KDM5A

Summary

KDM5A (lysine demethylase 5A, HGNC:9886) is a protein-coding gene on chromosome 12p13.33, encoding Lysine-specific demethylase 5A (P29375). Histone demethylase that specifically demethylates ‘Lys-4’ of histone H3, thereby playing a central role in histone code.

This gene encodes a member of the Jumonji, AT-rich interactive domain 1 (JARID1) histone demethylase protein family. The encoded protein plays a role in gene regulation through the histone code by specifically demethylating lysine 4 of histone H3. The encoded protein interacts with many other proteins, including retinoblastoma protein, and is implicated in the transcriptional regulation of Hox genes and cytokines. This gene may play a role in tumor progression.

Source: NCBI Gene 5927 — RefSeq curated summary.

At a glance

• Gene–disease (curated): El Hayek-Chahrour neurodevelopmental disorder (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 311 total — 7 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 35
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Transcription factor: yes — 22 downstream targets (CollecTRI)
• MANE Select transcript: NM_001042603

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9886
Approved symbol	KDM5A
Name	lysine demethylase 5A
Location	12p13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000073614
Ensembl biotype	protein_coding
OMIM	180202
Entrez	5927

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 5 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000399788, ENST00000535014, ENST00000535269, ENST00000536014, ENST00000540156, ENST00000540168, ENST00000540838, ENST00000541335, ENST00000543507, ENST00000544760, ENST00000544777

RefSeq mRNA: 1 — MANE Select: NM_001042603 NM_001042603

CCDS: CCDS41736

Canonical transcript exons

ENST00000399788 — 28 exons

Exon	Start	End
ENSE00000437599	323082	323206
ENSE00000437602	318106	318461
ENSE00000711821	310885	311064
ENSE00000711823	313056	313194
ENSE00000711827	320995	321109
ENSE00000711853	322417	322567
ENSE00000711860	323600	323781
ENSE00000711863	328835	329029
ENSE00000711869	333487	333649
ENSE00000711872	334241	334422
ENSE00000711875	350621	350779
ENSE00000711877	352205	352324
ENSE00000711879	354076	354234
ENSE00000711881	355158	355249
ENSE00000711885	362963	363097
ENSE00000711886	365934	366104
ENSE00000711888	385897	385974
ENSE00001194767	356432	356537
ENSE00001318833	388927	389320
ENSE00001598956	280057	285662
ENSE00001628636	331819	331938
ENSE00001658094	295573	295793
ENSE00001677388	292759	293169
ENSE00001693829	307454	308005
ENSE00001760353	297041	297200
ENSE00001791408	306946	307089
ENSE00002698605	309803	309964
ENSE00003785158	384031	384153

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 95.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.2137 / max 344.4867, expressed in 1789 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128883	10.0321	1745
128885	5.0744	1672
128881	1.3159	476
128884	0.7913	451

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	95.89	gold quality
caput epididymis	UBERON:0004358	95.88	gold quality
cranial nerve II	UBERON:0000941	95.64	gold quality
nipple	UBERON:0002030	95.55	gold quality
cauda epididymis	UBERON:0004360	95.31	gold quality
corpus epididymis	UBERON:0004359	95.29	gold quality
saphenous vein	UBERON:0007318	95.04	gold quality
trabecular bone tissue	UBERON:0002483	95.00	gold quality
pericardium	UBERON:0002407	94.61	gold quality
tongue squamous epithelium	UBERON:0006919	94.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.26	gold quality
superior surface of tongue	UBERON:0007371	94.25	gold quality
trigeminal ganglion	UBERON:0001675	93.78	gold quality
pylorus	UBERON:0001166	93.66	gold quality
bone marrow cell	CL:0002092	93.47	gold quality
calcaneal tendon	UBERON:0003701	93.44	gold quality
bone marrow	UBERON:0002371	93.40	gold quality
adrenal tissue	UBERON:0018303	93.33	gold quality
sperm	CL:0000019	93.26	gold quality
corpus callosum	UBERON:0002336	93.06	gold quality
pharyngeal mucosa	UBERON:0000355	92.85	gold quality
buccal mucosa cell	CL:0002336	92.82	gold quality
renal medulla	UBERON:0000362	92.44	gold quality
cardia of stomach	UBERON:0001162	92.44	gold quality
tonsil	UBERON:0002372	92.07	gold quality
tongue	UBERON:0001723	91.90	gold quality
vena cava	UBERON:0004087	91.90	gold quality
mammary duct	UBERON:0001765	91.86	gold quality
male germ cell	CL:0000015	91.41	gold quality
skin of hip	UBERON:0001554	91.38	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

22 targets.

Target	Regulation
AVP
BGLAP
BMP4
CD24
CD55
CDH17
CDKN1A
CDKN1B
FGFR1
HMGB1
HMOX1	Activation
MARK1
ME3
MIR212
PER2
PGR	Unknown
PTEN	Repression
RBP2
SAP18
TERT
TNFRSF11A
TRI-AAT9-1

Upstream regulators (CollecTRI, top): BMAL1, EPAS1, HIF1A

Literature-anchored findings (GeneRIF, showing 40)

• that RBP2-H1 exerts a broad tumor-suppressive function partially mediated by pRb modulation (PMID:16645588)
• Study shows that RBP2 is displaced from Hox genes during embryonic stem cell differentiation correlating with an increase of their di- and trimethylated histone 3 lysine 4 levels and expression. (PMID:17320161)
• RBP2 associates with MRG15 complex to maintain reduced H3K4 methylation at transcribed regions, which may ensure the transcriptional elongation state (PMID:17573780)
• ARID is required for RBP2 demethylase activity in cells and that DNA recognition is essential to regulate transcription (PMID:18270511)
• During differentiation, RBP2 exerts inhibitory effects on multiple genes through direct interaction with their promoters. (PMID:18722178)
• fusing an H3K4-trimethylation-binding PHD finger, such as the carboxy-terminal PHD finger of JARID1A, to a common fusion partner NUP98, generated potent oncoproteins that arrested haematopoietic differentiation and induced acute myeloid leukaemia (PMID:19430464)
• Mad1 recruits RBP2 to the hTERT promoter that, in turn, demethylates H3-K4, thereby contributing to a stable repression of the hTERT gene in normal or differentiated malignant cells. (PMID:19762557)
• RBP2 is overexpressed in gastric cancer, and its inhibition triggers senescence of malignant cells at least partially by derepressing its target genes cyclin-dependent kinase inhibitors. (PMID:19850045)
• that H3K4 tri- and dimethylation play an important role and JARID1A is the histone-demethylating enzyme responsible for removal of this mark (PMID:21348942)
• JARID1A or a locus in strong linkage disequilibrium with it is a positional candidate for susceptibility to AS. (PMID:21562575)
• Evidence was provided that chronic drug exposure generated drug-tolerant cells via epigenetic mechanisms involving molecules such as CD44 and KDM5A. (PMID:21935404)
• Jarid1a/b-mediated H3K4 demethylation contributes to silencing of retinoblastoma target genes in senescent cells, suggesting a mechanism by which retinoblastoma triggers gene silencing. (PMID:22615382)
• In terminally differentiated cells, common KDM5A and E2F4 gene targets were bound by the pRB-related protein p130, a DREAM complex component. (PMID:23093672)
• High expression of KDM3B and KDM5A is associated with a better prognosis (no recurrence after mastectomy p=0.005 and response to docetaxel p=0.005)in breast cancer patients. (PMID:23266085)
• our results establish an oncogenic role for RBP2 in lung tumorigenesis and progression and uncover novel RBP2 targets mediating this role. (PMID:23722541)
• MiR-212 directly regulates the expression of RBP2 and inhibits cell growth in gastric cancer, which may provide new clues to treatment. (PMID:23794145)
• RBP2 is overexpressed in HCC and negatively regulated by hsa-miR-212. The hsa-miR-212-RBP2-CDKI pathway may be important in the pathogenesis of HCC. (PMID:23922798)
• LSD1 is a more sensitive molecular marker than RBP2 on thyroid cancer diagnosis. (PMID:24068396)
• JARID1A, JMY, and PTGER4 polymorphisms are related to ankylosing spondylitis in Chinese Han patients. (PMID:24069348)
• RBP2 down-regulated the expression of E-cadherin, up-regulated the expression of N-cadherin and snail, and induced epithelial-mesenchymal transition in non-small cell lung cancer cells. (PMID:24376841)
• Epigenetic changes mediated by JARID1A, SMYD3 and DNA methylation may be responsible, at least in part, for the functional progesterone withdrawal that precipitates human labour. (PMID:24442343)
• RBP2 is critical for breast cancer metastasis to the lung in multiple in vivo models. Mechanistically, RBP2 promotes metastasis as a pleiotropic positive regulator of many metastasis genes, including TNC. (PMID:24582965)
• Overexpression of RBP2 and activation of VEGF might play important roles in human gastric cancer development and progression. (PMID:24716659)
• RBP2 may link chronic inflammation to tumor development. (PMID:25015565)
• RBP2 promotes HIF-1alpha-VEGF-induced angiogenesis of non-small cell lung cancer via the Akt pathway. (PMID:25162518)
• KDM5A and the NuRD complex cooperatively function to control developmentally regulated genes (PMID:25190814)
• Data indicate that lysine (K)-specific demethylase 5A RBP2 (JARID1A; KDM5A) epigenetically downregulated micrRNA-21 (miR-21) in blast transformation of chronic myeloid leukemia (CML). (PMID:25575817)
• KDM5A is regulated by its reader domain through a positive-feedback mechanism (PMID:25686748)
• Treatment-induced temozolimide resistance in glioblastoma cells involves KDM5A mediated epigenetic mechanisms. (PMID:26566863)
• Characterization of a Linked Jumonji Domain of the KDM5/JARID1 Family of Histone H3 Lysine 4 Demethylases. (PMID:26645689)
• promotes overexpression and activation of BCL2 in acute lymphoblastic leukemia development and progression (PMID:27008505)
• KDM5A 5A inhibitor blocks cancer cell growth and drug resistance (PMID:27224921)
• the radiation sensitivity observed following depletion of Jarid1A is not caused by a deficiency in repair of DNA double-strand breaks. (PMID:27253695)
• Ectopic overexpression of RBP2 can induce cancer stem cell-like (CSC) phenotypes through epithelial to mesenchymal transition in renal cell carcinoma cells by converting them to a more mesenchymal phenotype. (PMID:27282106)
• miR-34a promotes the osteogenic differentiation of human adipose-derived stem cells via the RBP2/NOTCH1/CYCLIN D1 coregulatory network. (PMID:27453008)
• KDM5A-mediated H3K4me3 modification participated in the etiology of osteoporosis and may provide new strategies to improve the clinical efficacy of BMP2 in osteoporotic conditions. (PMID:27512956)
• both KDM5A and KDM5B are involved in the lengthening of DICER1 (PMID:28138513)
• KDM5A demethylates H3K4 to allow ZMYND8-NuRD to operate within damaged chromatin to repair DNA double strand breaks. (PMID:28572115)
• This study aimed to explore the expression level of RBP2 in hepatocellular carcinoma (HCC) and its prognostic significance. (PMID:28582381)
• KDM5A suppresses ovarian cancer cell apoptosis under paclitaxel treatment. (PMID:28714030)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000104567
mus_musculus	Kdm5a	ENSMUSG00000030180
rattus_norvegicus	Kdm5a	ENSRNOG00000010591
drosophila_melanogaster	Kdm5	FBGN0031759
caenorhabditis_elegans		WBGENE00004319

Paralogs (10): JARID2 (ENSG00000008083), KDM5D (ENSG00000012817), KDM4A (ENSG00000066135), KDM4C (ENSG00000107077), KDM5B (ENSG00000117139), KDM5C (ENSG00000126012), KDM4B (ENSG00000127663), KDM4D (ENSG00000186280), KDM4E (ENSG00000235268), KDM4F (ENSG00000255855)

Protein

Protein identifiers

Lysine-specific demethylase 5A — P29375 (reviewed: P29375)

Alternative names: Histone demethylase JARID1A, Jumonji/ARID domain-containing protein 1A, Retinoblastoma-binding protein 2, [histone H3]-trimethyl-L-lysine(4) demethylase 5A

All UniProt accessions (5): P29375, E7EV89, F5GZ99, F5GZR8, F5H322

UniProt curated annotations — full annotation on UniProt →

Function. Histone demethylase that specifically demethylates ‘Lys-4’ of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 ‘Lys-9’, H3 ‘Lys-27’, H3 ‘Lys-36’, H3 ‘Lys-79’ or H4 ‘Lys-20’. Demethylates trimethylated and dimethylated but not monomethylated H3 ‘Lys-4’. Regulates specific gene transcription through DNA-binding on 5’-CCGCCC-3’ motif. May stimulate transcription mediated by nuclear receptors. Involved in transcriptional regulation of Hox proteins during cell differentiation. May participate in transcriptional repression of cytokines such as CXCL12. Plays a role in the regulation of the circadian rhythm and in maintaining the normal periodicity of the circadian clock. In a histone demethylase-independent manner, acts as a coactivator of the CLOCK-BMAL1-mediated transcriptional activation of PER1/2 and other clock-controlled genes and increases histone acetylation at PER1/2 promoters by inhibiting the activity of HDAC1. Seems to act as a transcriptional corepressor for some genes such as MT1F and to favor the proliferation of cancer cells.

Subunit / interactions. Interacts with SUZ12; the interaction is direct. Interacts with the viral protein-binding domain of RB1. Interacts with ESR1, MYC, MYCN and LMO2. Interacts with HDAC1; this interaction impairs histone deacetylation by HDAC1. Interacts with BMAL1 and CLOCK. Interacts (via PHD-type 1 zinc finger) with histone H3 unmodified at ‘Lys-4’ and (via PHD-type 3 zinc finger) with histone H3 di- and trimethylated at ‘Lys-4’.

Subcellular location. Nucleus. Nucleolus.

Disease relevance. A chromosomal aberration involving KDM5A has been found in M5 type acute myeloid leukemia. Translocation t(11;12)(p15;p13) with NUP98. Chromosomal aberrations involving KDM5A have been found in M7 type childhood acute myeloid leukemia. Translocation t(11;12)(p15;p13) with NUP98. El Hayek-Chahrour neurodevelopmental syndrome (NEDEHC) [MIM:620820] An autosomal recessive neurodevelopmental disorder characterized by lack of speech, intellectual disability, autism, and developmental delay. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. The inhibitors KDOAM-25, CPI-455 and others inhibits its demethylase activity, resulting to cell growth arrest in cancer cells.

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

Domain organisation. The GSGFP motif is required for the interaction with SUZ12. The ARID domain specifically binds to the CCGCCC motif and is required for the lysine-specific histone demethylase activity. The PHD-type 3 zinc finger is required for the interaction with histone H3 di- and trimethylated at ‘Lys-4’.

Similarity. Belongs to the JARID1 histone demethylase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P29375-1	1	yes
P29375-2	2

RefSeq proteins (1): NP_001036068* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001606	ARID_dom	Domain
IPR001965	Znf_PHD	Domain
IPR003347	JmjC_dom	Domain
IPR003349	JmjN	Domain
IPR004198	Znf_C5HC2	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013637	Lys_sp_deMease-like_dom	Domain
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR019787	Znf_PHD-finger	Domain
IPR036431	ARID_dom_sf	Homologous_superfamily
IPR047970	KDM5A_PHD2	Domain
IPR047972	KDM5A_PHD3	Domain
IPR047973	KDM5A_PHD1	Domain
IPR047974	KDM5A_ARID	Domain
IPR048615	KDM5_C-hel	Domain

Pfam: PF00628, PF01388, PF02373, PF02375, PF02928, PF08429, PF21323

Enzyme classification (BRENDA):

• EC 1.14.11.67 — [histone H3]-trimethyl-L-lysine4 demethylase (BRENDA: 13 organisms, 78 substrates, 122 inhibitors, 22 Km, 20 kcat entries)

Substrate kinetics (BRENDA)

17 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[ACETYLATED HISTONE H3 21MER]-N6,N6,N6-TRIMETHYL	0.0168–0.0955	2
[ACETYLATED HISTONE H3 21MER]-N6,N6-DIMETHYL-L-L	0.0547–0.229	2
[HISTONE H3]-N6,N6-DIMETHYL-L-LYSINE4	0.0107–0.0128	2
[HISTONE H3 N-TERMINAL 13MER] N6,N6,N6-TRIMETHYL	0.489	1
[HISTONE H3 N-TERMINAL 18MER MUTANT K14A/R17A/K1	0.514	1
[HISTONE H3 N-TERMINAL 18MER MUTANT K14AC/K18AC]	0.249	1
[HISTONE H3 N-TERMINAL 18MER] N6,N6,N6-TRIMETHYL	0.0623	1
[HISTONE H3 N-TERMINAL 21MER MUTANT K9A] N6,N6,N	0.0219	1
[HISTONE H3 N-TERMINAL 21MER MUTANT Q5A] N6,N6,N	0.4152	1
[HISTONE H3 N-TERMINAL 21MER MUTANT R2A] N6,N6,N	0.1536	1
[HISTONE H3 N-TERMINAL 21MER MUTANT R8A] N6,N6,N	0.0551	1
[HISTONE H3 N-TERMINAL 21MER MUTANT T3A] N6,N6,N	0.009	1
[HISTONE H3 N-TERMINAL 21MER MUTANT T6A] N6,N6,N	0.0965	1
[HISTONE H3 N-TERMINAL 21MER MUTANT T6S] N6,N6,N	0.0147	1
[HISTONE H3 N-TERMINAL 21MER MUTANT T6V] N6,N6,N	0.0394	1

Catalyzed reactions (Rhea), 1 shown:

• N(6),N(6),N(6)-trimethyl-L-lysyl(4)-[histone H3] + 3 2-oxoglutarate + 3 O2 = L-lysyl(4)-[histone H3] + 3 formaldehyde + 3 succinate + 3 CO2 (RHEA:60208)

UniProt features (128 total): helix 37, strand 26, modified residue 12, mutagenesis site 9, turn 8, binding site 7, region of interest 5, sequence variant 5, zinc finger region 4, domain 3, compositionally biased region 3, sequence conflict 3, cross-link 2, chain 1, short sequence motif 1, site 1, splice variant 1

Structure

Experimental structures (PDB)

46 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6BGY	X-RAY DIFFRACTION	1.22
5IVB	X-RAY DIFFRACTION	1.39
6DQ4	X-RAY DIFFRACTION	1.39
6BH2	X-RAY DIFFRACTION	1.45
5IVY	X-RAY DIFFRACTION	1.45
6DQ8	X-RAY DIFFRACTION	1.46
5IVJ	X-RAY DIFFRACTION	1.57
5IVC	X-RAY DIFFRACTION	1.57
6DQ6	X-RAY DIFFRACTION	1.59
6BGV	X-RAY DIFFRACTION	1.59
5IW0	X-RAY DIFFRACTION	1.63
6BGW	X-RAY DIFFRACTION	1.64
6BH5	X-RAY DIFFRACTION	1.65
5IVF	X-RAY DIFFRACTION	1.68
6BGU	X-RAY DIFFRACTION	1.68
6BGZ	X-RAY DIFFRACTION	1.69
6DQF	X-RAY DIFFRACTION	1.69
6DQE	X-RAY DIFFRACTION	1.69
5ISL	X-RAY DIFFRACTION	1.69
6BH3	X-RAY DIFFRACTION	1.7
6DQ9	X-RAY DIFFRACTION	1.75
6DQC	X-RAY DIFFRACTION	1.75
5IVE	X-RAY DIFFRACTION	1.78
6DQB	X-RAY DIFFRACTION	1.79
5IVV	X-RAY DIFFRACTION	1.85
6DQ7	X-RAY DIFFRACTION	1.85
6BGX	X-RAY DIFFRACTION	1.88
6DQA	X-RAY DIFFRACTION	1.89
6DQ5	X-RAY DIFFRACTION	1.89
3GL6	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29375-F1	70.98	0.28

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 1485–1486 (breakpoint for translocation to form the nup98-kdm5a fusion protein)

Ligand- & substrate-binding residues (7): 409; 483; 485; 491; 493; 501; 571

Post-translational modifications (14): 204, 1111, 1330, 1331, 1343, 1345, 1438, 1488, 1595, 1598, 1603, 1666, 191, 1007

Mutagenesis-validated functional residues (9):

Position	Phenotype
112	decreases dna-binding.
152	abolishes dna-binding.
156	decreases dna-binding.
157	decreases dna-binding.
626	no effect on lysine-specific histone demethylase activity; when associated with s-636.
636	no effect on lysine-specific histone demethylase activity; when associated with s-626.
1609	no effect on interaction with histone h3 di- and trimethylated at ’lys-4’.
1625	abolishes interaction with histone h3 di- and trimethylated at ’lys-4’.
1634–1635	abolishes interaction with histone h3 di- and trimethylated at ’lys-4’.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-3214842	HDMs demethylate histones
R-HSA-9821002	Chromatin modifications during the maternal to zygotic transition (MZT)
R-HSA-1266738	Developmental Biology
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization
R-HSA-9816359	Maternal to zygotic transition (MZT)

MSigDB gene sets: 346 (showing top): GOBP_CIRCADIAN_RHYTHM, GNF2_BNIP2, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, HOFMANN_CELL_LYMPHOMA_UP, GOBP_CIRCADIAN_REGULATION_OF_GENE_EXPRESSION, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, BLALOCK_ALZHEIMERS_DISEASE_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, MODULE_123, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, CHO_NR4A1_TARGETS, GNF2_DDX5, GNF2_PTPRC, SOX5_01

GO Biological Process (10): negative regulation of transcription by RNA polymerase II (GO:0000122), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), circadian regulation of gene expression (GO:0032922), transcription initiation-coupled chromatin remodeling (GO:0045815), positive regulation of DNA-templated transcription (GO:0045893), facultative heterochromatin formation (GO:0140718), chromatin organization (GO:0006325), rhythmic process (GO:0048511), obsolete regulation of DNA-binding transcription factor activity (GO:0051090)

GO Molecular Function (15): transcription cis-regulatory region binding (GO:0000976), DNA binding (GO:0003677), transcription coactivator activity (GO:0003713), enzyme inhibitor activity (GO:0004857), zinc ion binding (GO:0008270), chromatin DNA binding (GO:0031490), histone demethylase activity (GO:0032452), histone H3K4me/H3K4me2/H3K4me3 demethylase activity (GO:0034647), histone binding (GO:0042393), chromatin binding (GO:0003682), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), histone H3K4 demethylase activity (GO:0032453), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), protein-DNA complex (GO:0032993)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Maternal to zygotic transition (MZT)	1
Chromatin organization	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
regulation of gene expression	2
catalytic activity	2
binding	2
cellular anatomical structure	2
nuclear lumen	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
chromatin organization	1
regulation of RNA biosynthetic process	1
circadian rhythm	1
transcription initiation at RNA polymerase II promoter	1
positive regulation of gene expression, epigenetic	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
heterochromatin formation	1
cellular component organization	1
biological_process	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
nucleic acid binding	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
enzyme regulator activity	1
molecular function inhibitor activity	1
transition metal ion binding	1
DNA binding	1
chromatin binding	1
protein demethylase activity	1
histone modifying activity	1
2-oxoglutarate-dependent dioxygenase activity	1
histone H3K4 demethylase activity	1
protein binding	1
histone H3 demethylase activity	1
cation binding	1
oxidoreductase activity	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

3804 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KDM5A	CLOCK	O15516	983
KDM5A	BMAL1	O00327	982
KDM5A	NUP98	P52948	896
KDM5A	PHF23	Q9BUL5	859
KDM5A	SUZ12	Q15022	827
KDM5A	MORF4L1	Q9UBU8	818
KDM5A	KDM1A	O60341	814
KDM5A	HDAC1	Q13547	773
KDM5A	RB1	P06400	763
KDM5A	KDM2B	Q8NHM5	755
KDM5A	ARID4A	P29374	743
KDM5A	ARID4B	Q4LE39	735
KDM5A	EZH2	Q15910	734
KDM5A	EMSY	Q7Z589	717
KDM5A	CEBPB	P17676	713

IntAct

73 interactions, top by confidence:

A	B	Type	Score
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
HDAC1	TNRC18	psi-mi:“MI:0914”(association)	0.790
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
MORF4L1	SIN3B	psi-mi:“MI:0914”(association)	0.730
HDAC1	ZNF609	psi-mi:“MI:0914”(association)	0.730
KDM5A		psi-mi:“MI:0407”(direct interaction)	0.680
KDM5A	SIN3B	psi-mi:“MI:0914”(association)	0.640
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
SIN3B	TNRC18	psi-mi:“MI:0914”(association)	0.530
RBBP4	TNRC18	psi-mi:“MI:0914”(association)	0.530
RBBP7	SMARCA5	psi-mi:“MI:0914”(association)	0.530
GATAD1	SIN3B	psi-mi:“MI:0914”(association)	0.530
RBBP7	EPOP	psi-mi:“MI:0914”(association)	0.530
RB1	KDM5A	psi-mi:“MI:0914”(association)	0.500
RB1	KDM5A	psi-mi:“MI:0915”(physical association)	0.500
KDM5A		psi-mi:“MI:0871”(demethylation reaction)	0.440
Rbm8a	GOSR1	psi-mi:“MI:0914”(association)	0.350
GATAD1	SIN3B	psi-mi:“MI:0914”(association)	0.350
PHF12	SIN3B	psi-mi:“MI:0914”(association)	0.350
TM9SF4		psi-mi:“MI:0914”(association)	0.350
FOXK2	PHF20L1	psi-mi:“MI:0914”(association)	0.350

BioGRID (129): KDM5A (Protein-peptide), KDM5A (Affinity Capture-MS), KDM5A (Affinity Capture-MS), KDM5A (Affinity Capture-MS), KDM5A (Two-hybrid), KDM5A (Affinity Capture-MS), KDM5A (Affinity Capture-MS), KDM5A (Affinity Capture-MS), KDM5A (Affinity Capture-MS), KDM5A (Affinity Capture-MS), KDM5A (Affinity Capture-MS), KDM5A (Affinity Capture-MS), KDM5A (Affinity Capture-MS), KDM5A (Affinity Capture-MS), KDM5A (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IB93, A1A5P5, A1Z7K9, A2XDG4, A3AF13, A3KMI0, A6QR55, B2GUZ1, D3ZJ96, F6V6I0, F6Z5C0, F8VPZ3, O22207, P29375, P35123, P51784, Q09879, Q13107, Q14149, Q2HJE4, Q30DN6, Q3UXZ9, Q3V0C5, Q5D006, Q5I043, Q5RCD3, Q5ZID5, Q5ZM45, Q62240, Q6NZP1, Q76LT8, Q80U87, Q80Y84, Q86UV5, Q8BWR4, Q8NFA0, Q8R5C8, Q8R5H1, Q93Y01, Q96RU2

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

14 interactions.

A	Effect	B	Mechanism
KDM5A	“down-regulates quantity by destabilization”	PTEN	“transcriptional regulation”
KDM5A	“up-regulates activity”	H3C1	demethylation
KDM5A	“up-regulates activity”	H3-4	demethylation
KDM5A	“up-regulates activity”	H3-3A	demethylation
KDM5A	“up-regulates activity”	“Histone H3”	demethylation
HIF1A	“up-regulates quantity by expression”	KDM5A	“transcriptional regulation”
EPAS1	“up-regulates quantity by expression”	KDM5A	“transcriptional regulation”
KDM5A	down-regulates	RBPJ/NOTCH	binding
2-oxoglutarate(2-)	“up-regulates activity”	KDM5A	“chemical activation”
AKT1	“up-regulates activity”	KDM5A	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 58 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of TP53 Activity through Acetylation	5	54.4×	1e-05
Regulation of PTEN gene transcription	5	21.2×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
chromatin remodeling	9	12.2×	3e-05
negative regulation of cell migration	5	10.3×	5e-03
chromatin organization	5	9.2×	7e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — GBC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	6
Uncertain significance	207
Likely benign	31
Benign	12

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
2866731	NM_001042603.3(KDM5A):c.23dup (p.Tyr9fs)	Pathogenic
3235139	NM_001042603.3(KDM5A):c.672+1488_1149+711del	Pathogenic
3235140	NM_001042603.3(KDM5A):c.2541+1G>T	Pathogenic
3235141	NM_001042603.3(KDM5A):c.1429T>G (p.Phe477Val)	Pathogenic
3339065	NM_001042603.3(KDM5A):c.2494C>T (p.Gln832Ter)	Pathogenic
4733816	NC_000012.12:g.333650del	Pathogenic
998056	t(11;12)(p15;p13)	Pathogenic
2500343	NM_001042603.3(KDM5A):c.1A>T (p.Met1Leu)	Likely pathogenic
2500344	NM_001042603.3(KDM5A):c.4283G>T (p.Arg1428Leu)	Likely pathogenic
3375408	NM_001042603.3(KDM5A):c.4074+1G>A	Likely pathogenic
3911581	NM_001042603.3(KDM5A):c.1807C>T (p.Arg603Ter)	Likely pathogenic
4531407	NM_001042603.3(KDM5A):c.50del (p.Pro17fs)	Likely pathogenic
563972	GRCh37/hg19 12p13.33(chr12:310521-1550563)x1	Likely pathogenic

SpliceAI

5552 predictions. Top by Δscore:

Variant	Effect	Δscore
12:295661:T:TA	donor_gain	1.0000
12:295801:A:T	acceptor_gain	1.0000
12:295810:CA:C	acceptor_gain	1.0000
12:295811:A:T	acceptor_gain	1.0000
12:297199:TC:T	acceptor_gain	1.0000
12:297200:CC:C	acceptor_gain	1.0000
12:297201:C:CC	acceptor_gain	1.0000
12:297201:C:G	acceptor_loss	1.0000
12:297202:T:C	acceptor_loss	1.0000
12:297772:A:C	donor_gain	1.0000
12:297798:CCATA:C	donor_gain	1.0000
12:306943:TACC:T	donor_loss	1.0000
12:306944:ACCT:A	donor_loss	1.0000
12:307905:T:TA	donor_gain	1.0000
12:308003:CAC:C	acceptor_gain	1.0000
12:308004:ACCTG:A	acceptor_loss	1.0000
12:308006:C:CC	acceptor_gain	1.0000
12:309798:CTTAC:C	donor_loss	1.0000
12:309800:TACCA:T	donor_loss	1.0000
12:309801:AC:A	donor_gain	1.0000
12:309801:ACCAC:A	donor_gain	1.0000
12:309802:C:G	donor_loss	1.0000
12:309802:CC:C	donor_gain	1.0000
12:309802:CCA:C	donor_gain	1.0000
12:309802:CCACC:C	donor_gain	1.0000
12:309837:T:TA	donor_gain	1.0000
12:309960:AGCAC:A	acceptor_gain	1.0000
12:309961:GCAC:G	acceptor_gain	1.0000
12:309962:CAC:C	acceptor_gain	1.0000
12:309962:CACC:C	acceptor_gain	1.0000

AlphaMissense

11150 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:285557:A:G	C1658R	1.000
12:285564:A:C	C1655W	1.000
12:285565:C:G	C1655S	1.000
12:285565:C:T	C1655Y	1.000
12:285566:A:G	C1655R	1.000
12:285566:A:T	C1655S	1.000
12:285609:A:C	C1640W	1.000
12:285610:C:A	C1640F	1.000
12:285610:C:G	C1640S	1.000
12:285610:C:T	C1640Y	1.000
12:285611:A:G	C1640R	1.000
12:285611:A:T	C1640S	1.000
12:285618:A:C	H1637Q	1.000
12:285618:A:T	H1637Q	1.000
12:285620:G:C	H1637D	1.000
12:285620:G:T	H1637N	1.000
12:285621:A:C	F1636L	1.000
12:285621:A:T	F1636L	1.000
12:285622:A:G	F1636S	1.000
12:285623:A:G	F1636L	1.000
12:285624:C:A	W1635C	1.000
12:285624:C:G	W1635C	1.000
12:285626:A:G	W1635R	1.000
12:285626:A:T	W1635R	1.000
12:285634:C:G	C1632S	1.000
12:285634:C:T	C1632Y	1.000
12:285635:A:G	C1632R	1.000
12:285635:A:T	C1632S	1.000
12:285643:T:A	D1629V	1.000
12:285643:T:G	D1629A	1.000

dbSNP variants (sampled 300 via entrez): RS1000017947 (12:280239 G>C), RS1000039021 (12:360725 T>G), RS1000049651 (12:365475 C>G), RS1000067097 (12:388903 C>A,T), RS1000131403 (12:286598 T>C), RS1000132435 (12:389696 T>C), RS1000276730 (12:354008 T>C), RS1000277636 (12:316173 A>G), RS1000279797 (12:333015 C>A), RS1000280907 (12:293397 A>G), RS1000306668 (12:365810 C>G), RS1000336351 (12:327915 G>A,C), RS1000337318 (12:365492 T>G), RS1000339543 (12:338997 T>C), RS1000355642 (12:289152 G>GC)

Disease associations

OMIM: gene MIM:180202 | disease phenotypes: MIM:620820

GenCC curated gene-disease

Disease	Classification	Inheritance
El Hayek-Chahrour neurodevelopmental disorder	Strong	Autosomal recessive
neurodevelopmental disorder	Moderate	Autosomal dominant
congenital heart disease	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital heart disease	Limited	AD

Mondo (5): El Hayek-Chahrour neurodevelopmental disorder (MONDO:0970951), intellectual disability (MONDO:0001071), acute megakaryoblastic leukemia without down syndrome (MONDO:0018004), neurodevelopmental disorder (MONDO:0700092), congenital heart disease (MONDO:0005453)

Orphanet (2): Acute megakaryoblastic leukemia in children without Down syndrome (Orphanet:329469), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

35 total (30 of 35 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000520	Proptosis
HP:0000627	Posterior embryotoxon
HP:0000670	Carious teeth
HP:0000729	Autistic behavior
HP:0000767	Pectus excavatum
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001288	Gait disturbance
HP:0001344	Absent speech
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001680	Coarctation of aorta
HP:0001822	Hallux valgus
HP:0002007	Frontal bossing
HP:0002079	Hypoplasia of the corpus callosum
HP:0004209	Clinodactyly of the 5th finger
HP:0004691	2-3 toe syndactyly

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000649_10	Chronic kidney disease	1.000000e-09
GCST005951_70	Body mass index	1.000000e-11
GCST007096_215	Pulse pressure	3.000000e-08
GCST90020027_1633	Waist-hip index	4.000000e-08
GCST90020029_426	Waist circumference adjusted for body mass index	6.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0005763	pulse pressure measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2424504 (SINGLE PROTEIN), CHEMBL4296073 (PROTEIN FAMILY), CHEMBL6066054 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193826 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 104,978 (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
CHEMBL550348	DEFERASIROX	4	1,593
CHEMBL633	AMIODARONE	4	29,704
CHEMBL964	DISULFIRAM	4	38,611
CHEMBL109480	TANESPIMYCIN	3	3,645
CHEMBL278315	GELDANAMYCIN	2	30,673
CHEMBL383824	ALVESPIMYCIN	2	752

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 (3 total), top 3:

Ligand	Action	Affinity	Parameter
KDM5 inhibitor N71	Irreversible inhibition	6.49	pIC50
PBIT	Inhibition	5.22	pIC50
GSK-J1	Inhibition	5.17	pIC50

Binding affinities (BindingDB)

529 measured of 822 human assays (822 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
cis-(1R,2R)-2-fluoro-N-[(3R)-1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]cyclopropane-1-carboxamide	IC50	0.025 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
2-[(3S)-1-(5-butan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]-1-[(1S,2S)-2-fluorocyclopropyl]ethanone	IC50	0.037 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
2-[(3S)-1-(5-butan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]-1-[(1R,2R)-2-fluorocyclopropyl]ethanone	IC50	0.038 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
3-ethyl-1-[(3R)-1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]pyridin-2-one	IC50	0.039 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
N-[(3S,4S)-4-hydroxy-1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]cyclopropanecarboxamide	IC50	0.046 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
2-ethoxy-N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]benzamide	IC50	0.047 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
N-[(3R)-1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]cyclopropanecarboxamide	IC50	0.049 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
N-[(3S,4S)-4-fluoro-1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]cyclopropanecarboxamide	IC50	0.05 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
3-cyclopropyl-1-[(3R)-1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]pyridin-2-one	IC50	0.051 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
1-fluoro-N-[(3R)-1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]cyclopropane-1-carboxamide	IC50	0.051 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]-1H-indole-6-carboxamide	IC50	0.053 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
2-phenylmethoxy-N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]benzamide	IC50	0.054 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
1-methyl-3-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]urea	IC50	0.058 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
3-methyl-1-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]pyridin-2-one	IC50	0.058 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
1-methyl-N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]cyclopropane-1-carboxamide	IC50	0.059 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]cyclopropanecarboxamide	IC50	0.065 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]-2-propoxybenzamide	IC50	0.065 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
1-methyl-N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]pyrazole-3-carboxamide	IC50	0.066 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]-1H-indole-5-carboxamide	IC50	0.066 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
1-methyl-N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]cyclobutane-1-carboxamide	IC50	0.071 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
2-methoxy-N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]benzamide	IC50	0.073 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
3-fluoro-N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]benzamide	IC50	0.074 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
1-methyl-N-[(3R)-1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]cyclopropane-1-carboxamide	IC50	0.074 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
2-fluoro-N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]benzamide	IC50	0.075 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]-1H-pyrrolo[2,3-b]pyridine-6-carboxamide	IC50	0.076 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
N-[(3S)-1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]benzamide	IC50	0.077 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]-1H-pyrrolo[3,2-b]pyridine-5-carboxamide	IC50	0.078 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
N-[(3R)-1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]benzamide	IC50	0.078 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
N-[(3R)-1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]spiro[2.2]pentane-2-carboxamide	IC50	0.078 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
1-methyl-N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]indole-5-carboxamide	IC50	0.08 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
3-propan-2-yl-1-[(3R)-1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]pyridin-2-one	IC50	0.082 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
1-propan-2-yl-3-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]urea	IC50	0.083 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]cyclobutanecarboxamide	IC50	0.083 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
1-cyclopropyl-3-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]urea	IC50	0.087 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
2-propan-2-yloxy-N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]benzamide	IC50	0.092 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
[3-[6-methoxy-4-(1-methylpyrazol-4-yl)-2-pyridinyl]pyrrolidin-1-yl]-(5-propan-2-yl-1H-pyrazol-3-yl)methanone	IC50	0.094 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
2-chloro-N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]benzamide	IC50	0.098 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
[3-[4-(1-benzylpyrazol-4-yl)-6-methyl-2-pyridinyl]pyrrolidin-1-yl]-(5-propan-2-yl-1H-pyrazol-3-yl)methanone	IC50	0.11 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
1-ethyl-N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]pyrazole-3-carboxamide	IC50	0.11 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
2-(2-hydroxyethoxy)-N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]benzamide	IC50	0.11 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
1-(1-methylpyrazol-4-yl)-N-[1-(1H-pyrazole-5-carbonyl)pyrrolidin-3-yl]pyrazole-3-carboxamide	IC50	0.11 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
1-methyl-N-[(3S)-1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]cyclopropane-1-carboxamide	IC50	0.11 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
cis-(1S,2S)-2-fluoro-N-[(3S)-1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]cyclopropane-1-carboxamide	IC50	0.11 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
N-[1-[5-(5-phenylpentan-2-yl)-1H-pyrazole-3-carbonyl]pyrrolidin-3-yl]cyclopropanecarboxamide	IC50	0.12 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
[3-[6-methyl-4-(3-methylphenyl)-2-pyridinyl]pyrrolidin-1-yl]-(5-propan-2-yl-1H-pyrazol-3-yl)methanone	IC50	0.12 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]oxolane-3-carboxamide	IC50	0.12 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]cyclopentanecarboxamide	IC50	0.12 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
3-methoxy-N-[1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]benzamide	IC50	0.12 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
N-[1-[5-(4-phenylbutan-2-yl)-1H-pyrazole-3-carbonyl]pyrrolidin-3-yl]cyclopropanecarboxamide	IC50	0.12 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors
[3-(6-methyl-4-phenoxy-2-pyridinyl)pyrrolidin-1-yl]-(5-propan-2-yl-1H-pyrazol-3-yl)methanone	IC50	0.13 nM	US-10022354: Pyrrolidine amide compounds as histone demethylase inhibitors

ChEMBL bioactivities

1148 potent at pChembl≥5 of 1211 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.60	IC50	0.025	nM	CHEMBL5945932
10.43	IC50	0.037	nM	CHEMBL6053239
10.42	IC50	0.038	nM	CHEMBL5908882
10.41	IC50	0.039	nM	CHEMBL5784930
10.34	IC50	0.046	nM	CHEMBL5877919
10.33	IC50	0.047	nM	CHEMBL5767733
10.31	IC50	0.049	nM	CHEMBL4088737
10.30	IC50	0.05	nM	CHEMBL5798182
10.29	IC50	0.051	nM	CHEMBL5982539
10.29	IC50	0.051	nM	CHEMBL5810582
10.28	IC50	0.053	nM	CHEMBL5769925
10.27	IC50	0.054	nM	CHEMBL5857962
10.24	IC50	0.058	nM	CHEMBL5893489
10.24	IC50	0.058	nM	CHEMBL6049070
10.23	IC50	0.059	nM	CHEMBL6040479
10.19	IC50	0.065	nM	CHEMBL5826403
10.18	IC50	0.066	nM	CHEMBL5963139
10.18	IC50	0.066	nM	CHEMBL5931344
10.15	IC50	0.071	nM	CHEMBL6063394
10.14	IC50	0.073	nM	CHEMBL5820582
10.13	IC50	0.074	nM	CHEMBL5830112
10.13	IC50	0.074	nM	CHEMBL6052581
10.12	IC50	0.076	nM	CHEMBL6027927
10.12	IC50	0.075	nM	CHEMBL5954405
10.11	IC50	0.077	nM	CHEMBL6042879
10.11	IC50	0.078	nM	CHEMBL5743849
10.11	IC50	0.078	nM	CHEMBL5286372
10.11	IC50	0.078	nM	CHEMBL5974502
10.10	IC50	0.08	nM	CHEMBL5921049
10.09	IC50	0.082	nM	CHEMBL6008287
10.08	IC50	0.083	nM	CHEMBL5774354
10.08	IC50	0.083	nM	CHEMBL4059597
10.06	IC50	0.087	nM	CHEMBL5762361
10.04	IC50	0.092	nM	CHEMBL5829576
10.03	IC50	0.094	nM	CHEMBL5984909
10.01	IC50	0.098	nM	CHEMBL5786013
9.96	IC50	0.11	nM	CHEMBL4077454
9.96	IC50	0.11	nM	CHEMBL6014540
9.96	IC50	0.11	nM	CHEMBL5852216
9.96	IC50	0.11	nM	CHEMBL5749705
9.96	IC50	0.11	nM	CHEMBL6054167
9.96	IC50	0.11	nM	CHEMBL5934009
9.92	IC50	0.12	nM	CHEMBL5986775
9.92	IC50	0.12	nM	CHEMBL4071397
9.92	IC50	0.12	nM	CHEMBL5859588
9.92	IC50	0.12	nM	CHEMBL5906941
9.92	IC50	0.12	nM	CHEMBL5795610
9.92	IC50	0.12	nM	CHEMBL5848305
9.89	IC50	0.13	nM	CHEMBL4092189
9.89	IC50	0.13	nM	CHEMBL4067490

PubChem BioAssay actives

346 with measured affinity, of 745 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
2-[[[2-[2-[butyl(methyl)amino]ethyl-ethylamino]-2-oxoethyl]amino]methyl]pyridine-4-carboxylic acid	2106949: Inhibition of KDM5A (unknown origin) incubated for 2 hrs by Alphascreen assay	ic50	0.0012	uM
2-[[[2-[2-(dimethylamino)ethyl-ethylamino]-2-oxoethyl]amino]methyl]pyridine-4-carboxylic acid	2106949: Inhibition of KDM5A (unknown origin) incubated for 2 hrs by Alphascreen assay	ic50	0.0014	uM
6-ethyl-3-[1-[4-(hydroxymethyl)-2-pyridinyl]pyrazol-4-yl]-5-methyl-1H-pyrazolo[1,5-a]pyrimidin-7-one	1289426: Inhibition of recombinant full length FLAG-tagged KDM5A (unknown origin) expressed in sf9 cells using biotin-H3K4me3 (1 to 21 residues as substrate preincubated for 10 mins followed by substrate addition measured after 30 mins by mass spetcrometric analysis	ic50	0.0023	uM
2-[4-[2-(dimethylamino)ethyl]-5-[(4-fluorophenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391727: Inhibition of KDM5A (unknown origin) preincubated with enzyme	ic50	0.0030	uM
2-[5-[(4-cyanophenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391727: Inhibition of KDM5A (unknown origin) preincubated with enzyme	ic50	0.0040	uM
5-[4-[2-[hexyl(methyl)amino]ethyl]phenyl]-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1624959: Inhibition of human C-terminal FLAG-tagged KDM5A (1 to 1090 residues) expressed in baculovirus infected Sf9 insect cells using H3(1-21)K4(Me3)-GGK(Biotin)/2-OG as substrate measured after 1 hr by Alphalisa assay	ic50	0.0044	uM
5-[4-[[heptyl(methyl)amino]methyl]phenyl]-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1934033: Inhibition of KDM5A (unknown origin ) by Alphalisa analysis	ic50	0.0044	uM
7-oxo-6-propan-2-yl-5-(1H-pyrazol-4-yl)-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0053	uM
7-oxo-5-(1-phenylpyrazol-4-yl)-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0056	uM
2-[5-[(4-bromophenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391727: Inhibition of KDM5A (unknown origin) preincubated with enzyme	ic50	0.0060	uM
5-(furan-2-yl)-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0062	uM
5-(1-cyclopropylpyrazol-4-yl)-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0079	uM
6-cyclobutyl-7-oxo-5-phenyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0092	uM
5-methyl-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0093	uM
5-ethyl-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0095	uM
2-chloro-N-[2-[4-(3-cyano-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidin-5-yl)pyrazol-1-yl]ethyl]acetamide	1934022: Inhibition of KDM5A (unknown origin ) by Alphascreen assay	ic50	0.0100	uM
7-oxo-5-phenyl-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627989: Inhibition of KDM5A (unknown origin) using ART(Kme3)QTARKSTGGKAPRKQLA-NovaTagPEG-biotin/1 uM 2-OG as substrate/co-factor by TR-FRET assay	ic50	0.0100	uM
7-oxo-6-propan-2-yl-5-pyrimidin-5-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0100	uM
5-[1-(2-cyanoethyl)pyrazol-4-yl]-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0101	uM
5-[1-(2-methoxyethyl)pyrazol-4-yl]-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0104	uM
6-ethyl-7-oxo-5-(6-oxo-1H-pyridin-3-yl)-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627989: Inhibition of KDM5A (unknown origin) using ART(Kme3)QTARKSTGGKAPRKQLA-NovaTagPEG-biotin/1 uM 2-OG as substrate/co-factor by TR-FRET assay	ic50	0.0110	uM
5-(1-ethylpyrazol-4-yl)-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0111	uM
5-(1-cyclobutylpyrazol-4-yl)-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0112	uM
5-benzyl-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0119	uM
2-[5-[(4-chloro-2-methoxyphenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391727: Inhibition of KDM5A (unknown origin) preincubated with enzyme	ic50	0.0120	uM
7-oxo-6-propan-2-yl-5-pyridin-3-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0123	uM
6-but-3-yn-2-yl-7-oxo-5-phenyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0128	uM
6-ethyl-7-oxo-5-pyridin-3-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627989: Inhibition of KDM5A (unknown origin) using ART(Kme3)QTARKSTGGKAPRKQLA-NovaTagPEG-biotin/1 uM 2-OG as substrate/co-factor by TR-FRET assay	ic50	0.0130	uM
2-[5-[(4-chloro-2-methylphenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391727: Inhibition of KDM5A (unknown origin) preincubated with enzyme	ic50	0.0130	uM
7-oxo-5-(2-phenylethyl)-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0131	uM
5-(1-methylpyrazol-4-yl)-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0133	uM
7-oxo-6-propan-2-yl-5-(1-propan-2-ylpyrazol-4-yl)-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0138	uM
7-oxo-6-propan-2-yl-5-[3-(trifluoromethyl)phenyl]-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0139	uM
5-(1-tert-butylpyrazol-4-yl)-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1289426: Inhibition of recombinant full length FLAG-tagged KDM5A (unknown origin) expressed in sf9 cells using biotin-H3K4me3 (1 to 21 residues as substrate preincubated for 10 mins followed by substrate addition measured after 30 mins by mass spetcrometric analysis	ic50	0.0140	uM
2-[5-[(4-chlorophenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391727: Inhibition of KDM5A (unknown origin) preincubated with enzyme	ic50	0.0140	uM
6-ethyl-7-oxo-5-phenyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627989: Inhibition of KDM5A (unknown origin) using ART(Kme3)QTARKSTGGKAPRKQLA-NovaTagPEG-biotin/1 uM 2-OG as substrate/co-factor by TR-FRET assay	ic50	0.0150	uM
5-[1-(2-methylpropyl)pyrazol-4-yl]-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1289426: Inhibition of recombinant full length FLAG-tagged KDM5A (unknown origin) expressed in sf9 cells using biotin-H3K4me3 (1 to 21 residues as substrate preincubated for 10 mins followed by substrate addition measured after 30 mins by mass spetcrometric analysis	ic50	0.0150	uM
ethyl 4-hydroxy-2-oxo-1H-1,7-naphthyridine-3-carboxylate	1934033: Inhibition of KDM5A (unknown origin ) by Alphalisa analysis	ic50	0.0151	uM
6-but-3-en-2-yl-7-oxo-5-phenyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0155	uM
5-[1-(oxetan-3-yl)pyrazol-4-yl]-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0159	uM
7-oxo-5-[(E)-2-phenylethenyl]-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0175	uM
7-oxo-5-phenoxy-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0180	uM
2-[5-[(4-chloro-2-fluorophenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391727: Inhibition of KDM5A (unknown origin) preincubated with enzyme	ic50	0.0180	uM
6-butan-2-yl-7-oxo-5-phenyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0180	uM
7-oxo-6-propan-2-yl-5-[4-(trifluoromethyl)phenyl]-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0182	uM
2-[5-[(4-chloro-2-ethoxyphenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391727: Inhibition of KDM5A (unknown origin) preincubated with enzyme	ic50	0.0190	uM
6-ethyl-5-methyl-7-oxo-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627989: Inhibition of KDM5A (unknown origin) using ART(Kme3)QTARKSTGGKAPRKQLA-NovaTagPEG-biotin/1 uM 2-OG as substrate/co-factor by TR-FRET assay	ic50	0.0200	uM
6-ethenyl-7-oxo-5-phenyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0201	uM
5-(4-methylphenyl)-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0203	uM
5-(4-chlorophenyl)-7-oxo-6-propan-2-yl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonitrile	1627205: Inhibition of KDM5A (unknown origin)	ic50	0.0204	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Resveratrol	affects cotreatment, decreases expression, increases expression	2
Tretinoin	increases expression	2
Valproic Acid	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
Sodium Selenite	decreases expression, increases expression	2
FR900359	affects phosphorylation	1
crenigacestat	decreases reaction, increases expression	1
testosterone enanthate	affects expression	1
daidzein	increases expression, affects cotreatment	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
daidzin	affects cotreatment, increases expression	1
beta-lapachone	increases expression	1
cobaltous chloride	increases expression	1
benzo(e)pyrene	increases methylation	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	decreases expression	1
genistin	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
glycitein	affects cotreatment, increases expression	1
CGP 52608	increases reaction, affects binding	1
2-palmitoylglycerol	increases expression	1
glycitin	affects cotreatment, increases expression	1
abrine	increases expression	1
picoxystrobin	decreases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation	1
Leflunomide	increases expression	1
Aconitine	affects binding, increases reaction, increases expression, decreases reaction	1

ChEMBL screening assays

165 unique, capped per target: 165 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2427608	Binding	Inhibition of KDM5A (unknown origin) using H3K4me3 peptide and 2-oxoglutarate as substrate after 1 hr by FDH-coupled assay	Identification of the KDM2/7 histone lysine demethylase subfamily inhibitor and its antiproliferative activity. — J Med Chem

Cellosaurus cell lines

12 cell lines: 7 cancer cell line, 4 embryonic stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A3M2	SEES3-1V human KDM5A, clone1	Embryonic stem cell	Male
CVCL_A3M3	SEES3-1V human KDM5A, clone2	Embryonic stem cell	Male
CVCL_A3M4	SEES3-1V human KDM5A, clone3	Embryonic stem cell	Male
CVCL_A8DI	WAe009-A-60	Embryonic stem cell	Female
CVCL_B8J5	Abcam HCT 116 KDM5A KO	Cancer cell line	Male
CVCL_B8XZ	Abcam MCF-7 KDM5A KO	Cancer cell line	Female
CVCL_B9LG	Abcam A-549 KDM5A KO	Cancer cell line	Male
CVCL_E1LA	HyCyte HK-2 KO-hKDM5A	Transformed cell line	Male
CVCL_HD79	HCT 116 KDM5A(+/-)	Cancer cell line	Male
CVCL_HD80	HCT 116 KDM5A(-/-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
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