KDM6B

Summary

KDM6B (lysine demethylase 6B, HGNC:29012) is a protein-coding gene on chromosome 17p13.1, encoding Lysine-specific demethylase 6B (O15054). Histone demethylase that specifically demethylates ‘Lys-27’ of histone H3, thereby playing a central role in histone code. It is haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is a lysine-specific demethylase that specifically demethylates di- or tri-methylated lysine 27 of histone H3 (H3K27me2 or H3K27me3). H3K27 trimethylation is a repressive epigenetic mark controlling chromatin organization and gene silencing. This protein can also demethylate non-histone proteins such as retinoblastoma protein. Through its demethylation actvity this gene influences cellular differentiation and development, tumorigenesis, inflammatory diseases, and neurodegenerative diseases. This protein has two classical nuclear localization signals at its N-terminus. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 23135 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic intellectual disability (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 20
• Clinical variants (ClinVar): 827 total — 40 pathogenic, 66 likely-pathogenic
• Phenotypes (HPO): 233
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001348716

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29012
Approved symbol	KDM6B
Name	lysine demethylase 6B
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0346
Ensembl gene	ENSG00000132510
Ensembl biotype	protein_coding
OMIM	611577
Entrez	23135

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000254846, ENST00000448097, ENST00000570632, ENST00000571047, ENST00000572030, ENST00000575521, ENST00000911119, ENST00000911120, ENST00000911121, ENST00000911122, ENST00000911123

RefSeq mRNA: 2 — MANE Select: NM_001348716 NM_001080424, NM_001348716

CCDS: CCDS32552, CCDS86569

Canonical transcript exons

ENST00000448097 — 24 exons

Exon	Start	End
ENSE00000887429	7851478	7851549
ENSE00001289989	7852149	7852336
ENSE00001293941	7847105	7847452
ENSE00001294435	7850072	7850177
ENSE00001295161	7846579	7846740
ENSE00001295739	7847546	7849728
ENSE00001306662	7851648	7851796
ENSE00001308149	7851330	7851394
ENSE00001309512	7846819	7847016
ENSE00001313998	7851021	7851226
ENSE00001314215	7852495	7852636
ENSE00001315243	7849821	7849947
ENSE00001315814	7851951	7852065
ENSE00001316366	7846400	7846492
ENSE00001318065	7845872	7845970
ENSE00001322499	7846078	7846297
ENSE00001323896	7845550	7845691
ENSE00001325570	7853000	7853126
ENSE00001484745	7845314	7845456
ENSE00001484746	7844901	7845020
ENSE00001696731	7853498	7854796
ENSE00001728005	7853210	7853380
ENSE00002631634	7839906	7840024
ENSE00003910961	7834217	7834350

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 93.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.6285 / max 1233.8442, expressed in 1689 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159369	10.7530	858
159366	2.6146	1020
159336	2.3369	846
159371	1.5707	160
159370	1.2540	204
159337	1.1259	193
159367	0.9749	504
159372	0.6801	182
159365	0.5686	263
159368	0.3700	187

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	93.98	gold quality
sural nerve	UBERON:0015488	92.74	gold quality
cortical plate	UBERON:0005343	92.61	gold quality
granulocyte	CL:0000094	92.34	gold quality
colonic epithelium	UBERON:0000397	91.61	gold quality
ileal mucosa	UBERON:0000331	90.65	gold quality
left ovary	UBERON:0002119	90.51	gold quality
right ovary	UBERON:0002118	90.23	gold quality
ganglionic eminence	UBERON:0004023	89.94	gold quality
adenohypophysis	UBERON:0002196	89.89	gold quality
left uterine tube	UBERON:0001303	89.67	gold quality
leukocyte	CL:0000738	88.93	gold quality
monocyte	CL:0000576	88.91	gold quality
mononuclear cell	CL:0000842	88.84	gold quality
pituitary gland	UBERON:0000007	88.77	gold quality
vermiform appendix	UBERON:0001154	88.61	gold quality
omental fat pad	UBERON:0010414	88.41	gold quality
bone marrow cell	CL:0002092	88.38	gold quality
peritoneum	UBERON:0002358	88.36	gold quality
upper lobe of left lung	UBERON:0008952	87.88	gold quality
buccal mucosa cell	CL:0002336	87.72	gold quality
right lung	UBERON:0002167	87.64	gold quality
ovary	UBERON:0000992	87.51	gold quality
gall bladder	UBERON:0002110	87.45	gold quality
body of stomach	UBERON:0001161	87.44	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.43	gold quality
adipose tissue of abdominal region	UBERON:0007808	87.32	gold quality
upper lobe of lung	UBERON:0008948	87.29	gold quality
periodontal ligament	UBERON:0008266	87.21	gold quality
decidua	UBERON:0002450	87.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
IRF4	Activation
MIXL1	Activation
TBXT	Activation

Upstream regulators (CollecTRI, top): ASCL1, ATF4, CEBPG, EED, EOMES, EPAS1, EZH2, HES1, HIF1A, MBD2, NFATC1, SNAI1, SP7, STAT1, STAT3, STAT6, SUZ12, TCF23, TP53

miRNA regulators (miRDB)

83 targeting KDM6B, 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-4481	100.00	66.42	1669
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-3202	99.66	67.70	2737

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• the human JmjC-domain-containing proteins UTX and JMJD3 demethylate tri-methylated Lys 27 on histone H3 (PMID:17713478)
• JMJD3 was identified as a demethylase capable of removing the trimethyl group from histone H3 lysine 27 and upregulated in prostate cancer. (PMID:17923864)
• JMJD3 demethylates di- and trimethylated lysine 27 of histone H3 in vitro and in cells. (PMID:18003914)
• These results indicate that epigenetic derepression by JMJD3 controls mammalian epidermal differentiation. (PMID:18628393)
• JMJD3 expression is induced upon activation of the RAS-RAF signaling pathway (PMID:19451217)
• The role of the H3K27 demethylases Jmjd3 and UTX in gene expression, is discussed. (PMID:21209387)
• KDM6B may have a role in antigen-driven B-cell differentiation. (PMID:21242977)
• KDM6A- and KDM6B-responsive Homeobox genes are expressed at significantly higher levels, suggesting that HPV16 E7 results in reprogramming of host epithelial cells (PMID:21245294)
• H3K27 demethylation by JMJD3 at a poised enhancer of anti-apoptotic gene BCL2 determines ERalpha ligand dependency (PMID:21841772)
• An epigenetic gene coding for a histone demethylase such as JMJD3 is a VDR co-target that partially mediates the effects of 1,25(OH)(2)D(3) on human colon. (PMID:21890490)
• loss of BTG3 in normal cells induced cellular senescence, which was correlated with enhanced ERK-AP1 signaling and elevated expression of the histone H3K27me3 demethylase JMJD3/KDM6B (PMID:22020331)
• Knockdown of JMJD3 in THP-1 cells affected expression of key genes in NF-kappaB, chemokine and CD40 signalling. (PMID:22252741)
• PAN RNA interacts with demethylases JMJD3 and UTX, and the histone methyltransferase MLL2 (PMID:22589717)
• JMJD3 activates bivalent gene transcription by demethylating H3K27me3 and promoting transcriptional elongation. (PMID:22713873)
• The histone demethylases KDM4B and KDM6B play critical roles in osteogenic commitment of mesenchymal stem/stromal cells. (PMID:22770241)
• neurogenesis is promoted by an interplay between the TGFbeta pathway, Smad3, and the H3K27me3 histone demethylase (HDM) JMJD3 (PMID:22782721)
• KDM6B contributes to the activation of WNT3 and DKK1 at different differentiation stages when WNT3 and DKK1 are required for mesendoderm and definitive endoderm differentiation. (PMID:22907667)
• These data demonstrate a novel role of H3 Lys27 histone methylation in fibrosis in systemic sclerosis. (PMID:22915621)
• ATF4-dependent regulation of the JMJD3 gene during amino acid deprivation can be rescued in Atf4-deficient cells by inhibition of deacetylation. (PMID:22955275)
• Overexpression of KDM6B induced the expression of mesenchymal genes and promoted epithelial-mesenchymal transition. (PMID:23152497)
• Deregulation of JMJD3 may contribute to gliomagenesis via inhibition of the p53 pathway resulting in a block to terminal differentiation. (PMID:23236496)
• Overexpression of JMJD3 is associated with myelodysplastic syndrome. (PMID:23538751)
• Data suggest that the suppression of different key inflammatory regulators through JMJD3-attenuation would evaluate potential therapeutic targets and to elucidate the molecular mechanism of JMJD3-knockdown (KD) dependent effects in THP-1 cells. (PMID:23711388)
• results demonstrated critical role of histone demethylase in epigenetic regulation of odontogenic differentiation of dental MSCs. KDM6B may present potential therapeutic target in regeneration of tooth structures and repair of craniofacial defects. (PMID:24158144)
• Studies indicate that Jmjd3 is able to enhance the polarization of M2 microglia by modifying histone H3K27me3, and it has a pivotal role in the switch of microglia phenotypes that may contribute to the immune pathogenesis of PD. (PMID:24212761)
• Histone demethylase Jmjd3 is required for the development of subsets of retinal bipolar cells. (PMID:24572572)
• Subcellular localization of Jmjd3 is dynamically regulated and has pivotal roles for H3K27me3 status. (PMID:24646476)
• JMJD3 promotes osteogenesis in differentiating human mesenchymal stem cells, with MIR146A regulating JMJD3. (PMID:24726732)
• JMJD3 is recruited to p53 responsive elements via its interaction with p53 and therefore could act as a fail-safe mechanism to remove low levels of H3K27me3 and H3K27me2 to allow for efficient acetylation of H3K27. (PMID:24797517)
• JMJD3 at the nexus of epigenetic regulation of inflammation and the aging process (PMID:24925089)
• our results propose a significant role for the KDM6B-C/EBPalpha axis in the pancreatic ductal adenocarcinoma phenotype. (PMID:24947179)
• demonstrated that miR-941 and KDM6B regulated the epithelial-mesenchymal transition process and affected cell migratory/invasive properties (PMID:25049231)
• Incubation of nickel chloride upregulated the expression of H3K27me3 demethylase jumonji domain-containing protein 3 (JMJD3) in kidney cancer cells, which was accompanied by the reduction in the protein level of H3K27me3. Enhanced demethylation of H3K27me3 may represent a novel mechanism underlying the carcinogenicity of nickel compounds. (PMID:25427687)
• KDM6B is a new hypoxia response gene regulated by HIF-2alpha (PMID:25520177)
• Results show that JMJD3 protein is overexpressed in high-grade glioma cells and correlated with dysfunctional activation of senescence-related processes, including proinflammatory cytokines and stem cell tropism toward tumors. (PMID:25652587)
• JMJD3 promotes SAHF formation by demethylating RB at K810, which reduce the level of phosphorylation of RB protein at S807/811, and this interplay promotes the formation of senescence-associated heterochromatin foci in senescent WI38 cells. (PMID:25698448)
• Data indicate a reverse correlation between the mRNA levels of histone H3 lysine-27 demethylase (JMJD3) and global histone h3 lysine 27 methylation (H3K27me3). (PMID:25791244)
• Demethylation of IGFBP5 by Histone Demethylase KDM6B Promotes Mesenchymal Stem Cell-Mediated Periodontal Tissue Regeneration by Enhancing Osteogenic Differentiation and Anti-Inflammation Potentials. (PMID:25827480)
• JMJD3 is an epigenetic regulator in development and disease. (Review) (PMID:26193001)
• binding of SMAD2/3, the intracellular effectors of activin signaling, was significantly enriched at the Pmepa1 gene, which encodes a negative feedback regulator of TGF-beta signaling in cancer cells, and at the Kdm6b gene, which encodes an epigenetic regulator promoting transcriptional plasticity. (PMID:26215835)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	kdm6bb	ENSDARG00000056929
danio_rerio	kdm6ba	ENSDARG00000088087
mus_musculus	Kdm6b	ENSMUSG00000018476
rattus_norvegicus	Kdm6b	ENSRNOG00000037613
drosophila_melanogaster	Utx	FBGN0260749
caenorhabditis_elegans		WBGENE00007813
caenorhabditis_elegans		WBGENE00009089
caenorhabditis_elegans		WBGENE00017046
caenorhabditis_elegans		WBGENE00017571

Paralogs (2): KDM6A (ENSG00000147050), UTY (ENSG00000183878)

Protein

Protein identifiers

Lysine-specific demethylase 6B — O15054 (reviewed: O15054)

Alternative names: JmjC domain-containing protein 3, Jumonji domain-containing protein 3, Lysine demethylase 6B, [histone H3]-trimethyl-L-lysine(27) demethylase 6B

All UniProt accessions (2): O15054, I3L0Z0

UniProt curated annotations — full annotation on UniProt →

Function. Histone demethylase that specifically demethylates ‘Lys-27’ of histone H3, thereby playing a central role in histone code. Demethylates trimethylated and dimethylated H3 ‘Lys-27’. Plays a central role in regulation of posterior development, by regulating HOX gene expression. Involved in inflammatory response by participating in macrophage differentiation in case of inflammation by regulating gene expression and macrophage differentiation. Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression by acting as a link between T-box factors and the SMARCA4-containing SWI/SNF remodeling complex.

Subunit / interactions. Interacts with TLE1. Component of the MLL4 complex, at least composed of KMT2B/MLL4, ASH2L, RBBP5, WDR5, and KDM6B. Interacts with TBX21, SMARCA4, SMARCC1 and SMARCC2.

Subcellular location. Nucleus.

Disease relevance. Stolerman neurodevelopmental syndrome (NEDSST) [MIM:618505] An autosomal dominant disorder characterized by global developmental delay, variable intellectual disability, poor language acquisition, and dysmorphic facial features including a prominent nasal bridge and coarse features. Some patients manifest autism spectrum disorder. Musculoskeletal features may be present and include widened and thickened hands and fingers, joint hypermobility, clinodactyly of the fifth fingers, and toe syndactyly. The disease is caused by variants affecting the gene represented in this entry.

Induction. By 12-O-tetradecanoylphorbol-13-acetate (TPA) in myeloid leukemia cells.

Similarity. Belongs to the UTX family.

Isoforms (2)

UniProt ID	Names	Canonical?
O15054-2	2	yes
O15054-1	1

RefSeq proteins (2): NP_001073893, NP_001335645* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003347	JmjC_dom	Domain
IPR046941	KDM6_GATAL_sf	Homologous_superfamily
IPR048560	KDM6A_B-like_GATAL	Domain
IPR048562	KDM6A_B-like_C-hel	Domain
IPR051630	Corepressor-Demethylase	Family

Pfam: PF02373, PF21322, PF21326

Enzyme classification (BRENDA):

• EC 1.14.11.68 — [histone H3]-trimethyl-L-lysine27 demethylase (BRENDA: 8 organisms, 20 substrates, 7 inhibitors, 0 Km, 0 kcat entries)
• EC 1.14.18.B1 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• N(6),N(6),N(6)-trimethyl-L-lysyl(27)-[histone H3] + 2 2-oxoglutarate + 2 O2 = N(6)-methyl-L-lysyl(27)-[histone H3] + 2 formaldehyde + 2 succinate + 2 CO2 (RHEA:60224)

UniProt features (94 total): compositionally biased region 22, strand 21, helix 20, binding site 7, sequence variant 7, region of interest 5, turn 5, chain 1, domain 1, modified residue 1, cross-link 1, splice variant 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
2XXZ	X-RAY DIFFRACTION	1.8
6F6D	X-RAY DIFFRACTION	1.82
4ASK	X-RAY DIFFRACTION	1.86
2XUE	X-RAY DIFFRACTION	2
5FP3	X-RAY DIFFRACTION	2.05
5OY3	X-RAY DIFFRACTION	2.14

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15054-F1	58.54	0.31

Functional residue map

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

Ligand- & substrate-binding residues (7): 1390; 1392; 1470; 1575; 1578; 1602; 1605

Post-translational modifications (2): 224, 1109

Mutagenesis-validated functional residues (1):

Position	Phenotype
1390–1392	abolishes lysine-specific histone demethylase activity.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-3214842	HDMs demethylate histones
R-HSA-9821002	Chromatin modifications during the maternal to zygotic transition (MZT)
R-HSA-1266738	Developmental Biology
R-HSA-2262752	Cellular responses to stress
R-HSA-2559583	Cellular Senescence
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9816359	Maternal to zygotic transition (MZT)

MSigDB gene sets: 739 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GSE45365_NK_CELL_VS_CD11B_DC_DN, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_6HR_DN, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_INFLAMMATORY_RESPONSE, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, NAGASHIMA_NRG1_SIGNALING_UP, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_UP, GOBP_FOREBRAIN_DEVELOPMENT, BILD_HRAS_ONCOGENIC_SIGNATURE, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT

GO Biological Process (16): inflammatory response to antigenic stimulus (GO:0002437), chromatin remodeling (GO:0006338), heart development (GO:0007507), regulation of gene expression (GO:0010468), response to activity (GO:0014823), hippocampus development (GO:0021766), cell fate commitment (GO:0045165), endothelial cell differentiation (GO:0045446), positive regulation of transcription by RNA polymerase II (GO:0045944), mesodermal cell differentiation (GO:0048333), cardiac muscle cell differentiation (GO:0055007), response to fungicide (GO:0060992), cellular response to hydrogen peroxide (GO:0070301), positive regulation of cold-induced thermogenesis (GO:0120162), chromatin organization (GO:0006325), inflammatory response (GO:0006954)

GO Molecular Function (11): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), beta-catenin binding (GO:0008013), chromatin DNA binding (GO:0031490), histone demethylase activity (GO:0032452), metal ion binding (GO:0046872), histone H3K27me2/H3K27me3 demethylase activity (GO:0071558), chromatin binding (GO:0003682), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), sequence-specific DNA binding (GO:0043565), dioxygenase activity (GO:0051213)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), MLL3/4 complex (GO:0044666)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Cellular Senescence	1
Chromatin modifying enzymes	1
Maternal to zygotic transition (MZT)	1
Cellular responses to stimuli	1
Cellular responses to stress	1
Chromatin organization	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell differentiation	2
DNA binding	2
binding	2
inflammatory response	1
immune response	1
chromatin organization	1
animal organ development	1
circulatory system development	1
gene expression	1
regulation of macromolecule biosynthetic process	1
response to stimulus	1
pallium development	1
limbic system development	1
anatomical structure development	1
cellular developmental process	1
endothelium development	1
epithelial cell differentiation	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
mesoderm formation	1
cardiocyte differentiation	1
cardiac muscle tissue development	1
striated muscle cell differentiation	1
response to toxic substance	1
response to antibiotic	1
cellular response to reactive oxygen species	1
response to hydrogen peroxide	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
cellular component organization	1
defense response	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
protein binding	1
chromatin binding	1
protein demethylase activity	1
histone modifying activity	1
cation binding	1

Protein interactions and networks

STRING

8090 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KDM6B	TBX21	Q9UL17	923
KDM6B	SMARCA4	P51532	921
KDM6B	WDR5	P61964	858
KDM6B	RBBP5	Q15291	857
KDM6B	EZH2	Q15910	850
KDM6B	H3-3A	P06351	833
KDM6B	H3C1	P02295	833
KDM6B	H3-4	Q16695	833
KDM6B	H3-7	Q5TEC6	833
KDM6B	H3-5	Q6NXT2	833
KDM6B	H3C14	Q71DI3	833
KDM6B	ASH2L	Q9UBL3	796
KDM6B	PPARA	Q07869	788
KDM6B	TP53	P04637	785
KDM6B	SUZ12	Q15022	770

IntAct

16 interactions, top by confidence:

A	B	Type	Score
SOX2	KDM6B	psi-mi:“MI:0915”(physical association)	0.400
KLF4	KDM6B	psi-mi:“MI:0915”(physical association)	0.400
KDM6B	H1-2	psi-mi:“MI:0915”(physical association)	0.400
KDM6B	ESR1	psi-mi:“MI:0915”(physical association)	0.400
ESR1	KDM6B	psi-mi:“MI:0915”(physical association)	0.400
KDM6B	CSNK2B	psi-mi:“MI:0915”(physical association)	0.370
TK1	KDM6B	psi-mi:“MI:0915”(physical association)	0.370
Cbx1		psi-mi:“MI:0914”(association)	0.350
KDM6B	PFN2	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
SSRP1	DDX39A	psi-mi:“MI:0914”(association)	0.350
	PHF20L1	psi-mi:“MI:0914”(association)	0.350
KDM6B		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (135): KDM6B (Affinity Capture-MS), KDM6B (Affinity Capture-Western), KDM3A (Negative Genetic), KDM6B (Negative Genetic), PRMT5 (Negative Genetic), KMT2A (Negative Genetic), PRMT7 (Negative Genetic), KDM6B (Synthetic Growth Defect), KDM6B (Affinity Capture-MS), ACACA (Affinity Capture-MS), GMPS (Affinity Capture-MS), FLAD1 (Affinity Capture-MS), DNAJA2 (Affinity Capture-MS), KARS (Affinity Capture-MS), DDX20 (Affinity Capture-MS)

ESM2 similar proteins: A0A2Z4LIS9, A6QPM6, A7X8B3, A7X8B5, A7X8B7, A7X8C4, A7X8C7, A7X8C9, A7XW16, A7XW20, A7XW25, O08664, O15054, O43151, O70218, O89113, P09066, P14652, P17542, P19419, P19622, P22091, P23683, P49640, P70061, P78412, P82976, P97503, Q00587, Q04890, Q05916, Q05917, Q12950, Q15270, Q17QW1, Q3U133, Q5JPB2, Q5NCY0, Q6ZW13, Q80WY3

Diamond homologs: O14607, O15054, O15550, O70546, P79457, Q5NCY0, Q6B4Z3, Q95QK3, A0A096LPI5, O14628, Q6UX73, Q86U02, Q8N769, Q8N7M2, Q8NDZ0

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
STAT6	“up-regulates quantity by expression”	KDM6B	“transcriptional regulation”
KDM6B	“up-regulates quantity by expression”	IRF4	“transcriptional regulation”
KDM6B	down-regulates	M1_polarization
KDM6B	up-regulates	M2_polarization
KDM6B	“down-regulates activity”	H3C1	demethylation
KDM6B	“down-regulates activity”	“Histone H3”	demethylation
HIF1A	“up-regulates quantity by expression”	KDM6B	“transcriptional regulation”
EPAS1	“up-regulates quantity by expression”	KDM6B	“transcriptional regulation”
2-oxoglutarate(2-)	“up-regulates activity”	KDM6B	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	40
Likely pathogenic	66
Uncertain significance	470
Likely benign	175
Benign	28

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1098619	NM_001348716.2(KDM6B):c.1146C>A (p.Cys382Ter)	Pathogenic
1186711	NM_001348716.2(KDM6B):c.2164dup (p.Gln722fs)	Pathogenic
1327377	NM_001348716.2(KDM6B):c.2923C>T (p.Arg975Ter)	Pathogenic
1690922	NM_001348716.2(KDM6B):c.1299_1300del (p.His434fs)	Pathogenic
1698734	NM_001348716.2(KDM6B):c.3046dup (p.Arg1016fs)	Pathogenic
1699056	NM_001348716.2(KDM6B):c.496C>T (p.Arg166Ter)	Pathogenic
1704423	NM_001348716.2(KDM6B):c.1537dup (p.Arg513fs)	Pathogenic
1704425	NM_001348716.2(KDM6B):c.3300del (p.Lys1101fs)	Pathogenic
1704426	NM_001348716.2(KDM6B):c.654_655del (p.Glu220fs)	Pathogenic
1704432	NM_001348716.2(KDM6B):c.4118T>C (p.Met1373Thr)	Pathogenic
1704454	NM_001348716.2(KDM6B):c.2012_2013del (p.Leu670_Phe671insTer)	Pathogenic
1704463	NM_001348716.2(KDM6B):c.4500C>A (p.Tyr1500Ter)	Pathogenic
1710419	NM_001348716.2(KDM6B):c.1072del (p.Ser358fs)	Pathogenic
2040759	NM_001348716.2(KDM6B):c.4298del (p.Tyr1432_Leu1433insTer)	Pathogenic
2230372	NM_001348716.2(KDM6B):c.4388G>A (p.Trp1463Ter)	Pathogenic
2430766	NM_001348716.2(KDM6B):c.3466C>T (p.Arg1156Ter)	Pathogenic
2686035	NM_001348716.2(KDM6B):c.4737+5G>A	Pathogenic
3113889	NM_001348716.2(KDM6B):c.1984_1990dup (p.Pro664fs)	Pathogenic
3251100	NM_001348716.2(KDM6B):c.2278_2336del (p.Thr760fs)	Pathogenic
3254676	NM_001348716.2(KDM6B):c.1315_1324del (p.Gly439fs)	Pathogenic
3337214	NM_001348716.2(KDM6B):c.4165G>T (p.Gly1389Cys)	Pathogenic
3337264	NM_001348716.2(KDM6B):c.4090_4091del (p.Ser1364fs)	Pathogenic
3377255	NM_001348716.2(KDM6B):c.4550dup (p.Ser1518fs)	Pathogenic
3378404	NM_001348716.2(KDM6B):c.2041C>T (p.Gln681Ter)	Pathogenic
3382713	NM_001348716.2(KDM6B):c.4162_4165+1del	Pathogenic
3572485	NM_001348716.2(KDM6B):c.2851C>T (p.Arg951Ter)	Pathogenic
3647919	NM_001348716.2(KDM6B):c.4543del (p.Ile1515fs)	Pathogenic
3912075	NM_001348716.2(KDM6B):c.1804_1805del (p.Leu602fs)	Pathogenic
4042389	NM_001348716.2(KDM6B):c.1172del (p.Pro391fs)	Pathogenic
4042396	NM_001348716.2(KDM6B):c.2584C>T (p.Gln862Ter)	Pathogenic

SpliceAI

3290 predictions. Top by Δscore:

Variant	Effect	Δscore
17:7845871:GAT:G	acceptor_gain	1.0000
17:7845969:GG:G	donor_gain	1.0000
17:7845970:GG:G	donor_gain	1.0000
17:7845970:GGT:G	donor_loss	1.0000
17:7845971:GT:G	donor_loss	1.0000
17:7846294:GCAG:G	donor_gain	1.0000
17:7846297:GGT:G	donor_loss	1.0000
17:7846298:G:C	donor_loss	1.0000
17:7846298:G:GG	donor_gain	1.0000
17:7846395:CCCA:C	acceptor_loss	1.0000
17:7846396:CCAG:C	acceptor_loss	1.0000
17:7846397:CA:C	acceptor_loss	1.0000
17:7846492:GGTG:G	donor_loss	1.0000
17:7846493:G:C	donor_loss	1.0000
17:7846494:T:A	donor_loss	1.0000
17:7846575:TCAGC:T	acceptor_loss	1.0000
17:7846577:A:AG	acceptor_gain	1.0000
17:7846577:AGC:A	acceptor_loss	1.0000
17:7846578:G:GG	acceptor_gain	1.0000
17:7846578:GC:G	acceptor_gain	1.0000
17:7846578:GCA:G	acceptor_gain	1.0000
17:7846578:GCACA:G	acceptor_gain	1.0000
17:7846686:G:T	donor_gain	1.0000
17:7846719:G:GT	donor_gain	1.0000
17:7846720:A:T	donor_gain	1.0000
17:7846741:GT:G	donor_gain	1.0000
17:7846817:A:AG	acceptor_gain	1.0000
17:7846817:AGACT:A	acceptor_gain	1.0000
17:7846818:G:GG	acceptor_gain	1.0000
17:7846818:GACT:G	acceptor_gain	1.0000

AlphaMissense

10490 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:7849602:T:A	I1105N	1.000
17:7849602:T:C	I1105T	1.000
17:7849602:T:G	I1105S	1.000
17:7849608:T:A	L1107H	1.000
17:7849608:T:C	L1107P	1.000
17:7849611:T:A	I1108N	1.000
17:7849640:T:C	F1118L	1.000
17:7849641:T:C	F1118S	1.000
17:7849641:T:G	F1118C	1.000
17:7849642:T:A	F1118L	1.000
17:7849642:T:G	F1118L	1.000
17:7849647:C:A	A1120D	1.000
17:7849939:A:C	S1187R	1.000
17:7849941:C:A	S1187R	1.000
17:7849941:C:G	S1187R	1.000
17:7849943:T:A	I1188N	1.000
17:7850073:T:A	L1190Q	1.000
17:7850073:T:C	L1190P	1.000
17:7850083:A:C	K1193N	1.000
17:7850083:A:T	K1193N	1.000
17:7850106:T:C	L1201P	1.000
17:7850114:T:C	F1204L	1.000
17:7850115:T:C	F1204S	1.000
17:7850115:T:G	F1204C	1.000
17:7850116:C:A	F1204L	1.000
17:7850116:C:G	F1204L	1.000
17:7850117:T:C	C1205R	1.000
17:7850118:G:A	C1205Y	1.000
17:7850119:T:G	C1205W	1.000
17:7850148:T:A	I1215N	1.000

dbSNP variants (sampled 300 via entrez): RS1000018764 (17:7854003 G>A), RS1000023204 (17:7845495 C>G,T), RS1000087100 (17:7840082 T>C,G), RS1000398222 (17:7838855 C>CACTA), RS1000496288 (17:7833959 G>C), RS1000585997 (17:7844231 C>A), RS1000647606 (17:7845197 A>C,G), RS1000777879 (17:7848812 C>G,T), RS1001185042 (17:7842951 G>C), RS1001217531 (17:7843227 C>G), RS1001468622 (17:7832234 G>A), RS1001492524 (17:7847509 C>CGAGCAAT), RS1001813259 (17:7837343 C>G,T), RS1002223286 (17:7842116 C>G,T), RS1002377042 (17:7854232 A>C,G)

Disease associations

OMIM: gene MIM:611577 | disease phenotypes: MIM:618505, MIM:157900

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities	Strong	Autosomal dominant
neurodevelopmental disorder	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
syndromic intellectual disability	Limited	AR
syndromic intellectual disability	Definitive	AD

Mondo (4): neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities (MONDO:0032790), intellectual disability (MONDO:0001071), Mobius syndrome (MONDO:0008006), neurodevelopmental disorder (MONDO:0700092)

Orphanet (2): Moebius syndrome (Orphanet:570), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

233 total (30 of 233 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000011	Neurogenic bladder
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000122	Unilateral renal agenesis
HP:0000154	Wide mouth
HP:0000162	Glossoptosis
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000238	Hydrocephalus
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000268	Dolichocephaly
HP:0000272	Malar flattening
HP:0000276	Long face
HP:0000280	Coarse facial features
HP:0000283	Broad face
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000294	Low anterior hairline
HP:0000303	Mandibular prognathia
HP:0000311	Round face
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000321	Square face
HP:0000322	Short philtrum
HP:0000325	Triangular face
HP:0000337	Broad forehead

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST002702_27	Height	8.000000e-10
GCST004600_141	Eosinophil percentage of white cells	6.000000e-14
GCST004606_29	Eosinophil count	7.000000e-21
GCST004608_217	Granulocyte percentage of myeloid white cells	4.000000e-15
GCST004609_236	Monocyte percentage of white cells	8.000000e-16
GCST004617_119	Eosinophil percentage of granulocytes	1.000000e-10
GCST004624_11	Sum eosinophil basophil counts	4.000000e-18
GCST005908_41	Height	8.000000e-07
GCST007267_236	Systolic blood pressure	2.000000e-09
GCST007328_58	Alcohol consumption (drinks per week)	5.000000e-08
GCST007930_10	Medication use (agents acting on the renin-angiotensin system)	5.000000e-10
GCST010703_158	Brain morphology (MOSTest)	3.000000e-09
GCST90002381_110	Eosinophil count	1.000000e-55
GCST90002382_413	Eosinophil percentage of white cells	1.000000e-36
GCST90002386_176	High light scatter reticulocyte percentage of red cells	1.000000e-11
GCST90002387_19	Immature fraction of reticulocytes	5.000000e-09
GCST90002394_513	Monocyte percentage of white cells	3.000000e-37
GCST90002398_262	Neutrophil count	8.000000e-20
GCST90002400_203	Plateletcrit	2.000000e-17
GCST90002407_573	White blood cell count	2.000000e-18

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0007996	eosinophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0006335	systolic blood pressure
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0004346	neuroimaging measurement
EFO:0004833	neutrophil count
EFO:0007985	platelet crit

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D020331	Mobius Syndrome	C07.465.299.825; C10.292.319.825; C10.292.562.700.375.750; C11.590.436.400.750; C16.131.077.578; C16.614.595
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1938211 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 36,699 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL550348	DEFERASIROX	4	1,593
CHEMBL109480	TANESPIMYCIN	3	3,645
CHEMBL278315	GELDANAMYCIN	2	30,673
CHEMBL383824	ALVESPIMYCIN	2	752
CHEMBL5314494	ZAVONDEMSTAT	2	36

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 1.14.11.- Histone demethylases

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
GSK-J1	Inhibition	7.55	pIC50
zavondemstat	Inhibition	6.0	pIC50
compound 3 [PMID: 29633584]	Inhibition	5.82	pIC50
IOX1	Inhibition	5.8	pIC50
GSK-J4	Inhibition	5.07	pIC50

Binding affinities (BindingDB)

112 measured of 154 human assays (154 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-{1-[2-(2-ethoxyphenyl)ethyl]-1H-imidazol-4-yl}-4- [5-(trifluoromethyl)-1H-1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-[1-(2-methyl-1-phenylpropyl)-1H-imidazol-4-yl]-4- [5-(trifluoromethyl)-1H-1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[2-(2-chloro-6-fluorophenyl)ethyl]-1H- imidazol-4-yl}-4-[5-(trifluoromethyl)-1H-1,2,3- triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
4-[5-(trifluoromethyl)-1H-1,2,3-triazol-4-yl]-2-(1-{2- [4-(trifluoromethyl)phenyl]ethyl}-1H-imidazol-4- yl)pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[2-(4-ethylphenyl)ethyl]-1H-imidazol-4-yl}-4- [5-(trifluoromethyl)-1H-1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[2-(4-tert-butylphenyl)ethyl]-1H-imidazol-4- yl}-4-[5-(trifluoromethyl)-1H-1,2,3-triazol-4- yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[(5-fluoro-1,2,3,4-tetrahydronaphthalen-1- yl)methyl]-1H-imidazol-4-yl}-4-[5-(trifluoromethyl)- 1H-1,2,3,-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[(6-fluoro-1,2,3,4-tetrahydronaphthalen-1- yl)methyl]-1H-imidazol-4-yl}-4-[5-(trifluoromethyl)- 1H-1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[(7-fluoro-1,2,3,4-tetrahydronaphthalen-1- yl)methyl]-1H-imidazol-4-yl}-4-[5-(trifluoromethyl)- 1H-1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[(7-methyl-1,2,3,4-tetrahydronaphthalen-1- yl)methyl]-1H-imidazol-4-yl}-4-[5-(trifluoromethyl)- 1H-1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[(5-methoxy-1,2,3,4-tetrahydronaphthalen-1- yl)methyl]-1H-imidazol-4-yl}-4-[5-(trifluoromethyl)- 1H-1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[(6-methoxy-1,2,3,4-tetrahydronaphthalen-1- yl)methyl]-1H-imidazol-4-yl}-4-[5-(trifluoromethyl)- 1H-1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[(7-methoxy-1,2,3,4-tetrahydronaphthalen-1- yl)methyl]-1H-imidazol-4-yl}-4-[5-(trifluoromethyl)- 1H-1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[(8-methoxy-1,2,3,4-tetrahydro-naphthalen-1-yl)methyl]-1H-imidazol-4-yl}-4-[5-(trifluoromethyl)-1H-1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-(1-{[2-(2,2,2- trifluoroethoxy)phenyl]methyl}-1H- imidazol-4-yl)-4-[5-(trifluoromethyl)-1H- 1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
3-[({(1S)-6-[methyl(4-methylphenyl)amino]-1,2,3,4-tetra-hydroisoquinolyl}methyl)amino]pyridine-4-carboxylic acid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
3-[({(1R)-6-[methyl(4-methyl-phenyl)amino]-1,2,3,4-tetrahydroisoquinolyl} methyl)amino] pyridine-4-carboxylic acid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
3-{[((1S)-6-{methyl[4-(methylethyl)phenyl]amino}-1,2,3,4-tetrahydroisoquinolyl)methyl]amino}pyridine-4-carboxylic acid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
3-{[((1R)-6-{methyl[4-(methylethyl)phenyl]amino}-1,2,3,4-tetrahydroisoquinolyl)methyl]amino}pyridine-4-carboxylic acid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
3-[({(1S)-6-[4-(cyclopropylmethoxy)-2-methylphenyl]-1,2,3,4-tetrahydroisoquinolyl}methyl)amino]pyridine-4-carboxylic acid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
3-[({(1R)-6-[4-(cyclopropyl-methoxy)-2-methylphenyl]-1,2,3,4-tetrahydro-isoquinolyl}methyl) amino]pyridine-4-carboxylic acid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
(R)-3-(((2-methyl-6-(methyl(p-tolyl)amino)-1,2,3,4-tetra-hydroisoquinolin-1-yl)methyl)amino)isonicotinicacid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
(S)-3-(((2-methyl-6-(methyl(p-tolyl)amino)-1,2,3,4-tetra-hydroisoquinolin-1-yl)methyl)amino)isonicotinic acid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
(R)-3-(((6-((4-ethylphenyl)(methyl)amino)-2-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl)methyl)amino)isonico-tinic acid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
(S)-3-(((6-((4-ethylphenyl)(methyl)amino)-2-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl)methyl)amino)isonicotinic acid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
(R)-3-(((6-(2-ethylphenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-1-yl)methyl)amino)isonicotinic acid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
(S)-3-(((6-(2-ethylphenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-1-yl)methyl)amino) isonicotinic acid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
(R)-3-(((2-methyl-5-(methyl(p-tolyl)amino)iso-indolin-1-yl)methyl)amino)isonicotinic acid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
(S)-3-(((2-methyl-5-(methyl(p-tolyl)amino)isoindolin-1-yl)methyl)amino)isonicotinic acid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
(R)-3-(((5-((4-ethylphenyl)(methyl)amino)-2-methyl-isoindolin-1-yl)methyl)amino)isonicotinic acid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
(S)-3-(((5-((4-ethylphenyl)(methyl)amino)-2-methylisoindolin-1-yl)methyl)amino)isonicotinic acid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
(R)-3-(((2-methyl-5-(methyl(4-propylphenyl)amino)iso-indolin-1-yl)methyl)amino)isonicotinic acid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
(S)-3-(((2-methyl-5-(methyl(4-propylphenyl)amino)isoindolin-1-yl)methyl)amino)isonicotinic acid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
(R)-3-(((2-methyl-5-(o-tolyl)isoindolin-1-yl)methyl)amino) isonicotinic acid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
(S)-3-(((2-methyl-5-(o-tolyl)iso-indolin-1-yl)methyl)amino) isonicotinic acid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
(R)-3-(((5-(2-ethylphenyl)-2-methylisoindolin-1-yl)methyl)amino)isonicotinic acid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
(S)-3-(((5-(2-ethylphenyl)-2-methylisoindolin-1-yl)methyl)amino) isonicotinic acid	IC50	550 nM	US-10059687: Histone demethylase inhibitors
3-({[(1S)-6-[methyl(phenyl)amino]-1,2,3,4-tetrahydronaphthalen-1-	IC50	550 nM	US-10106534: Histone demethylase inhibitors
3-({[(1R)-6-[methyl(pyridin-2-yl)amino]-1,2,3,4-	IC50	550 nM	US-10106534: Histone demethylase inhibitors
3-({[7-(1,2,3,4-tetrahydroquinolin-1-yl)-3,4-dihydro-2H-1-	IC50	550 nM	US-10106534: Histone demethylase inhibitors
3-({[7-(2,3-dihydro-1H-indol-1-yl)-3,4-dihydro-2H-1-benzopyran-	IC50	550 nM	US-10106534: Histone demethylase inhibitors
3-({[(4R)-7-[methyl(phenyl)amino]-3,4-dihydro-2H-1-benzopyran-	IC50	550 nM	US-10106534: Histone demethylase inhibitors
3-({[(4R)-7-[(3-fluorophenyl)(methyl)amino]-3,4-dihydro-2H-1-	IC50	550 nM	US-10106534: Histone demethylase inhibitors
3-({[(4R)-7-[(4-fluorophenyl)(methyl)amino]-3,4-dihydro-2H-1-	IC50	550 nM	US-10106534: Histone demethylase inhibitors
3-({[(4R)-7-[methyl(4-methylphenyl)amino]-3,4-dihydro-2H-1-	IC50	550 nM	US-10106534: Histone demethylase inhibitors
3-({[(4R)-7-[(4-chlorophenyl)(methyl)amino]-3,4-dihydro-2H-1-	IC50	550 nM	US-10106534: Histone demethylase inhibitors
3-({[(4R)-7-[ethyl(phenyl)amino]-3,4-dihydro-2H-1-benzopyran-4-	IC50	550 nM	US-10106534: Histone demethylase inhibitors
3-{[(2-phenyl-5,6,7,8-tetrahydroquinolin-5-	IC50	550 nM	US-10106534: Histone demethylase inhibitors
3-[({2-[methyl(phenyl)amino]-5,6,7,8-tetrahydroquinolin-5-	IC50	550 nM	US-10106534: Histone demethylase inhibitors
3-({[7-(furan-3-yl)-3,4-dihydro-2H-1-benzopyran-4-	IC50	550 nM	US-10106534: Histone demethylase inhibitors

ChEMBL bioactivities

220 potent at pChembl≥5 of 291 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.80	IC50	16	nM	CHEMBL3188597
7.55	IC50	28	nM	CHEMBL3188597
7.22	IC50	60	nM	CHEMBL3188597
7.20	IC50	63.1	nM	CHEMBL3188597
7.00	IC50	100	nM	CHEMBL1230640
6.85	IC50	140	nM	CHEMBL1230640
6.82	IC50	150	nM	CHEMBL3188597
6.82	IC50	150	nM	CHEMBL3753391
6.70	IC50	200	nM	CHEMBL3752893
6.70	IC50	200	nM	CHEMBL1230640
6.68	IC50	210	nM	CHEMBL3752179
6.57	IC50	270	nM	CHEMBL3753740
6.50	IC50	316.2	nM	N-OXALYLGLYCINE
6.40	IC50	400	nM	GELDANAMYCIN
6.40	IC50	400	nM	ALVESPIMYCIN
6.40	IC50	400	nM	TANESPIMYCIN
6.31	IC50	490	nM	CHEMBL3752769
6.26	IC50	550	nM	CHEMBL3752835
6.26	IC50	550	nM	CHEMBL5852219
6.26	IC50	550	nM	CHEMBL6034240
6.26	IC50	550	nM	CHEMBL5948393
6.26	IC50	550	nM	CHEMBL6040781
6.26	IC50	550	nM	CHEMBL5803397
6.26	IC50	550	nM	CHEMBL5840012
6.26	IC50	550	nM	CHEMBL5824237
6.26	IC50	550	nM	CHEMBL5925945
6.26	IC50	550	nM	CHEMBL5755777
6.26	IC50	550	nM	CHEMBL5931402
6.26	IC50	550	nM	CHEMBL6051723
6.26	IC50	550	nM	CHEMBL5859402
6.26	IC50	550	nM	CHEMBL5833327
6.26	IC50	550	nM	CHEMBL5916140
6.26	IC50	550	nM	CHEMBL5884211
6.26	IC50	550	nM	CHEMBL5945337
6.22	IC50	600	nM	CHEMBL3752143
6.20	IC50	631	nM	CHEMBL3774408
6.13	IC50	740	nM	CHEMBL3752551
6.12	IC50	750	nM	CHEMBL3753449
6.10	IC50	794.3	nM	CHEMBL1982368
6.10	IC50	794.3	nM	CHEMBL3774399
6.07	IC50	860	nM	CHEMBL1982368
6.05	IC50	900	nM	CHEMBL3752294
6.03	IC50	940	nM	CHEMBL3752343
6.00	IC50	990	nM	CHEMBL3753199
6.00	IC50	1000	nM	CHEMBL3753326
6.00	IC50	1000	nM	CHEMBL3774692
6.00	IC50	1000	nM	CHEMBL4280291
6.00	IC50	1000	nM	CHEMBL4293697
5.96	IC50	1100	nM	CHEMBL51979
5.92	IC50	1200	nM	CHEMBL3754078

PubChem BioAssay actives

78 with measured affinity, of 339 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-[[2-pyridin-2-yl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]amino]propanoic acid	1594436: Inhibition of C-terminal FLAG-tagged human KDM6B expressed in expressed in Sf9 cells pre-incubated for 4 hrs before substrate addition and measured after 1 hr by AlphaScreen assay	ic50	0.0160	uM
8-hydroxyquinoline-5-carboxylic acid	1249069: Inhibition of KDM6B (unknown origin)	ic50	0.1000	uM
3-[[4-pyrazol-1-yl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	0.1500	uM
3-[[4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(1,3-thiazol-2-yl)pyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	0.2000	uM
3-[[4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(triazol-1-yl)pyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	0.2100	uM
3-[[4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-6-(triazol-2-yl)pyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	0.2700	uM
2-(carboxymethylamino)-2-oxoacetic acid	1249069: Inhibition of KDM6B (unknown origin)	ic50	0.3162	uM
[(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-13-hydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl] carbamate	1885317: Inhibition of KDM6B (unknown origin) measured by AlphaScreen assay	ic50	0.4000	uM
[(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-[2-(dimethylamino)ethylamino]-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl] carbamate	1885317: Inhibition of KDM6B (unknown origin) measured by AlphaScreen assay	ic50	0.4000	uM
[(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-19-(prop-2-enylamino)-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl] carbamate	1885317: Inhibition of KDM6B (unknown origin) measured by AlphaScreen assay	ic50	0.4000	uM
3-[[4-(3,4-dihydro-1H-isoquinolin-2-yl)-6-pyrazol-1-ylpyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	0.4900	uM
3-[[4-[4-(4-fluorophenyl)piperazin-1-yl]-6-pyrazol-1-ylpyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	0.5500	uM
3-[[4-[4-(4-fluorophenyl)piperazin-1-yl]-6-(1,3-thiazol-2-yl)pyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	0.6000	uM
3-(4-phenylbutylamino)pyridine-4-carboxylic acid	1282646: Inhibition of human KDM6B catalytic domain using H3(20 to 36 residues)K27Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	0.6310	uM
3-[[4-[4-(3,4-dichlorophenyl)piperazin-1-yl]-6-pyrazol-1-ylpyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	0.7400	uM
3-[[4-(4-phenylpiperidin-1-yl)-6-pyrazol-1-ylpyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	0.7500	uM
5-chloro-N-[(E)-[phenyl(pyridin-2-yl)methylidene]amino]pyridin-2-amine	1249069: Inhibition of KDM6B (unknown origin)	ic50	0.7943	uM
3-(3-phenylpropylamino)pyridine-4-carboxylic acid	1282646: Inhibition of human KDM6B catalytic domain using H3(20 to 36 residues)K27Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	0.7943	uM
[(5S)-5-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-6-aminohexanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-6-aminohexanoyl]amino]-5-amino-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-hydroxybutanoyl]amino]-6-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S,3R)-1-[[2-(carboxymethylamino)-2-oxoethyl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-6-oxohexyl]-trimethylazanium	1802884: AlphaScreen Assay from Article 10.1074/jbc.M114.555052: “Human UTY(KDM6C) is a male-specific N¿-methyl lysyl demethylase.”	kd	0.8000	uM
3-[[4-(4-pyridin-2-ylpiperazin-1-yl)-6-(1,3-thiazol-2-yl)pyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	0.9000	uM
3-[[4-[4-(3,4-dichlorophenyl)piperazin-1-yl]-6-(1,3-thiazol-2-yl)pyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	0.9400	uM
3-[[4-(3,4-dihydro-1H-isoquinolin-2-yl)-6-(1,3-thiazol-2-yl)pyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	0.9900	uM
3-[[4-pyrazol-1-yl-6-(4-pyridin-2-ylpiperazin-1-yl)pyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	1.0000	uM
2-[[[2-[2-(dimethylamino)ethyl-ethylamino]-2-oxoethyl]amino]methyl]pyridine-4-carboxylic acid	1802660: AlphaScreen Assay from Article 10.1016/j.chembiol.2017.02.006: “Potent and Selective KDM5 Inhibitor Stops Cellular Demethylation of H3K4me3 at Transcription Start Sites and Proliferation of MM1S Myeloma Cells.”	ic50	1.0000	uM
2-(2-amino-1,3-thiazol-4-yl)pyridine-4-carboxylic acid	1282554: Inhibition of KDM6B (unknown origin) using biotin-H3K27me3 (21 to 44 residues) as substrate preincubated for 15 mins followed by substrate addition measured after 5 mins by alphascreen assay	ic50	1.0000	uM
4-(hydroxyamino)-4-oxobutanoic acid	698695: Inhibition of human KDM6B catalytic domain expressed in Escherichia coli using methyl lysine peptide substrate by AlphaScreen assay	ic50	1.1000	uM
3-[[4-(4-phenylpiperidin-1-yl)-6-(triazol-2-yl)pyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	1.2000	uM
3-[[4-(4-phenylpiperidin-1-yl)-6-(1,3-thiazol-2-yl)pyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	1.2000	uM
2-(1,3-benzoxazol-2-yl)benzene-1,4-diol	1633635: Inhibition of recombinant human JMJD3 expressed in baculovirus infected Sf9 cells using biotinylated histone H3 peptide as substrate incubated for 15 mins followed by substrate addition and measured after 60 mins by AlphaScreen assay	ic50	1.2000	uM
3-(4-phenylbutanoylamino)pyridine-4-carboxylic acid	1282646: Inhibition of human KDM6B catalytic domain using H3(20 to 36 residues)K27Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	1.2589	uM
3-[[4-(4-pyridin-2-ylpiperazin-1-yl)-6-(triazol-2-yl)pyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	1.3000	uM
3-[[4-[4-(3,4-dichlorophenyl)piperazin-1-yl]-6-(triazol-2-yl)pyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	1.4000	uM
3-[[4-(3,4-dihydro-1H-isoquinolin-2-yl)-6-(triazol-1-yl)pyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	1.4000	uM
3-[[4-(3,4-dihydro-1H-isoquinolin-2-yl)-6-(triazol-2-yl)pyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	1.5000	uM
3-(2-methylpropylamino)pyridine-4-carboxylic acid	1282646: Inhibition of human KDM6B catalytic domain using H3(20 to 36 residues)K27Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	1.9953	uM
pyridine-2,4-dicarboxylic acid	1934010: Inhibition of KDM6B (unknown origin ) incubated for 20 mins by Alphascreen assay	ic50	2.0000	uM
3-[[4-(4-phenylpiperidin-1-yl)-6-(triazol-1-yl)pyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	2.1000	uM
3-[[4-[4-(2-methoxyphenyl)piperazin-1-yl]-6-(1,3-thiazol-2-yl)pyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	2.1000	uM
3-[[4-indazol-2-yl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	2.2000	uM
2-[5-[(4-chloro-2-methylphenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391740: Inhibition of KDM6B (unknown origin)	ic50	2.3000	uM
3-(2-phenylethylamino)pyridine-4-carboxylic acid	1282646: Inhibition of human KDM6B catalytic domain using H3(20 to 36 residues)K27Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	2.5119	uM
3-(butylamino)pyridine-4-carboxylic acid	1282646: Inhibition of human KDM6B catalytic domain using H3(20 to 36 residues)K27Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	2.5119	uM
3-[[4-[4-(4-fluorophenyl)piperazin-1-yl]-6-(triazol-2-yl)pyrimidin-2-yl]amino]propanoic acid	1272794: Inhibition of JMJD3 (unknown origin) using biotinylated H3K27me3 peptide as substrate after 1 hr by AlphaLISA assay	ic50	2.6000	uM
2-[4-[[4-[(1S,2R)-2-aminocyclopropyl]phenyl]carbamoyl]-2-pyridinyl]pyridine-4-carboxylic acid;2,2,2-trifluoroacetic acid	1066181: Inhibition of recombinant JMJD3 (unknown origin) incubated for 15 mins prior to substrate addition by AlphaScreen method	ic50	2.7000	uM
(E)-4-[hydroxy-[4-[[4-(naphthalen-1-ylcarbamoyloxymethyl)phenyl]methylamino]butyl]amino]-4-oxobut-2-enoic acid	754166: Inhibition of recombinant 6xHis-tagged JMJD3 (unknown origin) expressed in Escherichia coli BL21	ic50	3.1000	uM
ethyl 3-[[2-pyridin-2-yl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]amino]propanoate	2145050: Inhibition of epitope-tagged KDM6B (1026 to 1682 residues)(unknown origin) transfected in human U2OS cells using H3K27me2 peptide as substrate	ic50	3.1000	uM
Deferasirox	1872471: Inhibition of KDM6B (1043 to end residues) (unknown origin) using ATKAARK(me3)-SAPATGGVKKPHRYRPG-GK(biotin) as substrate preincubated for 10 mins followed by substrate addition measured after 45 mins by LANCE Ultra assay	ic50	3.9500	uM
3-[(2-phenylacetyl)amino]pyridine-4-carboxylic acid	1282646: Inhibition of human KDM6B catalytic domain using H3(20 to 36 residues)K27Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	3.9811	uM
3-(propylamino)pyridine-4-carboxylic acid	1282646: Inhibition of human KDM6B catalytic domain using H3(20 to 36 residues)K27Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	3.9811	uM
3-[(3-methylthiophen-2-yl)methylamino]pyridine-4-carboxylic acid	1282646: Inhibition of human KDM6B catalytic domain using H3(20 to 36 residues)K27Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	5.0119	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases methylation	4
Air Pollutants	affects expression, increases abundance, increases expression	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
entinostat	decreases expression, affects cotreatment	2
Cyclosporine	increases expression	2
Aflatoxin B1	decreases methylation	2
Particulate Matter	increases abundance, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases activity	1
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
Glupearl 19S	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
2-methyl-4-isothiazolin-3-one	increases expression	1
trichostatin A	decreases expression	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
nickel chloride	increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1

ChEMBL screening assays

75 unique, capped per target: 73 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1942542	Binding	Inhibition of KDM6B	Lysine demethylases inhibitors. — J Med Chem
CHEMBL5723086	Functional	Affinity Biochemical interaction: (AlphaLISA) EUB0002150aNa KDM6B	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2ZP	Abcam HEK293T KDM6B KO	Transformed cell line	Female
CVCL_B7XV	Abcam Raji KDM6B KO	Cancer cell line	Male
CVCL_B9YK	Abcam THP-1 KDM6B KO	Cancer cell line	Male
CVCL_C7AC	Abcam PC-3 KDM6B KO	Cancer cell line	Male
CVCL_SU51	HAP1 KDM6B (-) 1	Cancer cell line	Male
CVCL_SU52	HAP1 KDM6B (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

391 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,
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
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
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
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
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