KDM7A

Summary

KDM7A (lysine demethylase 7A, HGNC:22224) is a protein-coding gene on chromosome 7q34, encoding Lysine-specific demethylase 7A (Q6ZMT4). Histone demethylase required for brain development.

Enables histone demethylase activity; methylated histone binding activity; and transition metal ion binding activity. Predicted to be involved in chromatin remodeling; midbrain development; and regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. Implicated in melanoma.

Source: NCBI Gene 80853 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cerebral palsy (Limited, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 91 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_030647

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22224
Approved symbol	KDM7A
Name	lysine demethylase 7A
Location	7q34
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1718
Ensembl gene	ENSG00000006459
Ensembl biotype	protein_coding
OMIM	619640
Entrez	80853

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000397560, ENST00000472616, ENST00000478996, ENST00000895776, ENST00000912301, ENST00000942646

RefSeq mRNA: 1 — MANE Select: NM_030647 NM_030647

CCDS: CCDS43658

Canonical transcript exons

ENST00000397560 — 20 exons

Exon	Start	End
ENSE00000360316	140120442	140120529
ENSE00000726713	140096555	140096763
ENSE00000726716	140096899	140097047
ENSE00000726724	140097545	140097642
ENSE00000726740	140098879	140099033
ENSE00000726787	140111095	140111184
ENSE00000726816	140124621	140124783
ENSE00000726821	140126637	140126823
ENSE00000726824	140127442	140127583
ENSE00001155866	140099899	140100023
ENSE00001155872	140101951	140102160
ENSE00001155888	140119113	140119219
ENSE00001155914	140129493	140129653
ENSE00001155929	140084746	140091188
ENSE00001400748	140133539	140133656
ENSE00001401297	140139105	140139190
ENSE00001414149	140113491	140113582
ENSE00001890729	140176744	140176983
ENSE00003496538	140094056	140094138
ENSE00003509046	140091804	140092077

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 95.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.6782 / max 237.9970, expressed in 1656 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86537	5.5326	1310
86536	3.1107	1018
86538	2.7010	1056
86533	0.3338	146

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	95.40	gold quality
tendon of biceps brachii	UBERON:0008188	94.67	gold quality
gluteal muscle	UBERON:0002000	93.76	gold quality
bone marrow	UBERON:0002371	91.74	gold quality
upper leg skin	UBERON:0004262	91.72	gold quality
epithelium of nasopharynx	UBERON:0001951	91.66	gold quality
monocyte	CL:0000576	91.08	gold quality
mononuclear cell	CL:0000842	91.06	gold quality
leukocyte	CL:0000738	90.63	gold quality
cervix squamous epithelium	UBERON:0006922	90.17	silver quality
buccal mucosa cell	CL:0002336	90.10	gold quality
skin of hip	UBERON:0001554	89.57	gold quality
bone marrow cell	CL:0002092	89.47	gold quality
jejunal mucosa	UBERON:0000399	89.36	gold quality
trabecular bone tissue	UBERON:0002483	88.94	gold quality
squamous epithelium	UBERON:0006914	88.36	gold quality
gastrocnemius	UBERON:0001388	88.25	gold quality
blood	UBERON:0000178	88.16	gold quality
esophagus squamous epithelium	UBERON:0006920	88.08	gold quality
jejunum	UBERON:0002115	88.05	gold quality
pharyngeal mucosa	UBERON:0000355	87.86	gold quality
tendon	UBERON:0000043	87.65	gold quality
mucosa of sigmoid colon	UBERON:0004993	87.31	gold quality
sperm	CL:0000019	87.30	silver quality
muscle of leg	UBERON:0001383	87.02	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	87.02	gold quality
gingival epithelium	UBERON:0001949	86.98	gold quality
colonic epithelium	UBERON:0000397	86.84	gold quality
colonic mucosa	UBERON:0000317	86.79	gold quality
pericardium	UBERON:0002407	86.73	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-10	no	478.17
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EPAS1, HIF1A

miRNA regulators (miRDB)

480 targeting KDM7A, 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-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-188-3P	100.00	68.76	1240

Literature-anchored findings (GeneRIF, showing 13)

• KIAA1718 is a dual-specificity histone demethylase that regulates neural differentiation through FGF4. (PMID:20084082)
• increased JHDM1D expression suppresses tumor growth by down-regulating angiogenesis under nutrient starvation (PMID:22143793)
• Histone modifier genes (JMJD1C, RREB1, MINA, KDM7A) alter conotruncal heart phenotypes in 22q11.2 deletion syndrome. (PMID:26608785)
• G9a promotes H3K27 methylation of the E-cadherin promoter by upregulating PCL3 to increase PRC2 promoter recruitment and by downregulating the H3K27 demethylase KDM7A to silence E-cadherin gene (PMID:26688070)
• KDM7A mediates TNF-alpha-induced ICAM1 protein upregulation. (PMID:27565733)
• decreased expression in placenta associated with pre-eclampsia through down-regulating HLA-G (PMID:29662139)
• KDM7A is potentially a good therapeutic target for prostate cancer drugs. (PMID:30183076)
• Histone demethylase KDM7A is required for stem cell maintenance and apoptosis inhibition in breast cancer. (PMID:31236965)
• Coordinated demethylation of H3K9 and H3K27 is required for rapid inflammatory responses of endothelial cells. (PMID:32125007)
• Histone Demethylase KDM7A Regulates Androgen Receptor Activity, and Its Chemical Inhibitor TC-E 5002 Overcomes Cisplatin-Resistance in Bladder Cancer Cells. (PMID:32781788)
• The nuclear bodies formed by histone demethylase KDM7A. (PMID:32935279)
• JHDM1D-AS1 aggravates the development of gastric cancer through miR-450a-2-3p-PRAF2 axis. (PMID:33245963)
• Inhibition of KDM2/7 Promotes Notochordal Differentiation of hiPSCs. (PMID:39273051)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	kdm7aa	ENSDARG00000018111
danio_rerio	kdm7ab	ENSDARG00000018559
mus_musculus	Kdm7a	ENSMUSG00000042599
rattus_norvegicus	Kdm7a	ENSRNOG00000052445
caenorhabditis_elegans		WBGENE00005013
caenorhabditis_elegans		WBGENE00017920

Paralogs (4): KDM2B (ENSG00000089094), PHF8 (ENSG00000172943), KDM2A (ENSG00000173120), PHF2 (ENSG00000197724)

Protein

Protein identifiers

Lysine-specific demethylase 7A — Q6ZMT4 (reviewed: Q6ZMT4)

Alternative names: JmjC domain-containing histone demethylation protein 1D, Lysine-specific demethylase 7, [histone H3]-dimethyl-L-lysine9 demethylase 7A

All UniProt accessions (2): Q6ZMT4, H9KVD6

UniProt curated annotations — full annotation on UniProt →

Function. Histone demethylase required for brain development. Specifically demethylates dimethylated ‘Lys-9’, ‘Lys-27’ and ‘Lys-36’ (H3K9me2, H3K27me2, H3K36me2, respectively) of histone H3 and monomethylated histone H4 ‘Lys-20’ residue (H4K20Me1), thereby playing a central role in histone code. Specifically binds trimethylated ‘Lys-4’ of histone H3 (H3K4me3), affecting histone demethylase specificity: in presence of H3K4me3, it has no demethylase activity toward H3K9me2, while it has high activity toward H3K27me2. Demethylates H3K9me2 in absence of H3K4me3. Has activity toward H4K20Me1 only when nucleosome is used as a substrate and when not histone octamer is used as substrate.

Subcellular location. Nucleus.

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

Domain organisation. The PHD-type zinc finger mediates the binding to H3K4me3. Binding to H3K4me3 prevents its access to H3K9me2. The linker region is a critical determinant of demethylase specificity. It prevents the active site of JmjC to reach the target H3K9me2 when the PHD-type zinc finger binds to H3K4me3, while it favors selectivity toward H3K27me2.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the JHDM1 histone demethylase family. JHDM1D subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZMT4-1	1	yes
Q6ZMT4-2	2

RefSeq proteins (1): NP_085150* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001965	Znf_PHD	Domain
IPR003347	JmjC_dom	Domain
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
IPR041070	JHD	Domain
IPR050690	JHDM1_Histone_Demethylase	Family

Pfam: PF00628, PF02373, PF17811

Enzyme classification (BRENDA):

• EC 1.14.11.65 — [histone H3]-dimethyl-L-lysine9 demethylase (BRENDA: 9 organisms, 67 substrates, 84 inhibitors, 4 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[HISTONE H3]-N6,N6-DIMETHYL-L-LYSINE9	0.106–0.1061	2
[HISTONE H3]-N6-METHYL-L-LYSINE9	0.095–0.0952	2

Catalyzed reactions (Rhea), 4 shown:

• N(6),N(6)-dimethyl-L-lysyl(36)-[histone H3] + 2-oxoglutarate + O2 = N(6)-methyl-L-lysyl(36)-[histone H3] + formaldehyde + succinate + CO2 (RHEA:21788)
• N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + 2 2-oxoglutarate + 2 O2 = L-lysyl(9)-[histone H3] + 2 formaldehyde + 2 succinate + 2 CO2 (RHEA:60188)
• N(6),N(6)-dimethyl-L-lysyl(27)-[histone H3] + 2 2-oxoglutarate + 2 O2 = L-lysyl(27)-[histone H3] + 2 formaldehyde + 2 succinate + 2 CO2 (RHEA:67800)
• N(6)-methyl-L-lysyl(20)-[histone H4] + 2-oxoglutarate + O2 = L-lysyl(20)-[histone H4] + formaldehyde + succinate + CO2 (RHEA:67804)

UniProt features (67 total): helix 22, strand 17, turn 8, binding site 5, region of interest 4, compositionally biased region 3, splice variant 2, chain 1, domain 1, modified residue 1, sequence variant 1, sequence conflict 1, zinc finger region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
3KV9	X-RAY DIFFRACTION	2.29
3KV5	X-RAY DIFFRACTION	2.39
3U78	X-RAY DIFFRACTION	2.69
3KVB	X-RAY DIFFRACTION	2.69
3KVA	X-RAY DIFFRACTION	2.79
3KV6	X-RAY DIFFRACTION	2.89

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZMT4-F1	66.80	0.47

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 (5): 279; 282; 284; 299; 354

Post-translational modifications (1): 604

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-3214842	HDMs demethylate histones
R-HSA-6802952	Signaling by BRAF and RAF1 fusions
R-HSA-1643685	Disease
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-6802957	Oncogenic MAPK signaling

MSigDB gene sets: 329 (showing top): GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, PEREZ_TP63_TARGETS, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, BILD_HRAS_ONCOGENIC_SIGNATURE, ONKEN_UVEAL_MELANOMA_UP, MODULE_256, GOBP_MIDBRAIN_DEVELOPMENT, MODULE_206, GOBP_HEAD_DEVELOPMENT, CUI_TCF21_TARGETS_2_DN, MARTORIATI_MDM4_TARGETS_FETAL_LIVER_UP, GOBP_CHROMATIN_REMODELING, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, GOCC_NUCLEOLUS

GO Biological Process (6): chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), midbrain development (GO:0030901), positive regulation of DNA-templated transcription (GO:0045893), chromatin organization (GO:0006325), nervous system development (GO:0007399)

GO Molecular Function (13): transcription coregulator activity (GO:0003712), iron ion binding (GO:0005506), zinc ion binding (GO:0008270), 2-oxoglutarate-dependent dioxygenase activity (GO:0016706), histone demethylase activity (GO:0032452), histone H3K9 demethylase activity (GO:0032454), histone H4K20 demethylase activity (GO:0035575), histone H3K36 demethylase activity (GO:0051864), histone H3K27me2/H3K27me3 demethylase activity (GO:0071558), histone H3K9me/H3K9me2 demethylase activity (GO:0140683), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Oncogenic MAPK signaling	1
Chromatin organization	1
Disease	1
Diseases of signal transduction by growth factor receptors and second messengers	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
2-oxoglutarate-dependent dioxygenase activity	4
histone H3 demethylase activity	3
regulation of DNA-templated transcription	2
transition metal ion binding	2
nuclear lumen	2
chromatin organization	1
transcription by RNA polymerase II	1
brain development	1
anatomical structure development	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
cellular component organization	1
system development	1
transcription regulator activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
dioxygenase activity	1
protein demethylase activity	1
histone modifying activity	1
histone H4 demethylase activity	1
histone H3K9 demethylase activity	1
catalytic activity	1
cation binding	1
oxidoreductase activity	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

978 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KDM7A	KDM4A	O75164	773
KDM7A	KDM6B	O15054	742
KDM7A	JMJD1C	Q15652	667
KDM7A	KDM5A	P29375	644
KDM7A	KDM6A	O15550	632
KDM7A	KDM4C	Q9H3R0	629
KDM7A	KDM3A	Q9Y4C1	626
KDM7A	KDM4B	O94953	621
KDM7A	KDM4D	Q6B0I6	620
KDM7A	KDM1A	O60341	618
KDM7A	KDM5B	Q9UGL1	608
KDM7A	Q08EI0	Q08EI0	605
KDM7A	KDM3B	Q7LBC6	600
KDM7A	KDM5C	P41229	577
KDM7A	KDM8	Q8N371	564

IntAct

5 interactions, top by confidence:

A	B	Type	Score
KDM6B	PFN2	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
	PHF20L1	psi-mi:“MI:0914”(association)	0.350
KDM7A	ahpC	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): KDM7A (Affinity Capture-MS), KDM7A (Affinity Capture-RNA), KDM7A (Affinity Capture-MS), KDM7A (Affinity Capture-MS), KDM7A (Affinity Capture-MS), KDM7A (Affinity Capture-MS), KDM7A (Affinity Capture-RNA)

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: A2WXR5, A2XTW9, A2Y0Q2, A2Y4R8, B8ADZ3, B8AMA8, B8B8C5, B8B8I3, B8BJV8, O81488, P0CF52, P0CH95, Q12830, Q2R837, Q3UWM4, Q40359, Q5EA28, Q5RHD1, Q5XEM9, Q60DW3, Q6BER5, Q6BXJ4, Q6YTY3, Q6Z7F4, Q6ZMT4, Q75IR6, Q7F2Z1, Q7XUW3, Q80TJ7, Q84TV4, Q8C9B9, Q8H383, Q8LA16, Q8S8M9, Q9BTC0, Q9CWW7, Q9FFF5, Q9M2B4, Q9P0U4, Q9SRM4

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
HIF1A	“up-regulates quantity by expression”	KDM7A	“transcriptional regulation”
EPAS1	“up-regulates quantity by expression”	KDM7A	“transcriptional regulation”
2-oxoglutarate(2-)	“up-regulates activity”	KDM7A	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	90
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3955 predictions. Top by Δscore:

Variant	Effect	Δscore
7:140094051:TATAC:T	donor_loss	1.0000
7:140094052:ATACC:A	donor_loss	1.0000
7:140094053:TACCT:T	donor_loss	1.0000
7:140094054:A:T	donor_loss	1.0000
7:140094055:C:CA	donor_loss	1.0000
7:140094137:TC:T	acceptor_gain	1.0000
7:140094138:CC:C	acceptor_gain	1.0000
7:140094139:C:CC	acceptor_gain	1.0000
7:140094140:T:C	acceptor_loss	1.0000
7:140097043:CTTTT:C	acceptor_gain	1.0000
7:140097060:T:TC	acceptor_gain	1.0000
7:140097476:T:TA	donor_gain	1.0000
7:140097520:A:AC	donor_gain	1.0000
7:140097521:C:CC	donor_gain	1.0000
7:140098874:CATA:C	donor_loss	1.0000
7:140098876:TACCA:T	donor_loss	1.0000
7:140098877:A:AC	donor_gain	1.0000
7:140098877:A:T	donor_loss	1.0000
7:140098877:AC:A	donor_gain	1.0000
7:140098878:C:A	donor_loss	1.0000
7:140098878:C:CA	donor_gain	1.0000
7:140098878:CC:C	donor_gain	1.0000
7:140098878:CCA:C	donor_gain	1.0000
7:140098878:CCAT:C	donor_gain	1.0000
7:140098878:CCATT:C	donor_gain	1.0000
7:140099029:CATCT:C	acceptor_gain	1.0000
7:140099030:ATCT:A	acceptor_gain	1.0000
7:140099031:TCT:T	acceptor_gain	1.0000
7:140099032:CT:C	acceptor_gain	1.0000
7:140099032:CTC:C	acceptor_gain	1.0000

AlphaMissense

6246 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:140111120:A:G	L468P	1.000
7:140119149:A:G	W404R	1.000
7:140119149:A:T	W404R	1.000
7:140119171:G:C	F396L	1.000
7:140119171:G:T	F396L	1.000
7:140119173:A:G	F396L	1.000
7:140119177:G:C	F394L	1.000
7:140119177:G:T	F394L	1.000
7:140119178:A:C	F394C	1.000
7:140119178:A:G	F394S	1.000
7:140119179:A:G	F394L	1.000
7:140119196:A:G	L388P	1.000
7:140120477:G:C	N368K	1.000
7:140120477:G:T	N368K	1.000
7:140120481:C:T	G367E	1.000
7:140120482:C:A	G367W	1.000
7:140120517:G:T	A355D	1.000
7:140120518:C:G	A355P	1.000
7:140120527:A:G	W352R	1.000
7:140120527:A:T	W352R	1.000
7:140124723:A:G	W317R	1.000
7:140124723:A:T	W317R	1.000
7:140126654:A:G	W291R	1.000
7:140126654:A:T	W291R	1.000
7:140126665:C:T	G287E	1.000
7:140126668:C:T	G286D	1.000
7:140126670:G:C	F285L	1.000
7:140126670:G:T	F285L	1.000
7:140126672:A:G	F285L	1.000
7:140126674:T:A	D284V	1.000

dbSNP variants (sampled 300 via entrez): RS1000094529 (7:140097799 C>T), RS1000119989 (7:140152854 G>A), RS1000135774 (7:140093179 G>C), RS1000170033 (7:140171474 ATATATTTATATT>A,ATATATT,ATATATTTATATTTATATT), RS1000174506 (7:140135932 G>A), RS1000175332 (7:140175419 C>T), RS1000221259 (7:140107356 C>T), RS1000227569 (7:140175635 G>A), RS1000246227 (7:140085941 T>C), RS1000258300 (7:140126132 T>A), RS1000307827 (7:140129915 A>C), RS1000336252 (7:140169974 A>C,T), RS1000343057 (7:140148437 TAGTAAC>T), RS1000379127 (7:140158227 A>G), RS1000381761 (7:140130202 A>T)

Disease associations

OMIM: gene MIM:619640 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
cerebral palsy	Limited	Autosomal dominant

Mondo (1): cerebral palsy (MONDO:0006497)

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004607_165	Plateletcrit	1.000000e-09
GCST90002400_59	Plateletcrit	8.000000e-22
GCST90002400_60	Plateletcrit	3.000000e-09
GCST90002402_38	Platelet count	9.000000e-14
GCST90002402_39	Platelet count	4.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007985	platelet crit
EFO:0004309	platelet count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002547	Cerebral Palsy	C10.228.140.140.254

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2163177 (SINGLE PROTEIN), CHEMBL3038496 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 29,704 (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
CHEMBL633	AMIODARONE	4	29,704

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 (1 total), top 1:

Ligand	Action	Affinity	Parameter
daminozide	Inhibition	5.68	pIC50

ChEMBL bioactivities

6 potent at pChembl≥5 of 15 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.72	IC50	190	nM	CHEMBL5723343
6.70	IC50	200	nM	CHEMBL2424812
5.80	IC50	1600	nM	CHEMBL1229308
5.72	IC50	1900	nM	CHEMBL4126235
5.68	IC50	2100	nM	CHEMBL2164243
5.25	IC50	5600	nM	CHEMBL4126406

PubChem BioAssay actives

5 with measured affinity, of 38 total; 5 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-[9-cyclopropylnonanoyl(hydroxy)amino]propanoic acid	770453: Inhibition of KDM7A (unknown origin) using K27me2 peptide as substrate by MALDI assay	ic50	0.2000	uM
3-[9-(dimethylamino)nonanoyl-hydroxyamino]propanoic acid	770453: Inhibition of KDM7A (unknown origin) using K27me2 peptide as substrate by MALDI assay	ic50	1.6000	uM
[(5S)-6-[[(2S)-5-amino-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S,3R)-1-[[2-[[2-[[(2S)-6-amino-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(1S)-1-carboxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]amino]-6-oxohexyl]-trimethylazanium	1496240: Displacement of C-terminally biotinylated-H3K4me3 (1 to 21 residues) peptide from KDM7A (PHD) (unknown origin) preincubated for 15 mins followed by peptide addition measured after 1 hr by luminescence-based AlphaScreen assay	ic50	1.9000	uM
4-(2,2-dimethylhydrazinyl)-4-oxobutanoic acid	698699: Inhibition of human KDM7A catalytic domain expressed in Escherichia coli by MALDI assay	ic50	2.1000	uM
trimethyl-[3-[4-(2-methyl-1-benzofuran-3-carbonyl)phenoxy]propyl]azanium iodide	1496244: Displacement of C-terminally biotinylated-H3K4me3 (1 to 21 residues) peptide from KDM7A (PHD-JmjC) (unknown origin) preincubated for 15 mins followed by peptide addition measured after 1 hr by luminescence-based AlphaScreen assay	ic50	5.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases methylation	3
Cyclosporine	increases expression	3
sodium arsenite	decreases expression, increases expression	2
didecyldimethylammonium	increases expression	2
(+)-JQ1 compound	increases expression	2
Acetaminophen	increases expression	2
Benzo(a)pyrene	decreases expression	2
Folic Acid	affects cotreatment, increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
sotorasib	affects cotreatment, decreases expression	1
alpha phellandrene	increases expression	1
bisphenol A	decreases methylation	1
arsenite	affects binding, decreases reaction	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
nickel chloride	increases expression	1
benzo(e)pyrene	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1

ChEMBL screening assays

10 unique, capped per target: 9 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2167521	Binding	Inhibition of human KDM7A catalytic domain expressed in Escherichia coli by MALDI assay	Plant growth regulator daminozide is a selective inhibitor of human KDM2/7 histone demethylases. — J Med Chem
CHEMBL5723316	Functional	Affinity Biochemical interaction: (AlphaScreen) EUB0002790a JHDM1D	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_B1G6	Abcam A-549 KDM7A KO 2	Cancer cell line	Male
CVCL_B2NP	Abcam A-549 KDM7A KO 1	Cancer cell line	Male
CVCL_SU53	HAP1 KDM7A (-) 1	Cancer cell line	Male
CVCL_SU54	HAP1 KDM7A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00154830	PHASE4	COMPLETED	Alterations of Functional Activities and Leg Stiffness After Hamstring Lengthening in Cerebral Palsy Children
NCT00432055	PHASE4	COMPLETED	Effects of Botulinum Toxin Type A in Adults With Cerebral Palsy
NCT00549471	PHASE4	TERMINATED	Improvement After Botulinum Toxin Injections to the Arms in Children With Cerebral Palsy
NCT00752934	PHASE4	TERMINATED	Does Oral Baclofen Improve Care and Comfort in Spastic Children in Nursing Homes?
NCT00964639	PHASE4	COMPLETED	Postoperative Pain in Children With Cerebral Palsy After Pelvic and Femoral Osteotomies
NCT01386255	PHASE4	WITHDRAWN	Placebo Controlled Study of Baclofen for GERD in Children With Cerebral Palsy
NCT02546999	PHASE4	COMPLETED	Does Botulinum Toxin A Make Walking Easier in Children With Cerebral Palsy?
NCT02633241	PHASE4	COMPLETED	A Pilot Study of Dexmedetomidine-Propofol in Children Undergoing Magnetic Resonance Imaging
NCT03117322	PHASE4	COMPLETED	Synbiotic, Prebiotics and Probiotics in Children With Cerebral Palsy and Constipation
NCT03648658	PHASE4	UNKNOWN	Paracetamol Study in Patients With Low Muscle Mass
NCT04074265	PHASE4	COMPLETED	Peri-operative Use of a Pain Injection in Pediatric Patients With Cerebral Palsy
NCT04273737	PHASE4	TERMINATED	Amantadine in Treating Cognitive & Motor Impairments in Adolescents and Adults With Cerebral Palsy
NCT04523935	PHASE4	COMPLETED	Excessive Crying in Children With Cerebral Palsy and Communication Deficits
NCT05887765	PHASE4	COMPLETED	Effect of Systematic Dexamethasone on the Duration of Popliteal Nerve Block for Anesthesia After Pediatric Ankle Surgery
NCT06176430	PHASE4	UNKNOWN	Comparison of Twice Weekly Versus Daily Iron Therapy in Treating Anemia in Children With Cerebral Palsy
NCT06189781	PHASE4	RECRUITING	Pain Injection Versus Epidural Anesthesia for Hip Surgery in Pediatric Patients With Cerebral Palsy
NCT00014989	PHASE3	COMPLETED	Beneficial Effects of Antenatal Magnesium Sulfate (BEAM Trial)
NCT00065949	PHASE3	UNKNOWN	Magnesium Sulfate to Prevent Brain Injury in Premature Infants
NCT00367068	PHASE3	COMPLETED	Dutch National ITB Study in Children With Cerebral Palsy
NCT00491894	PHASE3	COMPLETED	Safety and Efficacy Study of Oral Glycopyrrolate Liquid for the Treatment of Pathologic (Chronic Moderate to Severe) Drooling in Pediatric Patients 3 to 18 Years of Age With Cerebral Palsy or Other Neurologic Conditions
NCT00632528	PHASE3	COMPLETED	MEOPA to Improve Physical Therapy Results After Multilevel Surgery
NCT00822029	PHASE3	TERMINATED	Use of Oral Bisphosphonates in the Treatment of Osteoporosis of Non-walking Children With Cerebral Palsy
NCT00922077	PHASE3	COMPLETED	Individualized Neurodevelopmental Treatment
NCT01249417	PHASE3	COMPLETED	Dysport® Pediatric Lower Limb Spasticity Study
NCT01251380	PHASE3	COMPLETED	Dysport® Pediatric Lower Limb Spasticity Follow-on Study
NCT01437644	PHASE3	COMPLETED	The Post-Operative Pain in Cerebral Palsy (POPPIES) Trial
NCT01492608	PHASE3	COMPLETED	Magnesium Sulphate for Preterm Birth (MASP Study)
NCT01603602	PHASE3	COMPLETED	BOTOX® Treatment in Pediatric Upper Limb Spasticity
NCT01603615	PHASE3	COMPLETED	BOTOX® Open-Label Treatment in Pediatric Upper Limb Spasticity
NCT01603628	PHASE3	COMPLETED	BOTOX® Treatment in Pediatric Lower Limb Spasticity
NCT01603641	PHASE3	COMPLETED	BOTOX® Open-Label Treatment in Pediatric Lower Limb Spasticity
NCT01633736	PHASE3	UNKNOWN	Targeted Hip Strength Training in Children With Cerebral Palsy (CP)
NCT01898520	PHASE3	COMPLETED	A Safety, Efficacy and Tolerability Study of Sativex for the Treatment of Spasticity in Children Aged 8 to 18 Years
NCT01929434	PHASE3	COMPLETED	Efficacy of Stem Cell Transplantation Compared to Rehabilitation Treatment of Patients With Cerebral Paralysis
NCT02002884	PHASE3	COMPLETED	Dose-response Study of Efficacy and Safety of Botulinum Toxin Type A to Treat Spasticity of the Arm(s) or of Arm(s) and Leg(s) in Cerebral Palsy
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02839785	PHASE3	TERMINATED	Analgesia and Physiotherapy in Children With Cerebral Palsy (ANTALKINECP)
NCT03110341	PHASE3	UNKNOWN	Effect of Erythropoietin in Premature Infants on White Matter Lesions and Neurodevelopmental Outcome
NCT03302871	PHASE3	COMPLETED	Integrated Management Enhances Functional Gains in Children With Cerebral Palsy Treated by BoNT-A
NCT03306212	PHASE3	COMPLETED	Efficacy of Intermittent Serial Casting on Spastic Wrist Flexion Deformity