KAT6A

Summary

KAT6A (lysine acetyltransferase 6A, HGNC:13013) is a protein-coding gene on chromosome 8p11.21, encoding Histone acetyltransferase KAT6A (Q92794). Histone acetyltransferase that acetylates lysine residues in histone H3 and histone H4 (in vitro). It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the MOZ, YBFR2, SAS2, TIP60 family of histone acetyltransferases. The protein is composed of a nuclear localization domain, a double C2H2 zinc finger domain that binds to acetylated histone tails, a histone acetyl-transferase domain, a glutamate/aspartate-rich region, and a serine- and methionine-rich transactivation domain. It is part of a complex that acetylates lysine-9 residues in histone 3, and in addition, it acts as a co-activator for several transcription factors. Allelic variants of this gene are associated with an autosomal dominant form of cognitive disability. Chromosomal translocations of this gene are associated with acute myeloid leukemia. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 7994 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic intellectual disability (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 2,044 total — 116 pathogenic, 72 likely-pathogenic
• Phenotypes (HPO): 120
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 13 downstream targets (CollecTRI)
• MANE Select transcript: NM_006766

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13013
Approved symbol	KAT6A
Name	lysine acetyltransferase 6A
Location	8p11.21
Locus type	gene with protein product
Status	Approved
Aliases	MOZ
Ensembl gene	ENSG00000083168
Ensembl biotype	protein_coding
OMIM	601408
Entrez	7994

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 11 protein_coding, 8 retained_intron, 1 nonsense_mediated_decay

ENST00000265713, ENST00000396930, ENST00000406337, ENST00000418721, ENST00000426524, ENST00000463961, ENST00000470574, ENST00000485568, ENST00000647746, ENST00000647809, ENST00000648030, ENST00000648224, ENST00000648335, ENST00000649817, ENST00000649827, ENST00000650356, ENST00000650495, ENST00000855880, ENST00000919320, ENST00000967392

RefSeq mRNA: 2 — MANE Select: NM_006766 NM_001305878, NM_006766

CCDS: CCDS6124, CCDS83290

Canonical transcript exons

ENST00000265713 — 17 exons

Exon	Start	End
ENSE00000692153	41940842	41941444
ENSE00000692156	41942793	41943000
ENSE00000692210	41946591	41946684
ENSE00000692227	41949222	41949363
ENSE00000692300	41978642	41978777
ENSE00000692307	41980846	41980927
ENSE00000692308	41981839	41981954
ENSE00000818785	41977008	41977327
ENSE00000818786	41987455	41987563
ENSE00000818792	41943748	41943979
ENSE00001040899	41937256	41937568
ENSE00001128468	41955296	41955411
ENSE00001128473	41974704	41974822
ENSE00001247926	42051901	42051987
ENSE00001247935	41929479	41934867
ENSE00001762740	41947751	41947912
ENSE00002107560	42048378	42049302

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 96.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.3831 / max 559.5317, expressed in 1811 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92856	32.6761	1811
92859	0.4859	169
92857	0.1512	76
92858	0.0699	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nipple	UBERON:0002030	96.74	gold quality
medial globus pallidus	UBERON:0002477	96.21	gold quality
globus pallidus	UBERON:0001875	95.95	gold quality
mammary duct	UBERON:0001765	95.53	gold quality
upper arm skin	UBERON:0004263	95.44	gold quality
upper leg skin	UBERON:0004262	95.39	gold quality
ileal mucosa	UBERON:0000331	95.20	gold quality
skin of hip	UBERON:0001554	95.12	gold quality
colonic epithelium	UBERON:0000397	94.95	gold quality
epithelium of mammary gland	UBERON:0003244	94.95	gold quality
cardia of stomach	UBERON:0001162	94.90	gold quality
mammalian vulva	UBERON:0000997	94.89	gold quality
cerebellar vermis	UBERON:0004720	94.87	gold quality
superficial temporal artery	UBERON:0001614	94.80	gold quality
trabecular bone tissue	UBERON:0002483	94.72	gold quality
bone marrow cell	CL:0002092	94.66	gold quality
corpus callosum	UBERON:0002336	94.56	gold quality
lateral globus pallidus	UBERON:0002476	94.47	gold quality
sural nerve	UBERON:0015488	94.36	gold quality
visceral pleura	UBERON:0002401	94.34	gold quality
saphenous vein	UBERON:0007318	94.20	gold quality
pylorus	UBERON:0001166	94.02	gold quality
germinal epithelium of ovary	UBERON:0001304	93.97	gold quality
olfactory bulb	UBERON:0002264	93.93	gold quality
bone element	UBERON:0001474	93.90	gold quality
tibialis anterior	UBERON:0001385	93.88	gold quality
parotid gland	UBERON:0001831	93.83	gold quality
parietal pleura	UBERON:0002400	93.79	gold quality
inferior vagus X ganglion	UBERON:0005363	93.76	gold quality
penis	UBERON:0000989	93.75	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6386	no	382.48
E-GEOD-124858	no	145.17
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

13 targets.

Target	Regulation
BRPF1
CCL3	Activation
CD34
CREBBP
CXCL8	Activation
GSTP1	Activation
HOXA9	Activation
KMT2A
NFKB
RARB
RUNX1	Activation
RUNX2	Activation
SMARCA2

Upstream regulators (CollecTRI, top): YY1

miRNA regulators (miRDB)

298 targeting KAT6A, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• MOZ complexes with TIF2 as a recombinant fusion protein which induces acute myelocytic leukemia. (PMID:12676584)
• MOZ-TIF2 oncogenic fusion protein suppresses transcription by nuclear receptors and p53 (PMID:15657427)
• MOZ-TIF2 associates with the RARbeta2 promoter in vivo, resulting in altered recruitment of CBP/p300, aberrant histone modification, and down-regulation of the RARbeta2 gene (PMID:16613851)
• analysis of MYST3-CBP fusion transcripts in t(8;16)(p11;p13) acute myeloid leukemias (PMID:17296583)
• A MYST3-NCOA3 gene fusion was found in AML-M5. The breakpoint in MYST3 occurs in intron-17. (PMID:17805331)
• MYST3 rearrangement was associated with a poor prognosis, as 50% of patients deceased during the first 10 months (PMID:18528428)
• MOZ is essential for the generation and maintenance of hematopoietic stem cells (HSC) and for the appropriate development of myeloid, erythroid and B-lineage cell progenitors. (PMID:18754862)
• These findings indicate that BRPF proteins play a key role in assembling and activating MOZ/MORF acetyltransferase complexes. (PMID:18794358)
• a gain of the MYB locus, was found recurrently and only in the MYST3-linked AMLs (7/18 vs 0/34). MYST3-AMLs have also a specific a gene expression profile, which includes overexpression of MYB, CD4 and HOXA genes (PMID:18818702)
• Monocytic leukemia zinc finger (MOZ) interacts with p53 to induce p21 expression and cell-cycle arrest. (PMID:19001415)
• The role of the interaction between MOZ and MLL in CD34+ cells in which both proteins have a critical role in hematopoietic cell-fate decision. (PMID:20581860)
• Recognition of unmodified histone H3 by the first PHD finger of bromodomain-PHD finger protein 2 provides insights into the regulation of histone acetyltransferases monocytic leukemic zinc-finger protein (MOZ) and MOZ-related factor (MORF). (PMID:21880731)
• PHD12 facilitates the localization of MOZ onto the promoter locus of the HOXA9 gene, thereby promoting the H3 acetylation around the promoter region. (PMID:22713874)
• MYST3-CREBBP rearrangement harbors a distinctive microRNA signature targeting RET proto-oncogene in acute myeloid leukemia with translocation (8;16)(p11;p13). (PMID:23022987)
• These data suggest that the tandem of plant homeodomain 1/2 fingers play a role in MOZ and MORF histone acetyltransferase association with histon H3 regions enriched in acetylated marks. (PMID:23063713)
• Studies indicate the critical function of MOZ (MYST3 or KAT6A(1)) in haematopoiesis. (PMID:23347099)
• MOZ is an acetyltransferase of p53 at K120 and K382 and colocalizes with p53 in promyelocytic leukemia (PML) nuclear bodies following cellular stress. (PMID:23431171)
• Symplekin interacts and co-localizes with both MOZ and MLL in immature hematopoietic cells. Its inhibition leads to a decrease of the HOXA9 protein level but not of Hoxa9 mRNA. (PMID:23994619)
• The double PHD finger domain of MOZ/MYST3 induces alpha-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification. (PMID:24150941)
• MOZ-TIF2/BRPF1 complex upregulates HOX genes mediated by MOZ-dependent histone acetylation, leading to the development of leukemia. (PMID:24258712)
• These data suggest that KAT6A may be a novel oncogene in breast cancers bearing the 8p11-p12 amplicon. (PMID:25220592)
• We have identified KAT6A mutations as a frequent cause of syndromic developmental delay with microcephaly and dysmorphic features. (PMID:25728775)
• Heterozygous truncating mutations in KAT6A, as well as deletions of the same locus, cause a syndrome characterized by intellectual disability, craniosynostosis, cardiac defects, feeding difficulties, and distinct facial features. (PMID:25728777)
• findings establish that MOZ and BMI1 play opposing roles during the onset of Hox gene expression in the ES cell model and during body segment identity specification in vivo. (PMID:25922517)
• In this study we report the frequency of FGFR1 and KAT6A involvement in patients with hematological malignancies and 8p11 abnormalities. (PMID:26667788)
• Given the similar findings in animal models and our patient’s phenotypes, we hypothesize that KAT6A could play a role in development of the brain, face, and heart in humans (PMID:27133397)
• Studies show that misregulation of MOZ/MORF results in tumorigenesis and developmental disorders. Results also provide evidence that these 2 proteins play important role in regulating cell proliferation and stem cell maintenance. [review] (PMID:27185879)
• The demonstrate that the histone acetylation-binding double PHD finger (DPF) domains of human MOZ (also known as KAT6A) and DPF2 (also known as BAF45d) accommodate a wide range of histone lysine acylation with the strongest preference for propionylation (Kcr). (PMID:27775714)
• MYST3 binds to the proximal promoter region of ERalpha gene, and inactivating mutations in its HAT domain abolished its ability to regulate ERalpha, suggesting MYST3 functioning as a histone acetyltransferase that activates ERalpha promoter. (PMID:27893709)
• Overexpression of KAT6A or TRIM24 promoted PIK3CA expression, AKT phosphorylation, and cell proliferation. (PMID:29021135)
• the first inherited variant in KAT6A and suggest missense variants in KAT6A to be associated with an inheritable, milder clinical presentation compared to previously reported de novo, truncating mutations in this gene. (PMID:29899504)
• Our data expand the genotypic and phenotypic spectrum for individuals with genetic pathogenic variants in KAT6A and we outline appropriate clinical management. (PMID:30245513)
• Report renal cell carcinomas with NEAT1-TFE3 and KAT6A-TFE3 gene fusions. (PMID:30622287)
• Long non-coding RNA DANCR promotes colorectal tumor growth by binding to lysine acetyltransferase 6A. (PMID:31863900)
• Five new cases of syndromic intellectual disability due to KAT6A mutations: widening the molecular and clinical spectrum. (PMID:32041641)
• Acute Monoblastic Leukemia with Erythrophagocytosis and Absence of KAT6A Rearrangement (PMID:32519830)
• KAT6A amplifications are associated with shorter progression-free survival and overall survival in patients with endometrial serous carcinoma. (PMID:32877461)
• Expanding the genetic landscape of Rett syndrome to include lysine acetyltransferase 6A (KAT6A). (PMID:33386251)
• KAT6A, a novel regulator of beta-catenin, promotes tumorigenicity and chemoresistance in ovarian cancer by acetylating COP1. (PMID:33995658)
• KAT6A Acetylation of SMAD3 Regulates Myeloid-Derived Suppressor Cell Recruitment, Metastasis, and Immunotherapy in Triple-Negative Breast Cancer. (PMID:34392614)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	kat6a	ENSDARG00000018907
mus_musculus	Kat6a	ENSMUSG00000031540
rattus_norvegicus	Kat6a	ENSRNOG00000025174
drosophila_melanogaster	tth	FBGN0030502
drosophila_melanogaster	d4	FBGN0033015
caenorhabditis_elegans		WBGENE00016200

Paralogs (9): DPF1 (ENSG00000011332), RSF1 (ENSG00000048649), KAT8 (ENSG00000103510), PHF10 (ENSG00000130024), DPF2 (ENSG00000133884), KAT7 (ENSG00000136504), KAT6B (ENSG00000156650), KAT5 (ENSG00000172977), DPF3 (ENSG00000205683)

Protein

Protein identifiers

Histone acetyltransferase KAT6A — Q92794 (reviewed: Q92794)

Alternative names: MOZ, YBF2/SAS3, SAS2 and TIP60 protein 3, Monocytic leukemia zinc finger protein, Runt-related transcription factor-binding protein 2, Zinc finger protein 220

All UniProt accessions (8): Q92794, A0A3B3IS53, A0A3B3ISU5, A0A3B3ISZ3, A0A3B3ITI3, A0A3F2YNX6, A5PLL3, C9JJY6

UniProt curated annotations — full annotation on UniProt →

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. May play a role in leukemogenic gene transcription.

Subunit / interactions. Component of the MOZ/MORF complex composed at least of ING5, KAT6A, KAT6B, MEAF6 and one of BRPF1, BRD1/BRPF2 and BRPF3. Interacts with RUNX1; phosphorylation of RUNX1 enhances the interaction. Interacts with RUNX2. Interacts with p53/TP53. Interacts with PML (isoform PML-4) and this interaction positively regulates its acetylation activity towards p53/TP53. When acetylated or crotonylated, interacts with MLLT1/ENL; the interaction is direct. When acetylated or crotonylated, interacts with MLLT3/AF9; the interaction is direct.

Subcellular location. Nucleus. Nucleolus. Nucleoplasm. PML body.

Post-translational modifications. Autoacetylated; autoacetylation at Lys-604 is required for proper function (Ref.27). Acetylation at Lys-1007 and Lys-1014 is required for the interaction with MLLT1/ENL and MLLT3/AF9. Crotonylated; crotonylation at Lys-1007 and Lys-1014 promotes the interaction with MLLT1/ENL and MLLT3/AF9. Phosphorylation at Thr-369 by PKB/AKT1 inhibits its interaction with PML and negatively regulates its acetylation activity towards p53/TP53.

Disease relevance. Chromosomal aberrations involving KAT6A may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with CREBBP. Translocation t(8;22)(p11;q13) with EP300. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription. 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. 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. Arboleda-Tham syndrome (ARTHS) [MIM:616268] An autosomal dominant disorder characterized by intellectual disability, dysmorphic facial features, delayed psychomotor development, and lack of speech. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The N-terminus is involved in transcriptional activation while the C-terminus is involved in transcriptional repression.

Similarity. Belongs to the MYST (SAS/MOZ) family.

RefSeq proteins (2): NP_001292807, NP_006757* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001965	Znf_PHD	Domain
IPR002717	HAT_MYST-type	Domain
IPR005818	Histone_H1/H5_H15	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR016181	Acyl_CoA_acyltransferase	Homologous_superfamily
IPR019787	Znf_PHD-finger	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR040706	Zf-MYST	Domain
IPR048589	SAMD1-like_WH	Domain
IPR050603	MYST_HAT	Family

Pfam: PF00628, PF01853, PF17772, PF21524

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), 1 shown:

• L-lysyl-[protein] + acetyl-CoA = N(6)-acetyl-L-lysyl-[protein] + CoA + H(+) (RHEA:45948)

UniProt features (135 total): compositionally biased region 28, strand 21, modified residue 21, helix 18, region of interest 14, turn 10, mutagenesis site 5, domain 3, zinc finger region 3, binding site 3, site 3, cross-link 2, chain 1, active site 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
5B78	X-RAY DIFFRACTION	1.4
3V43	X-RAY DIFFRACTION	1.47
7Y43	X-RAY DIFFRACTION	1.5
5B77	X-RAY DIFFRACTION	1.55
4LK9	X-RAY DIFFRACTION	1.6
4LKA	X-RAY DIFFRACTION	1.61
5B76	X-RAY DIFFRACTION	1.65
5B75	X-RAY DIFFRACTION	1.7
9DZN	X-RAY DIFFRACTION	1.72
8H7A	X-RAY DIFFRACTION	1.92
6LSB	X-RAY DIFFRACTION	2
9ARR	X-RAY DIFFRACTION	2.1
2OZU	X-RAY DIFFRACTION	2.3
9ARO	X-RAY DIFFRACTION	2.3
4LLB	X-RAY DIFFRACTION	2.5
8DD5	X-RAY DIFFRACTION	2.58
9FKR	X-RAY DIFFRACTION	2.69
2RC4	X-RAY DIFFRACTION	3
4LJN	X-RAY DIFFRACTION	3
1M36	SOLUTION NMR
2LN0	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92794-F1	49.12	0.17

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 (4): 680 (proton donor/acceptor); 813–814 (breakpoint for translocation to form kat6a-asxl2); 1117–1118 (breakpoint for translocation to form kat6a-ep300 and kat6a-ncoa2); 1546–1547 (breakpoint for translocation to form kat6a-crebbp)

Ligand- & substrate-binding residues (3): 645–649; 654–660; 684

Post-translational modifications (23): 172, 350, 355, 369, 420, 473, 604, 787, 812, 815, 899, 941, 954, 974, 1007, 1007, 1014, 1014, 1089, 1090 …

Mutagenesis-validated functional residues (5):

Position	Phenotype
543	abrogates hat activity.
545	reduced affinity for dna.
657	abrogates hat activity.
727	slightly reduced affinity for dna.
732	reduced affinity for dna.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-3214847	HATs acetylate histones
R-HSA-6804758	Regulation of TP53 Activity through Acetylation
R-HSA-212436	Generic Transcription Pathway
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-4839726	Chromatin organization
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 634 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_CHROMOSOME_ORGANIZATION, ATACCTC_MIR202, HSIAO_HOUSEKEEPING_GENES, CACCAGC_MIR138, GOBP_CELLULAR_SENESCENCE, USF_C, AGGCACT_MIR5153P, GOBP_REGULATION_OF_HEMOPOIESIS, SOX9_B1, FOSTER_TOLERANT_MACROPHAGE_UP, GOBP_PROTEIN_ACETYLATION, BLALOCK_ALZHEIMERS_DISEASE_UP, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, CCTGTGA_MIR513

GO Biological Process (17): nucleosome assembly (GO:0006334), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), protein acetylation (GO:0006473), positive regulation of gene expression (GO:0010628), myeloid cell differentiation (GO:0030099), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), regulation of developmental process (GO:0050793), chromosome organization (GO:0051276), cellular senescence (GO:0090398), regulation of signal transduction by p53 class mediator (GO:1901796), regulation of hemopoiesis (GO:1903706), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), positive regulation of macromolecule biosynthetic process (GO:0010557), obsolete positive regulation of nucleobase-containing compound metabolic process (GO:0045935)

GO Molecular Function (19): DNA binding (GO:0003677), chromatin binding (GO:0003682), transcription coregulator activity (GO:0003712), transcription coactivator activity (GO:0003713), histone acetyltransferase activity (GO:0004402), zinc ion binding (GO:0008270), histone H3 acetyltransferase activity (GO:0010484), acetyltransferase activity (GO:0016407), histone H3K14 acetyltransferase activity (GO:0036408), histone H4K5 acetyltransferase activity (GO:0043995), histone H4K8 acetyltransferase activity (GO:0043996), histone H4K12 acetyltransferase activity (GO:0043997), histone H4K16 acetyltransferase activity (GO:0046972), DNA-binding transcription factor binding (GO:0140297), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), metal ion binding (GO:0046872), protein-lysine-acetyltransferase activity (GO:0061733)

GO Cellular Component (10): chromatin (GO:0000785), nucleosome (GO:0000786), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), PML body (GO:0016605), nuclear speck (GO:0016607), MOZ/MORF histone acetyltransferase complex (GO:0070776), histone acetyltransferase complex (GO:0000123)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Regulation of TP53 Activity	1
RNA Polymerase II Transcription	1
Chromatin organization	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
histone H4 acetyltransferase activity	4
DNA-templated transcription	3
regulation of DNA-templated transcription	3
cellular anatomical structure	3
chromatin organization	2
regulation of gene expression	2
hemopoiesis	2
binding	2
chromatin	2
nuclear lumen	2
nucleosome organization	1
protein-DNA complex assembly	1
regulation of RNA biosynthetic process	1
transcription by RNA polymerase II	1
protein acylation	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
cell differentiation	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
developmental process	1
regulation of biological process	1
organelle organization	1
cellular process	1
cellular response to stress	1
signal transduction by p53 class mediator	1
regulation of intracellular signal transduction	1
regulation of immune system process	1
regulation of cell development	1
regulation of multicellular organismal development	1
cellular component organization	1
macromolecule biosynthetic process	1
positive regulation of biosynthetic process	1
regulation of macromolecule biosynthetic process	1
positive regulation of macromolecule metabolic process	1
nucleic acid binding	1
transcription regulator activity	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
protein-lysine-acetyltransferase activity	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

71 interactions, top by confidence:

A	B	Type	Score
CSNK2A1	EIF3J	psi-mi:“MI:0914”(association)	0.810
CSNK2B	RPS6KA4	psi-mi:“MI:0914”(association)	0.640
KAT6A	KMT2A	psi-mi:“MI:0403”(colocalization)	0.560
KMT2A	KAT6A	psi-mi:“MI:0403”(colocalization)	0.560
KAT6A	KMT2A	psi-mi:“MI:0915”(physical association)	0.560
KMT2A	KAT6A	psi-mi:“MI:0915”(physical association)	0.560
WDR5	KAT6A	psi-mi:“MI:0403”(colocalization)	0.560
KAT6A	WDR5	psi-mi:“MI:0915”(physical association)	0.560
WDR5	KAT6A	psi-mi:“MI:0915”(physical association)	0.560
STT3A	RPN1	psi-mi:“MI:0914”(association)	0.560
ING4	KAT7	psi-mi:“MI:0914”(association)	0.530
ING5	KAT7	psi-mi:“MI:0914”(association)	0.530
RPN1	APBB1	psi-mi:“MI:0914”(association)	0.530
USP7	KAT6A	psi-mi:“MI:0407”(direct interaction)	0.440
KAT6A	RANGAP1	psi-mi:“MI:0915”(physical association)	0.400
KAT6A	KMT2A	psi-mi:“MI:0915”(physical association)	0.400
KAT6A	UBE2U	psi-mi:“MI:0915”(physical association)	0.370
Tubgcp6	MRE11	psi-mi:“MI:0914”(association)	0.350
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
RPL10	RPS6	psi-mi:“MI:0914”(association)	0.350
L1TD1	PPP1R12C	psi-mi:“MI:0914”(association)	0.350
KAT6A	ING5	psi-mi:“MI:0914”(association)	0.350
Myo1c	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (578): KAT6A (Far Western), TP53 (Biochemical Activity), KAT6A (Biochemical Activity), HIST3H3 (Biochemical Activity), HIST4H4 (Biochemical Activity), KAT6A (Affinity Capture-MS), KAT6A (Affinity Capture-MS), KAT6A (Affinity Capture-MS), KAT6A (Affinity Capture-MS), KAT6A (Affinity Capture-MS), PHF14 (Affinity Capture-MS), TNRC6B (Affinity Capture-MS), PNPLA8 (Affinity Capture-MS), RSF1 (Affinity Capture-MS), ING5 (Affinity Capture-MS)

ESM2 similar proteins: A0A0A6YYL3, A0JP26, A2A2Z9, A2RUR9, A6NC57, A6NI47, A6QR20, A8MYB1, A9JSR5, A9ZSY0, B2RU33, B7ZQJ9, F1M5M3, H3BUK9, O15050, P51954, P98182, Q19UN5, Q4UJ75, Q501X2, Q5CZ79, Q5DW34, Q5SQ80, Q5TYW2, Q5VUR7, Q66HB6, Q6NSI1, Q6S545, Q6S5H5, Q6S8J7, Q71S21, Q7TPV2, Q7TSC3, Q7ZT11, Q80X59, Q811D2, Q86Y13, Q86YR6, Q8IVF6, Q8IYA2

Diamond homologs: A0A286Y9D1, A1YVX4, A7E320, B2KF05, B2RRD7, B6CHA3, F4KBP5, F6UA42, G5E8P1, G5EBZ4, O54826, O75164, O94880, O94953, P0CB22, P29375, P34447, P41229, P41230, P47156, P55197, P55198, P55201, Q0P4S5, Q12311, Q20318, Q22516, Q29EQ3, Q30DN6, Q38JA7, Q3UXZ9, Q5E9T7, Q5RD88, Q5TKR9, Q62240, Q6GQJ2, Q6IE81, Q6IE82, Q6IQX0, Q6K431

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
KAT6A	up-regulates	RUNX1	binding
KAT6A	up-regulates	RUNX2	binding
KAT6A	“form complex”	KAT6A/KAT6B	binding
KAT6A	“form complex”	KAT6A/PML	binding
KAT6A	up-regulates	TP53	acetylation
KAT6A	“up-regulates quantity by expression”	CCL3	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 64 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
PD-L1(CD274) glycosylation and translocation to plasma membrane	7	77.3×	5e-10
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	8	57.2×	4e-10
Maturation of spike protein	7	39.5×	4e-08
Maturation of DENV proteins	8	36.0×	6e-09
Regulation of PTEN stability and activity	5	19.6×	5e-04
KEAP1-NFE2L2 pathway	5	12.8×	2e-03
SRP-dependent cotranslational protein targeting to membrane	5	10.7×	3e-03
HATs acetylate histones	6	10.1×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
obsolete protein N-linked glycosylation via asparagine	7	80.0×	1e-09
protein N-linked glycosylation	8	35.7×	1e-08
regulation of DNA replication	5	31.1×	5e-05
chromatin organization	6	10.1×	2e-03
regulation of cell cycle	6	7.6×	6e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — ESCA.

Clinical variants and AI predictions

ClinVar

2044 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	116
Likely pathogenic	72
Uncertain significance	698
Likely benign	669
Benign	244

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1034308	NM_006766.5(KAT6A):c.2463del (p.Asn821fs)	Pathogenic
1048764	NM_006766.5(KAT6A):c.1146_1147insG (p.Tyr383fs)	Pathogenic
1082502	NM_006766.5:c.3411del	Pathogenic
1172592	NM_006766.5(KAT6A):c.1506del (p.Asp503fs)	Pathogenic
1285569	NM_006766.5(KAT6A):c.1405C>T (p.Arg469Ter)	Pathogenic
1323134	NM_006766.5(KAT6A):c.4398_4399del (p.Gln1467fs)	Pathogenic
1325410	NM_006766.5(KAT6A):c.1312C>T (p.Arg438Ter)	Pathogenic
1345022	NM_006766.5(KAT6A):c.3230del (p.Asn1077fs)	Pathogenic
162616	NM_006766.5(KAT6A):c.3116_3117del (p.Ile1038_Ser1039insTer)	Pathogenic
1697352	NM_006766.5(KAT6A):c.376A>T (p.Lys126Ter)	Pathogenic
1698914	NM_006766.5(KAT6A):c.1133C>G (p.Ser378Ter)	Pathogenic
1699609	NM_006766.5(KAT6A):c.4273_4274del (p.Val1425fs)	Pathogenic
1787663	NM_006766.5(KAT6A):c.2203C>T (p.Arg735Ter)	Pathogenic
180229	NM_006766.5(KAT6A):c.3385C>T (p.Arg1129Ter)	Pathogenic
180230	NM_006766.5(KAT6A):c.3070C>T (p.Arg1024Ter)	Pathogenic
1805333	NM_006766.5(KAT6A):c.3631_3632del (p.Thr1210_Val1211insTer)	Pathogenic
1805338	NM_006766.5(KAT6A):c.3377del (p.Ser1126fs)	Pathogenic
1805561	NM_006766.5(KAT6A):c.3820G>T (p.Glu1274Ter)	Pathogenic
1805653	NM_006766.5(KAT6A):c.3399_3400dup (p.Lys1134fs)	Pathogenic
180678	NM_006766.5(KAT6A):c.3879dup (p.Glu1294fs)	Pathogenic
1997700	NM_006766.5(KAT6A):c.4003C>T (p.Gln1335Ter)	Pathogenic
2122759	NM_006766.5(KAT6A):c.5282_5283insT (p.Thr1762fs)	Pathogenic
2135274	NM_006766.5(KAT6A):c.2232del (p.Phe744fs)	Pathogenic
2430855	NM_006766.5(KAT6A):c.3348_3349dup (p.Asp1117fs)	Pathogenic
2473862	NM_006766.5(KAT6A):c.214A>T (p.Lys72Ter)	Pathogenic
2584389	NM_006766.5(KAT6A):c.5505_5506del (p.Asn1836fs)	Pathogenic
2631071	NM_006766.5(KAT6A):c.3483_3484del (p.His1162fs)	Pathogenic
2658577	NM_006766.5(KAT6A):c.1302_1303del (p.Glu435fs)	Pathogenic
2663817	NM_006766.5(KAT6A):c.2927del (p.Gly976fs)	Pathogenic
2663859	NM_006766.5(KAT6A):c.3344_3350del (p.Asp1115fs)	Pathogenic

SpliceAI

3025 predictions. Top by Δscore:

Variant	Effect	Δscore
8:41934865:TGT:T	acceptor_gain	1.0000
8:41934868:C:CC	acceptor_gain	1.0000
8:41934874:A:T	acceptor_gain	1.0000
8:41937251:CATA:C	donor_loss	1.0000
8:41937252:ATAC:A	donor_loss	1.0000
8:41937253:TA:T	donor_loss	1.0000
8:41937254:A:AC	donor_gain	1.0000
8:41937255:C:CA	donor_loss	1.0000
8:41937255:C:CC	donor_gain	1.0000
8:41937255:CCAT:C	donor_gain	1.0000
8:41937564:GGTTT:G	acceptor_gain	1.0000
8:41937565:GTTT:G	acceptor_gain	1.0000
8:41937566:TTT:T	acceptor_gain	1.0000
8:41937567:TT:T	acceptor_gain	1.0000
8:41937569:C:CC	acceptor_gain	1.0000
8:41937570:T:A	acceptor_loss	1.0000
8:41937571:G:C	acceptor_gain	1.0000
8:41937573:T:C	acceptor_gain	1.0000
8:41937573:T:TC	acceptor_gain	1.0000
8:41937576:A:AC	acceptor_gain	1.0000
8:41937576:A:C	acceptor_gain	1.0000
8:41940837:GTTAC:G	donor_loss	1.0000
8:41940840:ACCTT:A	donor_loss	1.0000
8:41940841:C:CT	donor_loss	1.0000
8:41941440:CCCAC:C	acceptor_gain	1.0000
8:41941441:CCACC:C	acceptor_gain	1.0000
8:41941442:CAC:C	acceptor_gain	1.0000
8:41941443:ACC:A	acceptor_loss	1.0000
8:41941451:T:C	acceptor_gain	1.0000
8:41941451:T:TC	acceptor_gain	1.0000

AlphaMissense

13328 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:41933570:G:C	F1550L	1.000
8:41933570:G:T	F1550L	1.000
8:41933572:A:G	F1550L	1.000
8:41942901:C:A	W776C	1.000
8:41942901:C:G	W776C	1.000
8:41942903:A:G	W776R	1.000
8:41942903:A:T	W776R	1.000
8:41943784:A:G	L731P	1.000
8:41943784:A:T	L731H	1.000
8:41943868:A:G	L703P	1.000
8:41943893:A:G	W695R	1.000
8:41943893:A:T	W695R	1.000
8:41943916:C:A	G687V	1.000
8:41943916:C:T	G687D	1.000
8:41943917:C:G	G687R	1.000
8:41946592:G:C	F665L	1.000
8:41946592:G:T	F665L	1.000
8:41946593:A:G	F665S	1.000
8:41946594:A:G	F665L	1.000
8:41946602:A:G	L662P	1.000
8:41946604:A:C	F661L	1.000
8:41946604:A:T	F661L	1.000
8:41946605:A:G	F661S	1.000
8:41946606:A:G	F661L	1.000
8:41946647:A:T	I647K	1.000
8:41946649:A:C	C646W	1.000
8:41946650:C:T	C646Y	1.000
8:41946651:A:G	C646R	1.000
8:41946656:A:T	V644D	1.000
8:41946658:A:C	N643K	1.000

dbSNP variants (sampled 300 via entrez): RS1000106054 (8:41987070 G>A), RS1000109710 (8:41997620 C>G,T), RS1000138957 (8:42035161 A>G), RS1000156400 (8:42039067 A>G), RS1000187209 (8:42020643 T>C), RS1000194988 (8:41956309 C>A,T), RS1000218181 (8:41971582 T>C), RS1000225997 (8:41956581 T>C), RS1000234850 (8:41999233 T>A), RS1000274397 (8:41946264 C>G,T), RS1000300339 (8:42014587 T>A,C), RS1000355701 (8:42004997 C>G), RS1000366954 (8:41984382 C>A), RS1000367045 (8:42005295 C>T), RS1000385976 (8:41990883 T>C)

Disease associations

OMIM: gene MIM:601408 | disease phenotypes: MIM:616268, MIM:123100

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
syndromic intellectual disability	Definitive	AD

Mondo (8): autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome (MONDO:0014558), neurodevelopmental disorder (MONDO:0700092), syndromic intellectual disability (MONDO:0000508), autism spectrum disorder (MONDO:0005258), craniosynostosis (MONDO:0015469), intellectual disability (MONDO:0001071), congenital heart disease (MONDO:0005453), vein of Galen aneurysm (MONDO:0015196)

Orphanet (6): KAT6-related intellectual disability-craniofacial anomalies-cardiac defects syndrome (Orphanet:457193), Rare genetic syndromic intellectual disability (Orphanet:183763), Craniosynostosis (Orphanet:1531), Vein of Galen malformation (Orphanet:1053), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

120 total (30 of 120 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000028	Cryptorchidism
HP:0000126	Hydronephrosis
HP:0000154	Wide mouth
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000303	Mandibular prognathia
HP:0000307	Pointed chin
HP:0000308	Microretrognathia
HP:0000322	Short philtrum
HP:0000324	Facial asymmetry
HP:0000325	Triangular face
HP:0000341	Narrow forehead
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000385	Small earlobe
HP:0000389	Chronic otitis media
HP:0000395	Prominent antihelix
HP:0000403	Recurrent otitis media
HP:0000426	Prominent nasal bridge
HP:0000455	Broad nasal tip
HP:0000456	Bifid nasal tip
HP:0000465	Webbed neck
HP:0000483	Astigmatism
HP:0000486	Strabismus

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006914_19	Sleep duration	2.000000e-08

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C536535	Vein of Galen aneurysm (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3774298 (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)

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
PF-9363	Inhibition	9.57	pIC50
compound 35 [US12091406]	Inhibition	8.0	pIC50
prifetrastat	Inhibition	7.52	pKi

Binding affinities (BindingDB)

145 measured of 145 human assays (783 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6-(Dimethylamino)-N-((2-methylquinolin-8-yl)sulfonyl)-4-(trifluoromethyl)benzofuran-2-carboxamide	IC50	1.47 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 107	IC50	2.29 nM	US-12357603: Acyl sulfonamides for treating cancer
N-((5-(tert-butyl)-2-methoxyphenyl)sulfonyl)-6-(dimethylamino)benzofuran-2-carboxamide	IC50	2.63 nM	US-12357603: Acyl sulfonamides for treating cancer
N-[(5-(tert-butyl)-2-cyclobutoxyphenyl)sulfonyl]-6-(dimethylamino)benzofuran-2-carboxamide	IC50	2.67 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 227	IC50	4 nM	US-12357603: Acyl sulfonamides for treating cancer
N-((5-(tert-butyl)-2-(cyclopropylmethoxy)phenyl)sulfonyl)-6-(dimethylamino)benzofuran-2-carboxamide	IC50	4.36 nM	US-12357603: Acyl sulfonamides for treating cancer
6-(Dimethylamino)-N-(2-ethoxy-5-sec-butyl-phenyl)sulfonyl-benzofuran-2-carboxamide (rac)	IC50	4.4 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 108	IC50	4.6 nM	US-12357603: Acyl sulfonamides for treating cancer
6-(Dimethylamino)-N-((2-ethoxyphenyl)sulfonyl)-4-(trifluoromethyl)benzofuran-2-carboxamide	IC50	5.73 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 109	IC50	7.09 nM	US-12357603: Acyl sulfonamides for treating cancer
N-([1,1’-biphenyl]-2-ylsulfonyl)-6-(dimethylamino)-4-(trifluoromethyl)benzofuran-2-carboxamide	IC50	7.14 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 113	IC50	7.25 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 110	IC50	7.48 nM	US-12357603: Acyl sulfonamides for treating cancer
N-[2-(cyclopropylmethoxy)-5-isopropyl-phenyl]sulfonyl-6-(dimethylamino)benzofuran-2-carboxamide	IC50	7.91 nM	US-12357603: Acyl sulfonamides for treating cancer
N-((2-((2,2-difluorocyclopropyl)methoxy)-5-isopropylphenyl)sulfonyl)-6-(dimethylamino)benzofuran-2-carboxamide (rac)	IC50	8.47 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 111	IC50	8.93 nM	US-12357603: Acyl sulfonamides for treating cancer
N-[(2-(Benzyloxy)-5-(tert-butyl)phenyl)sulfonyl]-6-(dimethylamino)benzofuran-2-carboxamide	IC50	8.95 nM	US-12357603: Acyl sulfonamides for treating cancer
6-(Dimethylamino)-N-[5-isopropyl-2-(2,2,2-trifluoroethoxy)phenyl]sulfonyl-benzofuran-2-carboxamide	IC50	11 nM	US-12357603: Acyl sulfonamides for treating cancer
6-(Dimethylamino)-N-(2-ethoxy-5-phenoxy-phenyl)sulfonyl-benzofuran-2-carboxamide	IC50	11.8 nM	US-12357603: Acyl sulfonamides for treating cancer
N-[(5-(tert-butyl)-2-(2,2,2-trifluoroethoxy)phenyl)sulfonyl]-6-(dimethylamino)benzofuran-2-carboxamide	IC50	11.8 nM	US-12357603: Acyl sulfonamides for treating cancer
N-(2-Benzyloxy-5-isopropyl-phenyl)sulfonyl-6-(dimethylamino)benzofuran-2-carboxamide	IC50	12.8 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 129	IC50	13.5 nM	US-12357603: Acyl sulfonamides for treating cancer
N-((5-(tert-butyl)-2-isopropoxyphenyl)sulfonyl)-6-(dimethylamino)benzofuran-2-carboxamide	IC50	15.4 nM	US-12357603: Acyl sulfonamides for treating cancer
N-((2-Cyclobutoxy-5-isopropylphenyl)sulfonyl)-6-(dimethylamino)benzofuran-2-carboxamide	IC50	15.9 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 112	IC50	17.7 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 126	IC50	20.5 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 225	IC50	22.7 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 143	IC50	29.3 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 222	IC50	30.6 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 134	IC50	30.7 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 84	IC50	40.6 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 221	IC50	44.4 nM	US-12357603: Acyl sulfonamides for treating cancer
6-(Dimethylamino)-N-(phenylsulfonyl)-4-(trifluoromethyl)benzofuran-2-carboxamide	IC50	44.9 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 83	IC50	48.8 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 118	IC50	52.4 nM	US-12357603: Acyl sulfonamides for treating cancer
6-(Dimethylamino)-N-[2-ethoxy-5-(trifluoromethyl)phenyl]sulfonyl-benzofuran-2-carboxamide	IC50	54 nM	US-12357603: Acyl sulfonamides for treating cancer
N-(5-Aminoquinoline-8-sulfonyl)-6-(dimethylamino)-1-benzofuran-2-carboxamide	IC50	56.4 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 138	IC50	56.7 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 135	IC50	57.9 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 224	IC50	58.3 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 115	IC50	64.6 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 86	IC50	64.9 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 127	IC50	71.2 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 91	IC50	74.2 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 137	IC50	81.5 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 124	IC50	92.8 nM	US-12357603: Acyl sulfonamides for treating cancer
6-(Dimethylamino)-N-(2-ethoxy-4-fluoro-phenyl)sulfonyl-benzofuran-2-carboxamide	IC50	94.9 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 87	IC50	97.3 nM	US-12357603: Acyl sulfonamides for treating cancer
6-(Dimethylamino)-N-(2-ethoxy-5-fluoro-phenyl)sulfonyl-benzofuran-2-carboxamide	IC50	97.3 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 147	IC50	98.6 nM	US-12357603: Acyl sulfonamides for treating cancer

ChEMBL bioactivities

581 potent at pChembl≥5 of 775 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.57	Ki	0.27	nM	CHEMBL5723326
9.52	Ki	0.3	nM	CHEMBL6000330
9.49	Ki	0.32	nM	CHEMBL5792567
9.48	Ki	0.33	nM	CHEMBL5940985
9.47	Ki	0.34	nM	CHEMBL5927368
9.46	Ki	0.35	nM	CHEMBL5993180
9.46	Ki	0.35	nM	CHEMBL5723326
9.44	Ki	0.36	nM	CHEMBL6063716
9.42	Ki	0.38	nM	CHEMBL5886450
9.42	Ki	0.38	nM	CHEMBL5723326
9.40	Ki	0.4	nM	CHEMBL5853409
9.37	Ki	0.43	nM	CHEMBL5852195
9.35	Ki	0.45	nM	CHEMBL5955544
9.34	Ki	0.46	nM	CHEMBL5812221
9.34	Ki	0.46	nM	CHEMBL5853409
9.34	Ki	0.46	nM	CHEMBL5723326
9.33	Ki	0.47	nM	CHEMBL5746641
9.31	Ki	0.49	nM	CHEMBL5959733
9.31	Ki	0.49	nM	CHEMBL5883288
9.29	Ki	0.51	nM	CHEMBL5818085
9.29	Ki	0.51	nM	CHEMBL6000330
9.28	Ki	0.53	nM	CHEMBL5998930
9.27	Ki	0.54	nM	CHEMBL5853561
9.26	Ki	0.55	nM	CHEMBL5852195
9.23	Ki	0.59	nM	CHEMBL5853561
9.19	Ki	0.65	nM	CHEMBL5993180
9.19	Ki	0.64	nM	CHEMBL6057979
9.19	Ki	0.64	nM	CHEMBL5996948
9.18	Ki	0.66	nM	CHEMBL5723326
9.17	Ki	0.68	nM	CHEMBL6005841
9.15	Ki	0.7	nM	CHEMBL5818085
9.14	Ki	0.72	nM	CHEMBL5815468
9.13	Ki	0.74	nM	CHEMBL5723326
9.13	Ki	0.74	nM	CHEMBL5928174
9.12	Ki	0.75	nM	CHEMBL5723326
9.11	Ki	0.77	nM	CHEMBL5771110
9.10	Ki	0.8	nM	CHEMBL5723326
9.08	Ki	0.83	nM	CHEMBL5723326
9.08	Ki	0.83	nM	CHEMBL5886450
9.06	Ki	0.87	nM	CHEMBL5927368
9.04	Ki	0.92	nM	CHEMBL5941367
9.02	Ki	0.95	nM	CHEMBL5941367
9.00	Ki	1.01	nM	CHEMBL5812221
8.99	Ki	1.02	nM	CHEMBL5996948
8.97	Ki	1.07	nM	CHEMBL5955544
8.96	Ki	1.11	nM	CHEMBL5857566
8.96	Ki	1.1	nM	CHEMBL5867166
8.95	Ki	1.12	nM	CHEMBL5959733
8.94	Ki	1.14	nM	CHEMBL5883288
8.93	Ki	1.17	nM	CHEMBL6005841

PubChem BioAssay actives

283 with measured affinity, of 345 total; 50 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
3-fluoro-N’-(2-fluorophenyl)sulfonyl-5-pyridin-2-ylbenzohydrazide	2138641: Inhibition of KAT6A (unknown origin) by SPR analysis	ic50	0.0020	uM
N’-(benzenesulfonyl)-3-fluoro-5-pyridin-2-ylbenzohydrazide	1576684: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0020	uM
N’-(2-fluorophenyl)sulfonyl-3-methoxy-5-pyridin-2-ylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0050	uM
3-chloro-N’-(2-fluorophenyl)sulfonyl-5-(furan-2-yl)benzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0055	uM
N’-(2-fluorophenyl)sulfonyl-3-pyridin-2-ylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0060	uM
N’-(2-fluorophenyl)sulfonyl-3-methyl-5-(3-methylpyrazol-1-yl)benzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0070	uM
N’-(benzenesulfonyl)-2-fluoro-3-methyl-5-phenylbenzohydrazide	1576684: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0080	uM
N’-(2-fluorophenyl)sulfonyl-3-methyl-5-pyridin-2-ylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0080	uM
3-fluoro-N’-(2-fluorophenyl)sulfonyl-5-(triazol-2-yl)benzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0090	uM
N’-(2-fluorophenyl)sulfonyl-3-methyl-5-pyrimidin-2-ylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0090	uM
3-fluoro-N’-(2-fluorophenyl)sulfonyl-5-(furan-2-yl)benzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0094	uM
N’-(benzenesulfonyl)-3-chloro-2-fluoro-5-phenylbenzohydrazide	1576684: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0100	uM
N’-(2-fluorophenyl)sulfonyl-3-(furan-2-yl)-5-methylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0110	uM
N’-(2-fluorophenyl)sulfonyl-3-methoxy-5-pyrazol-1-ylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0130	uM
N’-(2-fluorophenyl)sulfonyl-3-methyl-5-(5-methylpyrazol-1-yl)benzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0130	uM
N’-(2-fluorophenyl)sulfonyl-3-thiophen-3-ylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0140	uM
3-fluoro-N’-(2-fluorophenyl)sulfonyl-5-pyrimidin-2-ylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0140	uM
N’-(2-fluorophenyl)sulfonyl-3-methyl-5-(4-methylpyrazol-1-yl)benzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0140	uM
N’-(2-fluorophenyl)sulfonyl-3-methyl-5-propan-2-yloxybenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0150	uM
3-ethoxy-N’-(2-fluorophenyl)sulfonyl-5-methylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0160	uM
N’-(2-fluorophenyl)sulfonyl-3-methyl-5-prop-2-enoxybenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0160	uM
N’-(benzenesulfonyl)-2-fluoro-3-methyl-5-(2-methylprop-2-enoxy)benzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0170	uM
N’-(benzenesulfonyl)-2-fluoro-5-phenylbenzohydrazide	1576684: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0170	uM
5-chloro-2-fluoro-N’-(2-fluorophenyl)sulfonyl-3-phenylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0170	uM
N’-(2-fluorophenyl)sulfonyl-3-(3-methylpyrazol-1-yl)benzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0180	uM
N’-(2-fluorophenyl)sulfonyl-3-methyl-5-(triazol-2-yl)benzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0180	uM
3-fluoro-N’-(2-fluorophenyl)sulfonyl-5-prop-2-enoxybenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0200	uM
N’-(2-fluorophenyl)sulfonyl-3-(furan-2-yl)benzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0200	uM
3-fluoro-N’-(2-fluorophenyl)sulfonyl-5-(3-methylpyrazol-1-yl)benzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0230	uM
3-fluoro-N’-(2-fluorophenyl)sulfonyl-5-pyrazol-1-ylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0230	uM
3-chloro-N’-(2-fluorophenyl)sulfonyl-5-thiophen-2-ylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0240	uM
N’-(2-fluorophenyl)sulfonyl-3-methoxy-5-pyrimidin-2-ylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0240	uM
3-(ethoxymethyl)-N’-(2-fluorophenyl)sulfonyl-5-methylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0240	uM
N’-(2-fluorophenyl)sulfonyl-3-thiophen-2-ylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0250	uM
3-fluoro-N’-(2-fluoro-5-hydroxyphenyl)sulfonyl-5-pyrazol-1-ylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0260	uM
N’-(2-fluorophenyl)sulfonyl-3-methyl-5-pyrazol-1-ylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0270	uM
3-cyclopropyloxy-N’-(2-fluorophenyl)sulfonyl-5-methylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0270	uM
N’-(2-fluorophenyl)sulfonyl-3-(4-fluoropyrazol-1-yl)-5-methylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0290	uM
N’-(benzenesulfonyl)-5-(ethoxymethyl)-2-fluoro-3-methylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0290	uM
N’-(2-fluorophenyl)sulfonyl-3-prop-2-enoxybenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0300	uM
N-[2-(2-fluorophenyl)-2-oxoethyl]quinoline-8-sulfonamide	2138642: Inhibition of recombinant human KAT6A catalytic domain using [3H]-acetyl-coA as substrate pretreated with compound for 20 mins followed by substrate addition and measured after 4 hrs by liquid scintillation counter analysis	ic50	0.0300	uM
3-fluoro-N’-(2-fluorophenyl)sulfonyl-5-(5-methylpyrazol-1-yl)benzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0310	uM
3-fluoro-N’-(2-fluorophenyl)sulfonyl-5-(4-methylpyrazol-1-yl)benzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0320	uM
N’-(benzenesulfonyl)-2-fluoro-3-methyl-5-(triazol-2-yl)benzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0380	uM
N’-(2-fluorophenyl)sulfonyl-3-pyrazol-1-ylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0430	uM
3-chloro-2-fluoro-N’-naphthalen-2-ylsulfonylbenzohydrazide	1576684: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0430	uM
2-fluoro-N’-(2-fluorophenyl)sulfonyl-5-methyl-3-pyridin-2-ylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0440	uM
2-fluoro-N’-(2-fluorophenyl)sulfonyl-3-methyl-5-phenylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0480	uM
N’-(benzenesulfonyl)-2-fluoro-5-(4-fluoropyrazol-1-yl)-3-methylbenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0520	uM
N’-(benzenesulfonyl)-2-fluoro-3-methyl-5-propoxybenzohydrazide	1605563: Inhibition of N-terminal NusA-fused His6-tagged human KAT6A (507 to 778 residues) expressed in Escherichia coli BL21 (DE3) cells using 0.4 uM acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0520	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation	4
bisphenol A	affects cotreatment, increases methylation, decreases methylation, increases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
geldanamycin	increases expression	1
bufotalin	increases expression	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression, increases oxidation	1
trichostatin A	decreases expression	1
arsenite	affects binding, decreases reaction	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
deguelin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
(+)-JQ1 compound	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	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation, decreases methylation	1
Panobinostat	affects cotreatment, decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation	1
Benzene	increases expression	1
Caffeine	increases phosphorylation	1
Cisplatin	decreases expression	1

ChEMBL screening assays

42 unique, capped per target: 39 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3779396	Binding	Inhibition of human MOZ using histone H3 substrate at 10 uM incubated for 2 to 4 mins by SDS-PAGE based autoradiography in presence of [14C]acetyl-CoA relative to control	KATching-Up on Small Molecule Modulators of Lysine Acetyltransferases. — J Med Chem
CHEMBL5210050	Functional	Affinity Phenotypic Cellular interaction (Growth inhibition assays in EMRK1184 lymphoma cells) EUB0000329a MYST3	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomics Library wave 3

Cellosaurus cell lines

5 cell lines: 3 embryonic stem cell, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A3K7	SEES3-1V human KAT6A, clone1	Embryonic stem cell	Male
CVCL_A3K8	SEES3-1V human KAT6A, clone2	Embryonic stem cell	Male
CVCL_A3K9	SEES3-1V human KAT6A, clone3	Embryonic stem cell	Male
CVCL_ST91	HAP1 KAT6A (-) 1	Cancer cell line	Male
CVCL_XP89	HAP1 KAT6A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice