00000963388

RefSeq mRNA: 2 — MANE Select: NM_021078 NM_001376227, NM_021078

CCDS: CCDS11417

Canonical transcript exons

ENST00000225916 — 18 exons

Exon	Start	End
ENSE00001233454	42120966	42121367
ENSE00001842471	42113111	42113842
ENSE00002373797	42119245	42119436
ENSE00002967597	42119537	42119718
ENSE00003482456	42117678	42117814
ENSE00003508426	42117907	42118017
ENSE00003524107	42120706	42120829
ENSE00003524579	42114358	42114394
ENSE00003544658	42115723	42115833
ENSE00003576232	42117388	42117596
ENSE00003578253	42114490	42114604
ENSE00003622113	42114892	42115035
ENSE00003634195	42120030	42120119
ENSE00003669318	42120225	42120370
ENSE00003670953	42114219	42114282
ENSE00003671862	42114000	42114084
ENSE00003677724	42118297	42118403
ENSE00003683386	42117035	42117161

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 98.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.0048 / max 293.3452, expressed in 1776 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166099	17.3936	1776
166098	0.3569	155
166097	0.2542	64

Top tissues by expression

291 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.70	gold quality
left ovary	UBERON:0002119	97.91	gold quality
right ovary	UBERON:0002118	97.80	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.68	gold quality
right adrenal gland cortex	UBERON:0035827	97.62	gold quality
right frontal lobe	UBERON:0002810	97.49	gold quality
right adrenal gland	UBERON:0001233	97.41	gold quality
cerebellar hemisphere	UBERON:0002245	97.19	gold quality
cerebellar cortex	UBERON:0002129	97.09	gold quality
left uterine tube	UBERON:0001303	96.93	gold quality
left adrenal gland cortex	UBERON:0035825	96.88	gold quality
adrenal cortex	UBERON:0001235	96.86	gold quality
body of uterus	UBERON:0009853	96.85	gold quality
endocervix	UBERON:0000458	96.83	gold quality
lower esophagus mucosa	UBERON:0035834	96.80	gold quality
left adrenal gland	UBERON:0001234	96.68	gold quality
tibial nerve	UBERON:0001323	96.50	gold quality
ectocervix	UBERON:0012249	96.16	gold quality
cerebellum	UBERON:0002037	96.06	gold quality
apex of heart	UBERON:0002098	95.96	gold quality
right lobe of liver	UBERON:0001114	95.95	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.90	gold quality
body of pancreas	UBERON:0001150	95.79	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.66	gold quality
right lobe of thyroid gland	UBERON:0001119	95.65	gold quality
adenohypophysis	UBERON:0002196	95.59	gold quality
omental fat pad	UBERON:0010414	95.44	gold quality
peritoneum	UBERON:0002358	95.42	gold quality
cingulate cortex	UBERON:0003027	95.35	gold quality
spleen	UBERON:0002106	95.34	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.37

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
PPARGC1A	Repression

Upstream regulators (CollecTRI, top): ESR1, EZH2, KAT7, NKX2-5, NR1H2, TAF1

miRNA regulators (miRDB)

38 targeting KAT2A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-3938	98.72	66.07	834
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-558	97.50	67.16	977
HSA-MIR-4430	97.47	65.61	1813

Literature-anchored findings (GeneRIF, showing 40)

• crystal structure of the GCN5 HAT bound to a peptide-CoA conjugate containing CoA covalently attached through an isopropionyl linker to Lys-14 of a 20-aa N-terminal fragment of histone H3 (PMID:12391296)
• requirement in transcription activation via c-myc transformation domain (PMID:12660246)
• All human TACC family proteins can bind in vitro to GCN5L2. (PMID:14767476)
• GCN5 preferentially controls cell cycle-related genes, as well as apoptosis-related genes (PMID:15715965)
• PCAF/GCN5-dependent acetylation of C/EBPbeta serves as an important molecular switch in determining the transcriptional regulatory potential of this transcription factor. (PMID:17301242)
• suggest a novel STAF65gamma-dependent function of STAGA-type complexes in cell proliferation and transcription activation by MYC postloading of TFIID and RNA polymerase II that involves direct recruitment of core Mediator (PMID:17967894)
• GCN5 regulates CDK9 function by specifically acetylating the catalytic core of the enzyme especially a Lys needed for ATP coordination & the phosphotransfer reaction. (PMID:18250157)
• GCN5L acetyltransferase stably associates with Mediator together with the TRRAP polypeptide. (PMID:18418385)
• ATAC Is a GCN5/PCAF-containing acetylase complex with a novel NC2-like histone fold module that interacts with the TATA-binding protein (PMID:18838386)
• p300 acts as a critical coactivator of FXR induction of SHP by acetylating histones at the promoter and FXR itself (PMID:18842595)
• ADA2a and ADA2b, two human homologues of yeast Ada2, each have the ability to form a heterotrimer with ADA3 and GCN5L but that only the ADA2b homologue is found in STAGA. (PMID:18936164)
• Knockdown of p300 reduces acetylation of Atg5, Atg7, Atg8, and Atg12, although overexpressed p300 increases the acetylation of these same proteins. (PMID:19124466)
• GCN5, a histone acetyltransferase, associates with COMMD1 and other components of the ligase, promotes RelA ubiquitination, and represses kappaB-dependent transcription (PMID:19339690)
• GCN5 specifically acetylates CDC6 at three lysine residues flanking its cyclin-docking motif, and this modification is crucial for the subsequent phosphorylation of the protein by Cyclin A-CDKs at a specific residue close to the acetylation site. (PMID:19343071)
• PGC-1beta is a substrate for general control of amino-acid synthesis (GCN5) and is acetylated on at least 10 lysine residues that are distributed along multiple domains of the protein. (PMID:19491097)
• Gcn5 regulates TRF1 levels through effects on Usp22 activity and SAGA integrity. (PMID:19683498)
• In this study the authors demonstrate that another cellular histone acetyltransferase, GCN5, acetylates HIV-1 integrase leading to enhanced 3’-end processing and strand transfer activities. (PMID:20226045)
• Data show that Pygo2 associates with MLL2 histone methyltransferase and STAGA histone acetyltransferase to facilitate their interaction with beta-catenin and Wnt1-induced, TCF/LEF-dependent transactivation in breast cancer cells. (PMID:20937768)
• Deletion of GCN5/PCAF in cells specifically and dramatically reduces acetylation on histone H3K9. (PMID:21131905)
• GCN5 differentially affects expression of multiple genes; ethanol-induced histone H3-lysine 9 acetylation is mediated via GCN5, and GCN5 is involved in ethanol-induced expression of the putative choline transporter SLC44A2. (PMID:21367571)
• Data show that And-1 forms a complex with both histone H3 and Gcn5. (PMID:21725360)
• Human HAT complexes, sharing the same catalytic GCN5 or PCAF subunit are targeted to different genomic loci representing functionally distinct regulatory elements. (PMID:22055187)
• Genetic variants in KAT2A does not contribute to the development of Lynch syndrome. (PMID:22086303)
• H1.4K34 acetylation is mediated by GCN5 and is preferentially enriched at promoters of active genes, where it stimulates transcription by increasing H1 mobility and recruiting a general transcription factor. (PMID:22465951)
• acetylation mechanism by GCN5 (PMID:22574209)
• GCN5 as a new negative regulator of transactivation by E1A and suggest that its KAT activity is required for optimal virus replication. (PMID:22623781)
• GCN5 takes part in transcription regulation of POLH gene through alterations in the chromatin structure by direct interaction with its 5’-flanking region, and protects vertebrate cells against UV-induced DNA damage via controlling POLH gene expression. (PMID:23033487)
• These data provide a first look at quantitating the specificity and selectivity of multiple lysines on a single substrate (histone H3) by Gcn5. (PMID:23437046)
• GCN5 has a role in potentiating growth of non-small cell lung cancer by promoting E2F1, cyclin D1, and cyclin E1 expression (PMID:23543735)
• Expression of PCAF was upregulated in PCa cells through suppression of miR-17. Phenethyl isothiocyanate treatment significantly decreased PCAF expression and promoted transcription of miR-17 in LNCaP cells. (PMID:23661605)
• These results demonstrate that GCN5, through its acetyltransferase activity, inhibits PGC1alpha-induced enhancement of hepatitis B virus transcription and replication both in vitro and in vivo. (PMID:23913178)
• PR acetylation at Lys-183 by p300 potentiates PR activity through accelerated binding of its direct target genes without affecting PR tethering on other transcription factors. (PMID:24302725)
• P300 acetyltransferase is a molecular determinant of androge receptor degradation. (PMID:24480624)
• Purified GCN5 binds to an N-terminal sub-domain of MYC TAD. (PMID:24705139)
• Genetic studies indicate that Gcn5 and USP22 have important roles during development, which may presage important functions for these proteins in human diseases. [review] (PMID:25111486)
• Gcn5 and PCAF repress IFN-beta production in an enzymatic activity-independent and non-transcriptional manner: by inhibiting the innate immune signaling kinase TBK1 in the cytoplasm. (PMID:25269644)
• our results represent the first work demonstrating that GCN5 and PCAF exhibit different functions and antagonistically regulate the XBP-1S-mediated transcription. (PMID:25426559)
• HBXIP promotes the migration of breast cancer cells through modulating microtubule acetylation mediated by GCN5. (PMID:25686500)
• The antifibrotic effects of SIRT1 in systemic sclerosis were due in part to decreased expression and function of the acetyltransferase p300. (PMID:25707573)
• DDIT3 and KAT2A cooperatively up-regulate TNFRSF10A and TNFRSF10B. (PMID:25770212)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	kat2a	ENSDARG00000104734
mus_musculus	Kat2a	ENSMUSG00000020918
rattus_norvegicus	Kat2a	ENSRNOG00000018364
drosophila_melanogaster	Acf	FBGN0027620
caenorhabditis_elegans		WBGENE00001470

Paralogs (11): BAZ1B (ENSG00000009954), BAZ2A (ENSG00000076108), CECR2 (ENSG00000099954), KAT2B (ENSG00000114166), BAZ2B (ENSG00000123636), BRDT (ENSG00000137948), BRD4 (ENSG00000141867), BRD3 (ENSG00000169925), BPTF (ENSG00000171634), BAZ1A (ENSG00000198604), BRD2 (ENSG00000204256)

Protein

Protein identifiers

Histone acetyltransferase KAT2A — Q92830 (reviewed: Q92830)

Alternative names: General control of amino acid synthesis protein 5-like 2, Histone acetyltransferase GCN5, Histone glutaryltransferase KAT2A, Histone succinyltransferase KAT2A, Lysine acetyltransferase 2A, STAF97

All UniProt accessions (3): Q92830, K7EPC4, K7ERS6

UniProt curated annotations — full annotation on UniProt →

Function. Protein lysine acyltransferase that can act as a acetyltransferase, glutaryltransferase, succinyltransferase or malonyltransferase, depending on the context. Acts as a histone lysine succinyltransferase: catalyzes succinylation of histone H3 on ‘Lys-79’ (H3K79succ), with a maximum frequency around the transcription start sites of genes. Succinylation of histones gives a specific tag for epigenetic transcription activation. Association with the 2-oxoglutarate dehydrogenase complex, which provides succinyl-CoA, is required for histone succinylation. In different complexes, functions either as an acetyltransferase (HAT) or as a succinyltransferase: in the SAGA and ATAC complexes, acts as a histone acetyltransferase. Has significant histone acetyltransferase activity with core histones, but not with nucleosome core particles. Has a a strong preference for acetylation of H3 at ‘Lys-9’ (H3K9ac). Also catalyzes acetylation of histone H1.4 (H1-4) at ‘Lys-34’ (H1.4K34ac), a modification enriched at promoters of active genes. Acetylation of histones gives a specific tag for epigenetic transcription activation. Recruited by the XPC complex at promoters, where it specifically mediates acetylation of histone variant H2A.Z.1/H2A.Z, thereby promoting expression of target genes. Involved in long-term memory consolidation and synaptic plasticity: acts by promoting expression of a hippocampal gene expression network linked to neuroactive receptor signaling. Acts as a positive regulator of T-cell activation: upon TCR stimulation, recruited to the IL2 promoter following interaction with NFATC2 and catalyzes acetylation of histone H3 at ‘Lys-9’ (H3K9ac), leading to promote IL2 expression. Required for growth and differentiation of craniofacial cartilage and bone by regulating acetylation of histone H3 at ‘Lys-9’ (H3K9ac). Regulates embryonic stem cell (ESC) pluripotency and differentiation. Also acetylates non-histone proteins, such as CEBPB, MRE11, PPARGC1A, PLK4 and TBX5. Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5. Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4. Acts as a negative regulator of gluconeogenesis by mediating acetylation and subsequent inactivation of PPARGC1A. Also acts as a histone glutaryltransferase: catalyzes glutarylation of histone H4 on ‘Lys-91’ (H4K91glu), a mark that destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes. (Microbial infection) In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat’s transactivating activity and may help inducing chromatin remodeling of proviral genes.

Subunit / interactions. Homooligomer; may form a tetramer of homodimers. Interacts with EP300, CREBBP and ADA2. Component of the TFTC-HAT complex, at least composed of TAF5L, TAF6L, TAF3, TADA3L, SUPT3H/SPT3, TAF2/TAFII150, TAF4/TAFII135, TAF5/TAFII100, KAT2A/GCN5L2, TAF10 and TRRAP. Component of the STAGA transcription coactivator-HAT complex, at least composed of SUPT3H, KAT2A, SUPT7L, TAF5L, TAF6L, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9. The STAGA core complex is associated with a subcomplex required for histone deubiquitination composed of ATXN7L3, ENY2 and USP22. Component of the ADA2A-containing complex (ATAC), composed of KAT14, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1. In the complex, it probably interacts directly with KAT14, MBIP and WDR5. Interacts with PML. Interacts with CEBPB. Interacts with TACC1, TACC2 and TACC3. Interacts with RELA. Interacts with NFATC2. Interacts with TBX5. Interacts with PLK4. Associates with the 2-oxoglutarate dehydrogenase complex. Interacts with XPC; leading to KAT2A recruitment to promoters and subsequent acetylation of histones. Interacts with ERCC3/XPB; leading to KAT2A recruitment to promoters and subsequent acetylation of histones. Interacts with ISL1. Interactions of ISL1 with MLIP1 or KAT2A may be mutually exclusive. (Microbial infection) Interacts with and acetylates HIV-1 Tat.

Subcellular location. Nucleus. Chromosome. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Tissue specificity. Expressed in all tissues tested.

Post-translational modifications. Acetylated at Lys-549, inhibiting the protein acetyltransferase activity. Deacetylation at Lys-549 by SIRT6 promotes phosphorylation at Ser-307 and Thr-735 and subsequent activation of the protein acetyltransferase activity, leading to acetylation and inactivation of PPARGC1A.

Domain organisation. Loop3 is required for substrate specificity and adopts different structural conformations in succinyl-CoA-bound and acetyl-CoA-bound forms. Tyr-645 has an important role in the selective binding of succinyl-CoA over acetyl-CoA.

Similarity. Belongs to the acetyltransferase family. GCN5 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92830-1	1, GCN5-L	yes
Q92830-2	2, GCN5-S

RefSeq proteins (2): NP_001363156, NP_066564* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000182	GNAT_dom	Domain
IPR001487	Bromodomain	Domain
IPR009464	PCAF_N	Domain
IPR016181	Acyl_CoA_acyltransferase	Homologous_superfamily
IPR016376	GCN5/PCAF	Family
IPR018359	Bromodomain_CS	Conserved_site
IPR036427	Bromodomain-like_sf	Homologous_superfamily
IPR037800	GCN5	Family

Pfam: PF00439, PF00583, PF06466

Enzyme classification (BRENDA):

• EC 2.3.1.48 — histone acetyltransferase (BRENDA: 41 organisms, 681 substrates, 1134 inhibitors, 140 Km, 96 kcat entries)

Substrate kinetics (BRENDA)

27 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ACETYL-COA	0.0002–0.046	51
HISTONE H3	0.007–2.09	23
HISTONE H4	—	11
HISTONE H4 PEPTIDE	0.0208–0.197	7
HISTONE	0.075–1.4	6
HISTONE H3 TAIL PEPTIDE	0.044–0.112	4
PICCOLONUA4 PEPTIDE	0.135–0.372	4
3-AZIDOPROPIONYL-COA	0.0002–0.0086	3
4-PENTYNOYL-COA	0.0009–0.0859	3
SPERMIDINE	0.18–0.27	3
5-HEXYNOYL-COA	0.0006–0.0117	2
6-HEPTYNOYL-COA	0.0003–0.0237	2
HISTONE H3-PEPTIDE	0.05–0.49	2
PROTEIN P53	1.28–4.63	2
3-AZIDOPROPANOYL-COA	0.0103	1

Catalyzed reactions (Rhea), 4 shown:

• succinyl-CoA + L-lysyl-[protein] = N(6)-succinyl-L-lysyl-[protein] + CoA + H(+) (RHEA:16261)
• glutaryl-CoA + L-lysyl-[protein] = N(6)-glutaryl-L-lysyl-[protein] + CoA + H(+) (RHEA:18009)
• L-lysyl-[histone] + acetyl-CoA = N(6)-acetyl-L-lysyl-[histone] + CoA + H(+) (RHEA:21992)
• L-lysyl-[protein] + acetyl-CoA = N(6)-acetyl-L-lysyl-[protein] + CoA + H(+) (RHEA:45948)

UniProt features (65 total): helix 13, mutagenesis site 9, strand 9, binding site 6, compositionally biased region 5, modified residue 4, turn 4, cross-link 3, sequence conflict 3, region of interest 3, domain 2, initiator methionine 1, chain 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
6J3P	X-RAY DIFFRACTION	1.6
1Z4R	X-RAY DIFFRACTION	1.74
5MLJ	X-RAY DIFFRACTION	1.8
5H84	X-RAY DIFFRACTION	2
3D7C	X-RAY DIFFRACTION	2.06
5H86	X-RAY DIFFRACTION	2.08
5TRL	X-RAY DIFFRACTION	2.3
8E6O	X-RAY DIFFRACTION	2.37
8H6C	X-RAY DIFFRACTION	2.5
8H66	X-RAY DIFFRACTION	2.8
5TRM	X-RAY DIFFRACTION	2.9
8H65	X-RAY DIFFRACTION	3
8H6D	X-RAY DIFFRACTION	3.26
1F68	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92830-F1	79.62	0.56

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 575 (proton donor/acceptor)

Ligand- & substrate-binding residues (6): 579–581; 579–581; 586–592; 586–592; 617; 617

Post-translational modifications (7): 2, 307, 549, 735, 728, 759, 791

Mutagenesis-validated functional residues (9):

Position	Phenotype
307	slightly reduced ability to acetylate and inhibit ppargc1a. strongly reduced ability to acetylate and inhibit ppargc1a;
549	mimics acetylation; reduced ability to acetylate and inhibit ppargc1a. strongly reduced ability to acetylate and inhibit
567	reduced ability to acetylate and inhibit ppargc1a.
575	catalytically dead mutant; abolished acyltransferase activity; when associated with a-615.
601	reduced ability to acetylate and inhibit ppargc1a.
615	catalytically dead mutant; abolished acyltransferase activity; when associated with a-575.
621–622	abolised protein acetyltransferase activity.
645	reduced histone succinylation without affecting histone acetylation. reduced gene expression.
735	slightly reduced ability to acetylate and inhibit ppargc1a. strongly reduced ability to acetylate and inhibit ppargc1a;

Function

Pathways and Gene Ontology

Reactome pathways

45 pathways

ID	Pathway
R-HSA-1912408	Pre-NOTCH Transcription and Translation
R-HSA-210744	Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells
R-HSA-2122947	NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2644606	Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2894862	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-3214847	HATs acetylate histones
R-HSA-350054	Notch-HLH transcription pathway
R-HSA-5250924	B-WICH complex positively regulates rRNA expression
R-HSA-5689880	Ub-specific processing proteases
R-HSA-73762	RNA Polymerase I Transcription Initiation
R-HSA-8941856	RUNX3 regulates NOTCH signaling
R-HSA-9013508	NOTCH3 Intracellular Domain Regulates Transcription
R-HSA-9013695	NOTCH4 Intracellular Domain Regulates Transcription
R-HSA-9733709	Cardiogenesis
R-HSA-9772755	Formation of WDR5-containing histone-modifying complexes
R-HSA-9793380	Formation of paraxial mesoderm
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)
R-HSA-1266738	Developmental Biology
R-HSA-157118	Signaling by NOTCH
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-186712	Regulation of beta-cell development
R-HSA-1912422	Pre-NOTCH Expression and Processing
R-HSA-1980143	Signaling by NOTCH1
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-212436	Generic Transcription Pathway
R-HSA-2644602	Signaling by NOTCH1 PEST Domain Mutants in Cancer
R-HSA-2644603	Signaling by NOTCH1 in Cancer
R-HSA-2894858	Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer
R-HSA-3247509	Chromatin modifying enzymes

MSigDB gene sets: 441 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_MEMORY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_HINDBRAIN_DEVELOPMENT, REACTOME_SIGNALING_BY_NOTCH, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, TGCGCANK_UNKNOWN

GO Biological Process (47): negative regulation of transcription by RNA polymerase II (GO:0000122), in utero embryonic development (GO:0001701), somitogenesis (GO:0001756), positive regulation of cytokine production (GO:0001819), neural tube closure (GO:0001843), gluconeogenesis (GO:0006094), regulation of DNA repair (GO:0006282), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), heart development (GO:0007507), long-term memory (GO:0007616), internal peptidyl-lysine acetylation (GO:0018393), telencephalon development (GO:0021537), metencephalon development (GO:0022037), midbrain development (GO:0030901), positive regulation of cell projection organization (GO:0031346), regulation of protein stability (GO:0031647), response to nutrient levels (GO:0031667), multicellular organism growth (GO:0035264), regulation of RNA splicing (GO:0043484), regulation of regulatory T cell differentiation (GO:0045589), negative regulation of gluconeogenesis (GO:0045721), positive regulation of gluconeogenesis (GO:0045722), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of embryonic development (GO:0045995), negative regulation of centriole replication (GO:0046600), fibroblast proliferation (GO:0048144), regulation of synaptic plasticity (GO:0048167), intracellular distribution of mitochondria (GO:0048312), regulation of T cell activation (GO:0050863), regulation of cell division (GO:0051302), regulation of cell cycle (GO:0051726), limb development (GO:0060173), regulation of cartilage development (GO:0061035), negative regulation of SCF-dependent proteasomal ubiquitin-dependent catabolic process (GO:0062026), cellular response to tumor necrosis factor (GO:0071356), peptidyl-lysine glutarylation (GO:0106227), regulation of bone development (GO:1903010)

GO Molecular Function (21): chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), histone acetyltransferase activity (GO:0004402), histone H3 acetyltransferase activity (GO:0010484), acetyltransferase activity (GO:0016407), protein phosphatase binding (GO:0019903), histone deacetylase binding (GO:0042826), histone H3K9 acetyltransferase activity (GO:0043992), histone H3K18 acetyltransferase activity (GO:0043993), histone H4K12 acetyltransferase activity (GO:0043997), protein-lysine-acetyltransferase activity (GO:0061733), histone succinyltransferase activity (GO:0106078), histone glutaryltransferase activity (GO:0106229), histone H1-4K34 acetyltransferase activity (GO:0140187), DNA-binding transcription factor binding (GO:0140297), protein binding (GO:0005515), N-acetyltransferase activity (GO:0008080), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), acyltransferase activity, transferring groups other than amino-acyl groups (GO:0016747), peptide glutaryltransferase activity (GO:0106228)

GO Cellular Component (14): histone acetyltransferase complex (GO:0000123), SAGA complex (GO:0000124), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), centrosome (GO:0005813), transcription factor TFTC complex (GO:0033276), mitotic spindle (GO:0072686), ATAC complex (GO:0140672), chromatin (GO:0000785), chromosome (GO:0005694), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), oxoglutarate dehydrogenase complex (GO:0045252)

Reactome top-level categories

Rollup of top-18 pathways:

Category	Pathways
Pre-NOTCH Expression and Processing	1
Regulation of beta-cell development	1
Signaling by NOTCH1	1
Signaling by NOTCH1 PEST Domain Mutants in Cancer	1
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	1
Chromatin modifying enzymes	1
Generic Transcription Pathway	1
Positive epigenetic regulation of rRNA expression	1
Deubiquitination	1
RNA Polymerase I Promoter Clearance	1
Transcriptional regulation by RUNX3	1
Signaling by NOTCH3	1
Signaling by NOTCH4	1
Developmental Biology	1
Epigenetic regulation by WDR5-containing histone modifying complexes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	3
histone modifying activity	3
SAGA-type complex	3
cellular anatomical structure	3
transcription by RNA polymerase II	2
chordate embryonic development	2
binding	2
histone H3 acetyltransferase activity	2
intracellular membraneless organelle	2
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
anterior/posterior pattern specification	1
segmentation	1
anatomical structure formation involved in morphogenesis	1
somite development	1
cytokine production	1
regulation of cytokine production	1
positive regulation of gene expression	1
positive regulation of multicellular organismal process	1
primary neural tube formation	1
tube closure	1
glucose metabolic process	1
hexose biosynthetic process	1
DNA repair	1
regulation of DNA metabolic process	1
regulation of cellular response to stress	1
chromatin organization	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of DNA-templated transcription	1
animal organ development	1
circulatory system development	1
memory	1
internal protein amino acid acetylation	1
peptidyl-lysine acetylation	1
forebrain development	1
hindbrain development	1
brain development	1
cell projection organization	1

Protein interactions and networks

STRING

3469 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KAT2A	TADA3	O75528	999
KAT2A	SGF29	Q96ES7	998
KAT2A	TRRAP	Q9Y4A5	997
KAT2A	TAF9	Q16594	994
KAT2A	WDR5	P61964	989
KAT2A	SOD2	P04179	987
KAT2A	COMMD1	Q8N668	982
KAT2A	KAT5	Q92993	982
KAT2A	TADA2A	O75478	975
KAT2A	AGXT	P21549	969
KAT2A	MYC	P01106	963
KAT2A	H3-3A	P06351	962
KAT2A	CUL2	Q13617	947
KAT2A	EP300	Q09472	942
KAT2A	H3C1	P02295	941
KAT2A	H3-4	Q16695	941

IntAct

152 interactions, top by confidence:

A	B	Type	Score
CDK8	MED1	psi-mi:“MI:0914”(association)	0.920
CDK8	MED1	psi-mi:“MI:0915”(physical association)	0.920
WDR5	KMT2D	psi-mi:“MI:0914”(association)	0.910
CDK8	MED14	psi-mi:“MI:0914”(association)	0.900
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
TAF12	TAF4	psi-mi:“MI:0914”(association)	0.760
TRRAP	ATXN7	psi-mi:“MI:0914”(association)	0.740
TADA3	TADA2A	psi-mi:“MI:0914”(association)	0.740
TADA2A	KAT2A	psi-mi:“MI:0915”(physical association)	0.710
ATXN7	TAF10	psi-mi:“MI:0914”(association)	0.690
ATXN7	TAF10	psi-mi:“MI:0915”(physical association)	0.690
E2F1	KAT2A	psi-mi:“MI:0915”(physical association)	0.650
E2F1	KAT2A	psi-mi:“MI:0914”(association)	0.650
KAT2B	TADA2A	psi-mi:“MI:0914”(association)	0.640
ATXN7L3	USP27X	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
TADA1	TADA3	psi-mi:“MI:0914”(association)	0.640
KAT2A	WDHD1	psi-mi:“MI:0915”(physical association)	0.620

BioGRID (435): HIST3H3 (Biochemical Activity), HIST2H2BE (Biochemical Activity), HIST2H2AC (Biochemical Activity), HIST4H4 (Biochemical Activity), PTF1A (Affinity Capture-Western), HIST1H3A (Biochemical Activity), HIST1H4A (Biochemical Activity), MYB (Biochemical Activity), gag-pol (Biochemical Activity), KAT2A (Affinity Capture-Western), gag-pol (Affinity Capture-Western), gag-pol (Reconstituted Complex), KAT2A (Affinity Capture-Western), KAT2A (Affinity Capture-Western), KAT2A (Protein-peptide)

ESM2 similar proteins: A0A0R4IXF6, A1A5R8, A9ZLX4, D3YXJ0, E9PUQ8, G3UZ78, O00750, O15164, O54828, P30052, P40818, P48984, P52963, P59997, P97496, Q02225, Q08AX9, Q08BR4, Q08D35, Q16760, Q1LUC3, Q2I6J1, Q3UWM4, Q498F0, Q5JSH3, Q5JTW2, Q5RHD1, Q60665, Q64398, Q68FF0, Q6INA9, Q6NSI8, Q6NVE8, Q6PDG5, Q6ZMT4, Q7ZVP1, Q80U87, Q86XP1, Q8C5W4, Q8N7X0

Diamond homologs: A0A0R4IXF6, A0A7U2QYM2, A2AHJ4, A2AUY4, A2BIL7, B2RRD7, B7ZS37, D4A7T3, E9Q2Z1, F1QW93, F1R5H6, F7DRV9, G5E8P1, O15164, O60885, O74350, O88379, O88665, O95696, P13709, P21675, P25440, P35817, P51123, P53236, P54816, P55201, P87152, Q02206, Q03330, Q07442, Q08D75, Q09948, Q12830, Q15059, Q1LUC3, Q23590, Q32S26, Q338B9, Q4R8Y1

SIGNOR signaling

25 interactions.

A	Effect	B	Mechanism
KAT2A	up-regulates	SMAD2	binding
KAT2A	up-regulates	SMAD3	binding
KAT2A	“up-regulates quantity”	SLC44A2
KAT2A	“form complex”	“SAGA complex”	binding
KAT2A	“down-regulates activity”	“Histone H3”	acetylation
KAT2A	“down-regulates activity”	H3C1	acetylation
KAT2A	“down-regulates activity”	H3-3A	acetylation
KAT2A	“down-regulates activity”	H3-4	acetylation
KAT2A	“down-regulates activity”	H3Y1	acetylation
KAT2A	“down-regulates activity”	H3Y2	acetylation
KAT2A	“down-regulates activity”	H3-2	acetylation
KAT2A	“down-regulates activity”	H3-5	acetylation
KAT2A	“down-regulates activity”	H3C15	acetylation
CDK4	“up-regulates activity”	KAT2A	phosphorylation
CyclinD/CDK4	“up-regulates activity”	KAT2A	phosphorylation
KAT2A	“down-regulates activity”	PLCG1	acetylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 116 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of WDR5-containing histone-modifying complexes	11	33.6×	2e-12
Epigenetic regulation by WDR5-containing histone modifying complexes	12	21.3×	3e-11
HATs acetylate histones	21	19.1×	7e-19
Chromatin organization	18	16.9×	3e-15
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	7	15.8×	2e-05
Chromatin modifying enzymes	19	15.8×	2e-15
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	6	14.9×	1e-04
NOTCH1 Intracellular Domain Regulates Transcription	5	13.7×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of cell division	9	62.7×	1e-12
regulation of DNA repair	18	45.2×	1e-22
regulation of RNA splicing	17	33.8×	2e-19
regulation of embryonic development	10	30.0×	1e-10
RNA polymerase II preinitiation complex assembly	9	22.2×	2e-08
transcription initiation-coupled chromatin remodeling	6	20.9×	3e-05
positive regulation of transcription initiation by RNA polymerase II	8	19.8×	5e-07
positive regulation of miRNA transcription	6	15.8×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

108 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	73
Likely benign	3
Benign	5

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2627105	NM_021078.3(KAT2A):c.2032_2055del (p.Leu678_Gln685del)	Likely pathogenic

SpliceAI

3240 predictions. Top by Δscore:

Variant	Effect	Δscore
17:42113838:CAGGT:C	acceptor_gain	1.0000
17:42113839:AGGT:A	acceptor_gain	1.0000
17:42113840:GGT:G	acceptor_gain	1.0000
17:42113840:GGTCT:G	acceptor_loss	1.0000
17:42113841:GT:G	acceptor_gain	1.0000
17:42113841:GTC:G	acceptor_loss	1.0000
17:42113842:TCTGG:T	acceptor_loss	1.0000
17:42113843:C:CC	acceptor_gain	1.0000
17:42113843:C:CG	acceptor_loss	1.0000
17:42113849:C:CT	acceptor_gain	1.0000
17:42113850:A:T	acceptor_gain	1.0000
17:42113852:C:CT	acceptor_gain	1.0000
17:42113853:A:T	acceptor_gain	1.0000
17:42113996:TCAC:T	donor_loss	1.0000
17:42113997:CACC:C	donor_loss	1.0000
17:42113998:A:AC	donor_gain	1.0000
17:42113999:C:CC	donor_gain	1.0000
17:42113999:C:G	donor_loss	1.0000
17:42114080:TGAGA:T	acceptor_gain	1.0000
17:42114081:GAGA:G	acceptor_gain	1.0000
17:42114082:AGA:A	acceptor_gain	1.0000
17:42114083:GA:G	acceptor_gain	1.0000
17:42114085:C:CC	acceptor_gain	1.0000
17:42114216:CAC:C	donor_loss	1.0000
17:42114217:ACCT:A	donor_loss	1.0000
17:42114278:CCTTC:C	acceptor_loss	1.0000
17:42114279:CTTC:C	acceptor_gain	1.0000
17:42114281:TCC:T	acceptor_loss	1.0000
17:42114282:CCTGG:C	acceptor_loss	1.0000
17:42114283:C:CC	acceptor_gain	1.0000

AlphaMissense

5465 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:42113701:A:G	L821P	1.000
17:42113739:G:C	N808K	1.000
17:42113739:G:T	N808K	1.000
17:42113744:A:C	Y807D	1.000
17:42113744:A:G	Y807H	1.000
17:42113751:A:C	C804W	1.000
17:42113752:C:T	C804Y	1.000
17:42113753:A:G	C804R	1.000
17:42113754:G:C	N803K	1.000
17:42113754:G:T	N803K	1.000
17:42113767:C:G	R799P	1.000
17:42113773:A:G	L797P	1.000
17:42113776:T:A	D796V	1.000
17:42113777:C:A	D796Y	1.000
17:42113785:A:G	F793S	1.000
17:42113804:A:C	Y787D	1.000
17:42113818:A:G	L782P	1.000
17:42113839:A:G	L775P	1.000
17:42114005:G:T	P772H	1.000
17:42114006:G:T	P772T	1.000
17:42114007:G:C	F771L	1.000
17:42114007:G:T	F771L	1.000
17:42114009:A:G	F771L	1.000
17:42114014:A:T	I769N	1.000
17:42114027:A:G	Y765H	1.000
17:42114061:G:C	F753L	1.000
17:42114061:G:T	F753L	1.000
17:42114062:A:G	F753S	1.000
17:42114063:A:G	F753L	1.000
17:42114063:A:T	F753I	1.000

dbSNP variants (sampled 300 via entrez): RS1001558565 (17:42120961 C>T), RS1001757855 (17:42120609 T>A,C), RS1002003211 (17:42113525 G>A), RS1002580833 (17:42122337 C>G,T), RS1002779150 (17:42122036 C>A), RS1004150090 (17:42115629 C>A,T), RS1004669117 (17:42113483 G>A,C), RS1005366459 (17:42116363 C>T), RS1005972700 (17:42121982 C>T), RS1006339474 (17:42121655 A>C,G), RS1007673064 (17:42118502 C>T), RS1008460904 (17:42113863 G>A), RS1009873594 (17:42119847 C>G,T), RS1011630366 (17:42114149 A>C,G), RS1011804686 (17:42121269 C>G,T)

Disease associations

OMIM: gene MIM:602301 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004785_17	Vitiligo	7.000000e-10
GCST005194_157	Coronary artery disease	3.000000e-07
GCST005195_68	Coronary artery disease	7.000000e-09
GCST005196_24	Coronary artery disease	2.000000e-10
GCST007447_1	vWF and FVIII levels	5.000000e-08
GCST008731_2	Inflammatory bowel disease	2.000000e-06
GCST010866_76	Coronary artery disease	3.000000e-12
GCST90002396_619	Mean reticulocyte volume	6.000000e-16

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004630	factor VIII measurement
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3885587 (PROTEIN FAMILY), CHEMBL4523707 (PROTEIN-PROTEIN INTERACTION), CHEMBL5501 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 2.3.1.48 Histone acetyltransferases (HATs)

Binding affinities (BindingDB)

228 measured of 253 human assays (253 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
US20250188030, Compound C71	KI	0.01 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound A37	KI	0.02 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound A38	KI	0.02 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C31	KI	0.02 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C40	KI	0.02 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound I17	KI	0.02 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound E3	KI	0.03 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound I16	KI	0.03 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound B31	KI	0.04 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound B34	KI	0.04 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound B35	KI	0.04 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C54	KI	0.04 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C60	KI	0.04 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C69	KI	0.04 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C70	KI	0.04 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound B20	KI	0.05 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C2	KI	0.05 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C3	KI	0.05 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C57	KI	0.05 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C73	KI	0.05 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C77	KI	0.05 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C90	KI	0.05 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound B26	KI	0.06 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C9	KI	0.06 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C37	KI	0.06 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C43	KI	0.06 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C79	KI	0.06 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C91	KI	0.06 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C7	KI	0.07 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C61	KI	0.07 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C67	KI	0.07 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C82	KI	0.07 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C87	KI	0.07 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound B16	KI	0.08 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C16	KI	0.08 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C63	KI	0.08 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C78	KI	0.08 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C83	KI	0.08 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound E4	KI	0.08 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound J11	KI	0.08 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound J16	KI	0.08 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound B5	KI	0.09 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound B22	KI	0.09 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound B24	KI	0.09 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound B30	KI	0.09 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C21	KI	0.09 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C38	KI	0.09 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound A36	KI	0.1 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound B17	KI	0.1 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds
US20250188030, Compound C18	KI	0.1 nM	US-20250188030: Biphenyl and Phenylpyridine Compounds

ChEMBL bioactivities

28 potent at pChembl≥5 of 60 total, top 25 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.90	Ki	1.259	nM	CHEMBL4069412
8.85	Ki	1.4	nM	CHEMBL4069412
7.89	IC50	13	nM	CHEMBL4103402
7.72	IC50	19	nM	CHEMBL4067343
7.55	Ki	28	nM	CHEMBL526343
7.36	Kd	44	nM	CHEMBL4872300
7.21	Kd	62	nM	CHEMBL4780673
7.16	IC50	70	nM	CHEMBL4088595
6.98	Kd	105	nM	CHEMBL4574669
6.80	Kd	158.5	nM	CHEMBL4465880
6.80	Kd	160	nM	CHEMBL5289762
6.66	IC50	220	nM	CHEMBL4570969
6.60	Kd	251.2	nM	CHEMBL4449894
6.39	Kd	410	nM	CHEMBL5282240
6.30	Kd	501.2	nM	CHEMBL4577486
5.69	IC50	2040	nM	CHEMBL1795608
5.21	IC50	6130	nM	CHEMBL2087789
5.20	IC50	6270	nM	CHEMBL1392315
5.15	IC50	7110	nM	CHEMBL1733695
5.10	IC50	7870	nM	CHEMBL1391552
5.08	IC50	8390	nM	CHEMBL106011
5.08	IC50	8370	nM	CHEMBL3621672
5.08	IC50	8400	nM	CHEMBL106011
5.07	IC50	8530	nM	CHEMBL1720939
5.06	IC50	8650	nM	CHEMBL1795613

PubChem BioAssay actives

14 with measured affinity, of 128 total; 12 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-bromo-2-methyl-5-[[(3R,5R)-1-methyl-5-phenylpiperidin-3-yl]amino]pyridazin-3-one	1436225: Binding affinity to human partial length GCN5 expressed in bacterial expression system by BROMOscan method	ki	0.0013	uM
4-chloro-2-methyl-5-[[(3R,5S)-1-methyl-5-(2-methylpropyl)piperidin-3-yl]amino]pyridazin-3-one	2027160: Inhibition of PCAF bromodomain/GCN5 bromodomain (unknown origin)	ic50	0.0130	uM
8-[[(1R,2R)-1-(dimethylamino)-1-phenylpropan-2-yl]amino]-6-methylpyrido[2,3-d]pyridazin-5-one	2027160: Inhibition of PCAF bromodomain/GCN5 bromodomain (unknown origin)	ic50	0.0190	uM
5-[4-(2-aminoethyl)anilino]-4-chloro-2-methylpyridazin-3-one	1769025: Binding affinity to GCN5L2 (unknown origin) by BROMOscan method	kd	0.0440	uM
6-[[(1S,2S)-1-[4-(benzenesulfonyl)phenyl]-1-(dimethylamino)propan-2-yl]amino]-2,4-dimethyl-1,2,4-triazine-3,5-dione	2027160: Inhibition of PCAF bromodomain/GCN5 bromodomain (unknown origin)	ic50	0.0700	uM
2-[[(3R,5R)-5-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-methylpiperidin-3-yl]amino]-3-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554036: Binding affinity to human N-terminal His-tagged GCN5 by isothermal titration calorimetry	kd	0.1050	uM
N-[4-bromo-3-[(3R)-3-cyclopropylpyrrolidin-1-yl]sulfonylphenyl]-2-(5-methyl-6,7-dihydro-4H-triazolo[4,5-c]pyridin-1-yl)acetamide	1561911: Binding affinity to human partial length GCN5L2 (E726 to K837 residues) expressed in bacterial expression system by BROMOscan assay	kd	0.1585	uM
6-[(E)-but-2-enyl]-4-[4-(2-hydroxypropan-2-yl)-2,5-dimethoxyphenyl]-2-methyl-1H-pyrrolo[2,3-c]pyridin-7-one	1958305: Binding affinity to human partial length GCN5L2 (E726 to K837 residues) expressed in bacterial expression system by BROMOscan assay	kd	0.1600	uM
N-[4-bromo-3-[(3S)-3-methylpyrrolidin-1-yl]sulfonylphenyl]-2-[(4S)-4-cyclopropyl-4-methyl-2,5-dioxoimidazolidin-1-yl]acetamide	1561911: Binding affinity to human partial length GCN5L2 (E726 to K837 residues) expressed in bacterial expression system by BROMOscan assay	kd	0.2512	uM
6-[(E)-but-2-enyl]-4-[4-(2-hydroxypropan-2-yl)-2-methoxyphenyl]-1H-pyrrolo[2,3-c]pyridin-7-one	1958305: Binding affinity to human partial length GCN5L2 (E726 to K837 residues) expressed in bacterial expression system by BROMOscan assay	kd	0.4100	uM
N-[4-chloro-3-[(3R)-3-cyclopropylpyrrolidin-1-yl]sulfonylphenyl]-2-(5-methyl-6,7-dihydro-4H-triazolo[4,5-c]pyridin-1-yl)acetamide	1561911: Binding affinity to human partial length GCN5L2 (E726 to K837 residues) expressed in bacterial expression system by BROMOscan assay	kd	0.5012	uM
2-(4-fluorophenyl)-[1,2]thiazolo[5,4-b]pyridin-3-one	1727407: Inhibition of recombinant human C-terminal FLAG-tagged GCN5 HAT domain (362 to 837 residues) expressed in baculovirus infected Sf9 cells using histone H3 (1 to 21 residues) as substrate	ic50	8.3900	uM

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	4
(+)-JQ1 compound	decreases expression	2
Arsenic	increases expression, affects cotreatment, decreases expression, increases abundance	2
Cadmium Chloride	decreases expression	2
bisphenol F	affects cotreatment, decreases expression	1
deoxynivalenol	affects reaction, increases expression	1
beta-lapachone	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
potassium chromate(VI)	increases expression	1
K 7174	decreases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	affects expression	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Bucladesine	affects binding, decreases reaction	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
Indomethacin	affects cotreatment, decreases expression	1
Manganese	decreases expression, increases abundance	1
Smoke	decreases expression	1
Superoxides	decreases abundance	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

ChEMBL screening assays

111 unique, capped per target: 109 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3391510	Binding	Competitive inhibition of recombinant full-length human PCAF catalytic domain/GCN5 expressed in Escherichia coli BL21(DE3) using [14C]-acetyl CoA as substrate after 1 to 10 mins by double reciprocal plot analysis	Development of second generation epigenetic agents — Medchemcomm
CHEMBL1738606	Functional	PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors of GCN5L2. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID504398]	PubChem BioAssay data set

Cellosaurus cell lines

7 cell lines: 4 cancer cell line, 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A3K4	SEES3-1V human KAT2A, clone1	Embryonic stem cell	Male
CVCL_A3K5	SEES3-1V human KAT2A, clone2	Embryonic stem cell	Male
CVCL_A3K6	SEES3-1V human KAT2A, clone3	Embryonic stem cell	Male
CVCL_B8J1	Abcam HCT 116 KAT2A KO	Cancer cell line	Male
CVCL_B9LC	Abcam A-549 KAT2A KO	Cancer cell line	Male
CVCL_ST87	HAP1 KAT2A (-) 1	Cancer cell line	Male
CVCL_ST88	HAP1 KAT2A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.