KDM4E

Summary

KDM4E (lysine demethylase 4E, HGNC:37098) is a protein-coding gene on chromosome 11q21, encoding Lysine-specific demethylase 4E (B2RXH2). Histone demethylase that demethylates trimethylated ‘Lys-9’ of histone H3 into monomethylated form, thereby playing a central role in histone code.

The protein encoded by this intronless gene is a member of a large family of histone lysine demethylases, which use oxygen and 2-oxoglutarate to demethylate di- and trimethylated lys9 of histone H3. Derepression of genes by demethylases is sometimes involved in viral infection or carcinogenesis, so inhibitors of these enzymes are desired.

Source: NCBI Gene 390245 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 107 total
• GTEx eGene: eQTL in 5 tissues, sQTL in 0 (q < 0.05)
• ChEMBL bioactivity: 356 clinical-phase molecules tested; no curated mechanism-of-action drug
• MANE Select transcript: NM_001161630
• Notable: 107 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37098
Approved symbol	KDM4E
Name	lysine demethylase 4E
Location	11q21
Locus type	gene with protein product
Status	Approved
Aliases	JMJD2E, KDM5E
Ensembl gene	ENSG00000235268
Ensembl biotype	protein_coding
OMIM	616581
Entrez	390245

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

MANE Select: ENST00000450979

ENST00000450979

RefSeq mRNA: 1 — MANE Select: NM_001161630 NM_001161630

CCDS: CCDS44713

Canonical transcript exons

ENST00000450979 — 1 exons

Exon	Start	End
ENSE00001783902	95025258	95027596

Expression profiles

Bgee: expression breadth broad, 14 present calls, max score 80.23.

Highest expression (Bgee): male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, placenta, tonsil, sural nerve.

Genetic regulation across tissues (GTEx eQTL / sQTL)

KDM4E is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 5 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

5 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	9.2e-08	+0.83	11:95038743:A:T
Skin Sun Exposed Lower leg	eqtl	1.2e-03	+0.29	11:94625376:C:T
Esophagus Muscularis	eqtl	7.0e-03	+0.53	11:94963832:A:C
Adipose Subcutaneous	eqtl	1.2e-02	+0.52	11:94951771:G:A
Brain Cerebellar Hemisphere	eqtl	3.2e-02	+0.55	11:95037890:A:G

Top tissues by expression

95 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.23	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.41	silver quality
placenta	UBERON:0001987	45.82	gold quality
tonsil	UBERON:0002372	43.58	gold quality
sural nerve	UBERON:0015488	42.88	gold quality
apex of heart	UBERON:0002098	41.07	silver quality
gall bladder	UBERON:0002110	40.85	gold quality
bone marrow cell	CL:0002092	40.42	gold quality
saliva-secreting gland	UBERON:0001044	40.04	silver quality
smooth muscle tissue	UBERON:0001135	39.88	silver quality
minor salivary gland	UBERON:0001830	39.01	silver quality
right lobe of thyroid gland	UBERON:0001119	38.47	silver quality
urinary bladder	UBERON:0001255	38.34	silver quality
muscle tissue	UBERON:0002385	38.15	gold quality
skeletal muscle tissue	UBERON:0001134	37.97	gold quality
lower esophagus mucosa	UBERON:0035834	37.41	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
thoracic mammary gland	UBERON:0005200	36.98	silver quality
lymph node	UBERON:0000029	36.50	gold quality
granulocyte	CL:0000094	36.49	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
endometrium	UBERON:0001295	36.25	gold quality
pituitary gland	UBERON:0000007	36.18	silver quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
right ovary	UBERON:0002118	35.11	gold quality
bone marrow	UBERON:0002371	35.05	gold quality
right coronary artery	UBERON:0001625	35.03	gold quality
right lung	UBERON:0002167	34.32	gold quality
mucosa of transverse colon	UBERON:0004991	34.28	gold quality
endocervix	UBERON:0000458	33.94	gold quality
right adrenal gland cortex	UBERON:0035827	33.78	gold quality
corpus callosum	UBERON:0002336	33.36	gold quality
adenohypophysis	UBERON:0002196	33.09	silver quality
liver	UBERON:0002107	33.07	gold quality
body of uterus	UBERON:0009853	33.05	gold quality
adrenal tissue	UBERON:0018303	33.03	gold quality
prefrontal cortex	UBERON:0000451	32.96	gold quality
omental fat pad	UBERON:0010414	32.54	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
left coronary artery	UBERON:0001626	32.09	gold quality
small intestine	UBERON:0002108	31.99	gold quality
fundus of stomach	UBERON:0001160	31.96	gold quality
blood	UBERON:0000178	31.92	gold quality
left adrenal gland cortex	UBERON:0035825	31.91	gold quality
left adrenal gland	UBERON:0001234	31.32	gold quality
cerebellum	UBERON:0002037	31.30	gold quality
cerebellar cortex	UBERON:0002129	31.23	gold quality
cerebellar hemisphere	UBERON:0002245	31.21	gold quality
adipose tissue	UBERON:0001013	31.15	gold quality
leukocyte	CL:0000738	31.02	gold quality
right hemisphere of cerebellum	UBERON:0014890	30.87	gold quality
monocyte	CL:0000576	30.75	gold quality
small intestine Peyer’s patch	UBERON:0003454	30.68	gold quality
muscle layer of sigmoid colon	UBERON:0035805	30.58	gold quality
testis	UBERON:0000473	30.54	gold quality
descending thoracic aorta	UBERON:0002345	30.47	gold quality
right testis	UBERON:0004534	30.42	silver quality
stomach	UBERON:0000945	30.32	gold quality
left testis	UBERON:0004533	30.27	silver quality
frontal cortex	UBERON:0001870	30.24	gold quality
primary visual cortex	UBERON:0002436	30.15	gold quality
intestine	UBERON:0000160	30.07	gold quality
rectum	UBERON:0001052	29.91	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
subcutaneous adipose tissue	UBERON:0002190	29.85	gold quality
lung	UBERON:0002048	29.68	gold quality
body of stomach	UBERON:0001161	29.58	gold quality
colon	UBERON:0001155	29.29	gold quality
vermiform appendix	UBERON:0001154	29.27	gold quality
Brodmann (1909) area 9	UBERON:0013540	28.88	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	28.79	gold quality
right uterine tube	UBERON:0001302	28.74	gold quality
right lobe of liver	UBERON:0001114	28.46	gold quality
thoracic aorta	UBERON:0001515	28.45	gold quality
cerebral cortex	UBERON:0000956	28.29	gold quality
duodenum	UBERON:0002114	28.14	gold quality
upper lobe of left lung	UBERON:0008952	28.09	gold quality
ascending aorta	UBERON:0001496	28.04	gold quality
Ammon’s horn	UBERON:0001954	28.00	gold quality
putamen	UBERON:0001874	27.67	gold quality
superior frontal gyrus	UBERON:0002661	27.45	gold quality
transverse colon	UBERON:0001157	27.31	gold quality
right frontal lobe	UBERON:0002810	26.88	gold quality
tibial artery	UBERON:0007610	26.75	gold quality
popliteal artery	UBERON:0002250	26.69	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	26.66	gold quality
caudate nucleus	UBERON:0001873	26.29	gold quality
temporal lobe	UBERON:0001871	25.90	gold quality
amygdala	UBERON:0001876	25.80	gold quality
hypothalamus	UBERON:0001898	25.78	gold quality
nucleus accumbens	UBERON:0001882	25.76	gold quality
calcaneal tendon	UBERON:0003701	25.48	gold quality
anterior cingulate cortex	UBERON:0009835	25.01	gold quality
mucosa of stomach	UBERON:0001199	18.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.29

HPA expression

RNA tissue specificity: Not detected

59 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Pons	tissue	0.4
Medulla oblongata	tissue	0.4
Amygdala	tissue	0.3
Thalamus	tissue	0.3
Hypothalamus	tissue	0.3
Spinal cord	tissue	0.3
Skin 1	tissue	0.2	high
Cerebral cortex	tissue	0.2	high
Salivary gland	tissue	0.2	medium
Basal ganglia	tissue	0.2	high
Choroid plexus	tissue	0.2
Midbrain	tissue	0.2
Cerebellum	tissue	0.2	medium
Substantia nigra	tissue	0.2
Pituitary gland	tissue	0.1
Testis	tissue	0.1	medium
Putamen	tissue	0.1
Nucleus accumbens	tissue	0.1
Spleen	tissue	0.1	medium
Locus coeruleus	tissue	0.1
Hippocampus	tissue	0.1	high
Hippocampal formation	tissue	0.1
Retrosplenial cortex	tissue	0.1
Cervix	tissue	0.0	high
Lymph node	tissue	0.0	high
Breast	tissue	0.0	medium
Stomach 1	tissue	0.0	medium
Heart muscle	tissue	0.0	medium
Ovary	tissue	0.0	low
Vagina	tissue	0.0	high
Seminal vesicle	tissue	0.0	medium
Esophagus	tissue	0.0	high
Rectum	tissue	0.0	high
Parathyroid gland	tissue	0.0	medium
Skeletal muscle	tissue	0.0	medium
Smooth muscle	tissue	0.0	medium
Colon	tissue	0.0	high
Urinary bladder	tissue	0.0	high
Pancreas	tissue	0.0	high
Endometrium 1	tissue	0.0	high
Epididymis	tissue	0.0	high
Placenta	tissue	0.0	medium
Thyroid gland	tissue	0.0	high
Lung	tissue	0.0	medium
Liver	tissue	0.0	medium
Small intestine	tissue	0.0	medium
Gallbladder	tissue	0.0	high
Kidney	tissue	0.0	medium
Duodenum	tissue	0.0	high
Prostate	tissue	0.0	medium
Adrenal gland	tissue	0.0	medium
Bone marrow	tissue	0.0	low
Tonsil	tissue	0.0	high
Fallopian tube	tissue	0.0	high
Appendix	tissue	0.0	high
Nasopharynx	tissue	-1.0	high
Bronchus	tissue	-1.0	high
Soft tissue 1	tissue	-1.0	low
Oral mucosa	tissue	-1.0	high

Brain sub-regions (HPA Brain Atlas): detected in 174; highest nTPM — Motor trigeminal nucleus (0.4), Nucleus gracilis (0.4), Nucleus raphe obscurus (0.4), Anterior cochlear nucleus, ventral (0.3), Anterior funiculus (white matter) (0.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting KDM4E by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 43 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-3923	99.52	69.21	446
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-4641	99.28	66.64	744
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-219A-1-3P	98.91	67.87	639
HSA-MIR-6754-5P	98.60	65.54	1627

Functional genomics

Regional missense constraint (gnomAD)

ENST00000450979 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
11:95,025,558–95,026,235	207 / 284.2	0.73	no
11:95,026,236–95,027,075	369 / 358.4	1.03	no

Literature-anchored findings (GeneRIF, showing 1)

• Results indicate that the histone demethylase activity is regulated by oxygen availability. (PMID:23092293)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	kdm4c	ENSDARG00000061504
drosophila_melanogaster	Kdm5	FBGN0031759
caenorhabditis_elegans		WBGENE00004319

Paralogs (10): JARID2 (ENSG00000008083), KDM5D (ENSG00000012817), KDM4A (ENSG00000066135), KDM5A (ENSG00000073614), KDM4C (ENSG00000107077), KDM5B (ENSG00000117139), KDM5C (ENSG00000126012), KDM4B (ENSG00000127663), KDM4D (ENSG00000186280), KDM4F (ENSG00000255855)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RD88	99.3%	Diamond
Pan troglodytes	Q5XUN4	98.8%	Diamond
Canis lupus familiaris	Q38JA7	97.6%	Diamond
Mus musculus	Q3UXZ9	96.7%	Diamond
Sus scrofa	A1YVX4	95.2%	Diamond
Rattus norvegicus	A1A5Q5	90.2%	Diamond
Gallus gallus	Q5F3R2	83.2%	Diamond
Caenorhabditis briggsae	Q61T02	73.3%	Diamond
Arabidopsis thaliana	F4I6G4	66.5%	Diamond
Oryza sativa Japonica Group	Q336N8	60.2%	Diamond
Saccharomyces cerevisiae S288C	P47156	53.3%	Diamond
Schizosaccharomyces pombe 972h-	Q9US53	38.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CWC15	protein-coding	51503
KDM4D	protein-coding	55693
KDM4F	protein-coding	100129053

Protein

Protein identifiers

Lysine-specific demethylase 4E — B2RXH2 (reviewed: B2RXH2)

Alternative names: KDM4D-like protein, Lysine-specific demethylase 4D-like, [histone H3]-trimethyl-L-lysine(9) demethylase 4E

All UniProt accessions (1): B2RXH2

UniProt curated annotations — full annotation on UniProt →

Function. Histone demethylase that demethylates trimethylated ‘Lys-9’ of histone H3 into monomethylated form, thereby playing a central role in histone code. Also demethylates trimethylated ‘Lys-56’ of histone H3 (H3K9me3) to generate the monomethylated state (H3K56me1).

Subcellular location. Nucleus.

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

Similarity. Belongs to the JHDM3 histone demethylase family.

RefSeq proteins (1): NP_001155102* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003347	JmjC_dom	Domain
IPR003349	JmjN	Domain

Pfam: PF02373, PF02375

Enzyme classification (BRENDA)

• EC 1.14.11.66 — [histone H3]-trimethyl-L-lysine9 demethylase (BRENDA: 7 organisms, 79 substrates, 168 inhibitors, 23 Km, 14 kcat entries)
• EC 1.14.11.B19 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
HISTONE H3 N6,N6,N6-TRIMETHYL-L-LYSINE9	0.023–0.048	5
HISTONE H3 N6,N6-DIMETHYL-L-LYSINE9	0.025–0.074	5
2-OXOGLUTARATE	0.0247	2
H31-15K9ME3	0.0232	2
O2	0.173	2
[HISTONE H3, A7H]-N6,N6,N6-TRIMETHYL-L-LYSINE 9	0.11	1
[HISTONE H3, A7R]-N6,N6,N6-TRIMETHYL-L-LYSINE 9	0.18	1
[HISTONE H3, G12P]-N6,N6,N6-TRIMETHYL-L-LYSINE 9	0.93	1
[HISTONE H3]-N6,N6,N6-TRIMETHYL-L-LYSINE 9	0.071	1

Catalyzed reactions (Rhea)

• N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + 2-oxoglutarate + O2 = N(6)-methyl-L-lysyl(9)-[histone H3] + formaldehyde + succinate + CO2 (RHEA:60192)
• N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3] + 2 2-oxoglutarate + 2 O2 = N(6)-methyl-L-lysyl(9)-[histone H3] + 2 formaldehyde + 2 succinate + 2 CO2 (RHEA:60200)
• N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3] + 2-oxoglutarate + O2 = N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + formaldehyde + succinate + CO2 (RHEA:60204)
• N(6),N(6),N(6)-trimethyl-L-lysyl(56)-[histone H3] + 2-oxoglutarate + O2 = N(6),N(6)-dimethyl-L-lysyl(56)-[histone H3] + formaldehyde + succinate + CO2 (RHEA:85927)
• N(6),N(6)-dimethyl-L-lysyl(56)-[histone H3] + 2-oxoglutarate + O2 = N(6)-methyl-L-lysyl(56)-[histone H3] + formaldehyde + succinate + CO2 (RHEA:85931)

UniProt features (56 total): helix 17, strand 15, binding site 11, sequence variant 4, turn 4, domain 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
2W2I	Crystal structure of the human 2-oxoglutarate oxygenase LOC390245	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-B2RXH2-F1	76.85	0.59

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Oxidoreductases, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

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 (11)

Position	Role
235	Zn(2+)
241	Zn(2+)
242	2-oxoglutarate
277	Fe cation
307	Zn(2+)
309	Zn(2+)
133	2-oxoglutarate
189	Fe cation
191	Fe cation
199	2-oxoglutarate
207	2-oxoglutarate

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-9819196	Zygotic genome activation (ZGA)	curated
R-HSA-1266738	Developmental Biology	—
R-HSA-9816359	Maternal to zygotic transition (MZT)	—

MSigDB gene sets: 24 (showing top): GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_CHROMATIN_REMODELING, GOMF_DEMETHYLASE_ACTIVITY, chr11q21, GOMF_DIOXYGENASE_ACTIVITY, GOMF_HISTONE_H3K9_DEMETHYLASE_ACTIVITY, MIR875_3P, MIR4441, MIR6780A_5P, MIR6505_5P, MIR6852_5P, MIR4270, MIR4308, MIR6754_5P, GOMF_PROTEIN_DEMETHYLASE_ACTIVITY

GO Biological Process (4): chromatin remodeling (GO:0006338), DNA-templated transcription (GO:0006351), regulation of gene expression (GO:0010468), chromatin organization (GO:0006325)

GO Molecular Function (6): histone H3K9 demethylase activity (GO:0032454), metal ion binding (GO:0046872), histone H3K9me2/H3K9me3 demethylase activity (GO:0140684), histone H3K56me2/H3K56me3 demethylase activity (GO:0140760), oxidoreductase activity (GO:0016491), dioxygenase activity (GO:0051213)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Maternal to zygotic transition (MZT)	1
Developmental Biology	1

GO top-level categories

15 GO namespaces:

Category	Terms
gene expression	2
histone H3 demethylase activity	2
2-oxoglutarate-dependent dioxygenase activity	2
cellular anatomical structure	2
chromatin organization	1
RNA biosynthetic process	1
regulation of macromolecule biosynthetic process	1
cellular component organization	1
cation binding	1
histone H3K9 demethylase activity	1
catalytic activity	1
oxidoreductase activity	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 13 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
nucleus	CC	direct assay
histone H3K56me2/H3K56me3 demethylase activity	MF	direct assay
histone H3K9me2/H3K9me3 demethylase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 316 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KDM4E	JMJD1C	Q15652	660
KDM4E	PHF8	Q9UPP1	574
KDM4E	KDM3A	Q9Y4C1	557
KDM4E	KDM2A	Q9Y2K7	538
KDM4E	KDM6B	O15054	533
KDM4E	KDM8	Q8N371	512
KDM4E	KDM1A	O60341	487
KDM4E	KDM7A	Q6ZMT4	468
KDM4E	EGLN1	Q9GZT9	440
KDM4E	KDM3B	Q7LBC6	429
KDM4E	MBD3L3	A6NE82	429
KDM4E	ZSCAN4	Q8NAM6	422
KDM4E	JMJD6	Q6NYC1	413
KDM4E	RIOX1	Q9H6W3	403
KDM4E	Q08EI0	Q08EI0	402

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
2-oxoglutarate(2-)	“up-regulates activity”	KDM4E	“chemical activation”

Disease & clinical

Genetic variants

Variant evidence for KDM4E: 107 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	99
Likely benign	6
Benign	2

SpliceAI

Top 4 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 4 predictions of 4):

Position(s)	Effect	Δscore	Sites
11:95026099	acceptor_gain	0.2300
11:95026315	donor_gain	0.2300
11:95027271	acceptor_gain	0.2100
11:95025985	acceptor_gain	0.2000

AlphaMissense

650 missense substitutions predicted likely pathogenic (of 3,341 scored), across 169 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M181	9	0.780	0.928
F272	8	0.892	0.981
F292	8	0.892	0.988
F186	8	0.873	0.982
F268	8	0.862	0.983
H202	8	0.849	0.963
F321	8	0.838	0.956
F28	8	0.822	0.960
H189	8	0.815	0.918
H277	8	0.793	0.946
H241	8	0.788	0.894
W149	7	0.930	0.983
W188	7	0.923	0.989
W54	7	0.902	0.962
F280	7	0.900	0.983
W297	7	0.900	0.973
F25	7	0.894	0.971
F142	7	0.882	0.959
W209	7	0.881	0.966
W182	7	0.879	0.961

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene MIM:616581 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST010002_198	Refractive error	3e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293226 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,469,353 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 356 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1200813	ACEBUTOLOL HYDROCHLORIDE	4	4,186
CHEMBL734	ACETOHYDROXAMIC ACID	4	7,130
CHEMBL600	ACETYLCYSTEINE	4	96,284
CHEMBL1201038	ACRISORCIN	4	1,965
CHEMBL709	ALFUZOSIN	4	6,651
CHEMBL945	AMILORIDE	4	64,123
CHEMBL1398126	AMILORIDE HYDROCHLORIDE	4	2,113
CHEMBL463	AMINOHIPPURIC ACID	4	2,279
CHEMBL1169	AMINOSALICYLIC ACID	4	52,061
CHEMBL1200964	AMITRIPTYLINE HYDROCHLORIDE	4	9,435
CHEMBL1096	AMLEXANOX	4	4,227
CHEMBL1113	AMOXAPINE	4	20,303
CHEMBL1082	AMOXICILLIN	4	113,715
CHEMBL174	AMPICILLIN	4	336,569
CHEMBL1200758	AMPICILLIN SODIUM	4	5,652
CHEMBL1200550	ANTAZOLINE PHOSPHATE	4	493
CHEMBL53	APOMORPHINE	4	26,040
CHEMBL3187985	APOMORPHINE HYDROCHLORIDE	4	5,317
CHEMBL25	ASPIRIN	4	696,632
CHEMBL1684	BENDROFLUMETHIAZIDE	4	14,178
CHEMBL1201039	BENZTHIAZIDE	4
CHEMBL12610	BENZYDAMINE	4
CHEMBL942	BISACODYL	4
CHEMBL290106	BITHIONOL	4
CHEMBL1447476	BITHIONOLATE SODIUM	4
CHEMBL844	BRIMONIDINE	4
CHEMBL1200503	BROMOCRIPTINE MESYLATE	4
CHEMBL223448	BROXYQUINOLINE	4
CHEMBL94394	BUFEXAMAC	4
CHEMBL1072	BUMETANIDE	4
CHEMBL1200399	BUSPIRONE HYDROCHLORIDE	4
CHEMBL820	BUSULFAN	4
CHEMBL1014	CANDESARTAN CILEXETIL	4
CHEMBL1560	CAPTOPRIL	4
CHEMBL73234	CARBETAPENTANE	4
CHEMBL1256696	CARBETAPENTANE CITRATE	4
CHEMBL1200748	CARBIDOPA	4
CHEMBL1201236	CARBIDOPA ANHYDROUS	4
CHEMBL1351	CARBOPLATIN	4
CHEMBL723	CARVEDILOL	4
CHEMBL680	CEFACLOR ANHYDROUS	4
CHEMBL1200530	CEFOXITIN SODIUM	4
CHEMBL1201043	CEPHAPIRIN SODIUM	4
CHEMBL58510	CHLOROQUINE PHOSPHATE	4
CHEMBL1200761	CHLOROTRIANISENE	4
CHEMBL1200596	CHLOROXINE	4
CHEMBL1713	CHLORPROMAZINE HYDROCHLORIDE	4
CHEMBL311498	CIANIDANOL	4
CHEMBL348000	CINCHOPHEN	4
CHEMBL1208	CINOXACIN	4
CHEMBL8	CIPROFLOXACIN	4
CHEMBL11359	CISPLATIN	4
CHEMBL497	CLIOQUINOL	4
CHEMBL315795	CLOMETHIAZOLE	4
CHEMBL2355051	CLOMIPHENE	4
CHEMBL3185958	CLOMIPHENE CITRATE	4
CHEMBL1200710	CLOMIPRAMINE HYDROCHLORIDE	4
CHEMBL1200796	CYCLOPHOSPHAMIDE	4
CHEMBL476	DACARBAZINE	4
CHEMBL178	DAUNORUBICIN	4

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Histone demethylases

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

Ligand	Action	Affinity	Parameter
ML324	Inhibition	6.04	pIC50
compound 6a [PMID: 18942826]	Inhibition	5.85	pIC50

Binding affinities (BindingDB)

125 measured of 151 human assays (158 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
GNF-Pf-1011	IC50	0.001 nM
CHEMBL4303308	IC50	1.7 nM
GSKJ1	IC50	2.8 nM
pyridine-2,3-dicarboxylic acid	KD	43 nM
CHEMBL5422782	IC50	50 nM
CHEMBL3621881	IC50	63 nM
3-[[(4R)-7-(N-methyl-4-propan-2-ylanilino)-3,4-dihydro-2H-chromen-4-yl]methylamino]pyridine-4-carboxylic acid	IC50	80 nM	US-10106534: Histone demethylase inhibitors
CHEMBL3775237	IC50	100 nM
CHEMBL3775889	IC50	100 nM
4’-(phenethylcarbamoyl)-[2,2’-bipyridine]-4-carboxylic acid (N3)	IC50	110 nM
CHEMBL5430087	IC50	110 nM
CHEMBL3621878	IC50	126 nM
N-hydroxy-N’-phenyloctanediamide	IC50	140 nM
CHEMBL1615036	IC50	180 nM
CHEMBL5429223	IC50	280 nM
CHEMBL1982368	IC50	290 nM
CHEMBL3770740	IC50	398 nM
CHEMBL5425339	IC50	500 nM
3-((1-methyl-1Hpyrrolo[2,3-b]pyridin-3-yl)amino)isonicotinic acid (N12)	IC50	550 nM	US-10336727: Histone demethylase inhibitors
CHEMBL5415306	IC50	580 nM
CHEMBL3771198	IC50	631 nM
CHEMBL3621880	IC50	631 nM
CHEMBL3769724	IC50	794 nM
CHEMBL5428941	IC50	900 nM
MLS002391556	IC50	920 nM
(2E,4E,6R)-7-[4-(dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-oxohepta-2,4-dienamide	EC50	1000 nM
CHEMBL3621873	IC50	1000 nM
CHEMBL5407378	IC50	1200 nM
CHEMBL5429166	IC50	1220 nM
CHEMBL3769511	IC50	1580 nM
CHEMBL5434665	IC50	1800 nM
CHEMBL5419332	IC50	1900 nM
CHEMBL3621879	IC50	2000 nM
CHEMBL5396670	IC50	2000 nM
R115 (Reactive Blue 2)	IC50	2100 nM
CHEMBL3621864	IC50	2510 nM
CHEMBL5423565	IC50	2600 nM
Isoquinoline 3	IC50	2800 nM
CHEMBL5402035	IC50	2800 nM
CHEMBL3621882	IC50	3160 nM
CHEMBL3621850	IC50	3160 nM
CHEMBL3114982	IC50	3600 nM
CHEMBL5414235	IC50	3950 nM
CHEMBL3621852	IC50	3980 nM
CHEMBL3621863	IC50	3980 nM
CHEMBL1571747	IC50	4000 nM
2-[4-(methoxycarbonyl)pyridin-2-yl]pyridine-4-carboxylic acid	IC50	4800 nM
CHEMBL4847015	IC50	5000 nM
CHEMBL4874810	IC50	5000 nM
CHEMBL3621851	IC50	5010 nM

ChEMBL bioactivities

4164 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.60	Potency	2.5	nM	CHEMBL1544420
8.49	Potency	3.2	nM	CHEMBL1603504
8.49	Potency	3.2	nM	CHEMBL1374322
8.35	Potency	4.5	nM	CHEMBL1559324
8.35	Potency	4.5	nM	CHEMBL1372339
8.30	Potency	5	nM	CHEMBL1325370
8.30	Potency	5	nM	CHEMBL1308357
8.30	Potency	5	nM	CHEMBL1428808
8.25	Potency	5.6	nM	CHEMBL1606382
8.25	Potency	5.6	nM	CHEMBL1300305
8.25	Potency	5.6	nM	CHEMBL1300426
8.25	Potency	5.6	nM	CHEMBL1306372
8.25	Potency	5.6	nM	CHEMBL1550801
8.25	Potency	5.6	nM	CHEMBL1529649
8.25	Potency	5.6	nM	CHEMBL1496461
8.25	Potency	5.6	nM	CHEMBL1309552
8.20	Potency	6.3	nM	CHEMBL1449902
8.20	Potency	6.3	nM	CHEMBL1379448
8.15	Potency	7.1	nM	CHEMBL1520088
8.15	Potency	7.1	nM	CHEMBL1429549
8.10	Potency	7.9	nM	CHEMBL1571065
8.10	Potency	7.9	nM	CHEMBL1613442
8.05	Potency	8.9	nM	CHEMBL1490098
8.05	Potency	8.9	nM	CHEMBL1481013
8.00	Potency	10	nM	CHEMBL1438192
8.00	Potency	10	nM	CHEMBL1536921
8.00	Potency	10	nM	CHEMBL1323319
8.00	Potency	10	nM	CHEMBL1550078
8.00	Potency	10	nM	CHEMBL1569153
8.00	Potency	10	nM	CHEMBL1523905
7.95	Potency	11.2	nM	CHEMBL1332029
7.90	Potency	12.6	nM	CHEMBL1368170
7.80	Potency	15.8	nM	CHEMBL1443455
7.80	Potency	15.8	nM	CHEMBL1426405
7.70	Potency	20	nM	CHEMBL1454904
7.70	Potency	20	nM	CHEMBL1385656
7.65	Potency	22.4	nM	CHEMBL1321077
7.65	Potency	22.4	nM	CHEMBL1496496
7.60	Potency	25.1	nM	CHEMBL1359903
7.60	Potency	25.1	nM	CHEMBL1491066
7.60	Potency	25.1	nM	CHEMBL1338699
7.60	Potency	25.1	nM	CHEMBL1506727
7.55	Potency	28.2	nM	CHEMBL3194644
7.55	Potency	28.2	nM	CHEMBL1450827
7.55	Potency	28.2	nM	CHEMBL1379349
7.55	Potency	28.2	nM	CHEMBL1408342
7.50	Potency	31.6	nM	CHEMBL1439227
7.50	Potency	31.6	nM	CHEMBL1511162
7.45	Potency	35.5	nM	CHEMBL1541984
7.45	Potency	35.5	nM	CHEMBL1486209

PubChem BioAssay actives

79 with measured affinity, of 215 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-(benzylamino)pyridine-4-carboxylic acid	1282653: Inhibition of KDM4E (unknown origin) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	0.0398	uM
3-(furan-2-ylmethylamino)pyridine-4-carboxylic acid	1282653: Inhibition of KDM4E (unknown origin) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	0.0398	uM
3-[(3-methylthiophen-2-yl)methylamino]pyridine-4-carboxylic acid	1282653: Inhibition of KDM4E (unknown origin) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	0.0501	uM
2-[4-(2-phenylethylcarbamoyl)-2-pyridinyl]pyridine-4-carboxylic acid	1928202: Inhibition of KDM4E (unknown origin)	ic50	0.1100	uM
2-(4-chloro-3-hydroxyphenoxy)-3H-pyrido[3,4-d]pyrimidin-4-one	1281020: Inhibition of KDM4E (unknown origin) by RFMS assay	ic50	0.1259	uM
2-[5-[(4-chloro-2-methylphenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391739: Inhibition of KDM4E (unknown origin)	ic50	0.1600	uM
2-[4-(2-aminoethylcarbamoyl)-2-pyridinyl]pyridine-4-carboxylic acid	700433: Inhibition of JMJD2E catalytic domain by mass spectrophotometric analysis	ic50	0.1800	uM
4-hydrazinyl-4-oxobutanoic acid	1885263: Inhibition of human KDM4E heterogenously expressed in Escherichia coli using biotin-H3(1-15)K9Me3 as substrate and measured by Alphascreen assay	ic50	0.2000	uM
8-hydroxyquinoline-5-carboxylic acid	1289358: Inhibition of human N-terminal His6-tagged KDM4E catalytic domain (1 to 337 residues) expressed in Escherichia coli using ARK(me3)STGGK as substrate preincubated for 15 mins measured after 30 mins by FDH coupled enzyme assay	ic50	0.2000	uM
3-[[(4R)-7-(N-methyl-4-propan-2-ylanilino)-3,4-dihydro-2H-chromen-4-yl]methylamino]pyridine-4-carboxylic acid	2244399: Inhibition of KDM4E (unknown origin)	ic50	0.2700	uM
5-chloro-N-[(E)-[phenyl(pyridin-2-yl)methylidene]amino]pyridin-2-amine	1885285: Inhibition of N-terminal His6-tagged human KDM4E (1 to 337 residues) measured by ELISA assay	ic50	0.2900	uM
pyridine-2,4-dicarboxylic acid	2010693: Inhibition of his6-tagged human recombinant KDM4E using K9me3 as substrate by SPE-MS analysis	ic50	0.3000	uM
2-(1-cyclopentylpyrazol-4-yl)oxy-3H-pyrido[3,4-d]pyrimidin-4-one	1281020: Inhibition of KDM4E (unknown origin) by RFMS assay	ic50	0.3981	uM
2-[(6-propan-2-yl-3-pyridinyl)oxy]-3H-pyrido[3,4-d]pyrimidin-4-one	1281020: Inhibition of KDM4E (unknown origin) by RFMS assay	ic50	0.3981	uM
2-pyridin-2-ylpyridine-4-carboxylic acid	1249057: Inhibition of KDM4E (unknown origin) by alpha screen assay	ic50	0.3981	uM
4-(hydroxyamino)-4-oxobutanoic acid	698697: Inhibition of human KDM4E expressed in Escherichia coli using methyl lysine peptide substrate by AlphaScreen assay	ic50	0.4000	uM
2-[4-[[4-[(1S,2R)-2-aminocyclopropyl]phenyl]carbamoyl]-2-pyridinyl]pyridine-4-carboxylic acid;2,2,2-trifluoroacetic acid	1066183: Inhibition of recombinant JMJD2E (unknown origin) incubated for 15 mins prior to substrate addition by AlphaScreen method	ic50	0.4200	uM
2-(1-benzylpyrazol-4-yl)oxy-3H-pyrido[3,4-d]pyrimidin-4-one	1281020: Inhibition of KDM4E (unknown origin) by RFMS assay	ic50	0.5012	uM
2-[1-(cyclohexylmethyl)pyrazol-4-yl]oxy-3H-pyrido[3,4-d]pyrimidin-4-one	1281020: Inhibition of KDM4E (unknown origin) by RFMS assay	ic50	0.5012	uM
2-(1H-benzimidazol-2-yl)-5-methyl-4-phenyl-1H-pyrazol-3-one	1785092: Inhibition of N-terminal His6-tagged KDM4E (1 to 337 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3)-R3 preincubated for 10 mins followed by substrate addition by fluorescence based FDH-coupled assay	ic50	0.9000	uM
N-[3-(dimethylamino)propyl]-4-(8-hydroxyquinolin-6-yl)benzamide	1885289: Inhibition of KDM4E (unknown origin) measured by Alphascreen assay	ic50	0.9200	uM
3-(1-phenylethylamino)pyridine-2,4-dicarboxylic acid	2010691: Inhibition of human recombinant KDM4E using biotinylated-H3K9me3 peptide as substrate by SPE-MS analysis	ic50	0.9900	uM
3-aminopyridine-4-carboxylic acid	1281020: Inhibition of KDM4E (unknown origin) by RFMS assay	ic50	1.2589	uM
3-fluoropyridine-2,4-dicarboxylic acid	2010692: Inhibition of KDM4E (unknown origin) by SPE-MS analysis	ic50	1.3000	uM
5-fluoropyridine-2,4-dicarboxylic acid	2010692: Inhibition of KDM4E (unknown origin) by SPE-MS analysis	ic50	1.6000	uM
9-chloro-5-(4-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol	604079: Non-competitive inhibition of JMJD2E relative to alpha-ketoglutarate	ki	1.9200	uM
(2S)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid;hydrate	604078: Uncompetitive inhibition of JMJD2E relative to alpha-ketoglutarate	ki	1.9800	uM
3-[(1-methylpyrrolo[2,3-b]pyridin-3-yl)amino]pyridine-4-carboxylic acid	1934012: Inhibition of KDM4E (unknown origin ) incubated for 20 mins by Alphascreen assay	ic50	2.3000	uM
3-(benzylamino)pyridine-2,4-dicarboxylic acid	2010691: Inhibition of human recombinant KDM4E using biotinylated-H3K9me3 peptide as substrate by SPE-MS analysis	ic50	2.3600	uM
3-[(4-methoxyphenyl)methylamino]pyridine-2,4-dicarboxylic acid	2010691: Inhibition of human recombinant KDM4E using biotinylated-H3K9me3 peptide as substrate by SPE-MS analysis	ic50	2.4500	uM
3-(2-fluoroanilino)pyridine-2,4-dicarboxylic acid	700450: Inhibition of human JMJD2E	ic50	2.5000	uM
2,2-dimethyl-3,4-dihydrobenzo[h]chromene-5,6-dione	604082: Inhibition of JMJD2E	ic50	3.0000	uM
5,6,7-trihydroxy-2-phenylchromen-4-one	604082: Inhibition of JMJD2E	ic50	3.0000	uM
3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one	604082: Inhibition of JMJD2E	ic50	3.0000	uM
5-(benzylamino)pyridine-2,4-dicarboxylic acid	2010698: Inhibition of N-terminal his6-tagged human recombinant KDM4E expressed in Escherichia coli using K9me3 as substrate by SPE-MS analysis	ic50	3.2000	uM
5-(cyclohexylmethylamino)pyridine-2,4-dicarboxylic acid	2010698: Inhibition of N-terminal his6-tagged human recombinant KDM4E expressed in Escherichia coli using K9me3 as substrate by SPE-MS analysis	ic50	3.2000	uM
N-[5-[4-[(1R,2S)-2-aminocyclopropyl]anilino]-5-oxopentyl]-8-hydroxyquinoline-5-carboxamide;hydrochloride	1066183: Inhibition of recombinant JMJD2E (unknown origin) incubated for 15 mins prior to substrate addition by AlphaScreen method	ic50	3.5000	uM
5-(4-phenylbutylamino)pyridine-2,4-dicarboxylic acid	2010698: Inhibition of N-terminal his6-tagged human recombinant KDM4E expressed in Escherichia coli using K9me3 as substrate by SPE-MS analysis	ic50	3.6000	uM
3-(1-phenylpropylamino)pyridine-2,4-dicarboxylic acid	2010691: Inhibition of human recombinant KDM4E using biotinylated-H3K9me3 peptide as substrate by SPE-MS analysis	ic50	3.6900	uM
N-[4-[(1S,2R)-2-aminocyclopropyl]phenyl]-8-hydroxyquinoline-5-carboxamide;hydrochloride	1066183: Inhibition of recombinant JMJD2E (unknown origin) incubated for 15 mins prior to substrate addition by AlphaScreen method	ic50	3.9000	uM
methyl 2-[2-(1H-benzimidazol-2-yl)-3-oxo-1H-pyrazol-5-yl]acetate	1885296: Inhibition of human KDM4E (1 to 378 residues) catalytic domain measured formaldehyde dehydrogenase (FDH)-coupled fluorescence assay	ic50	4.0000	uM
4-(2-methylhydrazinyl)-4-oxobutanoic acid	698697: Inhibition of human KDM4E expressed in Escherichia coli using methyl lysine peptide substrate by AlphaScreen assay	ic50	4.3000	uM
N,3-dihydroxybenzamide	604081: Inhibition of JMJD2E pre-incubated for 30 mins	ic50	4.8000	uM
N-[(5-chloro-8-hydroxyquinolin-7-yl)-(3-methylthiophen-2-yl)methyl]benzamide	1289329: Inhibition of KDM4E (unknown origin) preincubated for 15 mins followed by histone substrate addition measured after 1 hr by alphascreen assay	ic50	5.0000	uM
2-(1H-benzimidazol-2-yl)-5-methyl-4-prop-2-ynyl-1H-pyrazol-3-one	1785092: Inhibition of N-terminal His6-tagged KDM4E (1 to 337 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3)-R3 preincubated for 10 mins followed by substrate addition by fluorescence based FDH-coupled assay	ic50	5.0000	uM
2-(1H-benzimidazol-2-yl)-5-ethyl-4-phenyl-1H-pyrazol-3-one	1785092: Inhibition of N-terminal His6-tagged KDM4E (1 to 337 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3)-R3 preincubated for 10 mins followed by substrate addition by fluorescence based FDH-coupled assay	ic50	5.0000	uM
2-(4-methoxycarbonyl-2-pyridinyl)pyridine-4-carboxylic acid	1066183: Inhibition of recombinant JMJD2E (unknown origin) incubated for 15 mins prior to substrate addition by AlphaScreen method	ic50	5.0000	uM
(2R)-3-[4-(4-fluorophenyl)sulfonyloxyphenyl]-2-(oxaloamino)propanoic acid	604080: Binding affinity to JMJD2E	ic50	5.0000	uM
(2R)-3-[4-(4-tert-butylphenyl)sulfonyloxyphenyl]-2-(oxaloamino)propanoic acid	604080: Binding affinity to JMJD2E	ic50	5.0000	uM
2-[1-(1-acetylazetidin-3-yl)triazol-4-yl]pyridine-4-carboxylic acid	1249057: Inhibition of KDM4E (unknown origin) by alpha screen assay	ic50	5.0119	uM

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
ML324	affects binding, decreases reaction	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

67 unique, capped per target: 62 binding, 5 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1613914	Functional	PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors of Human Jumonji Domain Containing 2E (JMJD2E). (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL1798566	Binding	Uncompetitive inhibition of JMJD2E relative to alpha-ketoglutarate	Inhibitors of histone demethylases. — *Bioorg Med Chem*

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SU35	HAP1 KDM4E (-) 1	Cancer cell line	Male
CVCL_SU36	HAP1 KDM4E (-) 2	Cancer cell line	Male
CVCL_SU37	HAP1 KDM4E (-) 3	Cancer cell line	Male
CVCL_SU38	HAP1 KDM4E (-) 4	Cancer cell line	Male
CVCL_SU39	HAP1 KDM4E (-) 5	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

12 trials:

NCT	Phase	Status	Title
NCT03414970	Phase 3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	Phase 2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	Phase 2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	Phase 1/2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	Phase 1/2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	Early Phase 1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	Early Phase 1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT07628634	Early Phase 1	RECRUITING	Feasibility Study on the Effect of a Methionine-Reduced Diet on Serum Levels in Pts w/ Solid Tumors
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Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for KDM4E across ~30M SureChEMBL compounds — explore on Sugi Predict.