KDM2B

Summary

KDM2B (lysine demethylase 2B, HGNC:13610) is a protein-coding gene on chromosome 12q24.31, encoding Lysine-specific demethylase 2B (Q8NHM5). Histone demethylase that demethylates ‘Lys-4’ and ‘Lys-36’ of histone H3, thereby playing a central role in histone code.

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class. Multiple alternatively spliced transcript variants have been found for this gene, but the full-length nature of some variants has not been determined.

Source: NCBI Gene 84678 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 388 total — 13 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 2
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_032590

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13610
Approved symbol	KDM2B
Name	lysine demethylase 2B
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	PCCX2, CXXC2, Fbl10, JHDM1B
Ensembl gene	ENSG00000089094
Ensembl biotype	protein_coding
OMIM	609078
Entrez	84678

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 17 protein_coding, 3 retained_intron, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000377069, ENST00000377071, ENST00000446152, ENST00000536036, ENST00000538046, ENST00000538243, ENST00000538379, ENST00000538503, ENST00000539394, ENST00000540191, ENST00000541318, ENST00000541511, ENST00000542030, ENST00000542973, ENST00000543025, ENST00000543852, ENST00000545022, ENST00000611216, ENST00000717750, ENST00000717751, ENST00000717752, ENST00000717753, ENST00000717754, ENST00000717755, ENST00000717756

RefSeq mRNA: 2 — MANE Select: NM_032590 NM_001005366, NM_032590

CCDS: CCDS41849, CCDS41850

Canonical transcript exons

ENST00000377071 — 23 exons

Exon	Start	End
ENSE00001406256	121580786	121581023
ENSE00003547124	121494579	121494665
ENSE00003550447	121532806	121532959
ENSE00003561517	121534497	121534590
ENSE00003573900	121578802	121578946
ENSE00003595941	121520985	121521100
ENSE00003606508	121513276	121513402
ENSE00003609436	121509567	121510039
ENSE00004033322	121440816	121440977
ENSE00004033325	121445275	121445418
ENSE00004033326	121441070	121441233
ENSE00004033328	121442992	121443030
ENSE00004033331	121453120	121453344
ENSE00004033333	121574547	121574593
ENSE00004033335	121575781	121575859
ENSE00004033338	121444450	121444536
ENSE00004033342	121443680	121443793
ENSE00004033343	121549460	121549638
ENSE00004033344	121429096	121430469
ENSE00004033345	121439857	121440075
ENSE00004033347	121548877	121548983
ENSE00004033348	121442157	121442836
ENSE00004033359	121444012	121444272

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 97.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.0969 / max 489.3675, expressed in 1791 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133724	5.9136	1645
133736	2.4784	893
133737	1.4321	804
133728	1.4206	151
133733	1.3230	663
133739	0.8183	603
133735	0.6017	190
133738	0.3381	155
133727	0.2529	72
133734	0.2322	98

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oviduct epithelium	UBERON:0004804	97.72	gold quality
upper arm skin	UBERON:0004263	96.68	gold quality
cortical plate	UBERON:0005343	95.21	gold quality
ileal mucosa	UBERON:0000331	94.91	gold quality
buccal mucosa cell	CL:0002336	94.82	gold quality
ganglionic eminence	UBERON:0004023	94.16	gold quality
ventricular zone	UBERON:0003053	92.47	gold quality
cerebellar vermis	UBERON:0004720	91.53	gold quality
thymus	UBERON:0002370	90.58	gold quality
epithelium of nasopharynx	UBERON:0001951	89.47	gold quality
monocyte	CL:0000576	89.22	gold quality
esophagus squamous epithelium	UBERON:0006920	89.17	gold quality
leukocyte	CL:0000738	89.10	gold quality
tibialis anterior	UBERON:0001385	88.67	silver quality
lymph node	UBERON:0000029	88.31	gold quality
granulocyte	CL:0000094	88.24	gold quality
adult organism	UBERON:0007023	88.22	gold quality
vermiform appendix	UBERON:0001154	88.13	gold quality
tibia	UBERON:0000979	88.11	gold quality
upper leg skin	UBERON:0004262	87.91	gold quality
superficial temporal artery	UBERON:0001614	87.75	gold quality
pancreatic ductal cell	CL:0002079	87.62	silver quality
secondary oocyte	CL:0000655	87.55	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.51	gold quality
postcentral gyrus	UBERON:0002581	87.25	gold quality
mammalian vulva	UBERON:0000997	87.22	gold quality
gingiva	UBERON:0001828	87.16	gold quality
tonsil	UBERON:0002372	87.11	gold quality
gingival epithelium	UBERON:0001949	87.06	gold quality
epithelial cell of pancreas	CL:0000083	87.03	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	26.48
E-ANND-3	yes	4.91

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
CDK1	Repression
JUN
PPARG	Repression
UHRF1	Repression

Upstream regulators (CollecTRI, top): EPAS1, FOS, HIF1A, JUN, KDM2A, MBD2, NFKB

miRNA regulators (miRDB)

136 targeting KDM2B, 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-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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-LET-7C-3P	99.95	73.42	2862

Literature-anchored findings (GeneRIF, showing 40)

• validated occurrence of an unusual TG 3’ splice site in intron 15 (PMID:17672918)
• Results demonstrate that Fbl10 is a key regulator of c-Jun function. (PMID:17704768)
• identification of human JHDM1B as a nucleolar protein; JHDM1B preferentially binds the transcribed region of ribosomal DNA to repress the transcription of ribosomal RNA genes (PMID:17994099)
• A novel functional role for FBXL10 as an anti-apoptotic molecule, and describe a new apoptotic-related pathway that involves NF-jB/FBXL10/c-Fos/ c-FLIP. (PMID:21252908)
• It was found that JHDM1B mRNA is predominantly expressed in acute myeloid leukemia-derived aldehyde dehydrogenasehigh/CD34+ cells, and that aberrant expression of JHDM1B induces leukemia cell proliferation through modulation of cell cycle progression. (PMID:22086844)
• a regulatory role of Fbxl10 in cell morphology, chemokine expression, and the metabolic control of fibroblasts. (PMID:22825849)
• KDM2B specifically recognizes non-methylated DNA in CpG islands and recruits the polycomb repressive complex 1 (PRC1). This contributes to histone H2A lysine 119 ubiquitylation and gene repression. (PMID:23256043)
• KDM2B, an H3K36 histone demethylase implicated in bypass of cellular senescence and somatic cell reprogramming, is markedly overexpressed in PDAC, with levels increasing with disease grade and stage, and highest expression in metastases. (PMID:23321669)
• NDY1/KDM2B functions as a master regulator of polycomb complexes and controls self-renewal of breast cancer stem cells. (PMID:24853546)
• the KDM2B/let-7b/EZH2 axis is involved in epigenetic regulation in MDS, with direct effects on di- and tri-methylation of H3K27. (PMID:25225797)
• Low JHDM1B expression is associated with breast cancers. (PMID:25273595)
• Jhdm1b is a positive regulator of glycolysis, glutaminolysis, and pyrimidine synthesis in HeLa cells. (PMID:25877602)
• The protein lysine demethylases Kdm2a and Kdm2b regulate the turnover of non-phosphorylated beta-catenin specifically within the nucleus via direct interaction with the fourth and fifth armadillo repeats. (PMID:26004508)
• novel function of KDM2B in the negative regulation of cell proliferation by assembling an E3 ligase to targeting c-Fos protein degradation that is antagonized by mitogenic stimulations (PMID:26725323)
• KDM2B is an important mediator of hematopoietic cell development and has opposing roles in tumor progression that are dependent on cellular context. (PMID:26808549)
• we identified KDM2B, a reader for methylated CpGs, as the target of miR-448 that represses glycolysis and promotes oxidative phosphorylation in gastric cancer (PMID:26989077)
• we propose histone demethylase KDM2B and histone methyltransferase SETD1B as the two most plausible candidate genes involved in intellectual disability, autism, epilepsy, and craniofacial anomalies (PMID:27106595)
• A missense mutation in the KDM2B gene is associated with malignant peripheral nerve sheath tumors. (PMID:28124441)
• Data indicate that the reduction of JmjC domain-containing histone demethylase 1B (JHDM1B) leads to a more aggressive cellular phenotype in mammary gland cells, by virtue of its negative regulatory activity on ribosome biogenesis. (PMID:28415746)
• a novel regulatory role of KDM2B in autophagy and cell growth in gastric cancer cells, is reported. (PMID:28506929)
• The apoptosis phenotype was partly dependent on HRK upregulation, as HRK knockdown significantly abrogated the sensitization. KDM2B-silenced tumors exhibited slower growth in vivo. Taken together, our findings suggest a novel mechanism, where the key apoptosis components are under epigenetic control of KDM2B in glioblastoma multiforme cells. (PMID:28661478)
• High KDM2B expression is associated with Neuroblastomas. (PMID:28684529)
• FBXL10 is required for ERK1/2 phosphorylation in DLBCL cells. Furthermore, ERK1/2 activation and the proliferation rate of FBXL10-depleted cells can be rescued by downregulation of DUSP6 expression. (PMID:29352142)
• These results establish a clear functional link between the epigenetic factor KDM2B and the regulation of cell adhesion and Rho-GTPases signaling that controls actin reorganization and cell migration. (PMID:29408056)
• SS18-SSX1 deregulates developmental programs to drive transformation by hijacking a transcriptional repressive complex to aberrantly activate gene expression (PMID:29502955)
• findings identify KDM2B as an H3K79 demethylase and link its function to transcriptional repression via SIRT1-mediated chromatin silencing. (PMID:29763382)
• KDM2B regulates EZH2 and BMI1 in HCT116 colon tumor cells. Knockdown of this epigenetic factor induced potent up-regulation of the protein levels of the epithelial markers E-cadherin and ZO-1, while the mesenchymal marker N-cadherin was downregulated. (PMID:29772566)
• Data indicate a cell regulatory mechanism through which lysine-specific demethylase 2B (KDM2B) promotes triple negative breast cancer (TNBC) cell proliferation by binding to the promoters of cell cycle inhibitors p15INK4B, p16INK4A, and p57KIP2. (PMID:30060056)
• miR-146b promotes cell proliferation and increases chemosensitivity, but attenuates cell migration and invasion via FBXL10 in ovarian cancer. (PMID:30409964)
• During proliferation, KDM2B binds to the Box2 located in the Chka promoter repressing its transcription. KDM2B knockdown enhances the levels of CKalpha expression in neuroblast cells and induces neuronal differentiation. These results suggest that KDM2B is required for the appropriate regulation of CKalpha during neuronal differentiation and to the maintaining of the undifferentiated stage of neuroblast cells. (PMID:30629659)
• The histone modifier lysine (K)-specific demethylase 2B (KDM2B) plays a role in the differentiation of hematopoietic cells, and its expression appears to be deregulated in certain cancers of hematological and lymphoid origins. Epstein-Barr virus deregulates KDM2B expression and describe the underlying mechanisms. (PMID:30996097)
• KDM2B and Brg1 may have an inhibitory effect on the development of Chronic nasal sinusitis with nasal polyps nasal mucosal epithelial inflammation. (PMID:31041569)
• Tip60-dependent acetylation of KDM2B promotes osteosarcoma carcinogenesis. (PMID:31218831)
• HPV E7 protein downregulated the cellular abundance of Jumonji C histone demethylase 1B (JHDM1B), increasing the levels of H3K36 methylation within the promoter region of CTLA-4. (PMID:31590057)
• Lysine demethylase 2 (KDM2B) regulates hippo pathway via MOB1 to promote pancreatic ductal adenocarcinoma (PDAC) progression. (PMID:31941533)
• The histone demethylase KDM2B activates FAK and PI3K that control tumor cell motility. (PMID:32175798)
• Combined expression levels of KDM2A and KDM2B correlate with nucleolar size and prognosis in primary breast carcinomas. (PMID:32901907)
• Histone H3K79 demethylation by KDM2B facilitates proper DNA replication through PCNA dissociation from chromatin. (PMID:33029857)
• Inhibition of microRNA let-7b expression by KDM2B promotes cancer progression by targeting EZH2 in ovarian cancer. (PMID:33091189)
• Positional cloning and comprehensive mutation analysis identified a novel KDM2B mutation in a Japanese family with minor malformations, intellectual disability, and schizophrenia. (PMID:33402700)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	kdm2ba	ENSDARG00000036593
danio_rerio	kdm2bb	ENSDARG00000046010
mus_musculus	Kdm2b	ENSMUSG00000029475
rattus_norvegicus	Kdm2b	ENSRNOG00000025702
caenorhabditis_elegans		WBGENE00005013
caenorhabditis_elegans		WBGENE00017920

Paralogs (4): KDM7A (ENSG00000006459), PHF8 (ENSG00000172943), KDM2A (ENSG00000173120), PHF2 (ENSG00000197724)

Protein

Protein identifiers

Lysine-specific demethylase 2B — Q8NHM5 (reviewed: Q8NHM5)

Alternative names: CXXC-type zinc finger protein 2, F-box and leucine-rich repeat protein 10, F-box protein FBL10, F-box/LRR-repeat protein 10, JmjC domain-containing histone demethylation protein 1B, Jumonji domain-containing EMSY-interactor methyltransferase motif protein, Protein-containing CXXC domain 2, [Histone-H3]-lysine-36 demethylase 1B

All UniProt accessions (12): Q8NHM5, A0A0C4DGG3, F5GXC2, F5GXW2, F5H0A1, F5H4A7, F5H4X4, F5H5W7, F5H6N6, F5H7T7, F8WBN2, S4R3G4

UniProt curated annotations — full annotation on UniProt →

Function. Histone demethylase that demethylates ‘Lys-4’ and ‘Lys-36’ of histone H3, thereby playing a central role in histone code. Preferentially demethylates trimethylated H3 ‘Lys-4’ and dimethylated H3 ‘Lys-36’ residue while it has weak or no activity for mono- and tri-methylated H3 ‘Lys-36’. Preferentially binds the transcribed region of ribosomal RNA and represses the transcription of ribosomal RNA genes which inhibits cell growth and proliferation. May also serve as a substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.

Subunit / interactions. Interacts with SKP1, forming heterodimers. The heterodimeric KDM2B-SKP1 complex interacts with the PCGF1-BCORL1 heterodimeric complex to form a homotetrameric polycomb repression complex 1 (PRC1.1). Directly interacts with CUL1. The SKP1-KDM2B complex interacts with UBB.

Subcellular location. Nucleus. Nucleolus. Chromosome.

Activity regulation. Histone demethylase activity is inhibited by fumarate.

Cofactor. Binds 1 Fe(2+) ion per subunit.

Domain organisation. The LRR repeats are required for the interaction with the PCGF1-BCORL1 heterodimeric complex. The JmjC domain mediates demethylation activity. It is also required for repression of ribosomal RNA genes. The CXXC zinc finger mediates binding to DNA containing unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides. The F-box domain mediates interaction with UBB.

Similarity. Belongs to the JHDM1 histone demethylase family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8NHM5-1	1	yes
Q8NHM5-2	2
Q8NHM5-3	3
Q8NHM5-4	4
Q8NHM5-5	5

RefSeq proteins (2): NP_001005366, NP_115979* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001810	F-box_dom	Domain
IPR001965	Znf_PHD	Domain
IPR002857	Znf_CXXC	Domain
IPR003347	JmjC_dom	Domain
IPR006553	Leu-rich_rpt_Cys-con_subtyp	Repeat
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR019787	Znf_PHD-finger	Domain
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR041070	JHD	Domain
IPR041667	Cupin_8	Domain
IPR050690	JHDM1_Histone_Demethylase	Family
IPR057207	FBXL15_LRR	Domain

Pfam: PF02008, PF12937, PF13621, PF16866, PF17811, PF25372

Catalyzed reactions (Rhea), 1 shown:

• N(6),N(6)-dimethyl-L-lysyl(36)-[histone H3] + 2 2-oxoglutarate + 2 O2 = L-lysyl(36)-[histone H3] + 2 formaldehyde + 2 succinate + 2 CO2 (RHEA:42032)

UniProt features (117 total): helix 21, binding site 21, strand 14, compositionally biased region 10, modified residue 10, splice variant 10, repeat 7, turn 5, region of interest 4, sequence conflict 4, mutagenesis site 3, domain 2, zinc finger region 2, cross-link 2, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4O64	X-RAY DIFFRACTION	2.13
8HCU	X-RAY DIFFRACTION	2.2
5JH5	X-RAY DIFFRACTION	2.55
6BVA	X-RAY DIFFRACTION	2.66

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NHM5-F1	68.20	0.39

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 (21): 239; 242; 244; 259; 314; 613; 616; 619; 624; 627; 630; 646 …

Post-translational modifications (12): 57, 474, 477, 493, 497, 951, 975, 979, 1018, 1031, 857, 890

Mutagenesis-validated functional residues (3):

Position	Phenotype
1064	increased interaction with ubb.
1069	decreased ininteraction with ubb.
1072	increased interaction with ubb.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-3214842	HDMs demethylate histones
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization

MSigDB gene sets: 298 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_GROWTH, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEURAL_TUBE_DEVELOPMENT, GOBP_MALE_GAMETE_GENERATION, GOBP_VENTRICULAR_SYSTEM_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_EMBRYONIC_EPITHELIUM, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC

GO Biological Process (18): negative regulation of transcription by RNA polymerase II (GO:0000122), chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), spermatogenesis (GO:0007283), midbrain-hindbrain boundary morphogenesis (GO:0021555), fourth ventricle development (GO:0021592), lateral ventricle development (GO:0021670), third ventricle development (GO:0021678), initiation of neural tube closure (GO:0021993), positive regulation of cell growth (GO:0030307), forebrain development (GO:0030900), midbrain development (GO:0030901), hindbrain development (GO:0030902), negative regulation of neuron apoptotic process (GO:0043524), embryonic camera-type eye morphogenesis (GO:0048596), positive regulation of stem cell population maintenance (GO:1902459), negative regulation of neural precursor cell proliferation (GO:2000178), chromatin organization (GO:0006325)

GO Molecular Function (14): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA binding (GO:0003677), transcription coregulator activity (GO:0003712), zinc ion binding (GO:0008270), rRNA binding (GO:0019843), histone demethylase activity (GO:0032452), unmethylated CpG binding (GO:0045322), histone H3K36 demethylase activity (GO:0051864), histone H3K36me/H3K36me2 demethylase activity (GO:0140680), RNA binding (GO:0003723), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleolus (GO:0005730), PcG protein complex (GO:0031519)

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
anatomical structure development	6
ventricular system development	3
brain development	3
transcription by RNA polymerase II	2
embryonic morphogenesis	2
nucleic acid binding	2
nuclear lumen	2
intracellular membraneless organelle	2
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
chromatin organization	1
regulation of DNA-templated transcription	1
developmental process involved in reproduction	1
male gamete generation	1
midbrain-hindbrain boundary development	1
hindbrain development	1
telencephalon development	1
neural tube closure	1
morphogenesis of an epithelium	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
embryonic camera-type eye development	1
embryonic eye morphogenesis	1
camera-type eye morphogenesis	1
stem cell population maintenance	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
regulation of stem cell population maintenance	1
negative regulation of cell population proliferation	1
neural precursor cell proliferation	1
regulation of neural precursor cell proliferation	1
cellular component organization	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
transcription regulator activity	1

Protein interactions and networks

STRING

2226 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KDM2B	PCGF1	Q9BSM1	995
KDM2B	RNF2	Q99496	995
KDM2B	RYBP	Q8N488	995
KDM2B	SKP1	P34991	990
KDM2B	RING1	Q06587	990
KDM2B	YAF2	Q8IY57	965
KDM2B	BCOR	Q6W2J9	904
KDM2B	CBX7	O95931	831
KDM2B	BCORL1	Q5H9F3	798
KDM2B	EZH2	Q15910	781
KDM2B	KDM4B	O94953	769
KDM2B	JARID2	Q92833	762
KDM2B	CBX8	Q9HC52	759
KDM2B	KDM5A	P29375	755
KDM2B	USP7	Q93009	721

IntAct

120 interactions, top by confidence:

A	B	Type	Score
CBX8	BMI1	psi-mi:“MI:0914”(association)	0.970
RYBP	CSNK2A2	psi-mi:“MI:0914”(association)	0.900
PCGF1	BCOR	psi-mi:“MI:0914”(association)	0.880
RYBP	BMI1	psi-mi:“MI:0914”(association)	0.850
SKP1	KDM2B	psi-mi:“MI:0915”(physical association)	0.840
KDM2B	BCOR	psi-mi:“MI:0915”(physical association)	0.770
BCOR	KDM2B	psi-mi:“MI:0914”(association)	0.770
RYBP	E2F6	psi-mi:“MI:0914”(association)	0.740
RING1	CBX4	psi-mi:“MI:0914”(association)	0.730
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
RNF2	CBX4	psi-mi:“MI:0914”(association)	0.660
RBX1	SKP1	psi-mi:“MI:0914”(association)	0.640
YAF2	E2F6	psi-mi:“MI:0914”(association)	0.640
SKP1	MYCBP2	psi-mi:“MI:0914”(association)	0.640
BCOR	CBX4	psi-mi:“MI:0914”(association)	0.530
PCGF1	CBX4	psi-mi:“MI:0914”(association)	0.530
FAM9B	GEMIN2	psi-mi:“MI:0914”(association)	0.530
FOS	MYO1C	psi-mi:“MI:2364”(proximity)	0.480
ETV7	NFIB	psi-mi:“MI:2364”(proximity)	0.470
EN1	NFIB	psi-mi:“MI:2364”(proximity)	0.470
KDM2B	CBX3	psi-mi:“MI:0915”(physical association)	0.400
CEBPE	KDM2B	psi-mi:“MI:0915”(physical association)	0.370
LZTR1	KDM2B	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (259): KDM2B (Affinity Capture-MS), RNF2 (Affinity Capture-Western), SKP1 (Affinity Capture-Western), BCOR (Affinity Capture-Western), RNF2 (Affinity Capture-MS), SKP1 (Affinity Capture-MS), BCOR (Affinity Capture-MS), PCGF1 (Affinity Capture-MS), KDM2B (Affinity Capture-MS), ACBD3 (Co-fractionation), SKP1 (Affinity Capture-Western), KDM2B (Affinity Capture-MS), KDM2B (Affinity Capture-MS), KDM2B (Affinity Capture-MS), KDM2B (Affinity Capture-MS)

ESM2 similar proteins: A2WXR5, A2Y4R8, A7YY07, A9LMC0, B2KF05, B2RRD7, B8ADZ3, B8BJV8, G5E8P1, O81488, O95696, P55201, P56163, P58267, P58268, P58269, P58270, Q09477, Q0VDT2, Q12830, Q2R837, Q3U5C7, Q40359, Q567C6, Q5EA28, Q5U2Z0, Q5XEM9, Q60DW3, Q61103, Q6P1G2, Q6Z7F4, Q71QF9, Q7F2Z1, Q8BRB7, Q8NHM5, Q8S8M9, Q8UVR5, Q8WML3, Q92782, Q92784

Diamond homologs: B8BJV8, E6ZGB4, F4JL28, O74508, O75151, O94603, P0CF52, P0CH95, P40034, P59997, Q03012, Q08D35, Q12830, Q2R837, Q3UWM4, Q4WHB7, Q5A847, Q5AW75, Q5EA28, Q5RHD1, Q5U263, Q60V67, Q640I9, Q6BER5, Q6BXJ4, Q6C423, Q6CIC9, Q6FPL6, Q6P1G2, Q6P949, Q6ZMT4, Q80TJ7, Q8C9B9, Q8LA16, Q8NHM5, Q8S8M9, Q95Q98, Q9BTC0, Q9CWW7, Q9FEN9

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
KDM2B	“up-regulates activity”	RNF2	binding
HIF1A	“up-regulates quantity by expression”	KDM2B	“transcriptional regulation”
EPAS1	“up-regulates quantity by expression”	KDM2B	“transcriptional regulation”
KDM2B	down-regulates	Adipogenesis
KDM2B	“down-regulates quantity by repression”	CDK1	“transcriptional regulation”
KDM2B	“down-regulates quantity by repression”	UHRF1	“transcriptional regulation”
KDM2B	“down-regulates quantity by repression”	PPARG	“transcriptional regulation”
KDM2B	“up-regulates activity”	“Noncanonical PRC1”	binding
2-oxoglutarate(2-)	“up-regulates activity”	KDM2B	“chemical activation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 134 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
SUMOylation of DNA methylation proteins	5	35.7×	1e-05
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	10	32.0×	2e-10
Transcriptional Regulation by E2F6	7	21.8×	2e-06
Deactivation of the beta-catenin transactivating complex	8	19.8×	7e-07
SUMOylation of transcription cofactors	7	18.1×	6e-06
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	10	15.6×	2e-07
Transcriptional regulation by RUNX1	9	14.0×	1e-06
Gastrulation	5	13.8×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
neuron fate specification	5	27.2×	8e-05
positive regulation of miRNA transcription	11	24.8×	1e-10
branching involved in ureteric bud morphogenesis	6	17.0×	1e-04
cell fate commitment	7	16.0×	3e-05
cartilage development	6	11.7×	6e-04
chondrocyte differentiation	5	11.7×	2e-03
inner ear morphogenesis	5	11.7×	2e-03
somatic stem cell population maintenance	6	11.5×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	8
Uncertain significance	270
Likely benign	46
Benign	16

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
154387	GRCh38/hg38 12q24.31-24.32(chr12:120718786-127500215)x1	Pathogenic
2446153	NM_032590.5(KDM2B):c.1946G>A (p.Arg649Gln)	Pathogenic
2527753	NM_032590.5(KDM2B):c.1847G>T (p.Cys616Phe)	Pathogenic
2574714	NM_032590.5(KDM2B):c.1900AAG[1] (p.Lys635del)	Pathogenic
3340739	NM_032590.5(KDM2B):c.1913G>A (p.Gly638Asp)	Pathogenic
3342794	NM_032590.5(KDM2B):c.1846T>C (p.Cys616Arg)	Pathogenic
3602570	NM_032590.5(KDM2B):c.1880G>C (p.Cys627Ser)	Pathogenic
4529677	NM_032590.5(KDM2B):c.3005_3023del (p.Asn1002fs)	Pathogenic
4690237	NM_032590.5(KDM2B):c.1912G>A (p.Gly638Ser)	Pathogenic
4690242	NM_032590.5(KDM2B):c.1889G>C (p.Cys630Ser)	Pathogenic
4690243	NM_032590.4:c.1903_1905AAG	Pathogenic
4728098	NM_032590.5(KDM2B):c.2913del (p.Gln971fs)	Pathogenic
57207	GRCh38/hg38 12q24.23-24.33(chr12:118165459-133182322)x3	Pathogenic
2631460	NM_032590.5(KDM2B):c.500G>A (p.Arg167Gln)	Likely pathogenic
3235854	NM_032590.5(KDM2B):c.778-2A>G	Likely pathogenic
3340661	NM_032590.5(KDM2B):c.1913G>C (p.Gly638Ala)	Likely pathogenic
3349007	NM_032590.5(KDM2B):c.3325del (p.His1109fs)	Likely pathogenic
4081972	NM_032590.5(KDM2B):c.1838G>A (p.Cys613Tyr)	Likely pathogenic
4538103	NM_032590.5(KDM2B):c.1945C>T (p.Arg649Trp)	Likely pathogenic
4795799	NM_032590.5(KDM2B):c.1936dup (p.Cys646fs)	Likely pathogenic
4795800	NM_032590.5(KDM2B):c.758A>G (p.His253Arg)	Likely pathogenic

SpliceAI

5971 predictions. Top by Δscore:

Variant	Effect	Δscore
12:121430466:CAGT:C	acceptor_gain	1.0000
12:121430468:GT:G	acceptor_gain	1.0000
12:121430470:C:CC	acceptor_gain	1.0000
12:121433225:T:A	donor_gain	1.0000
12:121439851:ACT:A	donor_loss	1.0000
12:121439853:TCA:T	donor_loss	1.0000
12:121439854:CACC:C	donor_loss	1.0000
12:121439855:A:AC	donor_gain	1.0000
12:121439855:A:AG	donor_loss	1.0000
12:121439856:C:CC	donor_gain	1.0000
12:121439856:C:CG	donor_loss	1.0000
12:121439856:CCAGA:C	donor_gain	1.0000
12:121440071:CTGAC:C	acceptor_gain	1.0000
12:121440072:TGAC:T	acceptor_gain	1.0000
12:121440073:GAC:G	acceptor_gain	1.0000
12:121440074:AC:A	acceptor_gain	1.0000
12:121440075:CCTGG:C	acceptor_gain	1.0000
12:121440076:C:CC	acceptor_gain	1.0000
12:121440079:G:GC	acceptor_gain	1.0000
12:121440085:C:CT	acceptor_gain	1.0000
12:121440086:A:T	acceptor_gain	1.0000
12:121440812:TCAC:T	donor_loss	1.0000
12:121440814:A:AC	donor_gain	1.0000
12:121440815:C:CC	donor_gain	1.0000
12:121440815:CCTGG:C	donor_gain	1.0000
12:121440975:GCC:G	acceptor_gain	1.0000
12:121440976:CC:C	acceptor_gain	1.0000
12:121440976:CCC:C	acceptor_gain	1.0000
12:121440977:CC:C	acceptor_gain	1.0000
12:121440978:C:CC	acceptor_gain	1.0000

AlphaMissense

8794 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:121430358:A:G	F1314S	1.000
12:121439958:A:G	L1243P	1.000
12:121440845:A:G	L1194P	1.000
12:121441087:A:G	L1144P	1.000
12:121441091:A:G	W1143R	1.000
12:121441091:A:T	W1143R	1.000
12:121441096:A:G	L1141P	1.000
12:121441126:A:G	L1131P	1.000
12:121441132:A:G	L1129P	1.000
12:121441132:A:T	L1129H	1.000
12:121441141:G:T	P1126H	1.000
12:121441214:A:G	W1102R	1.000
12:121441214:A:T	W1102R	1.000
12:121442158:A:G	W1095R	1.000
12:121442158:A:T	W1095R	1.000
12:121442167:A:G	W1092R	1.000
12:121442167:A:T	W1092R	1.000
12:121442233:A:G	W1070R	1.000
12:121442233:A:T	W1070R	1.000
12:121444244:G:T	A740D	1.000
12:121444252:A:C	F737L	1.000
12:121444252:A:T	F737L	1.000
12:121444253:A:C	F737C	1.000
12:121444253:A:G	F737S	1.000
12:121444254:A:G	F737L	1.000
12:121444474:A:C	C722W	1.000
12:121444475:C:A	C722F	1.000
12:121444475:C:G	C722S	1.000
12:121444475:C:T	C722Y	1.000
12:121444476:A:G	C722R	1.000

dbSNP variants (sampled 300 via entrez): RS1000073253 (12:121560630 G>C), RS1000083797 (12:121563637 G>A), RS1000087303 (12:121539901 G>A), RS1000094382 (12:121497837 C>A,T), RS1000101709 (12:121453990 G>A), RS1000126077 (12:121480474 G>A), RS1000139542 (12:121540293 C>G), RS1000157297 (12:121481037 C>T), RS1000171238 (12:121580206 A>T), RS1000182350 (12:121439555 A>T), RS1000203521 (12:121433747 C>G,T), RS1000257416 (12:121433985 C>A), RS1000329383 (12:121517025 A>T), RS1000353108 (12:121460300 T>C,G), RS1000381753 (12:121517189 A>C)

Disease associations

OMIM: gene MIM:609078 | disease phenotypes: MIM:621474

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (4): neurodevelopmental disorder with congenital cardiac defects and variable renal and ocular abnormalities (MONDO:0980965), microcephaly (MONDO:0001149), severe combined immunodeficiency (MONDO:0015974), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): Severe combined immunodeficiency (Orphanet:183660)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000252	Microcephaly
HP:0004430	Severe combined immunodeficiency

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001527_12	Fasting blood glucose (BMI interaction)	2.000000e-06
GCST005186_11	Fasting blood glucose	6.000000e-07
GCST005830_132	Hand grip strength	1.000000e-09
GCST007928_34	Medication use (diuretics)	3.000000e-08
GCST007929_46	Medication use (calcium channel blockers)	7.000000e-10
GCST007930_150	Medication use (agents acting on the renin-angiotensin system)	6.000000e-10
GCST010988_504	Adult body size	2.000000e-09
GCST90002389_469	Lymphocyte percentage of white cells	2.000000e-10
GCST90002399_342	Neutrophil percentage of white cells	5.000000e-12

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0006941	grip strength measurement
EFO:0009928	Diuretic use measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
D016511	Severe Combined Immunodeficiency	C16.320.798.750; C16.614.815; C18.452.284.800; C20.673.795.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3779760 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 7,561 (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
CHEMBL70927	DEFERIPRONE	4	7,561

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

Binding affinities (BindingDB)

445 measured of 652 human assays (652 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-cyclobutyl-4-(1-tetralin-6-ylsulfonyl-4,5-dihydroimidazol-2-yl)piperazine	IC50	0.016 nM	US-10202354: Therapeutic compounds and uses thereof
4-[4-[[2-(4-cyclobutylpiperazin-1-yl)-4,5-dihydroimidazol-1-yl]sulfonyl]phe-nyl]phenol	IC50	0.021 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-[4-(3-thienyl)phenyl]sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.021 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-[4-(2-thienyl)phenyl]sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.027 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-(1-indan-5-ylsulfonyl-4,5-dihydroimidazol-2-yl)piperazine	IC50	0.031 nM	US-10202354: Therapeutic compounds and uses thereof
3-[4-[[2-(4-cyclobutylpiperazin-1-yl)-4,5-dihydroimidazol-1-yl]sulfonyl]phe-nyl]phenol	IC50	0.034 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-[4-(1,1-dimethylpropyl)phenyl]sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.035 nM	US-10202354: Therapeutic compounds and uses thereof
2-[4-[[2-(4-cyclobutylpiperazin-1-yl)-4,5-dihydroimidazol-1-yl]sulfonyl]phe-nyl]phenol	IC50	0.037 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[(4R)-4-cyclopropyl-1-(4-propan-2-ylphenyl)sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.039 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-[(6-methoxy-2-naphthyl)sulfonyl]-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.041 nM	US-10202354: Therapeutic compounds and uses thereof
1-[1-[(6-chloro-2-naphthyl)sulfonyl]-4,5-dihydroimidazol-2-yl]-4-cyclobutyl-piperazine	IC50	0.041 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-(1-((4-isopropylphenyl)sulfonyl)-4,5-dihydro-1H-imidazol-2-yl)piperazine	IC50	0.043 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-[4-(2-fluorophenyl)phe-nyl]sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.046 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[(4S)-4-cyclopropyl-1-(4-propan-2-ylphenyl)sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.047 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-(4-phenylphenyl)sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.048 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-[4-(1-methylpyrazol-3-yl)phenyl]sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.049 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-[4-(2-methylpyrazol-3-yl)phenyl]sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.049 nM	US-10202354: Therapeutic compounds and uses thereof
2-(4-cyclobutylpiperazin-1-yl)-3-(4-isopropylphenyl)sulfonyl-1,3-diazaspiro[4.4]non-1-ene	IC50	0.049 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-(3-phenylphenyl)sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.049 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-[4-	IC50	0.05 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-(4-phenoxyphenyl)sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.05 nM	US-10202354: Therapeutic compounds and uses thereof
2-[4-[[2-(4-cyclobutylpiperazin-1-yl)-4,5-dihydroimidazol-1-yl]sulfonyl]phenyl]benzonitrile	IC50	0.053 nM	US-10202354: Therapeutic compounds and uses thereof
(R)-1-cyclobutyl-4-[1-(4-isopropylphenyl)sulfonyl-4-methyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.054 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-(4-cyclopropylphenyl)sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.058 nM	US-10202354: Therapeutic compounds and uses thereof
5-[4-[[2-(4-cyclobutylpiperazin-1-yl)-4,5-dihydroimidazol-1-yl]sulfonyl]phe-nyl]pyrimidine	IC50	0.06 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-(2-naphthylsulfonyl)-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.062 nM	US-10202354: Therapeutic compounds and uses thereof
5-[[2-(4-cyclobutylpiperazin-1-yl)-4,5-dihydroimidazol-1-yl]sulfonyl]-1-methyl-indole	IC50	0.062 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-[4-(4-fluorophenyl)phe-nyl]sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.071 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-[4-(m-tolyl)phenyl]sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.074 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-[4-(o-tolyl)phenyl]sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.077 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-[(6-methyl-2-naphthyl)sulfonyl]-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.077 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-[4-(4-methoxyphenyl)phe-nyl]sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.08 nM	US-10202354: Therapeutic compounds and uses thereof
1-[4-tert-butylphenyl)sulfonyl-4,5-dihydroimidazol-2-yl]-4-cyclobutyl-piperazine	IC50	0.081 nM	US-10202354: Therapeutic compounds and uses thereof
1-[1-[4-(2-chlorophenyl)phe-nyl]sulfonyl-4,5-dihydroimidazol-2-yl]-4-cyclobutyl-piperazine	IC50	0.084 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-(3-cyclopropylphenyl)sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.087 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-(3,5-dimethylphenyl)sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.088 nM	US-10202354: Therapeutic compounds and uses thereof
N-[4-[[2-(4-cyclobutylpiperazin-1-yl)-4,5-dihydroimidazol-1-yl]sulfonyl]phenyl]acetamide	IC50	0.094 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-[4-(4-pyridyl)phenyl]sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.095 nM	US-10202354: Therapeutic compounds and uses thereof
4-[4-[[2-(4-cyclobutylpiperazin-1-yl)-4,5-dihydroimidazol-1-yl]sulfonyl]phe-nyl]benzonitrile	IC50	0.097 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-[4-(3-methoxyphenyl)phe-nyl]sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.098 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-[4-[2-(trifluoromethyl)phe-nyl]phenyl]sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.102 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-[4-(2-pyridyl)phenyl]sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.102 nM	US-10202354: Therapeutic compounds and uses thereof
6-[[2-(4-cyclobutylpiperazin-1-yl)-4,5-dihydroimidazol-1-yl]sulfonyl]-2-methyl-1,3-benzothiazole	IC50	0.112 nM	US-10202354: Therapeutic compounds and uses thereof
(S)-1-cyclobutyl-4-[1-(4-isopropylphenyl)sulfonyl-4-methyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.114 nM	US-10202354: Therapeutic compounds and uses thereof
1-[1-[4-(3-chlorophenyl)phe-nyl]sulfonyl-4,5-dihydroimidazol-2-yl]-4-cyclobutyl-piperazine	IC50	0.12 nM	US-10202354: Therapeutic compounds and uses thereof
N-[2-chloro-4-[[2-(4-cyclobutylpiperazin-1-yl)-4,5-dihydroimidazol-1-yl]sulfonyl]phenyl]acetamide	IC50	0.127 nM	US-10202354: Therapeutic compounds and uses thereof
6-[[2-(4-cyclobutylpiperazin-1-yl)-4,5-dihydroimidazol-1-yl]sulfonyl]naphthalene-2-carbonitrile	IC50	0.13 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-[4-[3-(trifluoromethyl)phe-nyl]phenyl]sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.134 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-(3,4-dichlorophenyl)sulfonyl-4,5-dihydromidazol-2-yl]piperazine	IC50	0.136 nM	US-10202354: Therapeutic compounds and uses thereof
1-cyclobutyl-4-[1-[4-(3-fluorophenyl)phe-nyl]sulfonyl-4,5-dihydroimidazol-2-yl]piperazine	IC50	0.138 nM	US-10202354: Therapeutic compounds and uses thereof

ChEMBL bioactivities

638 potent at pChembl≥5 of 655 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.80	IC50	0.016	nM	CHEMBL5804074
10.68	IC50	0.021	nM	CHEMBL6029845
10.68	IC50	0.021	nM	CHEMBL5751943
10.57	IC50	0.027	nM	CHEMBL6054309
10.51	IC50	0.031	nM	CHEMBL5852526
10.47	IC50	0.034	nM	CHEMBL6033900
10.46	IC50	0.035	nM	CHEMBL5871496
10.43	IC50	0.037	nM	CHEMBL5799134
10.41	IC50	0.039	nM	CHEMBL5784792
10.39	IC50	0.041	nM	CHEMBL5972096
10.39	IC50	0.041	nM	CHEMBL5787384
10.37	IC50	0.043	nM	CHEMBL5881868
10.34	IC50	0.046	nM	CHEMBL5908624
10.33	IC50	0.047	nM	CHEMBL5932709
10.32	IC50	0.048	nM	CHEMBL5859349
10.31	IC50	0.049	nM	CHEMBL5802360
10.31	IC50	0.049	nM	CHEMBL5773831
10.31	IC50	0.049	nM	CHEMBL6013213
10.31	IC50	0.049	nM	CHEMBL6036585
10.30	IC50	0.05	nM	CHEMBL5991420
10.30	IC50	0.05	nM	CHEMBL6045967
10.28	IC50	0.053	nM	CHEMBL6042454
10.27	IC50	0.054	nM	CHEMBL5822523
10.24	IC50	0.058	nM	CHEMBL5912028
10.22	IC50	0.06	nM	CHEMBL5973216
10.21	IC50	0.062	nM	CHEMBL5972161
10.21	IC50	0.062	nM	CHEMBL6059791
10.15	IC50	0.071	nM	CHEMBL5765252
10.13	IC50	0.074	nM	CHEMBL5797201
10.11	IC50	0.077	nM	CHEMBL5799025
10.11	IC50	0.077	nM	CHEMBL5805393
10.10	IC50	0.08	nM	CHEMBL5912451
10.09	IC50	0.081	nM	CHEMBL5877788
10.08	IC50	0.084	nM	CHEMBL5859215
10.06	IC50	0.087	nM	CHEMBL5958202
10.06	IC50	0.088	nM	CHEMBL5914299
10.03	IC50	0.094	nM	CHEMBL5867190
10.02	IC50	0.095	nM	CHEMBL5987806
10.01	IC50	0.098	nM	CHEMBL5742791
10.01	IC50	0.097	nM	CHEMBL5762980
9.99	IC50	0.102	nM	CHEMBL5779311
9.99	IC50	0.102	nM	CHEMBL5933092
9.95	IC50	0.112	nM	CHEMBL5850749
9.94	IC50	0.114	nM	CHEMBL5765806
9.92	IC50	0.12	nM	CHEMBL5835736
9.90	IC50	0.127	nM	CHEMBL6029354
9.89	IC50	0.13	nM	CHEMBL5916102
9.87	IC50	0.134	nM	CHEMBL5988173
9.87	IC50	0.136	nM	CHEMBL5814077
9.86	IC50	0.138	nM	CHEMBL5937744

PubChem BioAssay actives

21 with measured affinity, of 45 total; 20 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
2-[5-[(4-chloro-2-methylphenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1289414: Inhibition of recombinant human C-terminal FLAG-tagged KDM2B (1 to 650 residues) expressed in baculovirus infected sf9 cells using biotin-H3K36me2 substrate incubated for 30 mins by alphascreen assay	ic50	0.1000	uM
2-(1-methylimidazol-4-yl)pyridine-4-carboxylic acid	1289414: Inhibition of recombinant human C-terminal FLAG-tagged KDM2B (1 to 650 residues) expressed in baculovirus infected sf9 cells using biotin-H3K36me2 substrate incubated for 30 mins by alphascreen assay	ic50	0.1000	uM
2-[[[2-[2-(dimethylamino)ethyl-ethylamino]-2-oxoethyl]amino]methyl]pyridine-4-carboxylic acid	1289432: Inhibition of recombinant human C-terminal FLAG-tagged KDM2B (1 to 650 residues) expressed in baculovirus infected sf9 cells using biotin-H3K36me2 as substrate preincubated for 10 mins followed by substrate addition measured after 10 mins by AlphaLisa assay	ic50	0.1000	uM
2-(1-methylimidazol-4-yl)-4-(2H-tetrazol-5-yl)pyridine	1289414: Inhibition of recombinant human C-terminal FLAG-tagged KDM2B (1 to 650 residues) expressed in baculovirus infected sf9 cells using biotin-H3K36me2 substrate incubated for 30 mins by alphascreen assay	ic50	0.1000	uM
2-[5-(4-methoxyphenyl)-1-methylimidazol-4-yl]pyridine-4-carboxylic acid	1289414: Inhibition of recombinant human C-terminal FLAG-tagged KDM2B (1 to 650 residues) expressed in baculovirus infected sf9 cells using biotin-H3K36me2 substrate incubated for 30 mins by alphascreen assay	ic50	0.1000	uM
2-[5-[4-(cyclopropylmethoxy)phenyl]-1-methylimidazol-4-yl]pyridine-4-carboxylic acid	1289414: Inhibition of recombinant human C-terminal FLAG-tagged KDM2B (1 to 650 residues) expressed in baculovirus infected sf9 cells using biotin-H3K36me2 substrate incubated for 30 mins by alphascreen assay	ic50	0.1000	uM
2-[[(1-ethyl-2-oxopyrrolidin-3-yl)methylamino]methyl]pyridine-4-carboxylic acid	1288261: Inhibition of human KDM2B preincubated for 10 mins followed by substrate addition by AlphaLISA assay	ic50	0.2500	uM
2-[[[(3R)-1-ethyl-2-oxopiperidin-3-yl]methylamino]methyl]pyridine-4-carboxylic acid	1289432: Inhibition of recombinant human C-terminal FLAG-tagged KDM2B (1 to 650 residues) expressed in baculovirus infected sf9 cells using biotin-H3K36me2 as substrate preincubated for 10 mins followed by substrate addition measured after 10 mins by AlphaLisa assay	ic50	0.2500	uM
2-[[[(3S)-2-oxo-1-[(1R)-1-phenylethyl]piperidin-3-yl]methylamino]methyl]pyridine-4-carboxylic acid	1288261: Inhibition of human KDM2B preincubated for 10 mins followed by substrate addition by AlphaLISA assay	ic50	0.2500	uM
2-[[[(3S)-2-oxo-1-[(1R)-1-phenylethyl]pyrrolidin-3-yl]methylamino]methyl]pyridine-4-carboxylic acid	1288261: Inhibition of human KDM2B preincubated for 10 mins followed by substrate addition by AlphaLISA assay	ic50	0.2500	uM
2-[[[(3S)-1-[(1R)-1-(4-methoxyphenyl)ethyl]-2-oxopiperidin-3-yl]methylamino]methyl]pyridine-4-carboxylic acid	1288261: Inhibition of human KDM2B preincubated for 10 mins followed by substrate addition by AlphaLISA assay	ic50	0.2500	uM
2-[[[(3R)-2-oxo-1-[(1R)-1-phenylethyl]piperidin-3-yl]methylamino]methyl]pyridine-4-carboxylic acid	1288261: Inhibition of human KDM2B preincubated for 10 mins followed by substrate addition by AlphaLISA assay	ic50	0.2500	uM
ethyl 3-[[2-pyridin-2-yl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]amino]propanoate	2145034: Inhibition of KDM2B (1 to 650 residues)(unknown origin) by Alphalisa assay	ic50	2.1000	uM
4-(4-ethoxyphenyl)-1-prop-2-enoylpiperidine-4-carboxylic acid	1871101: Inhibition of GST-tagged human KDM2B (604 to 660 residues) expressed in Escherichia coli BL21 cells incubated for 30 mins by fluorescence polarization assay	ic50	3.6000	uM
4-phenyl-1-prop-2-enoylpiperidine-4-carboxylic acid	1871101: Inhibition of GST-tagged human KDM2B (604 to 660 residues) expressed in Escherichia coli BL21 cells incubated for 30 mins by fluorescence polarization assay	ic50	6.4000	uM
Deferiprone	1872466: Inhibition of KDM2B (unknown origin)	ic50	8.1000	uM
1-[4-phenyl-4-(2H-tetrazol-5-yl)piperidin-1-yl]prop-2-en-1-one	1871101: Inhibition of GST-tagged human KDM2B (604 to 660 residues) expressed in Escherichia coli BL21 cells incubated for 30 mins by fluorescence polarization assay	ic50	8.3000	uM
3-[[2-pyridin-3-yl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]amino]propanoic acid	2145034: Inhibition of KDM2B (1 to 650 residues)(unknown origin) by Alphalisa assay	ic50	8.3000	uM
7-oxo-5-phenyl-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1801991: KDM TR-FRET Assay from Article 10.1038/nchembio.2085: “An inhibitor of KDM5 demethylases reduces survival of drug-tolerant cancer cells.”	ic50	9.1000	uM
1-[4-(3-ethoxyphenyl)-4-(2H-tetrazol-5-yl)piperidin-1-yl]prop-2-en-1-one	1871101: Inhibition of GST-tagged human KDM2B (604 to 660 residues) expressed in Escherichia coli BL21 cells incubated for 30 mins by fluorescence polarization assay	ic50	9.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation, affects cotreatment, decreases expression	6
Acetaminophen	increases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Aflatoxin B1	increases expression, affects methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
bisphenol A	decreases methylation, affects cotreatment, increases methylation	1
sodium arsenite	decreases expression, increases abundance	1
aflatoxin B2	decreases methylation	1
tebuconazole	decreases expression	1
K 7174	decreases expression	1
pinostrobin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Calcitriol	decreases expression, affects cotreatment	1

ChEMBL screening assays

28 unique, capped per target: 28 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3782532	Binding	Inhibition of human KDM2B preincubated for 10 mins followed by substrate addition by AlphaLISA assay	Inhibition of Histone Demethylases Offers a Novel and Promising Approach for the Treatment of Cancer and Other Diseases. — ACS Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SU21	HAP1 KDM2B (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT01420627	PHASE3	COMPLETED	EZN-2279 in Patients With ADA-SCID
NCT06940570	PHASE3	SUSPENDED	Methadone as an Alternative Treatment for Children Underdoing HSCT
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
NCT00000603	PHASE2	COMPLETED	Cord Blood Stem Cell Transplantation Study (COBLT)
NCT00794508	PHASE2	COMPLETED	MND-ADA Transduction of CD34+ Cells From Children With ADA-SCID
NCT01182675	PHASE2	TERMINATED	Hematopoietic Stem Cell Transplantation (HSCT) for Children With SCID Utilizing Alemtuzumab, Plerixafor & Filgrastim
NCT01529827	PHASE2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT02177760	PHASE2	WITHDRAWN	Sirolimus Prophylaxis for aGVHD in TME SCID
NCT03619551	PHASE2	ACTIVE_NOT_RECRUITING	Conditioning SCID Infants Diagnosed Early
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
NCT00008450	PHASE1	COMPLETED	Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant
NCT00028236	PHASE1	COMPLETED	Stem Cell Gene Therapy to Treat X-Linked Severe Combined Immunodeficiency (XSCID)
NCT00152100	PHASE1	COMPLETED	Transplantation of Hematopoietic Cells in Children With Severe Combined Immunodeficiency Syndrome
NCT02860559	PHASE1	UNKNOWN	Safety and Early Efficacy Study of TBX-1400 in Patients With Severe Combined Immunodeficiency
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays