KAT6B

Summary

KAT6B (lysine acetyltransferase 6B, HGNC:17582) is a protein-coding gene on chromosome 10q22.2, encoding Histone acetyltransferase KAT6B (Q8WYB5). Histone acetyltransferase which may be involved in both positive and negative regulation of transcription. It is haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is a histone acetyltransferase and component of the MOZ/MORF protein complex. In addition to its acetyltransferase activity, the encoded protein has transcriptional activation activity in its N-terminal end and transcriptional repression activity in its C-terminal end. This protein is necessary for RUNX2-dependent transcriptional activation and could be involved in brain development. Mutations have been found in patients with genitopatellar syndrome. A translocation of this gene and the CREBBP gene results in acute myeloid leukemias. Three transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 23522 — RefSeq curated summary.

At a glance

• Gene–disease (curated): KAT6B-related multiple congenital anomalies syndrome (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 1,780 total — 114 pathogenic, 54 likely-pathogenic
• Phenotypes (HPO): 106
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 5 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_012330

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17582
Approved symbol	KAT6B
Name	lysine acetyltransferase 6B
Location	10q22.2
Locus type	gene with protein product
Status	Approved
Aliases	querkopf, qkf, Morf, MOZ2
Ensembl gene	ENSG00000156650
Ensembl biotype	protein_coding
OMIM	605880
Entrez	23522

Gene structure

Transcript identifiers

Ensembl transcripts: 48 — 34 protein_coding, 9 retained_intron, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000287239, ENST00000372711, ENST00000372714, ENST00000372724, ENST00000372725, ENST00000490365, ENST00000604130, ENST00000647554, ENST00000647637, ENST00000647642, ENST00000647666, ENST00000647890, ENST00000647891, ENST00000648048, ENST00000648159, ENST00000648302, ENST00000648369, ENST00000648370, ENST00000648483, ENST00000648539, ENST00000648696, ENST00000648725, ENST00000648793, ENST00000648828, ENST00000648892, ENST00000648899, ENST00000649006, ENST00000649119, ENST00000649305, ENST00000649375, ENST00000649442, ENST00000649463, ENST00000649645, ENST00000649657, ENST00000650048, ENST00000650232, ENST00000650330, ENST00000650380, ENST00000650434, ENST00000650517, ENST00000650610, ENST00000912234, ENST00000912235, ENST00000912236, ENST00000912237, ENST00000912238, ENST00000912239, ENST00000965830

RefSeq mRNA: 15 — MANE Select: NM_012330 NM_001256468, NM_001256469, NM_001370132, NM_001370133, NM_001370134, NM_001370136, NM_001370137, NM_001370138, NM_001370139, NM_001370140, NM_001370141, NM_001370142, NM_001370143, NM_001370144, NM_012330

CCDS: CCDS58084, CCDS58085, CCDS7345

Canonical transcript exons

ENST00000287239 — 18 exons

Exon	Start	End
ENSE00001027660	74981787	74981928
ENSE00001027663	74970020	74970101
ENSE00001027683	74972507	74972639
ENSE00001167091	74975399	74976330
ENSE00001167112	74969660	74969775
ENSE00001167118	74959970	74960078
ENSE00001167134	74842600	74843478
ENSE00001247860	74838683	74838752
ENSE00001247904	74977316	74977437
ENSE00001247937	75024958	75025249
ENSE00001458462	74826600	74826785
ENSE00001752953	74985080	74985241
ENSE00003513304	75021881	75022231
ENSE00003586140	75021126	75021285
ENSE00003615279	74979224	74979339
ENSE00003619546	74989019	74989112
ENSE00003692045	75020582	75020813
ENSE00003834914	75028489	75032624

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 94.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.6952 / max 162.9676, expressed in 1766 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105601	7.3065	1685
105600	1.8837	1021
105597	1.6591	861
105598	0.9407	501
105596	0.4044	217
205905	0.3033	135
105599	0.1975	80

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	94.75	gold quality
ventricular zone	UBERON:0003053	93.94	gold quality
sural nerve	UBERON:0015488	93.48	gold quality
bone marrow cell	CL:0002092	93.18	gold quality
corpus callosum	UBERON:0002336	93.00	gold quality
embryo	UBERON:0000922	92.58	gold quality
ganglionic eminence	UBERON:0004023	92.58	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.09	gold quality
colonic epithelium	UBERON:0000397	89.68	gold quality
bone marrow	UBERON:0002371	89.61	gold quality
skeletal muscle tissue	UBERON:0001134	88.01	gold quality
stromal cell of endometrium	CL:0002255	87.60	gold quality
muscle tissue	UBERON:0002385	86.64	gold quality
tonsil	UBERON:0002372	86.58	gold quality
adrenal tissue	UBERON:0018303	86.40	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.23	gold quality
calcaneal tendon	UBERON:0003701	85.87	gold quality
endometrium	UBERON:0001295	85.03	gold quality
urinary bladder	UBERON:0001255	84.19	gold quality
skeletal muscle organ	UBERON:0014892	84.06	gold quality
ovary	UBERON:0000992	83.95	gold quality
smooth muscle tissue	UBERON:0001135	83.93	gold quality
muscle of leg	UBERON:0001383	83.91	gold quality
gastrocnemius	UBERON:0001388	83.71	gold quality
uterine cervix	UBERON:0000002	83.58	gold quality
left ovary	UBERON:0002119	83.57	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.07	gold quality
islet of Langerhans	UBERON:0000006	82.98	gold quality
uterus	UBERON:0000995	82.90	gold quality
popliteal artery	UBERON:0002250	82.66	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.03

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

8 targets.

Target	Regulation
CCL3
FLT3
KAT6B
KDM1B
MYBL2
RUNX2	Activation
SMARCA2
SPP1

Upstream regulators (CollecTRI, top): GLI2, KAT6B, PGR

miRNA regulators (miRDB)

97 targeting KAT6B, 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-340-5P	100.00	72.50	4437
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-129-5P	99.88	70.26	3273
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-6515-3P	99.82	68.19	1933

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• role in regulating interleukin-5 expression (PMID:15271374)
• MORF4 has a role in cellular aging, and MRG15 associates with both histone deacetylases and histone acetyl transferase complexes [review] (PMID:17460191)
• These findings indicate that BRPF proteins play a key role in assembling and activating MOZ/MORF acetyltransferase complexes. (PMID:18794358)
• Data show that H3 acetylation by Myst4 is important for neural, craniofacial, and skeletal morphogenesis, mainly through its ability to specifically regulating the MAPK signaling pathway. (PMID:21804188)
• 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)
• Whole-exome-sequencing identifies mutations in histone acetyltransferase gene KAT6B in individuals with the Say-Barber-Biesecker variant of Ohdo syndrome (PMID:22077973)
• By exome sequencing, we found de novo heterozygous truncating mutations in KAT6B. (PMID:22265014)
• we identified de novo mutations of KAT6B in five individuals with Genitopatellar syndrome. (PMID:22265017)
• Propose that haploinsufficiency or loss of a function mediated by the C-terminal domain causes the common features, whereas gain-of-function activities would explain the features unique to genitopatellar syndrome. Review. (PMID:22715153)
• 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)
• Our results confirm the implication of KAT6B mutations in typical SBBYS syndrome and emphasize the importance of genotype-phenotype correlations at the KAT6B locus. (PMID:23436491)
• MORF double PHD finger binds to Histone H3 in a manner that is enhanced by acetylation of the lysine residues K9 and K14 (PMID:24150941)
• KAT5 and KAT6B regulate prostate cancer cell growth through PI3K-AKT signaling. (PMID:24294372)
• The study showed that markers rs11001178 (MYST4) showed weak associations. (PMID:24444492)
• Similar to those observed in other genetic disorders resulting from KAT6B mutations. (PMID:24458743)
• The relationship between MYO1C and KAT6B suggests that the two are interacting in chromatin remodelling for gene expression in human masseter muscle. This is the nuclear myosin1 (NM1) function of MYO1C. (PMID:24698832)
• KAT6B sequence variants are being reported in the Say-Barber-Biesecker type of blepharophimosis mental retardation syndromes (SBBS) and in the more severe genitopatellar syndrome. (PMID:25424711)
• This study shown MYST4 to be the risk factor for attention deficit/hyperactivity disorder. (PMID:25840828)
• Homozygous deletions of KAT6B and the loss of its mRNA occur in SCLC cell lines and primary tumors. KAT6B loss enhances cancer growth. Restoration induces tumor suppressor-like features involving a new type of histone H3 Lys23 acetyltransferase activity. (PMID:26208904)
• Kat6 c.3147G>A splice site mutation causes Say-Barber-Biesecker/Young-Simpson syndrome by inducing aberrant splicing. (PMID:26334766)
• 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)
• chronic inflammation compromises unfolded protein response function through MORF-mediated-PERK transcription. (PMID:27447113)
• Our findings support that phenotypes associated with typical KAT6B disease-causing variants should be referred to as ‘KAT6B spectrum disorders’ or ‘KAT6B related disorders’, rather than their current SBBYSS and GTPTS classification (PMID:27452416)
• With ptosis, hypotonia, and developmental delay as the main diagnostic features of our patient, the effect of histone acetyltransferase-encoding KAT6B gene haploinsufficiency was suspected to have a significant role in determining the phenotype. (PMID:27880066)
• Study identified the double plant homeodomain finger (DPF) of the lysine acetyltransferase MORF as a reader of global histone H3K14 acylation. (PMID:28286003)
• KAT6B mutation is associated with Craniosynostosis. (PMID:28696035)
• The present report highlights the pivotal role of clinical genetics in avoiding clear-cut genotype-phenotype categories in syndromic forms of intellectual disability. In addition, it further supports the evidence that a continuum exists within the clinical spectrum of KAT6B-associated disorders (PMID:29226580)
• The clinical and genetic characterization of these patients could contribute to the understanding of the KAT6B-related disorders. (PMID:30569622)
• A novel pathogenic frameshift variant of KAT6B identified by clinical exome sequencing in a newborn with the Say-Barber-Biesecker-Young-Simpson syndrome. (PMID:30921092)
• Data indicate that the acetyltransferase function of the catalytic histone acetyltransferase KAT6B (MORF) subunit is positively regulated by the DPF domain of MORF (MORFDPF). (PMID:31624313)
• Further delineation of the clinical spectrum of KAT6B disorders and allelic series of pathogenic variants. (PMID:32424177)
• High methylation of lysine acetyltransferase 6B is associated with the Cobb angle in patients with congenital scoliosis. (PMID:32448279)
• CircKIAA0907 Retards Cell Growth, Cell Cycle, and Autophagy of Gastric Cancer In Vitro and Inhibits Tumorigenesis In Vivo via the miR-452-5p/KAT6B Axis. (PMID:32722658)
• Novel Approach of Mandibular Distraction to Avoid Tracheostomy in KAT6B-related Gene Disorders. (PMID:33136874)
• Low Expression of KAT6B May Affect Prognosis in Hepatocellular Carcinoma. (PMID:34464167)
• Novel variants in KAT6B spectrum of disorders expand our knowledge of clinical manifestations and molecular mechanisms. (PMID:34519438)
• Recurrent KAT6B/A::KANSL1 Fusions Characterize a Potentially Aggressive Uterine Sarcoma Morphologically Overlapping With Low-grade Endometrial Stromal Sarcoma. (PMID:35575789)
• XBP1-elicited environment by chemotherapy potentiates repopulation of tongue cancer cells by enhancing miR-22/lncRNA/KAT6B-dependent NF-kappaB signalling. (PMID:36639835)
• MORF and MOZ acetyltransferases target unmethylated CpG islands through the winged helix domain. (PMID:36754959)
• Clinical features and underlying mechanisms of KAT6B disease in a Chinese boy. (PMID:37288707)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	kat6b	ENSDARG00000055429
mus_musculus	Kat6b	ENSMUSG00000021767
rattus_norvegicus	Kat6b	ENSRNOG00000012850
drosophila_melanogaster	tth	FBGN0030502
drosophila_melanogaster	d4	FBGN0033015
caenorhabditis_elegans		WBGENE00016200

Paralogs (9): DPF1 (ENSG00000011332), RSF1 (ENSG00000048649), KAT6A (ENSG00000083168), KAT8 (ENSG00000103510), PHF10 (ENSG00000130024), DPF2 (ENSG00000133884), KAT7 (ENSG00000136504), KAT5 (ENSG00000172977), DPF3 (ENSG00000205683)

Protein

Protein identifiers

Histone acetyltransferase KAT6B — Q8WYB5 (reviewed: Q8WYB5)

Alternative names: Histone acetyltransferase MOZ2, MOZ, YBF2/SAS3, SAS2 and TIP60 protein 4, Monocytic leukemia zinc finger protein-related factor

All UniProt accessions (22): Q8WYB5, A0A3B3IRI4, A0A3B3IRN9, A0A3B3IRV4, A0A3B3IS73, A0A3B3ISD0, A0A3B3ISD5, A0A3B3ISF5, A0A3B3ISI1, A0A3B3ISW3, A0A3B3ISX5, A0A3B3IT19, A0A3B3IT63, A0A3B3ITA4, A0A3B3ITC3, A0A3B3ITI0, A0A3B3ITP3, A0A3B3ITV5, A0A3B3IU70, A0A3B3IU71, A0A3B3IU93, A0A3B3IUA4

UniProt curated annotations — full annotation on UniProt →

Function. Histone acetyltransferase which may be involved in both positive and negative regulation of transcription. Required for RUNX2-dependent transcriptional activation. May be involved in cerebral cortex development. Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity.

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 and RUNX2.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitously expressed, with high levels in heart, pancreas, testis and ovary.

Post-translational modifications. Autoacetylated. Autoacetylation at Lys-815 is required for proper function.

Disease relevance. A chromosomal aberration involving KAT6B may be a cause acute myeloid leukemias. Translocation t(10;16)(q22;p13) with CREBBP. Ohdo syndrome, SBBYS variant (SBBYSS) [MIM:603736] A syndrome characterized by distinctive facial appearance with severe blepharophimosis, an immobile mask-like face, a bulbous nasal tip, and a small mouth with a thin upper lip. The condition presents in infancy with severe hypotonia and feeding problems. Associated skeletal problems include joint laxity, abnormally long thumbs and great toes, and dislocated or hypoplastic patellae. Structural cardiac defects are present in around 50% of cases, and dental anomalies, including small and pointed teeth, are common. Optic atrophy and conductive or sensorineural deafness are repeatedly reported. Many affected individuals have abnormalities of thyroid structure or function. SBBYSS is usually associated with severe intellectual disability, delayed motor milestones, and significantly impaired speech. The disease is caused by variants affecting the gene represented in this entry. Genitopatellar syndrome (GTPTS) [MIM:606170] A rare disorder consisting of microcephaly, severe psychomotor retardation, and characteristic coarse facial features, including broad nose and small or retracted chin, associated with congenital flexion contractures of the lower extremities, abnormal or missing patellae, and urogenital anomalies. 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.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8WYB5-1	1, Beta	yes
Q8WYB5-2	2, Alpha
Q8WYB5-3	3

RefSeq proteins (15): NP_001243397, NP_001243398, NP_001357061, NP_001357062, NP_001357063, NP_001357065, NP_001357066, NP_001357067, NP_001357068, NP_001357069, NP_001357070, NP_001357071, NP_001357072, NP_001357073, NP_036462* (*=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 (88 total): compositionally biased region 23, region of interest 12, sequence conflict 8, helix 8, modified residue 7, turn 6, strand 5, sequence variant 4, domain 3, zinc finger region 3, binding site 3, splice variant 2, chain 1, active site 1, site 1, cross-link 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5U2J	X-RAY DIFFRACTION	1.6
6OIE	X-RAY DIFFRACTION	2.08
8E4V	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WYB5-F1	49.67	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 (2): 891 (proton donor/acceptor); 1222–1223 (breakpoint for translocation to form kat6b-crebbp)

Ligand- & substrate-binding residues (3): 856–860; 865–871; 895

Post-translational modifications (8): 355, 647, 815, 1038, 1042, 1044, 1048, 673

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-3214847	HATs acetylate histones
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization

MSigDB gene sets: 478 (showing top): BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, GCM_ZNF198, GCM_PPM1D, LHX3_01, CHX10_01, MODULE_66, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_REGULATION_OF_HEMOPOIESIS, NKX62_Q2, BLALOCK_ALZHEIMERS_DISEASE_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, HFH3_01, GCM_SUFU, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_PROTEIN_DNA_COMPLEX_ORGANIZATION

GO Biological Process (11): nucleosome assembly (GO:0006334), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of developmental process (GO:0050793), regulation of hemopoiesis (GO:1903706), chromatin organization (GO:0006325), positive regulation of macromolecule biosynthetic process (GO:0010557), obsolete positive regulation of nucleobase-containing compound metabolic process (GO:0045935)

GO Molecular Function (14): 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), histone H3K14 acetyltransferase activity (GO:0036408), protein-containing complex binding (GO:0044877), protein-lysine-acetyltransferase activity (GO:0061733), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), metal ion binding (GO:0046872)

GO Cellular Component (6): chromatin (GO:0000785), nucleosome (GO:0000786), nucleus (GO:0005634), nucleoplasm (GO:0005654), MOZ/MORF histone acetyltransferase complex (GO:0070776), histone acetyltransferase complex (GO:0000123)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Chromatin organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	3
regulation of DNA-templated transcription	3
binding	3
transcription by RNA polymerase II	2
positive regulation of DNA-templated transcription	2
cellular anatomical structure	2
chromatin	2
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
developmental process	1
regulation of biological process	1
regulation of immune system process	1
hemopoiesis	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
protein-lysine-acetyltransferase activity	1
histone modifying activity	1
transition metal ion binding	1
histone acetyltransferase activity	1
histone H3 acetyltransferase activity	1
protein N-acetyltransferase activity	1
catalytic activity	1
transferase activity	1
cation binding	1
chromosome	1
protein-DNA complex	1

Protein interactions and networks

STRING

2140 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KAT6B	BRPF1	P55201	991
KAT6B	ASXL2	Q76L83	982
KAT6B	ING5	Q8WYH8	974
KAT6B	MEAF6	Q9HAF1	923
KAT6B	ING4	Q9UNL4	817
KAT6B	RUNX2	Q13950	765
KAT6B	H3-3A	P06351	731
KAT6B	H3-4	Q16695	731
KAT6B	H3-7	Q5TEC6	731
KAT6B	H3-5	Q6NXT2	731
KAT6B	H3C14	Q71DI3	731
KAT6B	H3C1	P02295	730
KAT6B	MORF4L1	Q9UBU8	715
KAT6B	RUNX1	Q01196	673
KAT6B	KAT2A	Q92830	657

IntAct

20 interactions, top by confidence:

A	B	Type	Score
BRD1	KAT7	psi-mi:“MI:0914”(association)	0.530
ING4	KAT7	psi-mi:“MI:0914”(association)	0.530
ING5	KAT7	psi-mi:“MI:0914”(association)	0.530
USP7	KAT6B	psi-mi:“MI:0407”(direct interaction)	0.440
HNRNPU	KAT6B	psi-mi:“MI:0915”(physical association)	0.400
KAT6B	CKMT1A	psi-mi:“MI:0915”(physical association)	0.400
KAT6B	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
Bub1	PEX10	psi-mi:“MI:0914”(association)	0.350
SGO1	ELOC	psi-mi:“MI:0914”(association)	0.350
Hdac6	TDG	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
ING5	CCDC85C	psi-mi:“MI:0914”(association)	0.350
MEAF6	KPNA5	psi-mi:“MI:0914”(association)	0.350
BRD1	ZZEF1	psi-mi:“MI:0914”(association)	0.350
KAT6B	ptsI	psi-mi:“MI:0915”(physical association)	0.000
KAT6B		psi-mi:“MI:0915”(physical association)	0.000
ATN1	KAT6B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (54): KAT6B (Biochemical Activity), KAT6B (Affinity Capture-MS), KAT6B (Affinity Capture-MS), KAT6B (Affinity Capture-MS), KAT6B (Affinity Capture-MS), KAT6B (Affinity Capture-RNA), KAT6B (Affinity Capture-MS), KAT6B (Affinity Capture-RNA), RUNX2 (Reconstituted Complex), RUNX2 (Affinity Capture-Western), RUNX2 (Biochemical Activity), RUNX1 (Affinity Capture-Western), KAT6B (Proximity Label-MS), HIST1H2BH (Proximity Label-MS), KAT6B (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8F1M4, A0A8M9QN10, A0JMQ9, A6NIR3, A8DZE6, A8WH69, B2KF05, F1QCY8, O43147, O43900, O54880, P0C6P5, P59729, P97433, Q13009, Q18PD9, Q2NKQ1, Q32L09, Q3U5C7, Q58D79, Q5EB20, Q5PQS0, Q5U464, Q60592, Q6IVY4, Q6P0Q8, Q6ZQF7, Q6ZUJ8, Q71QF9, Q768S4, Q7T2V3, Q7TNN8, Q7TSI1, Q7ZVP1, Q803A0, Q80U12, Q80VL3, Q80Y24, Q8BPQ7, Q8BRB7

Diamond homologs: A1YVX4, A2A8L1, A2AUY4, A2BIL7, A6H619, A7E320, A8DZJ1, A9LMC0, B6CHA3, B7ZS37, B9RU15, C4QVX6, D3ZD32, E7EZF3, F4I240, F4JYC8, F4KE59, F6UA42, G5EBZ4, O43918, O88379, O94400, O97159, P29375, P41229, P41230, P46605, P47156, P48786, P56163, P58268, P58269, P58270, Q04996, Q09477, Q12830, Q12873, Q14839, Q23541, Q23590

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
KAT6B	up-regulates	RUNX2	binding
KAT6B	“form complex”	KAT6A/KAT6B	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 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
HATs acetylate histones	7	34.7×	7e-08

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 5 cancer types — BRCA, LGGNOS, MBL, NPC, PRAD.

Clinical variants and AI predictions

ClinVar

1780 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	114
Likely pathogenic	54
Uncertain significance	772
Likely benign	532
Benign	80

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027387	NM_012330.4(KAT6B):c.3906del (p.Ser1303fs)	Pathogenic
1033226	NM_012330.4(KAT6B):c.3428del (p.Ser1143fs)	Pathogenic
1064762	NM_012330.4(KAT6B):c.5058C>A (p.Tyr1686Ter)	Pathogenic
1065489	NM_012330.4(KAT6B):c.3995del (p.Pro1332fs)	Pathogenic
1069369	NM_012330.4(KAT6B):c.5409del (p.Phe1803fs)	Pathogenic
1070400	NM_012330.4(KAT6B):c.3987_3988del (p.Ala1331fs)	Pathogenic
1186640	NM_012330.4(KAT6B):c.3974_3987del (p.Arg1325fs)	Pathogenic
1215378	NM_012330.4(KAT6B):c.3040C>T (p.Gln1014Ter)	Pathogenic
1301894	NM_012330.4(KAT6B):c.5040C>G (p.Tyr1680Ter)	Pathogenic
1308647	NM_012330.4(KAT6B):c.4461_4470del (p.Ser1487fs)	Pathogenic
1323135	NM_012330.4(KAT6B):c.3295_3298del (p.Glu1099fs)	Pathogenic
1335042	NM_012330.4(KAT6B):c.3217G>T (p.Glu1073Ter)	Pathogenic
1342293	NM_012330.4(KAT6B):c.4572_4573dup (p.Thr1525fs)	Pathogenic
140470	NM_012330.3(KAT6B):c.3681_3696del16 (p.Asp1227Glufs)	Pathogenic
140472	NM_012330.4(KAT6B):c.3788_3789del (p.Lys1263fs)	Pathogenic
140474	NM_012330.4(KAT6B):c.4360_4368delinsAAAAACCAAAA (p.Glu1454fs)	Pathogenic
1679292	NM_012330.4(KAT6B):c.3665-1G>C	Pathogenic
1690359	NM_012330.4(KAT6B):c.4231G>T (p.Glu1411Ter)	Pathogenic
1698807	NM_012330.4(KAT6B):c.1993+1G>A	Pathogenic
1806175	NM_012330.4(KAT6B):c.5356G>T (p.Glu1786Ter)	Pathogenic
1879151	GRCh37/hg19 10q22.2(chr10:76780340-76781989)x1	Pathogenic
1993834	NM_012330.4(KAT6B):c.4528del (p.Glu1510fs)	Pathogenic
208700	NM_012330.4(KAT6B):c.4102dup (p.Glu1368fs)	Pathogenic
2091875	NM_012330.4(KAT6B):c.5146_5147del (p.Gln1716fs)	Pathogenic
2112300	NM_012330.4(KAT6B):c.3856C>T (p.Gln1286Ter)	Pathogenic
2123423	NM_012330.4(KAT6B):c.3169dup (p.Glu1057fs)	Pathogenic
2134903	NM_012330.4(KAT6B):c.5461C>T (p.Gln1821Ter)	Pathogenic
2229134	NM_012330.4(KAT6B):c.3373-2A>C	Pathogenic
2231535	NM_012330.4(KAT6B):c.2616del (p.Leu873fs)	Pathogenic
225094	NM_012330.4(KAT6B):c.3264dup (p.Glu1089fs)	Pathogenic

SpliceAI

3212 predictions. Top by Δscore:

Variant	Effect	Δscore
10:74838735:TTTG:T	donor_gain	1.0000
10:74842598:A:G	acceptor_gain	1.0000
10:74959962:T:TA	acceptor_gain	1.0000
10:74959967:T:G	acceptor_gain	1.0000
10:74959967:TA:T	acceptor_loss	1.0000
10:74959968:A:AG	acceptor_gain	1.0000
10:74959969:G:GG	acceptor_gain	1.0000
10:74959969:GC:G	acceptor_gain	1.0000
10:74959969:GCC:G	acceptor_gain	1.0000
10:74959969:GCCCC:G	acceptor_gain	1.0000
10:74960074:TAGTG:T	donor_gain	1.0000
10:74960076:GTG:G	donor_gain	1.0000
10:74960076:GTGGT:G	donor_loss	1.0000
10:74960079:G:GG	donor_gain	1.0000
10:74960080:T:TC	donor_loss	1.0000
10:74972637:GTT:G	donor_gain	1.0000
10:74972640:G:GG	donor_gain	1.0000
10:74989113:G:GG	donor_gain	1.0000
10:75020809:GGCAG:G	donor_gain	1.0000
10:75020810:GCAG:G	donor_gain	1.0000
10:75020810:GCAGG:G	donor_gain	1.0000
10:75020811:CAGGT:C	donor_loss	1.0000
10:75020812:AGGT:A	donor_loss	1.0000
10:75020814:G:GG	donor_gain	1.0000
10:75020814:GTGA:G	donor_loss	1.0000
10:75020815:T:A	donor_loss	1.0000
10:75021117:A:AG	acceptor_gain	1.0000
10:75021118:C:G	acceptor_gain	1.0000
10:75021119:A:AG	acceptor_gain	1.0000
10:75021121:TACA:T	acceptor_loss	1.0000

AlphaMissense

13811 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:74842964:T:A	V36D	1.000
10:74843176:T:A	W107R	1.000
10:74843176:T:C	W107R	1.000
10:74959994:T:A	C216S	1.000
10:74959994:T:C	C216R	1.000
10:74959995:G:A	C216Y	1.000
10:74959995:G:C	C216S	1.000
10:74959995:G:T	C216F	1.000
10:74959996:T:G	C216W	1.000
10:74960003:T:A	C219S	1.000
10:74960003:T:C	C219R	1.000
10:74960003:T:G	C219G	1.000
10:74960004:G:A	C219Y	1.000
10:74960004:G:C	C219S	1.000
10:74960005:T:G	C219W	1.000
10:74960009:G:T	G221W	1.000
10:74960049:T:C	L234P	1.000
10:74960057:T:A	C237S	1.000
10:74960057:T:C	C237R	1.000
10:74960058:G:A	C237Y	1.000
10:74960058:G:C	C237S	1.000
10:74960059:T:G	C237W	1.000
10:74960066:T:C	C240R	1.000
10:74960067:G:A	C240Y	1.000
10:74960068:T:G	C240W	1.000
10:74969671:T:C	C248R	1.000
10:74969672:G:A	C248Y	1.000
10:74969673:T:G	C248W	1.000
10:74969719:T:A	W264R	1.000
10:74969719:T:C	W264R	1.000

dbSNP variants (sampled 300 via entrez): RS1000000054 (10:74869360 C>T), RS1000006939 (10:74836706 T>A), RS1000011752 (10:74840034 C>T), RS1000013505 (10:75015354 C>T), RS1000033534 (10:74939569 T>G), RS1000043184 (10:74978417 G>A), RS1000067821 (10:75015014 C>T), RS1000079833 (10:74838253 C>G,T), RS1000092463 (10:74987402 C>G), RS1000140450 (10:74983984 T>C), RS1000149912 (10:74828718 C>T), RS1000154223 (10:74876193 G>A,C,T), RS1000158833 (10:74978701 G>A), RS1000163328 (10:74935909 G>A,C), RS1000168156 (10:74930876 A>G)

Disease associations

OMIM: gene MIM:605880 | disease phenotypes: MIM:606170, MIM:603736, MIM:175780, MIM:607595, MIM:180000, MIM:611773, MIM:618564, MIM:614519, MIM:300633, MIM:610805, MIM:604169, MIM:123100, MIM:156200, MIM:600512, MIM:187350, MIM:119800, MIM:219050, MIM:148050, MIM:256100

GenCC curated gene-disease

Disease	Classification	Inheritance
blepharophimosis - intellectual disability syndrome, SBBYS type	Definitive	Autosomal dominant
genitopatellar syndrome	Definitive	Autosomal dominant
KAT6B-related multiple congenital anomalies syndrome	Strong	Autosomal dominant
RASopathy	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
KAT6B-related multiple congenital anomalies syndrome	Definitive	AD
RASopathy	Disputed	AD

Mondo (27): genitopatellar syndrome (MONDO:0011640), blepharophimosis - intellectual disability syndrome, SBBYS type (MONDO:0011365), neurodevelopmental disorder (MONDO:0700092), brain small vessel disease 1 with or without ocular anomalies (MONDO:0008289), retinal arterial tortuosity (MONDO:0008373), autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome (MONDO:0012726), microangiopathy and leukoencephalopathy, pontine, autosomal dominant (MONDO:0032814), hemorrhage, intracerebral, susceptibility to (MONDO:0100533), hypospadias (MONDO:0005345), congenital anomaly of kidney and urinary tract (MONDO:0019719), obesity disorder (MONDO:0011122), intellectual disability (MONDO:0001071), left ventricular noncompaction (MONDO:0018901), TWIST1-related craniosynostosis (MONDO:0007399), intellectual disability, autosomal dominant (MONDO:0100172)

Orphanet (23): Genitopatellar syndrome (Orphanet:85201), Blepharophimosis-intellectual disability syndrome, SBBYS type (Orphanet:3047), Porencephaly (Orphanet:2940), COL4A1/2-related familial vascular leukoencephalopathy (Orphanet:36383), Pontine autosomal dominant microangiopathy with leukoencephalopathy (Orphanet:477749), HANAC syndrome (Orphanet:73229), Familial isolated retinal arteriolar tortuosity (Orphanet:75326), Familial porencephaly (Orphanet:99810), Renal or urinary tract malformation (Orphanet:93545), Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), Left ventricular noncompaction (Orphanet:54260), OBSOLETE: Isolated oxycephaly (Orphanet:63440), Epilepsy with auditory features (Orphanet:101046), KAT6B-related multiple congenital anomalies syndrome (Orphanet:597749), Ependymoma (Orphanet:251636)

HPO phenotypes

106 total (30 of 106 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000046	Small scrotum
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000066	Labial hypoplasia
HP:0000126	Hydronephrosis
HP:0000175	Cleft palate
HP:0000176	Submucous cleft hard palate
HP:0000193	Bifid uvula
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000269	Prominent occiput
HP:0000278	Retrognathia
HP:0000280	Coarse facial features
HP:0000316	Hypertelorism
HP:0000340	Sloping forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000414	Bulbous nose
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000445	Wide nose
HP:0000448	Prominent nose
HP:0000494	Downslanted palpebral fissures
HP:0000537	Epicanthus inversus

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010796_910	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST010796_911	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST012490_635	Femur bone mineral density x serum urate levels interaction	4.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004327	electrocardiography
EFO:0004531	urate measurement

MeSH disease descriptors (15)

Descriptor	Name	Tree numbers
D016569	Blepharophimosis	C11.250.090; C11.338.190; C16.131.384.190
D003025	Clubfoot	C05.330.488.655.063; C05.330.495.681.063; C05.660.585.512.380.813.063; C16.131.621.585.512.500.681.063
D003456	Cryptorchidism	C12.100.500.829.258; C12.200.294.829.258; C12.200.706.258; C12.800.258; C16.131.939.258; C19.391.829.258
D004806	Ependymoma	C04.557.465.625.600.380.290; C04.557.470.670.380.290; C04.557.580.625.600.380.290
D007021	Hypospadias	C12.050.351.875.466; C12.100.500.494.400; C12.200.294.494.400; C12.200.706.516; C12.800.516; C16.131.939.516
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
D014718	Vesico-Ureteral Reflux	C12.050.351.968.829.920; C12.200.777.829.920; C12.950.829.920
C567088	Angiopathy, Hereditary, With Nephropathy, Aneurysms, And Muscle Cramps (supp.)
C566906	Cakut (supp.)
C531642	Familial vascular leukoencephalopathy (supp.)
C565255	Genitopatellar Syndrome (supp.)
C537015	KBG syndrome (supp.)
C562941	Telecanthus (supp.)
C536717	Young Simpson syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3774300 (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 (2 total), top 2:

Ligand	Action	Affinity	Parameter
PF-9363	Inhibition	8.62	pIC50
prifetrastat	Inhibition	8.38	pKi

Binding affinities (BindingDB)

54 measured of 54 human assays (122 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
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
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
6-(Dimethylamino)-N-((2-ethoxyphenyl)sulfonyl)-4-(trifluoromethyl)benzofuran-2-carboxamide	IC50	5.73 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
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
US12357603, Example 129	IC50	13.5 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 134	IC50	30.7 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 83	IC50	48.8 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
US12357603, Example 87	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
US12357603, Example 93	IC50	100 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 148	IC50	104 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 88	IC50	105 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 223	IC50	106 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 114	IC50	114 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 226	IC50	114 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 85	IC50	115 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 149	IC50	123 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 89	IC50	131 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 132	IC50	134 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 142	IC50	139 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 121	IC50	179 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 119	IC50	185 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 90	IC50	194 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 144	IC50	226 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 123	IC50	275 nM	US-12357603: Acyl sulfonamides for treating cancer
US12357603, Example 117	IC50	294 nM	US-12357603: Acyl sulfonamides for treating cancer

ChEMBL bioactivities

100 potent at pChembl≥5 of 102 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.59	Ki	0.26	nM	CHEMBL5928174
9.44	Ki	0.36	nM	CHEMBL6063716
9.38	Ki	0.42	nM	CHEMBL5723326
9.32	Ki	0.48	nM	CHEMBL5815468
9.22	Ki	0.6	nM	CHEMBL5993180
9.17	Ki	0.68	nM	CHEMBL5852195
9.06	Ki	0.87	nM	CHEMBL5785798
9.05	Ki	0.89	nM	CHEMBL5792567
9.02	Ki	0.96	nM	CHEMBL5886450
9.01	Ki	0.98	nM	CHEMBL5853409
8.98	Ki	1.05	nM	CHEMBL5959733
8.94	Ki	1.14	nM	CHEMBL5852195
8.94	Ki	1.14	nM	CHEMBL5924783
8.92	Ki	1.21	nM	CHEMBL5818085
8.92	Ki	1.2	nM	CHEMBL5996948
8.92	Ki	1.2	nM	CHEMBL5853561
8.91	Ki	1.23	nM	CHEMBL5723326
8.89	Ki	1.3	nM	CHEMBL5723326
8.88	Ki	1.32	nM	CHEMBL5883288
8.87	Ki	1.34	nM	CHEMBL5785798
8.87	Ki	1.36	nM	CHEMBL5860247
8.86	Ki	1.38	nM	CHEMBL5723326
8.85	Ki	1.4	nM	CHEMBL5998930
8.81	Ki	1.55	nM	CHEMBL5723326
8.81	Ki	1.55	nM	CHEMBL5963038
8.81	Ki	1.56	nM	CHEMBL5941367
8.79	Ki	1.63	nM	CHEMBL5723326
8.76	Ki	1.73	nM	CHEMBL6057979
8.75	Ki	1.78	nM	CHEMBL5927368
8.73	Ki	1.88	nM	CHEMBL5847041
8.72	Ki	1.89	nM	CHEMBL5812221
8.72	Ki	1.9	nM	CHEMBL5792825
8.70	Ki	2	nM	CHEMBL5908760
8.68	Ki	2.1	nM	CHEMBL5947618
8.68	Ki	2.11	nM	CHEMBL5963038
8.67	Ki	2.14	nM	CHEMBL5847041
8.64	Ki	2.27	nM	CHEMBL6005999
8.63	Ki	2.33	nM	CHEMBL5996948
8.62	Ki	2.4	nM	CHEMBL5723326
8.62	Ki	2.39	nM	CHEMBL6005841
8.60	Ki	2.5	nM	CHEMBL5871508
8.60	Ki	2.5	nM	CHEMBL5759534
8.57	Ki	2.68	nM	CHEMBL5857566
8.56	Ki	2.73	nM	CHEMBL5955544
8.56	Ki	2.74	nM	CHEMBL5867166
8.55	Ki	2.81	nM	CHEMBL5830107
8.55	Ki	2.82	nM	CHEMBL5723326
8.54	Ki	2.9	nM	CHEMBL5760697
8.46	Ki	3.44	nM	CHEMBL5993009
8.44	Ki	3.67	nM	CHEMBL6008690

PubChem BioAssay actives

5 with measured affinity, of 17 total; 4 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
N’-(benzenesulfonyl)-2-fluoro-3-methyl-5-phenylbenzohydrazide	1576688: Inhibition of N-terminal GST-tagged recombinant human KAT6B (431 to end residues) expressed in baculovirus infected Sf9 insect cells using acetyl coenzyme A and N-terminal histone H4 peptide (sequence SGRGKGGKGLGKGGAKRHRKV-GGK-biotin) as substrate incubated for 60 mins by Alpha screen technology	ic50	0.0280	uM
2-fluoro-N’-naphthalen-2-ylsulfonylbenzohydrazide	2138650: Inhibition of full length recombinant human KAT6B catalytic domain using H4 peptide and [3H]-acetyl-coA as substrate incubated for 1 hr by liquid scintillation counter analysis	ic50	0.6900	uM
4-[(4Z)-4-[[5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl]methylidene]-3-methyl-5-oxopyrazol-1-yl]benzoic acid	1989067: Inhibition of recombinant human KAT6B (657 to 1069 residues) using histone H4 peptide and [3H]-acetyl-coA as substrates incubated for 1 hrs by liquid scintillation counter analysis	ic50	5.6000	uM
N-[2-(2-fluorophenyl)-2-oxoethyl]quinoline-8-sulfonamide	2138650: Inhibition of full length recombinant human KAT6B catalytic domain using H4 peptide and [3H]-acetyl-coA as substrate incubated for 1 hr by liquid scintillation counter analysis	ic50	8.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression, affects expression	5
trichostatin A	affects cotreatment, decreases expression	4
bisphenol A	affects cotreatment, decreases methylation, increases expression	2
Arsenic Trioxide	decreases expression, increases expression	2
Vehicle Emissions	decreases expression, increases abundance	2
Benzo(a)pyrene	increases mutagenesis, affects methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
chloroacetaldehyde	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
bleomycetin	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
adefovir dipivoxil	decreases expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1

ChEMBL screening assays

22 unique, capped per target: 20 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3779404	Binding	Inhibition of MORF (unknown origin) using N-terminal histone H3 substrate at 100 uM by fluorescence assay in presence of [3H]acetyl-CoA relative to control	KATching-Up on Small Molecule Modulators of Lysine Acetyltransferases. — J Med Chem
CHEMBL5210051	Functional	Affinity Phenotypic Cellular interaction (Growth inhibition assays in EMRK1184 lymphoma cells) EUB0000329a MYST4	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomics Library wave 3

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_D6PT	KMUGMCi008-A	Induced pluripotent stem cell	Male
CVCL_ST92	HAP1 KAT6B (-) 1	Cancer cell line	Male
CVCL_XP90	HAP1 KAT6B (-) 2	Cancer cell line	Male
CVCL_XP91	HAP1 KAT6B (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

309 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,
NCT02848157	PHASE4	COMPLETED	Effects of Dexmedetomidine as Adjunct to Pudendal Block for Pediatric Penile Surgery
NCT02861950	PHASE4	COMPLETED	Does Caudal Block Increase the Incidence of Urethrocutaneous Fistula Formation Following Hypospadias Repair in Infants?
NCT03902249	PHASE4	COMPLETED	Effect of Intravenous Dexamethasone With Pudendal Nerve Block on Postoperative Pain in Pediatric Hypospadias Repair
NCT05708989	PHASE4	WITHDRAWN	Caudal vs. Pudendal Block in Peds GU
NCT05837000	PHASE4	UNKNOWN	Dexmedetomidine, Ketamine and Magnesium Sulphate in Caudal Block for Hypospadias Repair
NCT05922605	PHASE4	UNKNOWN	Analgesic Effects of Caudal S-ketamine for Supplementation of Ropivacaine Caudal Analgesia in Children With Hypospadias
NCT07121764	PHASE4	COMPLETED	Postoperative Pain Relief in Children: Comparing Caudal Bupivacaine Alone Versus Bupivacaine With Dexmedetomidine for Infra-Umbilical Surgeries Under General Anesthesia
NCT07240649	PHASE4	NOT_YET_RECRUITING	Outcomes From Hyperbaric Oxygen (HBO2) Treatment for Emerging Indications
NCT00076362	PHASE4	COMPLETED	Pediatric Hypothalamic Obesity
NCT00079547	PHASE4	COMPLETED	The Safety and Effectiveness of Low and High Carbohydrate Diets
NCT00115063	PHASE4	TERMINATED	LOSS- Louisiana Obese Subjects Study
NCT00134303	PHASE4	COMPLETED	Trial Comparing Metformin Versus Placebo in Non Alcoholic Steatohepatitis (NASH) Patients Receiving Bariatric Surgery for Obesity
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
NCT01370798	PHASE3	COMPLETED	Local Oestrogen Versus Placebo as Preoperative Treatment in Patients With Severe Hypospadias: Effects on Post-operative Complications
NCT04423107	PHASE3	UNKNOWN	Assessment of Postop Hypospadias Pain
NCT04826484	PHASE3	TERMINATED	Opioid Reduction Initiative During Outpatient Pediatric Urologic Procedures Using Exparel
NCT07197203	PHASE3	NOT_YET_RECRUITING	Comparison of Caudal Block and Sacral Erector Spinae Plane Block With Dexmedetomidine in Pediatric Penile Hypospadias Repair
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
NCT05253456	PHASE2	COMPLETED	Modified Second Layer Repair for Distal Penile Hypospadias
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
NCT04479371	PHASE1	WITHDRAWN	Liposomal Bupivacaine vs Standard Penile Block for Hypospadias Repair
NCT04115345	PHASE1	COMPLETED	A Study of a Renal Autologous Cell Therapy (REACT) in Patients With Chronic Kidney Disease (CKD) From Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).
NCT05694169	PHASE1	TERMINATED	A Study of Participants With Chronic Kidney Disease Previously Treated With REACT
NCT04888936	Not specified	RECRUITING	Clinical, Genetic, and Epidemiologic Study of Children and Adults With RASopathies
NCT05761314	Not specified	RECRUITING	Solid Tumors in RASopathies
NCT06331117	Not specified	UNKNOWN	Effect of RAS/MAPK Pathway Hyperactivation on Growth’ and Bone’ Profile of the RASopathies
NCT06355622	Not specified	UNKNOWN	Prevalence and Characterization of Pain in RASopathies
NCT06489067	Not specified	RECRUITING	Study of the Thyroid Function and Echostructural Morphology in Patients Affected With Rasopathies (ECORAS2023)
NCT06776380	Not specified	RECRUITING	Pubertal Development in Patients with RASopathies
NCT07005297	Not specified	NOT_YET_RECRUITING	Clinical Genetics Branch Eligibility Screening Survey
NCT07344480	Not specified	RECRUITING	Retrospective Natural History Study of RASopathy-associated Cardiomyopathy (RAS-CM)