KDM4D

Summary

KDM4D (lysine demethylase 4D, HGNC:25498) is a protein-coding gene on chromosome 11q21, encoding Lysine-specific demethylase 4D (Q6B0I6). Histone demethylase that specifically demethylates ‘Lys-9’ of histone H3, thereby playing a central role in histone code.

Enables histone H3K9me2/H3K9me3 demethylase activity. Involved in inflammatory response. Acts upstream of or within several processes, including cellular response to ionizing radiation; double-strand break repair via homologous recombination; and positive regulation of double-strand break repair via nonhomologous end joining. Located in site of double-strand break. Biomarker of nephroblastoma.

Source: NCBI Gene 55693 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 63 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_018039

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25498
Approved symbol	KDM4D
Name	lysine demethylase 4D
Location	11q21
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10251
Ensembl gene	ENSG00000186280
Ensembl biotype	protein_coding
OMIM	609766
Entrez	55693

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000335080, ENST00000536741, ENST00000610872

RefSeq mRNA: 1 — MANE Select: NM_018039 NM_018039

CCDS: CCDS8302

Canonical transcript exons

ENST00000335080 — 3 exons

Exon	Start	End
ENSE00001514555	94975654	94975748
ENSE00001514556	94973709	94974068
ENSE00002055103	94997024	94999519

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 93.78.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9196 / max 74.4290, expressed in 529 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116297	0.9086	525
116296	0.0060	3
116298	0.0051	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	93.78	gold quality
left testis	UBERON:0004533	86.81	gold quality
testis	UBERON:0000473	86.47	gold quality
right testis	UBERON:0004534	86.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.72	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.12	gold quality
sperm	CL:0000019	80.60	silver quality
adult organism	UBERON:0007023	79.87	gold quality
secondary oocyte	CL:0000655	79.50	gold quality
male germ cell	CL:0000015	78.96	silver quality
oocyte	CL:0000023	72.71	gold quality
epithelium of nasopharynx	UBERON:0001951	68.90	gold quality
ventricular zone	UBERON:0003053	67.82	gold quality
islet of Langerhans	UBERON:0000006	64.57	gold quality
stromal cell of endometrium	CL:0002255	64.23	gold quality
mammary duct	UBERON:0001765	63.83	gold quality
ganglionic eminence	UBERON:0004023	63.26	gold quality
trabecular bone tissue	UBERON:0002483	62.86	gold quality
epithelium of mammary gland	UBERON:0003244	62.86	gold quality
nasal cavity epithelium	UBERON:0005384	62.35	gold quality
prefrontal cortex	UBERON:0000451	61.76	gold quality
myocardium	UBERON:0002349	61.65	gold quality
left ventricle myocardium	UBERON:0006566	61.12	gold quality
cardiac muscle of right atrium	UBERON:0003379	60.24	gold quality
upper arm skin	UBERON:0004263	59.86	gold quality
mucosa of paranasal sinus	UBERON:0005030	59.70	gold quality
vastus lateralis	UBERON:0001379	59.10	gold quality
quadriceps femoris	UBERON:0001377	58.71	gold quality
fallopian tube	UBERON:0003889	58.67	gold quality
right adrenal gland cortex	UBERON:0035827	58.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.57

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting KDM4D, 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-1277-5P	100.00	73.95	5056
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-7153-3P	99.00	65.35	608
HSA-MIR-5187-5P	98.54	67.94	952
HSA-MIR-4766-3P	98.48	67.94	1347
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-6728-5P	97.79	66.33	891
HSA-MIR-194-3P	97.36	65.96	1027
HSA-MIR-4693-5P	97.35	67.02	1234
HSA-MIR-409-5P	97.31	68.07	364
HSA-MIR-342-3P	96.44	67.48	1344
HSA-MIR-4654	95.86	65.72	751
HSA-MIR-151A-3P	95.52	65.29	516
HSA-MIR-4769-5P	95.37	66.09	570

Literature-anchored findings (GeneRIF, showing 16)

• identified two related histone demethylases, JMJD2A and JMJD2D (PMID:17555712)
• Results demonstrate that JMJD2D can stimulate cell proliferation and survival, suggesting that its inhibition may be helpful in the fight against cancer (PMID:22514644)
• The molecular basis for JMJD2 site specificity revealed by X-ray crystallography. (PMID:23219879)
• PARP1-dependent recruitment of KDM4D histone demethylase to DNA damage sites promotes double-strand break repair. (PMID:24550317)
• KDM4D-RNA interaction is required for KDM4D accumulation at DNA breakage sites (PMID:25714495)
• KDM4B and KDM4D expression may associate with an aggressive subtype of classical Hodgkin lymphoma and be linked with radioresistance (PMID:27630312)
• The results demonstrate a novel mechanism by which Kdm4d regulates DNA replication by reducing the H3K9me3 level to facilitate formation of preinitiation complex. (PMID:27679476)
• A high nuclear expression of KDM4D in samples of pancreatic resection margins significantly and independently predicted an earlier recurrence and could thus be used in the assessment of risk of relapse in clinical practice. (PMID:29599352)
• Results demonstrate that KDM4D mRNA and protein levels are upregulated in gastrointestinal stromal tumour (GIST). Its overexpression strongly promotes GIST cell proliferation, migration, invasion and angiogenesis. In contrast, its silencing reduced cell proliferation, migration, invasion and tumor angiogenesis. More importantly, these effects mediated by KDM4D might be dependent on the Hif1beta/VEGFA signaling pathway. (PMID:30060750)
• KDM4D facilitates TLR4 transcription through demethylation of H3K9, thus activating TLR4/NF-kappaB signaling pathways in hepatic stellate cells, contributing to HSC activation and collagen crosslinking, further, hepatic fibrosis progression. (PMID:30527625)
• Inflammation-induced JMJD2D promotes colitis recovery and colon tumorigenesis by activating Hedgehog signaling. (PMID:32094404)
• Demethylase-independent function of JMJD2D as a novel antagonist of p53 to promote Liver Cancer initiation and progression. (PMID:32754284)
• Histone demethylase JMJD2D activates HIF1 signaling pathway via multiple mechanisms to promote colorectal cancer glycolysis and progression. (PMID:32989255)
• Histone demethylase JMJD2D promotes the self-renewal of liver cancer stem-like cells by enhancing EpCAM and Sox9 expression. (PMID:33434575)
• KDM4D enhances osteo/dentinogenic differentiation and migration of SCAPs via binding to RPS5. (PMID:36579641)
• MicroRNA-409-5p Inhibits GIST Tumorigenesis and Improves Imatinib Resistance by Targeting KDM4D Expression. (PMID:37828372)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	kdm4c	ENSDARG00000061504
mus_musculus	Kdm4d	ENSMUSG00000053914
rattus_norvegicus	Kdm4d	ENSRNOG00000045905
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), KDM4E (ENSG00000235268), KDM4F (ENSG00000255855)

Protein

Protein identifiers

Lysine-specific demethylase 4D — Q6B0I6 (reviewed: Q6B0I6)

Alternative names: JmjC domain-containing histone demethylation protein 3D, Jumonji domain-containing protein 2D, [histone H3]-trimethyl-L-lysine(9) demethylase 4D

All UniProt accessions (1): Q6B0I6

UniProt curated annotations — full annotation on UniProt →

Function. Histone demethylase that specifically demethylates ‘Lys-9’ of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 ‘Lys-4’, H3 ‘Lys-27’, H3 ‘Lys-36’ nor H4 ‘Lys-20’. Demethylates both di- and trimethylated H3 ‘Lys-9’ residue, while it has no activity on monomethylated residues. Demethylation of Lys residue generates formaldehyde and succinate.

Subcellular location. Nucleus.

Post-translational modifications. Ubiquitinated via ‘Lys-63’-linked ubiquitin chains. Deubiquitinated by USP14 with the help of TRIM14 leading to stabilization.

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

Similarity. Belongs to the JHDM3 histone demethylase family.

RefSeq proteins (1): NP_060509* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003347	JmjC_dom	Domain
IPR003349	JmjN	Domain

Pfam: PF02373, PF02375

Enzyme classification (BRENDA):

• EC 1.14.11.27 — [histone H3]-dimethyl-L-lysine36 demethylase (BRENDA: 7 organisms, 38 substrates, 0 inhibitors, 0 Km, 0 kcat entries)
• EC 1.14.11.66 — [histone H3]-trimethyl-L-lysine9 demethylase (BRENDA: 7 organisms, 79 substrates, 168 inhibitors, 23 Km, 14 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), 1 shown:

• 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)

UniProt features (59 total): helix 17, strand 16, binding site 11, sequence variant 3, turn 3, domain 2, modified residue 2, compositionally biased region 2, chain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

284 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6H10	X-RAY DIFFRACTION	1.1
5PLK	X-RAY DIFFRACTION	1.14
5PLM	X-RAY DIFFRACTION	1.14
5PLN	X-RAY DIFFRACTION	1.14
5PLO	X-RAY DIFFRACTION	1.14
5PLV	X-RAY DIFFRACTION	1.14
5PMX	X-RAY DIFFRACTION	1.14
5PN0	X-RAY DIFFRACTION	1.14
5PNH	X-RAY DIFFRACTION	1.14
5PNR	X-RAY DIFFRACTION	1.14
5PNU	X-RAY DIFFRACTION	1.14
5PHL	X-RAY DIFFRACTION	1.14
5PHJ	X-RAY DIFFRACTION	1.15
5PMZ	X-RAY DIFFRACTION	1.15
5PIA	X-RAY DIFFRACTION	1.18
5PJH	X-RAY DIFFRACTION	1.18
6ETV	X-RAY DIFFRACTION	1.18
5PKH	X-RAY DIFFRACTION	1.19
5PKI	X-RAY DIFFRACTION	1.19
5PMW	X-RAY DIFFRACTION	1.19
5PL4	X-RAY DIFFRACTION	1.21
5PNN	X-RAY DIFFRACTION	1.21
6H0Y	X-RAY DIFFRACTION	1.21
5PKJ	X-RAY DIFFRACTION	1.22
5PMT	X-RAY DIFFRACTION	1.22
5PIW	X-RAY DIFFRACTION	1.23
5PNB	X-RAY DIFFRACTION	1.23
6H0W	X-RAY DIFFRACTION	1.23
5PH3	X-RAY DIFFRACTION	1.24
5PJ5	X-RAY DIFFRACTION	1.24

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6B0I6-F1	74.40	0.53

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): 210; 238; 244; 245; 280; 310; 312; 136; 192; 194; 202

Post-translational modifications (2): 26, 27

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: 133 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_REGULATION_OF_PHOSPHORYLATION, MODULE_255, GOBP_INFLAMMATORY_RESPONSE, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, MODULE_317, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_POSITIVE_REGULATION_OF_BINDING, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DNA_DAMAGE_RESPONSE, GOBP_RESPONSE_TO_RADIATION, GOBP_POSITIVE_REGULATION_OF_DNA_REPAIR

GO Biological Process (10): double-strand break repair via homologous recombination (GO:0000724), regulation of protein phosphorylation (GO:0001932), chromatin remodeling (GO:0006338), inflammatory response (GO:0006954), regulation of gene expression (GO:0010468), positive regulation of chromatin binding (GO:0035563), cellular response to ionizing radiation (GO:0071479), positive regulation of double-strand break repair via nonhomologous end joining (GO:2001034), chromatin organization (GO:0006325), DNA damage response (GO:0006974)

GO Molecular Function (9): damaged DNA binding (GO:0003684), chromatin DNA binding (GO:0031490), histone demethylase activity (GO:0032452), histone H3K9 demethylase activity (GO:0032454), metal ion binding (GO:0046872), histone H3K9me2/H3K9me3 demethylase activity (GO:0140684), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), dioxygenase activity (GO:0051213)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), pericentric heterochromatin (GO:0005721), site of double-strand break (GO:0035861), blood microparticle (GO:0072562)

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
cellular anatomical structure	3
chromatin binding	2
DNA binding	2
recombinational repair	1
double-strand break repair	1
protein phosphorylation	1
regulation of protein modification process	1
regulation of phosphorylation	1
chromatin organization	1
defense response	1
gene expression	1
regulation of macromolecule biosynthetic process	1
positive regulation of binding	1
response to ionizing radiation	1
cellular response to radiation	1
double-strand break repair via nonhomologous end joining	1
positive regulation of double-strand break repair	1
regulation of double-strand break repair via nonhomologous end joining	1
cellular component organization	1
cellular response to stress	1
protein demethylase activity	1
histone modifying activity	1
histone H3 demethylase activity	1
cation binding	1
2-oxoglutarate-dependent dioxygenase activity	1
histone H3K9 demethylase activity	1
binding	1
catalytic activity	1
oxidoreductase activity	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
chromosome, centromeric region	1
heterochromatin	1
site of DNA damage	1
extracellular region	1

Protein interactions and networks

STRING

736 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KDM4D	JMJD1C	Q15652	879
KDM4D	SUV39H1	O43463	729
KDM4D	KDM6B	O15054	641
KDM4D	KDM3A	Q9Y4C1	624
KDM4D	KDM7A	Q6ZMT4	620
KDM4D	KDM1A	O60341	601
KDM4D	ZRANB1	Q9UGI0	595
KDM4D	KDM3B	Q7LBC6	579
KDM4D	KDM2A	Q9Y2K7	558
KDM4D	PHF8	Q9UPP1	554
KDM4D	KDM8	Q8N371	531
KDM4D	PHF2	O75151	527
KDM4D	KDM2B	Q8NHM5	518
KDM4D	KDM6A	O15550	515
KDM4D	CTNNB1	P35222	515

IntAct

15 interactions, top by confidence:

A	B	Type	Score
KDM4D		psi-mi:“MI:0871”(demethylation reaction)	0.680
KDM4D		psi-mi:“MI:0407”(direct interaction)	0.680
KDM4D	CEP76	psi-mi:“MI:0915”(physical association)	0.560
TRPC4AP	SMCHD1	psi-mi:“MI:0914”(association)	0.530
KDM4D	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440
KDM4D	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
PPP1CC	KDM4D	psi-mi:“MI:0915”(physical association)	0.370
CUL4B	APBB1	psi-mi:“MI:0914”(association)	0.350
TRPC4AP	SMCHD1	psi-mi:“MI:0914”(association)	0.350
KDM4D	SMCHD1	psi-mi:“MI:0914”(association)	0.350
	EBAG9	psi-mi:“MI:0914”(association)	0.350
KDM4D	CEP76	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (45): KDM4D (Affinity Capture-MS), KDM4D (Reconstituted Complex), KDM4D (Affinity Capture-MS), KDM4D (Two-hybrid), KDM4D (Proximity Label-MS), CIRBP (Affinity Capture-MS), KDM4D (Affinity Capture-MS), SNRPD2 (Affinity Capture-MS), SMCHD1 (Affinity Capture-MS), GPATCH11 (Affinity Capture-MS), KDM4D (Affinity Capture-MS), KDM4D (Affinity Capture-MS), KDM4D (Affinity Capture-MS), KDM4D (Affinity Capture-MS), KDM4D (Affinity Capture-MS)

ESM2 similar proteins: A0A1W2PPD8, A1A5Q5, A2A3K4, A4H5X5, A7E379, B2RXH2, C0SUT9, D3ZKV9, F5HB62, O19132, O36371, O54705, O60291, O75164, O94953, P03177, P33802, P35228, Q1HVD1, Q29RJ0, Q3KSQ2, Q3U2K5, Q3UPF5, Q53WJ1, Q5R4R7, Q5R978, Q5RD88, Q5VW22, Q5VWQ0, Q6B0I6, Q6EEF3, Q6EMB2, Q6PI47, Q6X4W1, Q80T69, Q80TL4, Q8BFX3, Q8BW72, Q8CHB8, Q8K3Y6

Diamond homologs: A0A1W2PPD8, A1A5Q5, A1YVX4, B2RXH2, C0SUT9, F4I240, F4I6G4, F4KIX0, O64752, O75164, O94953, P29375, P39956, P41229, P41230, P47156, Q03833, Q10RP4, Q1LVC2, Q23541, Q30DN6, Q336N8, Q38JA7, Q3U2K5, Q3UXZ9, Q53WJ1, Q5F3R2, Q5N712, Q5RD88, Q5XUN4, Q61T02, Q62240, Q62315, Q6B0I6, Q6BDA0, Q6IQX0, Q80Y84, Q8BW72, Q8GUI6, Q8VCD7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
2-oxoglutarate(2-)	“up-regulates activity”	KDM4D	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

248 predictions. Top by Δscore:

Variant	Effect	Δscore
11:94974066:AAGG:A	donor_loss	0.9600
11:94974067:AGGT:A	donor_loss	0.9600
11:94974068:GG:G	donor_loss	0.9600
11:94974069:G:A	donor_loss	0.9600
11:94974070:T:G	donor_loss	0.9600
11:94997022:A:AG	acceptor_gain	0.9600
11:94997023:G:GG	acceptor_gain	0.9600
11:94997018:TTTTA:T	acceptor_loss	0.9500
11:94997019:TTTAG:T	acceptor_loss	0.9500
11:94997020:TTAG:T	acceptor_loss	0.9500
11:94997021:TAGAT:T	acceptor_loss	0.9500
11:94997022:A:AC	acceptor_loss	0.9500
11:94997023:GATTT:G	acceptor_gain	0.9500
11:94973905:G:GT	donor_gain	0.9300
11:94997023:GA:G	acceptor_gain	0.9300
11:94997023:GATT:G	acceptor_gain	0.9200
11:94988370:C:CA	acceptor_gain	0.9100
11:94997023:GAT:G	acceptor_gain	0.9100
11:94974109:T:TA	donor_gain	0.9000
11:94974110:T:TA	donor_gain	0.8900
11:94974111:G:GG	donor_gain	0.8400
11:94974071:A:C	donor_loss	0.8300
11:94974108:G:GT	donor_gain	0.7900
11:94975742:GTGC:G	donor_gain	0.7900
11:94975743:TGCT:T	donor_gain	0.7900
11:94975744:GCTG:G	donor_gain	0.7900
11:94973979:A:T	donor_gain	0.7800
11:94989480:A:G	donor_gain	0.7700
11:94974040:T:G	donor_gain	0.7600
11:94981372:G:T	donor_gain	0.7600

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000166412 (11:94981747 C>T), RS1000201931 (11:94972040 A>G), RS1000341126 (11:94979039 T>C), RS1000548414 (11:94985747 T>C), RS1000714570 (11:94993024 T>C), RS1000839289 (11:94978771 T>G), RS1001099370 (11:94993352 A>G), RS1001221819 (11:94982341 C>T), RS1001265345 (11:94990204 G>T), RS1002113250 (11:94977213 A>G,T), RS1002221048 (11:94984048 T>C), RS1002387127 (11:94999703 C>T), RS1002420261 (11:94977483 C>G), RS1002729356 (11:94991965 A>G), RS1002760799 (11:94973838 T>C)

Disease associations

OMIM: gene MIM:609766 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000253_20	Attention deficit hyperactivity disorder and conduct disorder	2.000000e-06
GCST003098_14	Diabetic kidney disease	4.000000e-06
GCST003098_38	Diabetic kidney disease	2.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL6138 (SINGLE PROTEIN), CHEMBL6195533 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 36 (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
CHEMBL5314494	ZAVONDEMSTAT	2	36

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 1.14.11.- Histone demethylases

ChEMBL bioactivities

105 potent at pChembl≥5 of 126 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.64	IC50	23	nM	CHEMBL4850758
7.64	IC50	23	nM	CHEMBL5206330
7.46	IC50	35	nM	CHEMBL4216044
7.44	Kd	36	nM	CHEMBL4850758
7.35	IC50	45	nM	CHEMBL4875100
7.30	IC50	50	nM	ZAVONDEMSTAT
7.25	IC50	56	nM	CHEMBL4866032
7.20	IC50	63.1	nM	CHEMBL3775612
7.10	IC50	79	nM	CHEMBL3775237
7.06	IC50	87	nM	CHEMBL4852549
7.00	IC50	100	nM	CHEMBL3775237
7.00	IC50	100	nM	CHEMBL3775889
7.00	IC50	100	nM	CHEMBL4865890
6.98	IC50	104	nM	CHEMBL4216044
6.96	IC50	110	nM	CHEMBL3786952
6.96	IC50	111	nM	CHEMBL4863496
6.96	IC50	109	nM	CHEMBL4849386
6.93	IC50	117	nM	CHEMBL4853213
6.90	IC50	126	nM	CHEMBL4870370
6.87	IC50	135	nM	CHEMBL4851604
6.85	IC50	141	nM	CHEMBL4848874
6.84	IC50	145	nM	CHEMBL4870256
6.81	IC50	155	nM	CHEMBL4865527
6.78	IC50	165	nM	CHEMBL4867448
6.77	IC50	170	nM	CHEMBL4852779
6.77	IC50	171	nM	CHEMBL4853385
6.76	IC50	173	nM	CHEMBL4867797
6.74	IC50	184	nM	CHEMBL4864457
6.73	IC50	187	nM	CHEMBL4869955
6.73	IC50	188	nM	CHEMBL4879231
6.72	IC50	192	nM	CHEMBL4847665
6.71	IC50	193	nM	CHEMBL4857387
6.70	IC50	199.5	nM	CHEMBL3775431
6.70	IC50	200	nM	CHEMBL4866118
6.70	IC50	200	nM	CHEMBL1230640
6.67	IC50	212	nM	CHEMBL4865163
6.66	IC50	220	nM	CHEMBL4866179
6.66	IC50	220	nM	CHEMBL4853701
6.65	IC50	223	nM	CHEMBL4850795
6.60	IC50	251.2	nM	CHEMBL3774845
6.54	IC50	285	nM	CHEMBL4871665
6.54	IC50	290	nM	CHEMBL1982368
6.53	Ki	293	nM	CHEMBL4850758
6.50	IC50	316.2	nM	CHEMBL3770740
6.48	IC50	330	nM	CHEMBL4851379
6.47	IC50	342	nM	CHEMBL4876010
6.46	IC50	351	nM	CHEMBL4857330
6.43	IC50	368	nM	CHEMBL4878349
6.42	IC50	382	nM	CHEMBL4870942
6.40	IC50	398.1	nM	CHEMBL3771198

PubChem BioAssay actives

89 with measured affinity, of 242 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
tert-butyl N-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-(4-pyridin-4-ylphenyl)methyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.0230	uM
tert-butyl 2-[(3S)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-(4-pyridin-4-ylphenyl)methyl]pyrrolidin-3-yl]acetate	1885306: Inhibition of KDM4D (unknown origin) measured by AlphaLisa-based screening assay	ic50	0.0230	uM
3-[[(1R)-6-(N-methylanilino)-1,2,3,4-tetrahydronaphthalen-1-yl]methylamino]pyridine-4-carboxylic acid	1885276: Inhibition of KDM4D (unknown origin) using H3K9me3 as substrate and measured by LANCE TR-FRET assay	ic50	0.0350	uM
tert-butyl N-[(3R)-1-[(5-cyano-2-pyridinyl)-(6-hydroxy-1,3-benzodioxol-5-yl)methyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.0450	uM
tert-butyl N-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-[4-(1,2,4-triazol-1-yl)phenyl]methyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.0560	uM
3-(benzylamino)pyridine-4-carboxylic acid	1282648: Inhibition of human KDM4D (11 to 341 residues) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	0.0631	uM
3-(furan-2-ylmethylamino)pyridine-4-carboxylic acid	1885265: Inhibition of KDM4D (unknown origin) measured by RapidFire mass spectrometry (RFMS)	ic50	0.0790	uM
tert-butyl N-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-[4-(2-methylimidazol-1-yl)phenyl]methyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.0870	uM
tert-butyl N-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-quinolin-4-ylmethyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.1000	uM
3-[(3-methylthiophen-2-yl)methylamino]pyridine-4-carboxylic acid	1282648: Inhibition of human KDM4D (11 to 341 residues) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	0.1000	uM
tert-butyl N-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-(3-imidazol-1-ylphenyl)methyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.1090	uM
2-[5-[(4-chloro-2-methylphenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391738: Inhibition of KDM4D (unknown origin)	ic50	0.1100	uM
tert-butyl N-[(3R)-1-[(4-chloro-2-fluorophenyl)-(6-hydroxy-1,3-benzodioxol-5-yl)methyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.1110	uM
tert-butyl N-[(3R)-1-[(2-chloro-4-fluorophenyl)-(6-hydroxy-1,3-benzodioxol-5-yl)methyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.1170	uM
tert-butyl N-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-(5-pyridin-4-yl-2-pyridinyl)methyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.1260	uM
tert-butyl N-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-pyridin-4-ylmethyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.1350	uM
tert-butyl N-[(3R)-1-[(4-cyanophenyl)-(6-hydroxy-1,3-benzodioxol-5-yl)methyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.1410	uM
tert-butyl N-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-(4-pyridin-2-ylphenyl)methyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.1450	uM
N-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-pyridin-4-ylmethyl]pyrrolidin-3-yl]cyclopropanecarboxamide	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.1550	uM
tert-butyl N-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-(6-pyridin-4-yl-3-pyridinyl)methyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.1650	uM
4-ethoxy-N-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-pyridin-4-ylmethyl]pyrrolidin-3-yl]benzamide	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.1700	uM
1-tert-butyl-3-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-pyridin-4-ylmethyl]pyrrolidin-3-yl]thiourea	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.1710	uM
tert-butyl N-[(3R)-1-[(2,4-difluorophenyl)-(6-hydroxy-1,3-benzodioxol-5-yl)methyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.1730	uM
tert-butyl N-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-(3-pyridin-3-ylphenyl)methyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.1840	uM
2-chloro-N-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-pyridin-4-ylmethyl]pyrrolidin-3-yl]benzamide	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.1870	uM
1-tert-butyl-3-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-pyridin-4-ylmethyl]pyrrolidin-3-yl]urea	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.1880	uM
tert-butyl N-[(3R)-1-[(4-fluorophenyl)-(6-hydroxy-1,3-benzodioxol-5-yl)methyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.1920	uM
N-[[(3S)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-pyridin-4-ylmethyl]pyrrolidin-3-yl]methyl]cyclopropanecarboxamide	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.1930	uM
3-[(2-phenylacetyl)amino]pyridine-4-carboxylic acid	1282648: Inhibition of human KDM4D (11 to 341 residues) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	0.1995	uM
6-[[(3R)-3-(dimethylamino)pyrrolidin-1-yl]-pyridin-4-ylmethyl]-1,3-benzodioxol-5-ol	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.2000	uM
8-hydroxyquinoline-5-carboxylic acid	1916571: Inhibition of KDM4D (unknown origin) expressed in Escherichia coli and measured after 1 hrs by alpha screen assay	ic50	0.2000	uM
tert-butyl N-[(3R)-1-[(2-hydroxy-3,6-dimethoxyphenyl)-pyridin-4-ylmethyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.2120	uM
tert-butyl N-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-(4-pyridin-3-ylphenyl)methyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.2200	uM
N-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-pyridin-4-ylmethyl]pyrrolidin-3-yl]-2-methylpropanamide	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.2200	uM
tert-butyl N-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-(3-pyridin-4-ylphenyl)methyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.2230	uM
3-(4-phenylbutanoylamino)pyridine-4-carboxylic acid	1282648: Inhibition of human KDM4D (11 to 341 residues) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	0.2512	uM
tert-butyl N-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-(3-pyridin-2-ylphenyl)methyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.2850	uM
5-chloro-N-[(E)-[phenyl(pyridin-2-yl)methylidene]amino]pyridin-2-amine	1772978: Inhibition of KDM4D (unknown origin)	ic50	0.2900	uM
2-(4-chloro-3-hydroxyphenoxy)-3H-pyrido[3,4-d]pyrimidin-4-one	1281019: Inhibition of KDM4D (unknown origin) by RFMS assay	ic50	0.3162	uM
tert-butyl N-[(3R)-1-[(4-cyano-2-fluorophenyl)-(6-hydroxy-1,3-benzodioxol-5-yl)methyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.3300	uM
2-ethoxy-N-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-pyridin-4-ylmethyl]pyrrolidin-3-yl]benzamide	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.3420	uM
3-fluoro-N-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-pyridin-4-ylmethyl]pyrrolidin-3-yl]benzamide	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.3510	uM
tert-butyl N-[(3R)-1-[(4-cyano-2-methoxyphenyl)-(6-hydroxy-1,3-benzodioxol-5-yl)methyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.3680	uM
tert-butyl N-[(3R)-1-[(4-cyano-3-fluorophenyl)-(6-hydroxy-1,3-benzodioxol-5-yl)methyl]pyrrolidin-3-yl]carbamate	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.3820	uM
2-(1-benzylpyrazol-4-yl)oxy-3H-pyrido[3,4-d]pyrimidin-4-one	1281019: Inhibition of KDM4D (unknown origin) by RFMS assay	ic50	0.3981	uM
2-[1-(cyclohexylmethyl)pyrazol-4-yl]oxy-3H-pyrido[3,4-d]pyrimidin-4-one	1281019: Inhibition of KDM4D (unknown origin) by RFMS assay	ic50	0.3981	uM
3-(3-phenylpropanoylamino)pyridine-4-carboxylic acid	1282648: Inhibition of human KDM4D (11 to 341 residues) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	0.3981	uM
N-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-pyridin-4-ylmethyl]pyrrolidin-3-yl]-2-methoxybenzamide	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.3990	uM
4-methyl-8-oxo-2,3,7,13-tetrazatricyclo[7.4.0.02,6]trideca-1(9),3,5,10,12-pentaene-5-carbonitrile	1467428: Inhibition of KDM4D (unknown origin) using biotinylated H3 derived peptide as substrate preincubated for 15 mins followed by substrate addition measured after 1 hr by AlphaLISA method	ic50	0.4100	uM
2-fluoro-N-[(3R)-1-[(6-hydroxy-1,3-benzodioxol-5-yl)-pyridin-4-ylmethyl]pyrrolidin-3-yl]benzamide	1772939: Inhibition of human KDM4D expressed in Escherichia coli BL21 (DE3) using biotinylated H3-derived peptide and 2-OG as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by AlphaLISA assay	ic50	0.4370	uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases methylation	3
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
fluorene-9-bisphenol	increases expression	1
methylmercuric chloride	decreases expression	1
kojic acid	increases expression	1
trichostatin A	decreases expression	1
sodium arsenite	affects expression	1
potassium chromate(VI)	increases expression	1
ferrous chloride	decreases expression	1
vanadyl sulfate	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Hydrogen Peroxide	increases expression	1
Nitric Oxide	increases expression	1
T-2 Toxin	increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	decreases expression	1
Lactic Acid	increases expression	1
Acrylamide	increases expression	1

ChEMBL screening assays

43 unique, capped per target: 41 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1054735	Binding	Inhibition of JMJD2D-mediated H3K9 demethylation activity at 3 mM	Synthesis and activity of N-oxalylglycine and its derivatives as Jumonji C-domain-containing histone lysine demethylase inhibitors. — Bioorg Med Chem Lett
CHEMBL1055465	Functional	Inhibition of JMJD2-mediated H3K36 demethylation in human 293T cells at 2.5 mM	Synthesis and activity of N-oxalylglycine and its derivatives as Jumonji C-domain-containing histone lysine demethylase inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SU33	HAP1 KDM4D (-) 1	Cancer cell line	Male
CVCL_SU34	HAP1 KDM4D (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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