KDM2A

Summary

KDM2A (lysine demethylase 2A, HGNC:13606) is a protein-coding gene on chromosome 11q13.2, encoding Lysine-specific demethylase 2A (Q9Y2K7). Histone demethylase that specifically demethylates ‘Lys-36’ of histone H3, thereby playing a central role in histone code. It is a selective cancer dependency (DepMap: 64.2% of cell lines).

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 and, in addition to an F-box, contains at least six highly degenerated leucine-rich repeats. This family member plays a role in epigenetic silencing. It nucleates at CpG islands and specifically demethylates both mono- and di-methylated lysine-36 of histone H3. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 22992 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• GWAS associations: 19
• Clinical variants (ClinVar): 131 total — 7 pathogenic, 10 likely-pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 64.2% of screened cell lines
• Transcription factor: yes — 10 downstream targets (CollecTRI)
• MANE Select transcript: NM_012308

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13606
Approved symbol	KDM2A
Name	lysine demethylase 2A
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1004, FBL11, LILINA, DKFZP434M1735, FBL7, FLJ00115, CXXC8, JHDM1A
Ensembl gene	ENSG00000173120
Ensembl biotype	protein_coding
OMIM	605657
Entrez	22992

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 11 protein_coding_CDS_not_defined, 5 protein_coding

ENST00000308783, ENST00000398645, ENST00000517637, ENST00000524657, ENST00000525041, ENST00000525379, ENST00000526258, ENST00000527157, ENST00000528380, ENST00000529006, ENST00000529124, ENST00000530342, ENST00000531696, ENST00000532436, ENST00000534486, ENST00000956405

RefSeq mRNA: 2 — MANE Select: NM_012308 NM_001256405, NM_012308

CCDS: CCDS44657, CCDS58148

Canonical transcript exons

ENST00000529006 — 21 exons

Exon	Start	End
ENSE00001634650	67180079	67180217
ENSE00001641865	67181846	67181892
ENSE00001657246	67181320	67181398
ENSE00001705982	67207510	67207688
ENSE00002184565	67119263	67120049
ENSE00003497654	67243009	67243092
ENSE00003532220	67248281	67248370
ENSE00003547964	67228037	67228163
ENSE00003550037	67253453	67253611
ENSE00003572517	67219288	67219403
ENSE00003586141	67215340	67215446
ENSE00003600188	67231566	67231960
ENSE00003630468	67252694	67252857
ENSE00003634370	67217731	67217884
ENSE00003643134	67215856	67215949
ENSE00003651764	67250086	67250798
ENSE00003661017	67121234	67121358
ENSE00003661070	67254203	67254418
ENSE00003674855	67245985	67246116
ENSE00003698170	67254874	67258082
ENSE00003723247	67245189	67245458

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 97.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.0055 / max 578.4323, expressed in 1823 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115397	21.4305	1816
115403	11.4837	1770
115406	10.3805	1729
115402	1.1902	650
115404	1.1510	592
115407	0.8412	307
115405	0.7890	444
115408	0.7393	130

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
amniotic fluid	UBERON:0000173	97.70	gold quality
germinal epithelium of ovary	UBERON:0001304	97.58	gold quality
tibia	UBERON:0000979	96.80	gold quality
buccal mucosa cell	CL:0002336	96.65	gold quality
sural nerve	UBERON:0015488	96.52	gold quality
lower esophagus mucosa	UBERON:0035834	96.43	gold quality
nipple	UBERON:0002030	96.34	gold quality
visceral pleura	UBERON:0002401	96.21	gold quality
parietal pleura	UBERON:0002400	96.15	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.10	gold quality
bone marrow cell	CL:0002092	96.00	gold quality
tonsil	UBERON:0002372	95.98	gold quality
granulocyte	CL:0000094	95.95	gold quality
pylorus	UBERON:0001166	95.95	gold quality
gingival epithelium	UBERON:0001949	95.93	gold quality
pleura	UBERON:0000977	95.88	gold quality
epithelium of nasopharynx	UBERON:0001951	95.80	gold quality
palpebral conjunctiva	UBERON:0001812	95.76	gold quality
blood	UBERON:0000178	95.75	gold quality
squamous epithelium	UBERON:0006914	95.55	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.49	gold quality
esophagus mucosa	UBERON:0002469	95.43	gold quality
esophagus squamous epithelium	UBERON:0006920	95.42	gold quality
cardia of stomach	UBERON:0001162	95.40	gold quality
cervix squamous epithelium	UBERON:0006922	95.36	gold quality
right testis	UBERON:0004534	95.26	gold quality
superficial temporal artery	UBERON:0001614	95.24	gold quality
vermiform appendix	UBERON:0001154	95.19	gold quality
skin of leg	UBERON:0001511	95.17	gold quality
lymph node	UBERON:0000029	95.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.58

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

10 targets.

Target	Regulation
BCOR
CD44
CDK6
CDKN1B
CDKN2B
EREG	Repression
FGFR1
KDM2B
NANOG	Unknown
SOX2	Unknown

Upstream regulators (CollecTRI, top): EPAS1, HIF1A, NFKB1, RELA

miRNA regulators (miRDB)

303 targeting KDM2A, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-8485	100.00	77.57	4731
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-4534	99.99	66.58	1907
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 64.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• KDM2A is required to sustain centromeric integrity and genomic stability, particularly during mitosis. (PMID:19001877)
• Data show that high levels of FBXL11 block the ability of NFkappaB to bind to DNA or activate gene expression. (PMID:19805303)
• Data describe a NF-kappaB regulatory pathway that is driven by reversible lysine methylation of p65, carried out by nuclear receptor-binding SET domain-containing protein 1 (NSD1) and F-box and leucine-rich repeat protein 11 (FBXL11). (PMID:20080798)
• KDM2A represses the transcription of ribosomal RNA. KDM2A was localized in nucleoli and bound to the ribosomal RNA gene promoter. (PMID:20379134)
• CpG islands recruit KDM2A protein, a histone H3 lysine 36 demethylase. (PMID:20417597)
• The oncometabolite 2-hydroxyglutarate is a competitive inhibitor of multiple alpha-ketoglutarate-dependent dioxygenases, including histone demethylases, prolyl hydroxylases, and the TET family of 5-methlycytosine hydroxylases. (PMID:21251613)
• results not only show that differently spliced transcripts from a gene result in totally opposite outcomes, but also present critical evidence of the complicated activities of KDM2A, which contains all of the five domains (PMID:22635273)
• FBXL11 inhibited osteo/dentinogenic differentiation potential in MSC cells by associating with BCOR, then increasing histone K4/36 methylation in Epiregulin promoter to repress Epiregulin transcription. (PMID:23074094)
• KDM2A is a H3K4 demethylase that regulates cell proliferation through p15(INK4B) and p27(Kip1) in stem cells from apical papilla. (PMID:23559091)
• KDMA2 is frequently overexpressed in NSCLC tumors & cell lines. It is needed for in vitro proliferation & invasion. KDM2A activated ERK1/2 by epigenetic repression of DUSP3 expression via demethylation of dimethylated H3K36 at the DUSP3 locus. (PMID:24200691)
• KDM2A represses histone deacetylase 3 and has a role in tumorigenicity of lung cancer cells (PMID:24482232)
• KDM2A binds to the rDNA promoter with unmethylated CpG sequences via the CxxC-ZF domain (PMID:24553073)
• a regulatory role for KDM2A in breast cancer cell invasion and migration, through the regulation of E2F1 function (PMID:25029110)
• Upregulation of KDM2A is very important in the progression of gastric cancer. (PMID:25245333)
• In this study, KDM2A was identified as a novel substrate of ATM. DSB enhanced the interaction between ATM and KDM2A, which induced ATM-mediated phosphorylation of KDM2A at T632. (PMID:25823024)
• 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)
• FBXL11 is proposed as a novel component of the circadian clock that regulates the circadian gene expression by a so far unknown mechanism. (PMID:26037310)
• Findings suggest that amplification and overexpression of the KDM2A short isoform is critical in breast cancer progression. (PMID:26207617)
• The results suggest that under mild glucose starvation AMP-activated kinase induces KDM2A-dependent reduction of rRNA transcription to control cell proliferation. (PMID:26416883)
• Authors conclude that KDM2A functions as an oncogene in breast cancer by upregulating JAG1 to promote stemness, chemoresistance and angiogenesis. (PMID:27029061)
• Silencing KDM2A, a histone demethylase and BCL6 co-repressor, de-repressed SFRP2 transcription by increasing histone H3K4 and H3K36 methylation at the SFRP2 promoter. (PMID:27074224)
• The miR-29b/KDM2A axis was involved in the RUNX3-mediated inhibition of gastric cancer cell proliferation and metastasis. (PMID:27497248)
• KDM2A-WWTR1 fusion is associated with ossifying fibromyxoid tumors. (PMID:27537276)
• Identify a nucleosome interaction module within KDM2A consisting of a CXXC type zinc finger, a PHD domain and a newly identified Heterochromatin Protein 1 (HP1) interaction motif that mediates direct binding between KDM2A and HP1. This nucleosome interaction module enables KDM2A to decode nucleosomal H3K9me3 modification in addition to CpG methylation signals. (PMID:28180290)
• KDM2A-SF forms distinct nuclear heterochromatic bodies in an HP1a dependent manner (PMID:28816576)
• KDM2B is crucial for glioblastoma maintenance, with it’s inhibition causing loss of glioblastoma stem-like cells survival, genomic stability, and chemoresistance. (PMID:29360266)
• MicroRNA3666 suppresses the growth and migration of glioblastoma cells by targeting KDM2A. (PMID:30483744)
• Study data revealed that KDM2A functions as a tumor oncogene, and the downregulation of KDM2A expression regulates Epithelialmesenchymal transition and epithelial ovarian cancer progression. (PMID:30483796)
• these findings suggested that KDM2A might be a key regulator of cell proliferation and cell cycle via impacting TGF-beta signaling pathway. (PMID:30604066)
• Lysine-specific demethylase 2A enhances binding of various nuclear factors to CpG-rich genomic DNAs by action of its CXXC-PHD domain. (PMID:30940825)
• p300 Acetylates JHDM1A to inhibit osteosarcoma carcinogenesis (PMID:31307234)
• Combined expression levels of KDM2A and KDM2B correlate with nucleolar size and prognosis in primary breast carcinomas. (PMID:32901907)
• Lysine demethylase 2A expression in cancer-associated fibroblasts promotes breast tumour growth. (PMID:33024266)
• Production of ROS by Gallic Acid Activates KDM2A to Reduce rRNA Transcription. (PMID:33050392)
• LncRNA LINC01278 accelerates colorectal cancer progression via miR-134-5p/KDM2A axis. (PMID:33155208)
• Expression pattern and regulatory effect of lysine-specific demethylase 2A gene in clear cell renal cell carcinoma. (PMID:34391411)
• Up-regulation of miR-663a inhibits the cancer stem cell-like properties of glioma via repressing the KDM2A-mediated TGF-beta/SMAD signaling pathway. (PMID:34424812)
• Nuclear receptor binding SET domain protein 1 promotes epithelial-mesenchymal transition in paclitaxel-resistant breast cancer cells via regulating nuclear factor kappa B and F-box and leucine-rich repeat protein 11. (PMID:34905470)
• NSD1 mediates antagonism between SWI/SNF and polycomb complexes and is required for transcriptional activation upon EZH2 inhibition. (PMID:35537449)
• Histone H3K36me2 demethylase KDM2A promotes bladder cancer progression through epigenetically silencing RARRES3. (PMID:35697678)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	kdm2aa	ENSDARG00000059653
danio_rerio	kdm2ab	ENSDARG00000078133
mus_musculus	Kdm2a	ENSMUSG00000054611
rattus_norvegicus	Kdm2a	ENSRNOG00000019145
caenorhabditis_elegans		WBGENE00005013
caenorhabditis_elegans		WBGENE00017920

Paralogs (4): KDM7A (ENSG00000006459), KDM2B (ENSG00000089094), PHF8 (ENSG00000172943), PHF2 (ENSG00000197724)

Protein

Protein identifiers

Lysine-specific demethylase 2A — Q9Y2K7 (reviewed: Q9Y2K7)

Alternative names: CXXC-type zinc finger protein 8, F-box and leucine-rich repeat protein 11, F-box protein FBL7, F-box protein Lilina, F-box/LRR-repeat protein 11, JmjC domain-containing histone demethylation protein 1A, [Histone-H3]-lysine-36 demethylase 1A

All UniProt accessions (3): Q9Y2K7, I3VM53, I3VM54

UniProt curated annotations — full annotation on UniProt →

Function. Histone demethylase that specifically demethylates ‘Lys-36’ of histone H3, thereby playing a central role in histone code. Preferentially demethylates dimethylated H3 ‘Lys-36’ residue while it has weak or no activity for mono- and tri-methylated H3 ‘Lys-36’. May also recognize and bind to some phosphorylated proteins and promote their ubiquitination and degradation. Required to maintain the heterochromatic state. Associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. Required to sustain centromeric integrity and genomic stability, particularly during mitosis. Regulates circadian gene expression by repressing the transcriptional activator activity of CLOCK-BMAL1 heterodimer and RORA in a catalytically-independent manner.

Subunit / interactions. Interacts with CBX5/HP1A; the interaction promotes CBX5 localization to chromatin. The SKP1-KDM2A complex interacts with UBB. Part of a SCF (SKP1-cullin-F-box) protein ligase complex.

Subcellular location. Nucleus. Nucleoplasm. Chromosome.

Tissue specificity. Widely expressed, with highest levels in brain, testis and ovary, followed by lung.

Post-translational modifications. Mono-ADP-ribosylated at Arg-1020 in response to DNA damage, leading to displacement from chromatin, resulting in increased dimethylation of histone H3 at ‘Lys-36’.

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

Domain organisation. The JmjC domain mediates demethylation activity and is required for satellite silencing. The CXXC zinc finger preferentially recognizes nonmethylated CpG DNA, and binding is blocked when the CpG DNA is methylated. It is essential for its ability to repress the transcriptional activator activity of CLOCK-BMAL1 heterodimer. The F-box domain mediates interaction with UBB.

Similarity. Belongs to the JHDM1 histone demethylase family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9Y2K7-1	1	yes
Q9Y2K7-2	2
Q9Y2K7-4	4
Q9Y2K7-5	5
Q9Y2K7-3	3

RefSeq proteins (2): NP_001243334, NP_036440* (*=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
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR019787	Znf_PHD-finger	Domain
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR041070	JHD	Domain
IPR050690	JHDM1_Histone_Demethylase	Family

Pfam: PF02008, PF12937, PF16866, PF17811

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 (129 total): helix 31, binding site 21, strand 19, modified residue 15, mutagenesis site 8, turn 7, repeat 6, splice variant 6, region of interest 4, compositionally biased region 3, sequence conflict 3, domain 2, zinc finger region 2, chain 1, cross-link 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
4BBQ	X-RAY DIFFRACTION	2.24
6BYH	X-RAY DIFFRACTION	2.61
2YU1	X-RAY DIFFRACTION	2.7
2YU2	X-RAY DIFFRACTION	2.7
7UV9	ELECTRON MICROSCOPY	3.2
6C16	X-RAY DIFFRACTION	3.27

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2K7-F1	73.87	0.50

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): 209; 212; 214; 229; 284; 571; 574; 577; 582; 585; 588; 604 …

Post-translational modifications (16): 28, 390, 394, 550, 558, 632, 692, 713, 718, 731, 825, 832, 869, 883, 1020, 505

Mutagenesis-validated functional residues (8):

Position	Phenotype
212–214	abolishes lysine-specific histone demethylase activity.
212	abolishes histone demethylase activity. no loss of its ability to repress the transcriptional activator activity of the
571	abolishes association with centromeric heterochromatin; when associated with a-574 and a-577.
574	abolishes association with centromeric heterochromatin; when associated with a-571 and a-577. loss of its ability to rep
577	abolishes association with centromeric heterochromatin; when associated with a-571 and a-574. loss of its ability to rep
620	no loss of its ability to repress the transcriptional activator activity of the clock-bmal1 heterodimer; when associated
623	no loss of its ability to repress the transcriptional activator activity of the clock-bmal1 heterodimer; when associated
892	reduced 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: 300 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GOBP_CIRCADIAN_RHYTHM, GCACCTT_MIR18A_MIR18B, TGGTGCT_MIR29A_MIR29B_MIR29C, AAGCAAT_MIR137, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, AP4_Q6, GOBP_CIRCADIAN_REGULATION_OF_GENE_EXPRESSION, chr11q13, CAGCTG_AP4_Q5, SP1_Q2_01, GOBP_REGULATION_OF_CIRCADIAN_RHYTHM, CAIRO_HEPATOBLASTOMA_CLASSES_DN

GO Biological Process (9): double-strand break repair via nonhomologous end joining (GO:0006303), chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), obsolete negative regulation of transcription by competitive promoter binding (GO:0010944), circadian regulation of gene expression (GO:0032922), regulation of circadian rhythm (GO:0042752), chromatin organization (GO:0006325), methylation (GO:0032259), rhythmic process (GO:0048511)

GO Molecular Function (12): transcription coregulator activity (GO:0003712), zinc ion binding (GO:0008270), histone demethylase activity (GO:0032452), unmethylated CpG binding (GO:0045322), histone H3K36 demethylase activity (GO:0051864), histone H3K36me/H3K36me2 demethylase activity (GO:0140680), DNA binding (GO:0003677), protein binding (GO:0005515), methyltransferase activity (GO:0008168), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (3): nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleus (GO:0005634)

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
circadian rhythm	2
double-strand break repair	1
chromatin organization	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
regulation of gene expression	1
regulation of biological process	1
cellular component organization	1
metabolic process	1
biological_process	1
transcription regulator activity	1
transition metal ion binding	1
protein demethylase activity	1
histone modifying activity	1
sequence-specific DNA binding	1
2-oxoglutarate-dependent dioxygenase activity	1
histone H3 demethylase activity	1
histone H3K36 demethylase activity	1
nucleic acid binding	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
cation binding	1
oxidoreductase activity	1
nuclear lumen	1
cellular anatomical structure	1
intracellular membraneless organelle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2158 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KDM2A	RELA	Q04206	778
KDM2A	SKP1	P34991	743
KDM2A	KDM4A	O75164	715
KDM2A	SKP2	Q13309	708
KDM2A	CCNF	P41002	703
KDM2A	KDM6B	O15054	692
KDM2A	KDM4C	Q9H3R0	645
KDM2A	KDM1A	O60341	643
KDM2A	KDM4B	O94953	641
KDM2A	KDM4E	B2RXH2	636
KDM2A	KDM5A	P29375	626
KDM2A	KDM6A	O15550	618
KDM2A	KDM3A	Q9Y4C1	589
KDM2A	KDM3B	Q7LBC6	587
KDM2A	SETD2	Q9BYW2	587

IntAct

47 interactions, top by confidence:

A	B	Type	Score
SKP1	KDM2A	psi-mi:“MI:0915”(physical association)	0.800
MAD2L1	INSR	psi-mi:“MI:0914”(association)	0.700
SKP1	MYCBP2	psi-mi:“MI:0914”(association)	0.640
MAD2L1	PPIP5K2	psi-mi:“MI:0914”(association)	0.530
KDM2A		psi-mi:“MI:0407”(direct interaction)	0.440
KDM2A		psi-mi:“MI:0414”(enzymatic reaction)	0.440
RELA	KDM2A	psi-mi:“MI:0915”(physical association)	0.400
KDM2A	UBE2G2	psi-mi:“MI:0915”(physical association)	0.370
KDM2A	ZNF512B	psi-mi:“MI:0915”(physical association)	0.370
SMAD3	KDM2A	psi-mi:“MI:0915”(physical association)	0.370
SMAD7	KDM2A	psi-mi:“MI:0915”(physical association)	0.370
Cbx1		psi-mi:“MI:0914”(association)	0.350
Skp1	XPO1	psi-mi:“MI:0914”(association)	0.350
KIF20B	ACSL3	psi-mi:“MI:0914”(association)	0.350
Chmp4c	SF1	psi-mi:“MI:0914”(association)	0.350
REEP5	CNOT1	psi-mi:“MI:0914”(association)	0.350
RAB5C		psi-mi:“MI:0914”(association)	0.350
CBX4	SDC2	psi-mi:“MI:0914”(association)	0.350
RBPJ	SAMD1	psi-mi:“MI:0914”(association)	0.350
CGB2	CGB1	psi-mi:“MI:0914”(association)	0.350
KDM2A	RPLP2	psi-mi:“MI:0914”(association)	0.350
CBX1	EXOC5	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
MAD2L1	MED19	psi-mi:“MI:0914”(association)	0.350
HORMAD2	WASH3P	psi-mi:“MI:0914”(association)	0.350
SKP1	BHLHE40	psi-mi:“MI:0914”(association)	0.350
PCGF1	ZNF609	psi-mi:“MI:0914”(association)	0.350
FHL3	COBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (132): KDM2A (Affinity Capture-MS), KDM2A (Co-fractionation), KDM2A (Co-fractionation), KDM2A (Co-fractionation), KDM2A (Co-fractionation), PPP1R2 (Co-fractionation), STAG2 (Co-fractionation), SKP1 (Affinity Capture-Western), KDM2A (Synthetic Lethality), KDM2A (Proximity Label-MS), KDM2A (Affinity Capture-MS), KDM2A (Affinity Capture-MS), KDM2A (Affinity Capture-MS), KDM2A (Affinity Capture-MS), KDM2A (Affinity Capture-MS)

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

Diamond homologs: 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

5 interactions.

A	Effect	B	Mechanism
KDM2A	down-regulates	RELA	demethylation
KDM2A	down-regulates	NfKb-p65/p50	demethylation
HIF1A	“up-regulates quantity by expression”	KDM2A	“transcriptional regulation”
EPAS1	“up-regulates quantity by expression”	KDM2A	“transcriptional regulation”
2-oxoglutarate(2-)	“up-regulates activity”	KDM2A	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	10
Uncertain significance	82
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
3778797	NM_012308.3(KDM2A):c.58C>T (p.Arg20Ter)	Pathogenic
3778798	NM_012308.3(KDM2A):c.579C>G (p.Tyr193Ter)	Pathogenic
3778799	NM_012308.3(KDM2A):c.1676dup (p.Ile560fs)	Pathogenic
3778800	NM_012308.3(KDM2A):c.1677del (p.Ile560fs)	Pathogenic
3778802	NM_012308.3(KDM2A):c.2667del (p.Asp889fs)	Pathogenic
3778803	NM_012308.3(KDM2A):c.2809_2812dup (p.Cys938Ter)	Pathogenic
59758	GRCh38/hg38 11q13.2(chr11:67016543-67256428)x3	Pathogenic
3359230	NM_012308.3(KDM2A):c.1772T>C (p.Met591Thr)	Likely pathogenic
3377192	NM_012308.3(KDM2A):c.850C>T (p.His284Tyr)	Likely pathogenic
3778794	NM_012308.3(KDM2A):c.422A>G (p.Tyr141Cys)	Likely pathogenic
3778796	NM_012308.3(KDM2A):c.2431C>A (p.His811Asn)	Likely pathogenic
3778801	NM_012308.3(KDM2A):c.2404dup (p.Thr802fs)	Likely pathogenic
3778805	NM_012308.3(KDM2A):c.704C>T (p.Pro235Leu)	Likely pathogenic
3778811	NM_012308.3(KDM2A):c.956G>A (p.Arg319Gln)	Likely pathogenic
3778813	NM_012308.3(KDM2A):c.1703G>A (p.Arg568Gln)	Likely pathogenic
3778814	NM_012308.3(KDM2A):c.1796G>C (p.Arg599Pro)	Likely pathogenic
4532151	NM_012308.3(KDM2A):c.1702C>G (p.Arg568Gly)	Likely pathogenic

SpliceAI

3591 predictions. Top by Δscore:

Variant	Effect	Δscore
11:67120049:GGTG:G	donor_loss	1.0000
11:67120050:G:T	donor_loss	1.0000
11:67120051:T:A	donor_loss	1.0000
11:67121232:A:AG	acceptor_gain	1.0000
11:67121233:G:GA	acceptor_gain	1.0000
11:67121233:GT:G	acceptor_gain	1.0000
11:67121354:GATTG:G	donor_gain	1.0000
11:67180075:CTAG:C	acceptor_loss	1.0000
11:67180076:TA:T	acceptor_loss	1.0000
11:67180077:A:AG	acceptor_gain	1.0000
11:67180077:AGC:A	acceptor_gain	1.0000
11:67180077:AGCGT:A	acceptor_gain	1.0000
11:67180078:G:GA	acceptor_gain	1.0000
11:67180078:GC:G	acceptor_gain	1.0000
11:67180078:GCG:G	acceptor_gain	1.0000
11:67180078:GCGT:G	acceptor_gain	1.0000
11:67180078:GCGTG:G	acceptor_gain	1.0000
11:67180157:G:GT	donor_gain	1.0000
11:67180218:G:GG	donor_gain	1.0000
11:67180218:GTC:G	donor_loss	1.0000
11:67181310:AT:A	acceptor_gain	1.0000
11:67181311:T:TA	acceptor_gain	1.0000
11:67207504:T:TA	acceptor_gain	1.0000
11:67207509:GGGA:G	acceptor_gain	1.0000
11:67207688:GGT:G	donor_loss	1.0000
11:67207689:G:GG	donor_gain	1.0000
11:67207689:GTTA:G	donor_loss	1.0000
11:67215440:TGCAG:T	donor_gain	1.0000
11:67215443:AGAAG:A	donor_loss	1.0000
11:67215444:GAA:G	donor_gain	1.0000

AlphaMissense

7651 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:67180148:T:C	F38L	1.000
11:67180150:T:A	F38L	1.000
11:67180150:T:G	F38L	1.000
11:67181863:T:C	F93S	1.000
11:67181878:T:A	V98D	1.000
11:67181892:G:A	G103R	1.000
11:67181892:G:C	G103R	1.000
11:67181892:G:T	G103W	1.000
11:67207510:G:A	G103E	1.000
11:67207518:C:A	R106S	1.000
11:67207519:G:C	R106P	1.000
11:67207531:T:A	V110D	1.000
11:67207578:T:A	W126R	1.000
11:67207578:T:C	W126R	1.000
11:67207579:G:C	W126S	1.000
11:67207628:T:A	N142K	1.000
11:67207628:T:G	N142K	1.000
11:67207635:A:C	S145R	1.000
11:67207637:C:A	S145R	1.000
11:67207637:C:G	S145R	1.000
11:67207639:T:A	L146H	1.000
11:67207639:T:C	L146P	1.000
11:67207644:T:C	F148L	1.000
11:67207645:T:C	F148S	1.000
11:67207646:T:A	F148L	1.000
11:67207646:T:G	F148L	1.000
11:67207660:T:C	L153P	1.000
11:67215352:G:C	D167H	1.000
11:67215353:A:C	D167A	1.000
11:67215353:A:T	D167V	1.000

dbSNP variants (sampled 300 via entrez): RS1000012707 (11:67164844 C>A), RS1000035252 (11:67230659 C>A,G,T), RS1000071816 (11:67126451 T>C), RS1000080769 (11:67183127 C>G), RS1000095289 (11:67160099 T>C), RS1000098636 (11:67140754 A>G), RS1000134459 (11:67123357 A>G), RS1000134540 (11:67183444 T>C), RS1000134931 (11:67119215 G>A,T), RS1000140360 (11:67254541 C>A,T), RS1000160325 (11:67123586 A>G), RS1000171574 (11:67207750 G>A), RS1000197694 (11:67201257 C>T), RS1000215326 (11:67163727 G>A,C,T), RS1000261699 (11:67204631 A>T)

Disease associations

OMIM: gene MIM:605657 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST004212_26	Height	2.000000e-12
GCST004601_158	Red blood cell count	3.000000e-10
GCST004602_197	Mean corpuscular volume	1.000000e-14
GCST006085_49	Prostate cancer	8.000000e-09
GCST007293_14	Body fat distribution (arm fat ratio)	9.000000e-08
GCST007294_129	Body fat distribution (trunk fat ratio)	8.000000e-28
GCST007294_95	Body fat distribution (trunk fat ratio)	1.000000e-35
GCST007295_43	Body fat distribution (leg fat ratio)	1.000000e-25
GCST007295_76	Body fat distribution (leg fat ratio)	1.000000e-21
GCST008163_514	Height	1.000000e-14
GCST012226_350	Waist circumference adjusted for body mass index	5.000000e-29
GCST012227_670	Hip circumference adjusted for BMI	1.000000e-34
GCST90000025_162	Appendicular lean mass	6.000000e-40
GCST90002403_204	Red blood cell count	2.000000e-23
GCST90020024_400	A body shape index	3.000000e-19
GCST90020025_1883	Waist-to-hip ratio adjusted for BMI	3.000000e-09
GCST90020027_1501	Waist-hip index	8.000000e-12
GCST90020028_1917	Hip circumference adjusted for BMI	5.000000e-40
GCST90020029_343	Waist circumference adjusted for body mass index	2.000000e-48

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count
EFO:0004341	body fat distribution
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1938210 (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

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
IOX2	Inhibition	7.28	pIC50
daminozide	Inhibition	5.82	pIC50

Binding affinities (BindingDB)

9 measured of 31 human assays (31 total across all organisms); most potent 9 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-[1-[(2-chlorophenyl)methyl]imidazol-4-yl]-4-(1H-triazol-4-yl)pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-[1-(1-phenylethyl)imidazol-4-yl]-4-(1H-triazol-4-yl)pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-[1-[2-(2-methoxyphenyl)ethyl]imidazol-4-yl]-4-(1H-triazol-4-yl)pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-[1-(1,2,3,4-tetrahydronaphthalen-1-ylmethyl)imidazol-4-yl]-4-(1H-triazol-4-yl)pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-[1-[2-(2-ethoxyphenyl)ethyl]imidazol-4-yl]-4-(1H-triazol-4-yl)pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-[1-[(2,3-dichlorophenyl)methyl]imidazol-4-yl]-4-(1H-triazol-4-yl)pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-[1-[[2-chloro-3-(trifluoromethyl)phenyl]methyl]imidazol-4-yl]-4-(1H-triazol-4-yl)pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-[1-(2-naphthalen-1-ylethyl)imidazol-4-yl]-4-(1H-triazol-4-yl)pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
1-benzyl-4-{1H-[1,2,3]triazolo[4,5-c]pyridin-6-yl}-1H-imidazole	IC50	300 nM	US-9896436: Histone demethylase inhibitors

ChEMBL bioactivities

96 potent at pChembl≥5 of 148 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.09	Kd	8.2	nM	CHEMBL2392184
8.03	Kd	9.3	nM	CHEMBL2392184
7.95	Ki	11.3	nM	CHEMBL2392184
7.72	Kd	19	nM	CHEMBL2392184
7.66	Kd	22	nM	CHEMBL2392184
7.20	IC50	63.1	nM	CHEMBL3621881
7.20	IC50	63	nM	CHEMBL5173876
7.00	IC50	100	nM	CHEMBL4294926
7.00	IC50	100	nM	CHEMBL4288093
7.00	IC50	100	nM	CHEMBL4283409
6.90	IC50	125.9	nM	CHEMBL3621878
6.87	IC50	135	nM	CHEMBL2392184
6.80	IC50	160	nM	CHEMBL5723343
6.73	Ki	185	nM	CHEMBL2392184
6.70	IC50	200	nM	CHEMBL1229308
6.70	IC50	200	nM	CHEMBL1230640
6.66	IC50	220	nM	CHEMBL3108958
6.60	IC50	250	nM	CHEMBL2164246
6.55	Ki	280	nM	CHEMBL3785340
6.55	EC50	280	nM	CHEMBL3785340
6.55	IC50	280	nM	CHEMBL3786265
6.55	IC50	280	nM	CHEMBL600353
6.55	IC50	280	nM	CHEMBL3786188
6.43	IC50	370	nM	CHEMBL2164245
6.40	IC50	398.1	nM	CHEMBL3621872
6.38	IC50	420	nM	CHEMBL2392185
6.38	Ki	420	nM	CHEMBL3786265
6.37	IC50	430	nM	CHEMBL51979
6.26	IC50	550	nM	CHEMBL4294926
6.26	IC50	550	nM	CHEMBL4288093
6.26	IC50	550	nM	CHEMBL4283409
6.24	IC50	570	nM	SUCCINYLACETONE
6.20	IC50	631	nM	CHEMBL3621880
6.18	EC50	660	nM	CHEMBL3785340
6.09	IC50	820	nM	CHEMBL3786952
6.05	IC50	900	nM	CHEMBL2392184
6.05	EC50	900	nM	CHEMBL3786188
6.03	EC50	930	nM	CHEMBL3786188
6.00	IC50	1000	nM	CHEMBL3621873
5.92	IC50	1200	nM	CHEMBL3774692
5.90	EC50	1260	nM	CHEMBL3786265
5.85	IC50	1400	nM	CHEMBL2392184
5.85	IC50	1420	nM	CHEMBL4585876
5.82	IC50	1500	nM	CHEMBL2164243
5.82	Ki	1500	nM	CHEMBL3786188
5.71	Ki	1970	nM	CHEMBL2164243
5.71	IC50	1970	nM	CHEMBL4592908
5.70	Ki	1980	nM	CHEMBL2392184
5.70	IC50	1995	nM	CHEMBL3621879
5.62	IC50	2400	nM	CHEMBL3775668

PubChem BioAssay actives

90 with measured affinity, of 195 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
disodium;9-[4-[[[4-(aminomethyl)phenyl]methyl-[4-[[(E)-3-carboxyprop-2-enoyl]-oxidoamino]butyl]carbamothioyl]amino]-2-carboxyphenyl]-6-oxoxanthen-3-olate	754169: Binding affinity to recombinant 6xHis-tagged JHDM1A (unknown origin) expressed in Escherichia coli BL21 by fluorescence polarization assay in presence of Fe2+ and sodium ascorbate	kd	0.0082	uM
(E)-4-[2-(4-benzylpyridine-3-carbonyl)hydrazinyl]-4-oxobut-2-enoic acid	1916587: Inhibition of human KDM2A preincubated for 15 mins followed by substrate addition and measured after 30 mins using Biotin-H3(28-48)K36Me2 peptide as substrate by AlphaScreen-based assay	ic50	0.0630	uM
2-[1-[(3R)-1-benzoylpiperidin-3-yl]triazol-4-yl]pyridine-4-carboxylic acid	1249053: Inhibition of KDM2A (unknown origin) using Biotin-H3(28-48)K36Me2 and H3(28-48)K36Me2 substrates incubated for 30 mins by alpha screen assay	ic50	0.0631	uM
2-[1-(1-benzoylpiperidin-3-yl)triazol-4-yl]pyridine-4-carboxylic acid	1249053: Inhibition of KDM2A (unknown origin) using Biotin-H3(28-48)K36Me2 and H3(28-48)K36Me2 substrates incubated for 30 mins by alpha screen assay	ic50	0.1259	uM
8-hydroxyquinoline-5-carboxylic acid	1916574: Inhibition of KDM2A (unknown origin) expressed in Escherichia coli and measured after 1 hrs by alpha screen assay	ic50	0.2000	uM
3-[9-(dimethylamino)nonanoyl-hydroxyamino]propanoic acid	770454: Inhibition of KDM2A (unknown origin)	ic50	0.2000	uM
2-[4-[[4-[(1S,2R)-2-aminocyclopropyl]phenyl]carbamoyl]-2-pyridinyl]pyridine-4-carboxylic acid;2,2,2-trifluoroacetic acid	1066186: Inhibition of recombinant FBXL11 (unknown origin) incubated for 15 mins prior to substrate addition by AlphaScreen method	ic50	0.2200	uM
4-hydrazinyl-4-oxobutanoic acid	698700: Inhibition of human KDM2A expressed in Escherichia coli using methyl lysine peptide substrate by AlphaScreen assay	ic50	0.2500	uM
4-[(E)-2-(1-hexylpyridin-1-ium-4-yl)ethenyl]-N,N-dimethylaniline iodide	1289400: Competitive inhibition of recombinant His6-tagged KDM2A (1 to 517 residues) (unknown origin) expressed in Escherichia coli BL21 cells using methylstat as substrate preincubated for 30 mins followed by substrate addition measured after 4 hrs by fluorescence polarization assay	ki	0.2800	uM
2-benzoyl-4-(4-methylphenyl)-9-phenyl-1,6-dithia-3,4,9-triazaspiro[4.4]non-2-en-8-one	1885309: Inhibition of KDM2A in human MIA PaCa-2 cells assessed as induction of H3K36me2 measured by immunofluorescence assay	ic50	0.2800	uM
4-[2-(1-hexylpyridin-1-ium-2-yl)ethenyl]-N,N-dimethylaniline iodide	1885309: Inhibition of KDM2A in human MIA PaCa-2 cells assessed as induction of H3K36me2 measured by immunofluorescence assay	ic50	0.2800	uM
4-[(E)-2-[1-[(4-fluorophenyl)methyl]pyridin-1-ium-4-yl]ethenyl]-N,N-dimethylaniline iodide	1885309: Inhibition of KDM2A in human MIA PaCa-2 cells assessed as induction of H3K36me2 measured by immunofluorescence assay	ic50	0.2800	uM
4-(2-methylhydrazinyl)-4-oxobutanoic acid	698700: Inhibition of human KDM2A expressed in Escherichia coli using methyl lysine peptide substrate by AlphaScreen assay	ic50	0.3700	uM
2-[1-(1-benzoylpyrrolidin-3-yl)triazol-4-yl]pyridine-4-carboxylic acid	1249053: Inhibition of KDM2A (unknown origin) using Biotin-H3(28-48)K36Me2 and H3(28-48)K36Me2 substrates incubated for 30 mins by alpha screen assay	ic50	0.3981	uM
(E)-4-[4-[[4-(aminomethyl)phenyl]methylamino]butyl-hydroxyamino]-4-oxobut-2-enoic acid	754167: Inhibition of recombinant 6xHis-tagged JHDM1A (unknown origin) expressed in Escherichia coli BL21 using SAPATGGVK(Me2)KPHRYRPGTVAL as substrate incubated for 15 mins prior to substrate addition measured after 50 mins by rapid fire mass spectrophotometric analysis	ic50	0.4200	uM
4-(hydroxyamino)-4-oxobutanoic acid	698700: Inhibition of human KDM2A expressed in Escherichia coli using methyl lysine peptide substrate by AlphaScreen assay	ic50	0.4300	uM
4,6-dioxoheptanoic acid	698700: Inhibition of human KDM2A expressed in Escherichia coli using methyl lysine peptide substrate by AlphaScreen assay	ic50	0.5700	uM
2-[1-[1-(3-phenylpropanoyl)piperidin-3-yl]triazol-4-yl]pyridine-4-carboxylic acid	1249053: Inhibition of KDM2A (unknown origin) using Biotin-H3(28-48)K36Me2 and H3(28-48)K36Me2 substrates incubated for 30 mins by alpha screen assay	ic50	0.6310	uM
2-[5-[(4-chloro-2-methylphenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391733: Inhibition of KDM2A (unknown origin)	ic50	0.8200	uM
2-[1-[1-(2-phenylacetyl)pyrrolidin-3-yl]triazol-4-yl]pyridine-4-carboxylic acid	1249053: Inhibition of KDM2A (unknown origin) using Biotin-H3(28-48)K36Me2 and H3(28-48)K36Me2 substrates incubated for 30 mins by alpha screen assay	ic50	1.0000	uM
2-(2-amino-1,3-thiazol-4-yl)pyridine-4-carboxylic acid	1282552: Inhibition of KDM2A (unknown origin) using biotin-H3K36me2 (28 to 48 residues) as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by alphascreen assay	ic50	1.2000	uM
8-[4-[2-[4-[4-[2-(dimethylamino)ethyl]phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556105: Inhibition of KDM2A (unknown origin) by Alphascreen assay	ic50	1.4200	uM
4-(2,2-dimethylhydrazinyl)-4-oxobutanoic acid	698691: Inhibition of human KDM2A expressed in Escherichia coli by formaldehyde dehydrogenase coupled assay	ic50	1.5000	uM
8-[4-[2-[4-[3-(pyrrolidin-1-ylmethyl)phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556105: Inhibition of KDM2A (unknown origin) by Alphascreen assay	ic50	1.9700	uM
2-[1-[1-(2-phenylacetyl)piperidin-3-yl]triazol-4-yl]pyridine-4-carboxylic acid	1249053: Inhibition of KDM2A (unknown origin) using Biotin-H3(28-48)K36Me2 and H3(28-48)K36Me2 substrates incubated for 30 mins by alpha screen assay	ic50	1.9953	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	2.0000	uM
8-[4-[2-[4-(3,5-dichlorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282552: Inhibition of KDM2A (unknown origin) using biotin-H3K36me2 (28 to 48 residues) as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by alphascreen assay	ic50	2.4000	uM
8-[4-[2-(4-thiophen-2-ylpiperidin-1-yl)ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282552: Inhibition of KDM2A (unknown origin) using biotin-H3K36me2 (28 to 48 residues) as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by alphascreen assay	ic50	2.4000	uM
2-[1-[1-(3-phenylpropanoyl)piperidin-4-yl]triazol-4-yl]pyridine-4-carboxylic acid	1249053: Inhibition of KDM2A (unknown origin) using Biotin-H3(28-48)K36Me2 and H3(28-48)K36Me2 substrates incubated for 30 mins by alpha screen assay	ic50	2.5119	uM
3-[hydroxy(9-phenylnonanoyl)amino]propanoic acid	770454: Inhibition of KDM2A (unknown origin)	ic50	2.9000	uM
2-[1-[(3S)-1-benzoylpiperidin-3-yl]triazol-4-yl]pyridine-4-carboxylic acid	1249053: Inhibition of KDM2A (unknown origin) using Biotin-H3(28-48)K36Me2 and H3(28-48)K36Me2 substrates incubated for 30 mins by alpha screen assay	ic50	3.1623	uM
4-[dimethylamino(methyl)amino]-4-oxobutanoic acid	698700: Inhibition of human KDM2A expressed in Escherichia coli using methyl lysine peptide substrate by AlphaScreen assay	ic50	3.7000	uM
8-[4-[2-[4-[3-(pyrrolidin-1-ylmethyl)-5-(trifluoromethyl)phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556105: Inhibition of KDM2A (unknown origin) by Alphascreen assay	ic50	3.7700	uM
4-phenyl-1-prop-2-enoylpiperidine-4-carboxylic acid	1871100: Inhibition of GST-tagged human KDM2A (562 to 618 residues) expressed in Escherichia coli BL21 cells incubated for 30 mins by fluorescence polarization assay	ic50	3.9000	uM
pyridine-2,4-dicarboxylic acid	1249066: Inhibition of KDM2A (unknown origin)	ic50	3.9811	uM
2-[1-[1-(2-phenylacetyl)piperidin-4-yl]triazol-4-yl]pyridine-4-carboxylic acid	1249053: Inhibition of KDM2A (unknown origin) using Biotin-H3(28-48)K36Me2 and H3(28-48)K36Me2 substrates incubated for 30 mins by alpha screen assay	ic50	3.9811	uM
2-pyridin-2-ylpyridine-4-carboxylic acid	1249053: Inhibition of KDM2A (unknown origin) using Biotin-H3(28-48)K36Me2 and H3(28-48)K36Me2 substrates incubated for 30 mins by alpha screen assay	ic50	3.9811	uM
4-(4-ethoxyphenyl)-1-prop-2-enoylpiperidine-4-carboxylic acid	1871100: Inhibition of GST-tagged human KDM2A (562 to 618 residues) expressed in Escherichia coli BL21 cells incubated for 30 mins by fluorescence polarization assay	ic50	4.2000	uM
1-[4-phenyl-4-(2H-tetrazol-5-yl)piperidin-1-yl]prop-2-en-1-one	1871100: Inhibition of GST-tagged human KDM2A (562 to 618 residues) expressed in Escherichia coli BL21 cells incubated for 30 mins by fluorescence polarization assay	ic50	4.4000	uM
8-[4-(2-spiro[1,2-dihydroindene-3,4’-piperidine]-1’-ylethyl)pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556105: Inhibition of KDM2A (unknown origin) by Alphascreen assay	ic50	4.5000	uM
8-[4-[2-[4-(3-fluorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556105: Inhibition of KDM2A (unknown origin) by Alphascreen assay	ic50	4.6800	uM
2-(4-methoxycarbonyl-2-pyridinyl)pyridine-4-carboxylic acid	1066186: Inhibition of recombinant FBXL11 (unknown origin) incubated for 15 mins prior to substrate addition by AlphaScreen method	ic50	4.8000	uM
2-[1-(1-benzoylazetidin-3-yl)triazol-4-yl]pyridine-4-carboxylic acid	1249053: Inhibition of KDM2A (unknown origin) using Biotin-H3(28-48)K36Me2 and H3(28-48)K36Me2 substrates incubated for 30 mins by alpha screen assay	ic50	5.0119	uM
2-[1-(1-butanoylpiperidin-3-yl)triazol-4-yl]pyridine-4-carboxylic acid	1249053: Inhibition of KDM2A (unknown origin) using Biotin-H3(28-48)K36Me2 and H3(28-48)K36Me2 substrates incubated for 30 mins by alpha screen assay	ic50	5.0119	uM
2-(2H-triazol-4-yl)pyridine-4-carboxylic acid	1249053: Inhibition of KDM2A (unknown origin) using Biotin-H3(28-48)K36Me2 and H3(28-48)K36Me2 substrates incubated for 30 mins by alpha screen assay	ic50	5.0119	uM
potassium 2-[1-(3-methylphenyl)triazol-4-yl]pyridine-4-carboxylate	1249053: Inhibition of KDM2A (unknown origin) using Biotin-H3(28-48)K36Me2 and H3(28-48)K36Me2 substrates incubated for 30 mins by alpha screen assay	ic50	6.3096	uM
2-[1-(2-phenoxyethyl)triazol-4-yl]pyridine-4-carboxylic acid	1249053: Inhibition of KDM2A (unknown origin) using Biotin-H3(28-48)K36Me2 and H3(28-48)K36Me2 substrates incubated for 30 mins by alpha screen assay	ic50	6.3096	uM
2-[1-(1-propanoylpiperidin-4-yl)triazol-4-yl]pyridine-4-carboxylic acid	1249053: Inhibition of KDM2A (unknown origin) using Biotin-H3(28-48)K36Me2 and H3(28-48)K36Me2 substrates incubated for 30 mins by alpha screen assay	ic50	6.3096	uM
2-[1-[1-(2-phenylacetyl)azetidin-3-yl]triazol-4-yl]pyridine-4-carboxylic acid	1249053: Inhibition of KDM2A (unknown origin) using Biotin-H3(28-48)K36Me2 and H3(28-48)K36Me2 substrates incubated for 30 mins by alpha screen assay	ic50	6.3096	uM
8-[4-[2-[4-(4-chlorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282552: Inhibition of KDM2A (unknown origin) using biotin-H3K36me2 (28 to 48 residues) as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by alphascreen assay	ic50	6.7400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
cobaltous chloride	increases expression	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, affects expression	2
Ozone	decreases expression, increases abundance, affects expression, affects cotreatment	2
Valproic Acid	affects expression, decreases methylation	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression	1
bisphenol A	increases acetylation, decreases methylation, affects binding, affects reaction, decreases activity (+5 more)	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
cupric chloride	increases expression	1
coumarin	affects phosphorylation	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
bisphenol S	affects cotreatment, decreases activity, decreases expression, increases acetylation, increases phosphorylation (+5 more)	1
PCI 5002	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Acetylcysteine	affects binding, decreases reaction, increases abundance, increases reaction	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Vehicle Emissions	affects binding, decreases reaction, increases abundance, increases reaction, affects reaction (+2 more)	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1

ChEMBL screening assays

48 unique, capped per target: 47 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1942536	Binding	Inhibition of KDM2A	Lysine demethylases inhibitors. — J Med Chem
CHEMBL5723315	Functional	Affinity Biochemical interaction: (AlphaScreen) EUB0002790a KDM2A	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SU17	HAP1 KDM2A (-) 1	Cancer cell line	Male
CVCL_SU18	HAP1 KDM2A (-) 2	Cancer cell line	Male
CVCL_SU19	HAP1 KDM2A (-) 3	Cancer cell line	Male
CVCL_SU20	HAP1 KDM2A (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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

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