KDM3A
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Also known as TSGAKIAA0742JHMD2A
Summary
KDM3A (lysine demethylase 3A, HGNC:20815) is a protein-coding gene on chromosome 2p11.2, encoding Lysine-specific demethylase 3A (Q9Y4C1). Histone demethylase that specifically demethylates ‘Lys-9’ of histone H3, thereby playing a central role in histone code.
Enables histone H3K9me/H3K9me2 demethylase activity; iron ion binding activity; and nuclear androgen receptor binding activity. Involved in androgen receptor signaling pathway; formaldehyde biosynthetic process; and positive regulation of DNA-templated transcription. Located in nucleoplasm. Implicated in cervical cancer and colon cancer. Biomarker of Ewing sarcoma; hepatocellular carcinoma; nasopharynx carcinoma; and prostate cancer.
Source: NCBI Gene 55818 — RefSeq curated summary.
At a glance
- GWAS associations: 4
- Clinical variants (ClinVar): 211 total
- Druggable target: yes
- MANE Select transcript:
NM_018433
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:20815 |
| Approved symbol | KDM3A |
| Name | lysine demethylase 3A |
| Location | 2p11.2 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | TSGA, KIAA0742, JHMD2A |
| Ensembl gene | ENSG00000115548 |
| Ensembl biotype | protein_coding |
| OMIM | 611512 |
| Entrez | 55818 |
Gene structure
Transcript identifiers
Ensembl transcripts: 24 — 14 protein_coding, 5 retained_intron, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay
ENST00000312912, ENST00000409064, ENST00000409556, ENST00000427678, ENST00000441719, ENST00000452034, ENST00000462197, ENST00000463013, ENST00000466058, ENST00000470160, ENST00000483866, ENST00000485171, ENST00000488971, ENST00000491383, ENST00000498528, ENST00000900197, ENST00000900198, ENST00000900199, ENST00000900200, ENST00000900201, ENST00000900202, ENST00000900203, ENST00000955942, ENST00000955943
RefSeq mRNA: 2 — MANE Select: NM_018433
NM_001146688, NM_018433
CCDS: CCDS1990
Canonical transcript exons
ENST00000312912 — 26 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001427049 | 86441371 | 86441444 |
| ENSE00003479777 | 86485729 | 86485859 |
| ENSE00003494208 | 86456805 | 86456877 |
| ENSE00003507633 | 86491141 | 86491275 |
| ENSE00003516178 | 86481930 | 86482102 |
| ENSE00003555318 | 86470204 | 86470408 |
| ENSE00003584782 | 86484942 | 86485029 |
| ENSE00003591841 | 86456983 | 86457071 |
| ENSE00003600266 | 86464053 | 86464216 |
| ENSE00003600440 | 86455085 | 86455187 |
| ENSE00003605435 | 86489520 | 86489659 |
| ENSE00003622555 | 86489318 | 86489437 |
| ENSE00003685493 | 86490881 | 86491057 |
| ENSE00003694483 | 86451103 | 86451213 |
| ENSE00003888685 | 86483987 | 86484158 |
| ENSE00003889116 | 86477877 | 86478029 |
| ENSE00003890418 | 86492039 | 86492716 |
| ENSE00003891330 | 86478170 | 86478265 |
| ENSE00003891384 | 86474776 | 86474990 |
| ENSE00003892260 | 86449807 | 86449962 |
| ENSE00003892294 | 86442018 | 86442233 |
| ENSE00003892503 | 86478608 | 86478735 |
| ENSE00003893448 | 86480167 | 86480362 |
| ENSE00003893959 | 86482458 | 86482694 |
| ENSE00003894883 | 86456442 | 86456566 |
| ENSE00003895332 | 86466372 | 86466883 |
Expression profiles
Bgee: expression breadth ubiquitous, 300 present calls, max score 99.00.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.0328 / max 650.2037, expressed in 1810 samples.
FANTOM5 promoters (2 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 21292 | 32.3542 | 1810 |
| 21293 | 0.6786 | 266 |
Top tissues by expression
300 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| secondary oocyte | CL:0000655 | 99.00 | gold quality |
| oocyte | CL:0000023 | 98.06 | gold quality |
| calcaneal tendon | UBERON:0003701 | 97.73 | gold quality |
| sperm | CL:0000019 | 97.25 | gold quality |
| ventricular zone | UBERON:0003053 | 96.95 | gold quality |
| male germ cell | CL:0000015 | 96.60 | gold quality |
| sural nerve | UBERON:0015488 | 96.54 | gold quality |
| upper leg skin | UBERON:0004262 | 96.25 | gold quality |
| skin of leg | UBERON:0001511 | 95.86 | gold quality |
| skin of abdomen | UBERON:0001416 | 95.62 | gold quality |
| zone of skin | UBERON:0000014 | 95.11 | gold quality |
| skin of hip | UBERON:0001554 | 94.90 | gold quality |
| left testis | UBERON:0004533 | 94.65 | gold quality |
| right testis | UBERON:0004534 | 94.30 | gold quality |
| right lung | UBERON:0002167 | 94.21 | gold quality |
| ganglionic eminence | UBERON:0004023 | 94.18 | gold quality |
| embryo | UBERON:0000922 | 94.16 | gold quality |
| tibial artery | UBERON:0007610 | 94.10 | gold quality |
| popliteal artery | UBERON:0002250 | 94.09 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 93.85 | gold quality |
| testis | UBERON:0000473 | 93.81 | gold quality |
| colonic epithelium | UBERON:0000397 | 93.63 | gold quality |
| artery | UBERON:0001637 | 93.56 | gold quality |
| lower esophagus mucosa | UBERON:0035834 | 93.49 | gold quality |
| muscle layer of sigmoid colon | UBERON:0035805 | 93.48 | gold quality |
| tibial nerve | UBERON:0001323 | 93.46 | gold quality |
| upper arm skin | UBERON:0004263 | 93.44 | gold quality |
| descending thoracic aorta | UBERON:0002345 | 93.43 | gold quality |
| aorta | UBERON:0000947 | 93.34 | gold quality |
| lower esophagus | UBERON:0013473 | 93.23 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 7.87 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): CREB1, E2F6, EPAS1, FOXN1, HIF1A, MBD2, NANOGP8, NCOA1, POU5F1, TCF12, TCF3, TFCP2L1, ZFP57
miRNA regulators (miRDB)
81 targeting KDM3A, 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-30A-5P | 100.00 | 76.31 | 3233 |
| HSA-MIR-30B-5P | 100.00 | 76.29 | 3248 |
| HSA-MIR-30C-5P | 100.00 | 76.29 | 3248 |
| HSA-MIR-30D-5P | 100.00 | 76.32 | 3233 |
| HSA-MIR-30E-5P | 100.00 | 76.32 | 3242 |
| HSA-MIR-4500 | 99.99 | 72.72 | 2367 |
| HSA-MIR-4282 | 99.99 | 75.36 | 6408 |
| HSA-MIR-548AW | 99.99 | 72.57 | 3559 |
| HSA-MIR-5696 | 99.98 | 72.36 | 4487 |
| HSA-MIR-27A-3P | 99.98 | 72.13 | 2955 |
| HSA-MIR-27B-3P | 99.98 | 72.13 | 2955 |
| HSA-MIR-9985 | 99.98 | 72.11 | 2939 |
| HSA-MIR-4789-5P | 99.98 | 70.76 | 2721 |
| HSA-LET-7A-5P | 99.98 | 72.29 | 1790 |
| HSA-LET-7B-5P | 99.98 | 72.31 | 1790 |
| HSA-LET-7C-5P | 99.98 | 72.29 | 1790 |
| HSA-LET-7E-5P | 99.98 | 72.29 | 1790 |
| HSA-LET-7F-5P | 99.98 | 72.56 | 1784 |
| HSA-LET-7G-5P | 99.98 | 72.37 | 1784 |
| HSA-LET-7I-5P | 99.98 | 72.37 | 1788 |
| HSA-MIR-98-5P | 99.98 | 72.33 | 1787 |
| HSA-MIR-1468-3P | 99.96 | 72.74 | 3797 |
| HSA-LET-7D-5P | 99.96 | 71.76 | 1632 |
| HSA-MIR-4458 | 99.96 | 71.64 | 1650 |
| HSA-MIR-128-3P | 99.95 | 71.17 | 2484 |
| HSA-MIR-216A-3P | 99.95 | 71.19 | 2505 |
| HSA-MIR-141-3P | 99.94 | 72.79 | 2421 |
| HSA-MIR-200A-3P | 99.94 | 72.68 | 2420 |
| HSA-MIR-4760-3P | 99.93 | 70.50 | 2385 |
| HSA-MIR-6508-5P | 99.92 | 70.67 | 2465 |
Literature-anchored findings (GeneRIF, showing 40)
- These findings demonstrate that JMJD1A can be stimulated by hypoxia both in vitro and in vivo involving binding of HIF-1 to a specific HRE in the JMJD1A promoter. (PMID:18538129)
- Results show that many genes regulated by hypoxia and HIF-1alpha show patterns of induction with JMJD (Jumonji-domain containing)1A and JMJD2B demonstrating robust, and JMJD2C more modest, up-regulation by hypoxia. (PMID:18713068)
- histone demethylases JMJD1A and JMJD2B are transcriptional targets of hypoxia-inducible factor HIF (PMID:18984585)
- Immunohistochemical staining has revealed that JMJD1A is widely expressed in tissues, even in cells that are not known to express the androgen receptor, and is significantly increased in smooth muscle cells upon hypoxia treatment. (PMID:19471969)
- Hypoxic regulation of JMJD1A acts as a signal amplifier to facilitate hypoxic gene expression, ultimately enhancing tumor growth. (PMID:19858293)
- Data show that the JMJD1A/ABH2 family of dioxygenases is highly sensitive to inhibition by carcinogenic nickel ions. (PMID:20042601)
- identification of genetic alterations & expression changes of LSD1, JHDM2A & GASC1 in prostate cancer (PC); as no genetic alterations & only modest expression changes were found, it is unlikely they play a major role in progression of PC (PMID:20127736)
- Jumonji domain containing 1A is a novel prognostic marker for colorectal cancer. (PMID:20823141)
- the increased expression of JMJD1A might be associated with the progression of kidney cancer. (PMID:21275466)
- Up-regulation of miR-155 in nasopharyngeal carcinoma is partly driven by LMP1 and LMP2A, and results in downregulation of JMJD1A. (PMID:21541331)
- our results suggest that JMJD1A is a sensitive recurrence marker, and JMJD1A can promote malignant transformation via epithelial-mesenchymal transition. (PMID:21607773)
- study demonstrates KDM3A is overexpressed in various types of cancer and directly activates transcription of HOXA1 through demethylation of histone H3K9 by binding to its promoter region (PMID:22020899)
- Findings suggest that both Ni(2+) and ascorbate can regulate the expression of histone demethylase JMJD1A, which is important for cancer development or inhibition. (PMID:22318714)
- KDM3A is recruited to the SLC2A3 locus in an HIF1-dependent manner and demethylates H3K9me2 so as to upregulate its expression. (PMID:22645302)
- Exposing cells to either chemical or cellular sources of (*)NO resulted in a significant increase in dimethyl Lys-9 on histone 3 (H3K9me2), the preferred substrate for KDM3A. (PMID:23546878)
- Our results suggest that LANA may play a role in regulation of epigenetic marks on the KSHV genome, which is in part through association with the histone demethylase KDM3A. (PMID:23576503)
- Data indicate that JMJD1A gene silencing abrogated the hypoxia-induced adrenomedullin (ADM) expression and inhibited HepG2 and Hep3B cell growth. (PMID:23583388)
- A single amino acid in KDM3A, T667, affects histone demethylase activity towards H3K9me1 and -me2. (PMID:23593242)
- Expression of JHDM2A was significantly increased but HDAC2, HDAC7, and SUV39H2 were significantly down-regulated in Systemic Sclerosis B cells relative to controls (PMID:23891737)
- JMJD1A forms a homodimer through its catalytic domains, bringing the two active sites close together (PMID:24214985)
- Studies identify the histone demethylase KDM3A as a new, miR-regulated, tumor promoter in Ewing Sarcoma. (PMID:24362521)
- data identify a novel pathway through which N-Myc causes neuroblastoma cell migration and invasion, and provide important evidence for further development of more potent JMJD1A/MALAT1 inhibitors for the prevention of tumor metastasis. (PMID:24742640)
- Studies found that JMJD1A was consistently and significantly downregulated at both RNA and protein levels in human germ cell tumors. (PMID:25071150)
- ACK1 interacts with KDM3A to regulate the mammary tumor oncogene HOXA1. (PMID:25148682)
- mitogen- and stress-activated protein kinase 1 (MSK1) specifically phosphorylates KDM3A at Ser264 (p-KDM3A), which is enriched in the regulatory regions of gene loci in the human genome. (PMID:25535969)
- Loss of JMJD1A expression is associated with liver fibrosis. (PMID:25609425)
- JMJD1A is phosphorylated at S265 by protein kinase A (PKA), and this is pivotal to activate the beta1-adrenergic receptor gene (Adrb1) and downstream targets including Ucp1 in brown adipocytes. (PMID:25948511)
- a critical role for JMJD1A in regulating proliferation and survival of prostate cancer cells by controlling c-Myc expression at transcriptional and post-translational levels (PMID:26279298)
- JMJD1A-MALAT1-MAPK signaling might participate in the JMJD1A-induced cell proliferation of gastric cancer. (PMID:26617828)
- These results indicate that the KDM3A-KLF2-IRF4 pathway plays an essential role in multiple myeloma cell survival and homing to the bone marrow, and therefore represents a therapeutic target. (PMID:26728187)
- JMJD1A could promote non-small cell lung cancer tumorigenesis (PMID:26945572)
- The KDM3A to PRM1 mRNA expression ratio can be used as a reliable marker of successful testicular sperm extraction in men with obstructive and non-obstructive azoospermia with 95% sensitivity. (PMID:27027467)
- Study identified KDM3A an H3K9me2 demethylase, as responsible for the H3K9me2 reduction and critical for breast tumor transformation. (PMID:27034728)
- depletion of KDM3A was capable of reactivating mutated p53 to induce the expression of pro-apoptotic genes in breast cancer with mutant p53. KDM3A knockdown also potently inhibited tumorigenic potentials of breast cancer stem-like cells and rendered them sensitive to apoptosis induced by chemotherapeutic drugs. (PMID:27270439)
- The authors find that KDM3A promotes anoikis through transcriptional activation of BNIP3 and BNIP3L, which encode pro-apoptotic proteins. (PMID:27472901)
- ormal stromal restricts cancer cell proliferation through JMJD1a-dependent modulation of gene expression. (PMID:27488962)
- deficient expression of JMJD1A/JMJD1A might be reflecting and/or contributing to round spermatid maturation arrest (PMID:27692601)
- our findings reveal a novel mechanism by which KDM3A promotes ovarian CSCs, proliferation and chemoresistance and thus, highlights the significance of KDM3A as a novel therapeutic target for resistant ovarian cancer. (PMID:27694900)
- In the present report, hypoxia is shown to activate a HIF-KDM3A-MMP12 signaling cascade that promotes trophoblast invasion and trophoblast-directed uterine spiral artery remodeling. (PMID:27807143)
- JMJD1A and c-Myc levels are independent prognostic factors for cervical cancer patients (PMID:27835890)
Cross-species orthologs
3 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| mus_musculus | Kdm3a | ENSMUSG00000053470 |
| rattus_norvegicus | Kdm3a | ENSRNOG00000007814 |
| drosophila_melanogaster | Kdm3 | FBGN0037703 |
Paralogs (3): KDM3B (ENSG00000120733), HR (ENSG00000168453), JMJD1C (ENSG00000171988)
Protein
Protein identifiers
Lysine-specific demethylase 3A — Q9Y4C1 (reviewed: Q9Y4C1)
Alternative names: JmjC domain-containing histone demethylation protein 2A, Jumonji domain-containing protein 1A, [histone H3]-dimethyl-L-lysine(9) demethylase 3A
All UniProt accessions (4): Q9Y4C1, C9J7Q7, C9JC73, F8WE62
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. Preferentially demethylates mono- and dimethylated H3 ‘Lys-9’ residue, with a preference for dimethylated residue, while it has weak or no activity on trimethylated H3 ‘Lys-9’. Demethylation of Lys residue generates formaldehyde and succinate. Involved in hormone-dependent transcriptional activation, by participating in recruitment to androgen-receptor target genes, resulting in H3 ‘Lys-9’ demethylation and transcriptional activation. Involved in spermatogenesis by regulating expression of target genes such as PRM1 and TNP1 which are required for packaging and condensation of sperm chromatin. Involved in obesity resistance through regulation of metabolic genes such as PPARA and UCP1.
Subunit / interactions. Interacts with VRK1.
Subcellular location. Cytoplasm. Nucleus.
Cofactor. Binds 1 Fe(2+) ion per subunit.
Domain organisation. The JmjC domain and the C6-type zinc-finger are required for the demethylation activity. Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs are known to mediate the association with nuclear receptors.
Similarity. Belongs to the JHDM2 histone demethylase family.
RefSeq proteins (2): NP_001140160, NP_060903* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR003347 | JmjC_dom | Domain |
| IPR045109 | LSDs-like | Family |
| IPR054294 | KDM3A/B_DUF7030 | Domain |
| IPR054503 | KDM3AB_Tudor | Domain |
| IPR054504 | PWWP_KDM3B | Domain |
Pfam: PF02373, PF22987, PF22988, PF22989
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), 1 shown:
- 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)
UniProt features (31 total): sequence conflict 8, modified residue 5, sequence variant 5, binding site 3, region of interest 3, mutagenesis site 2, chain 1, domain 1, zinc finger region 1, short sequence motif 1, compositionally biased region 1
Structure
Experimental structures (PDB)
0 structures.
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q9Y4C1-F1 | 69.06 | 0.34 |
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 (3): 1249; 1120; 1122
Post-translational modifications (5): 264, 325, 445, 766, 895
Mutagenesis-validated functional residues (2):
| Position | Phenotype |
|---|---|
| 1120 | abolishes lysine-specific histone demethylase activity. |
| 1120 | abolishes histone demethylase activity. |
Function
Pathways and Gene Ontology
Reactome pathways
7 pathways
| ID | Pathway |
|---|---|
| R-HSA-3214842 | HDMs demethylate histones |
| R-HSA-9029569 | NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux |
| R-HSA-162582 | Signal Transduction |
| R-HSA-3247509 | Chromatin modifying enzymes |
| R-HSA-4839726 | Chromatin organization |
| R-HSA-9006931 | Signaling by Nuclear Receptors |
| R-HSA-9024446 | NR1H2 and NR1H3-mediated signaling |
MSigDB gene sets: 346 (showing top):
GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, E2F_Q4_01, TGCGCANK_UNKNOWN, CCAWYNNGAAR_UNKNOWN, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, MENSE_HYPOXIA_UP, FOXO4_01, GOBP_MALE_GAMETE_GENERATION, FOXO1_01, GGGTGGRR_PAX4_03, AATGGAG_MIR136, USF_C, EFC_Q6
GO Biological Process (17): regulation of transcription by RNA polymerase II (GO:0006357), spermatid nucleus elongation (GO:0007290), hormone-mediated signaling pathway (GO:0009755), androgen receptor signaling pathway (GO:0030521), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), formaldehyde biosynthetic process (GO:0046293), positive regulation of cold-induced thermogenesis (GO:0120162), cellular response to leukemia inhibitory factor (GO:1990830), regulation of stem cell population maintenance (GO:2000036), regulation of stem cell differentiation (GO:2000736), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), spermatogenesis (GO:0007283), regulation of gene expression (GO:0010468), cell differentiation (GO:0030154), demethylation (GO:0070988)
GO Molecular Function (12): transcription coregulator activity (GO:0003712), iron ion binding (GO:0005506), zinc ion binding (GO:0008270), chromatin DNA binding (GO:0031490), histone H3K9 demethylase activity (GO:0032454), nuclear androgen receptor binding (GO:0050681), histone H3K9me/H3K9me2 demethylase activity (GO:0140683), chromatin binding (GO:0003682), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)
GO Cellular Component (7): histone deacetylase complex (GO:0000118), chromatin (GO:0000785), male germ cell nucleus (GO:0001673), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), membrane (GO:0016020)
Reactome top-level categories
Rollup of top-5 pathways:
| Category | Pathways |
|---|---|
| Chromatin modifying enzymes | 1 |
| NR1H2 and NR1H3-mediated signaling | 1 |
| Chromatin organization | 1 |
| Signal Transduction | 1 |
| Signaling by Nuclear Receptors | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| cellular anatomical structure | 4 |
| regulation of DNA-templated transcription | 2 |
| transcription by RNA polymerase II | 2 |
| transition metal ion binding | 2 |
| binding | 2 |
| nucleus organization | 1 |
| spermatid nucleus differentiation | 1 |
| signal transduction | 1 |
| cellular response to hormone stimulus | 1 |
| nuclear receptor-mediated steroid hormone signaling pathway | 1 |
| DNA-templated transcription | 1 |
| positive regulation of RNA biosynthetic process | 1 |
| regulation of transcription by RNA polymerase II | 1 |
| positive regulation of DNA-templated transcription | 1 |
| small molecule biosynthetic process | 1 |
| aldehyde biosynthetic process | 1 |
| formaldehyde metabolic process | 1 |
| positive regulation of multicellular organismal process | 1 |
| cold-induced thermogenesis | 1 |
| regulation of cold-induced thermogenesis | 1 |
| cellular response to cytokine stimulus | 1 |
| response to leukemia inhibitory factor | 1 |
| stem cell population maintenance | 1 |
| regulation of developmental process | 1 |
| regulation of multicellular organismal process | 1 |
| regulation of cell differentiation | 1 |
| stem cell differentiation | 1 |
| cellular component organization | 1 |
| chromatin organization | 1 |
| developmental process involved in reproduction | 1 |
| male gamete generation | 1 |
| gene expression | 1 |
| regulation of macromolecule biosynthetic process | 1 |
| cellular developmental process | 1 |
| metabolic process | 1 |
| transcription regulator activity | 1 |
| DNA binding | 1 |
| chromatin binding | 1 |
| histone H3 demethylase activity | 1 |
| nuclear receptor binding | 1 |
Protein interactions and networks
STRING
1316 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| KDM3A | SMARCA4 | P51532 | 924 |
| KDM3A | PPARG | P37231 | 879 |
| KDM3A | PRM1 | P04553 | 866 |
| KDM3A | KDM4C | Q9H3R0 | 862 |
| KDM3A | TNP1 | P09430 | 855 |
| KDM3A | KDM4B | O94953 | 836 |
| KDM3A | KDM4A | O75164 | 827 |
| KDM3A | NUPR1 | O60356 | 809 |
| KDM3A | KDM1A | O60341 | 805 |
| KDM3A | HIF1A | Q16665 | 785 |
| KDM3A | H3-3A | P06351 | 737 |
| KDM3A | H3C14 | Q71DI3 | 737 |
| KDM3A | H3-5 | Q6NXT2 | 737 |
| KDM3A | H3C1 | P02295 | 737 |
| KDM3A | H3-4 | Q16695 | 737 |
| KDM3A | H3-7 | Q5TEC6 | 737 |
IntAct
40 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| RASSF6 | STK4 | psi-mi:“MI:0914”(association) | 0.780 |
| KDM3A | STAT1 | psi-mi:“MI:0915”(physical association) | 0.590 |
| STAT1 | KDM3A | psi-mi:“MI:0915”(physical association) | 0.590 |
| KDM3A | RPS6KA5 | psi-mi:“MI:0915”(physical association) | 0.540 |
| RPS6KA5 | KDM3A | psi-mi:“MI:0217”(phosphorylation reaction) | 0.540 |
| KDM3A | RPS6KA5 | psi-mi:“MI:0217”(phosphorylation reaction) | 0.540 |
| TCEAL1 | CHEK1 | psi-mi:“MI:0914”(association) | 0.530 |
| KDM3A | RPS6KA5 | psi-mi:“MI:0915”(physical association) | 0.520 |
| KDM3A | MYCBP | psi-mi:“MI:0915”(physical association) | 0.400 |
| LAMA3 | KDM3A | psi-mi:“MI:0915”(physical association) | 0.400 |
| KDM3A | RIPK2 | psi-mi:“MI:0915”(physical association) | 0.370 |
| Dut | NPAT | psi-mi:“MI:0914”(association) | 0.350 |
| POLR2F | BDP1 | psi-mi:“MI:0914”(association) | 0.350 |
| Chmp3 | DTL | psi-mi:“MI:0914”(association) | 0.350 |
| Chmp6 | NSF | psi-mi:“MI:0914”(association) | 0.350 |
| ORF73 | ECI2 | psi-mi:“MI:0914”(association) | 0.350 |
| RASSF6 | STK4 | psi-mi:“MI:0914”(association) | 0.350 |
| TCEAL1 | PDCD5 | psi-mi:“MI:0914”(association) | 0.350 |
| CBX2 | TRANK1 | psi-mi:“MI:0914”(association) | 0.350 |
| CBX1 | EXOC5 | psi-mi:“MI:0914”(association) | 0.350 |
BioGRID (87): KDM3A (Affinity Capture-MS), KDM3A (Affinity Capture-MS), TNK2 (Affinity Capture-Western), KDM3A (Affinity Capture-Western), ARFGAP2 (Co-fractionation), ARPP19 (Co-fractionation), GART (Co-fractionation), IRF2BP1 (Co-fractionation), KDM3A (Co-fractionation), KDM3A (Co-fractionation), KDM3A (Co-fractionation), KDM3A (Co-fractionation), KIAA0368 (Co-fractionation), KDM3A (Affinity Capture-MS), KDM3A (Affinity Capture-MS)
ESM2 similar proteins: A0A0R4IYX6, A0A1D5NVS8, A0A1L8H0H2, A0AVK6, A5GFT6, A7XYH5, A7XYJ6, B7ZS37, B8A5Y1, D4A666, E1B7L7, E1BKK0, E1BLP6, F1LMN3, F6YVB9, F8VPJ6, Q12766, Q13029, Q14B70, Q2HNT1, Q2HNT2, Q2KHR2, Q4V9H5, Q58FA4, Q5DTH5, Q5ZIE8, Q5ZIX8, Q5ZJ69, Q5ZM88, Q63679, Q63755, Q68FE9, Q69ZF8, Q6DRC5, Q6P4F7, Q6PCM1, Q6ZSZ6, Q76L83, Q80Y19, Q8BHZ4
Diamond homologs: C0SUU8, C0SV12, F4HZD1, Q15652, Q5HZN1, Q5ZIX8, Q63679, Q6IRB8, Q6PCM1, Q6ZPY7, Q7LBC6, Q8H1S7, Q8VYB9, Q9SSE9, Q9VHC5, Q9Y4C1, Q69ZK6, P97609, Q61645
SIGNOR signaling
11 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| HIF1A | “up-regulates quantity by expression” | KDM3A | “transcriptional regulation” |
| EPAS1 | “up-regulates quantity by expression” | KDM3A | “transcriptional regulation” |
| TNK2 | “down-regulates activity” | KDM3A | phosphorylation |
| KDM3A | “up-regulates activity” | H3-2 | demethylation |
| KDM3A | “up-regulates activity” | H3C15 | demethylation |
| KDM3A | “up-regulates activity” | H3-3A | demethylation |
| KDM3A | “up-regulates activity” | H3-4 | demethylation |
| KDM3A | “up-regulates activity” | H3-5 | demethylation |
| JAK2 | “up-regulates activity” | KDM3A | phosphorylation |
| NANOGP8 | “down-regulates quantity by repression” | KDM3A | “transcriptional regulation” |
| 2-oxoglutarate(2-) | “up-regulates activity” | KDM3A | “chemical activation” |
Disease & clinical
Clinical variants and AI predictions
ClinVar
211 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 139 |
| Likely benign | 19 |
| Benign | 15 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
4162 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 2:86440948:TTG:T | donor_gain | 1.0000 |
| 2:86440963:G:GG | donor_gain | 1.0000 |
| 2:86449876:A:T | donor_gain | 1.0000 |
| 2:86451101:A:AG | acceptor_gain | 1.0000 |
| 2:86451102:G:GG | acceptor_gain | 1.0000 |
| 2:86451102:GAC:G | acceptor_gain | 1.0000 |
| 2:86455079:TTTCA:T | acceptor_loss | 1.0000 |
| 2:86455080:TTCAG:T | acceptor_loss | 1.0000 |
| 2:86455081:TCAG:T | acceptor_loss | 1.0000 |
| 2:86455082:CA:C | acceptor_loss | 1.0000 |
| 2:86455083:A:AG | acceptor_gain | 1.0000 |
| 2:86455083:AG:A | acceptor_gain | 1.0000 |
| 2:86455084:G:GG | acceptor_gain | 1.0000 |
| 2:86455084:GG:G | acceptor_gain | 1.0000 |
| 2:86455084:GGAT:G | acceptor_gain | 1.0000 |
| 2:86455183:AAAAG:A | donor_loss | 1.0000 |
| 2:86455184:AAAG:A | donor_loss | 1.0000 |
| 2:86455185:AAG:A | donor_loss | 1.0000 |
| 2:86455186:AG:A | donor_loss | 1.0000 |
| 2:86455187:GG:G | donor_loss | 1.0000 |
| 2:86455188:G:A | donor_loss | 1.0000 |
| 2:86455189:T:A | donor_loss | 1.0000 |
| 2:86456439:A:AG | acceptor_gain | 1.0000 |
| 2:86456439:AAG:A | acceptor_gain | 1.0000 |
| 2:86456439:AAGGT:A | acceptor_gain | 1.0000 |
| 2:86456440:A:G | acceptor_gain | 1.0000 |
| 2:86456441:G:GG | acceptor_gain | 1.0000 |
| 2:86456441:GGT:G | acceptor_gain | 1.0000 |
| 2:86456563:GGAG:G | donor_gain | 1.0000 |
| 2:86456564:G:GT | donor_gain | 1.0000 |
AlphaMissense
8702 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 2:86470272:T:C | F530L | 1.000 |
| 2:86470273:T:C | F530S | 1.000 |
| 2:86470274:C:A | F530L | 1.000 |
| 2:86470274:C:G | F530L | 1.000 |
| 2:86470280:G:C | Q532H | 1.000 |
| 2:86470280:G:T | Q532H | 1.000 |
| 2:86470290:T:A | C536S | 1.000 |
| 2:86470290:T:C | C536R | 1.000 |
| 2:86470291:G:A | C536Y | 1.000 |
| 2:86470291:G:C | C536S | 1.000 |
| 2:86470291:G:T | C536F | 1.000 |
| 2:86470292:T:G | C536W | 1.000 |
| 2:86470320:T:A | C546S | 1.000 |
| 2:86470320:T:C | C546R | 1.000 |
| 2:86470321:G:A | C546Y | 1.000 |
| 2:86470321:G:C | C546S | 1.000 |
| 2:86470321:G:T | C546F | 1.000 |
| 2:86470322:C:G | C546W | 1.000 |
| 2:86470329:T:A | C549S | 1.000 |
| 2:86470329:T:C | C549R | 1.000 |
| 2:86470330:G:C | C549S | 1.000 |
| 2:86470331:T:G | C549W | 1.000 |
| 2:86470386:T:A | C568S | 1.000 |
| 2:86470386:T:C | C568R | 1.000 |
| 2:86470386:T:G | C568G | 1.000 |
| 2:86470387:G:A | C568Y | 1.000 |
| 2:86470387:G:C | C568S | 1.000 |
| 2:86470387:G:T | C568F | 1.000 |
| 2:86470388:C:G | C568W | 1.000 |
| 2:86470389:C:A | R569S | 1.000 |
dbSNP variants (sampled 300 via entrez): RS1000034803 (2:86480915 C>G,T), RS1000069536 (2:86446620 G>T), RS1000212817 (2:86469625 CAT>C), RS1000307747 (2:86462746 G>A), RS1000323306 (2:86462810 T>C), RS1000348074 (2:86441936 C>G), RS1000376152 (2:86435217 A>C), RS1000560695 (2:86468806 G>A,C), RS1000576927 (2:86451333 A>T), RS1000619634 (2:86469536 C>T), RS1000713472 (2:86471246 AAT>A), RS1000733348 (2:86439140 T>A), RS1000801958 (2:86487024 G>A), RS1000820288 (2:86470800 T>C), RS1000835034 (2:86440025 A>G)
Disease associations
OMIM: gene MIM:611512 | disease phenotypes: MIM:608957
GenCC curated gene-disease
Mondo (2): susceptibility to respiratory infections associated with CD8alpha chain mutation (MONDO:0012161), prostate cancer (MONDO:0008315)
Orphanet (2): Susceptibility to respiratory infections associated with CD8alpha chain mutation (Orphanet:169085), Familial prostate cancer (Orphanet:1331)
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
4 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST003139_21 | Glomerular filtration rate in chronic kidney disease | 6.000000e-06 |
| GCST006061_54 | Atrial fibrillation | 3.000000e-10 |
| GCST006061_55 | Atrial fibrillation | 4.000000e-11 |
| GCST007239_5 | Ovarian cancer | 2.000000e-06 |
MeSH disease descriptors (2)
| Descriptor | Name | Tree numbers |
|---|---|---|
| D011471 | Prostatic Neoplasms | C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750 |
| C563824 | CD8 Deficiency, Familial (supp.) |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL1938209 (SINGLE PROTEIN)
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 |
|---|---|---|---|
| IOX1 | Inhibition | 7.0 | pIC50 |
ChEMBL bioactivities
32 potent at pChembl≥5 of 66 total, top 32 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 7.24 | IC50 | 57 | nM | CHEMBL3774692 |
| 6.85 | IC50 | 140 | nM | CHEMBL3108958 |
| 6.80 | IC50 | 158.5 | nM | CHEMBL1230640 |
| 6.77 | IC50 | 170 | nM | CHEMBL1230640 |
| 6.70 | IC50 | 200 | nM | CHEMBL1230640 |
| 6.40 | IC50 | 400 | nM | CHEMBL5173876 |
| 5.96 | IC50 | 1100 | nM | CHEMBL3108956 |
| 5.90 | IC50 | 1259 | nM | CHEMBL3621852 |
| 5.73 | IC50 | 1850 | nM | CHEMBL4592908 |
| 5.70 | IC50 | 1995 | nM | N-OXALYLGLYCINE |
| 5.70 | IC50 | 2020 | nM | CHEMBL4585876 |
| 5.64 | IC50 | 2300 | nM | CHEMBL3775262 |
| 5.64 | IC50 | 2300 | nM | CHEMBL3786952 |
| 5.50 | IC50 | 3162 | nM | CHEMBL3621857 |
| 5.48 | IC50 | 3300 | nM | CHEMBL316034 |
| 5.32 | IC50 | 4800 | nM | CHEMBL3775899 |
| 5.28 | IC50 | 5300 | nM | CHEMBL3774537 |
| 5.25 | IC50 | 5680 | nM | CHEMBL4516101 |
| 5.24 | IC50 | 5700 | nM | CHEMBL3775867 |
| 5.24 | IC50 | 5780 | nM | CHEMBL4449500 |
| 5.21 | IC50 | 6100 | nM | CHEMBL3775894 |
| 5.21 | IC50 | 6130 | nM | CHEMBL4525269 |
| 5.19 | IC50 | 6420 | nM | CHEMBL4447515 |
| 5.10 | IC50 | 7943 | nM | CHEMBL3621854 |
| 5.10 | IC50 | 7943 | nM | CHEMBL3621855 |
| 5.10 | IC50 | 7943 | nM | CHEMBL316034 |
| 5.08 | IC50 | 8300 | nM | CHEMBL3775668 |
| 5.07 | IC50 | 8500 | nM | CHEMBL3183531 |
| 5.05 | IC50 | 9000 | nM | CHEMBL3775272 |
| 5.04 | IC50 | 9100 | nM | CHEMBL3108955 |
| 5.01 | IC50 | 9700 | nM | CHEMBL3108954 |
| 5.00 | IC50 | 1e+04 | nM | CHEMBL3621858 |
PubChem BioAssay actives
37 with measured affinity, of 137 total; 31 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-amino-1,3-thiazol-4-yl)pyridine-4-carboxylic acid | 1282553: Inhibition of KDM3A (unknown origin) using biotin-H3K9me2 (1 to 21 residues) as substrate preincubated for 15 mins followed by substrate addition measured after 5 mins by alphascreen assay | ic50 | 0.0570 | uM |
| 2-[4-[[4-[(1S,2R)-2-aminocyclopropyl]phenyl]carbamoyl]-2-pyridinyl]pyridine-4-carboxylic acid;2,2,2-trifluoroacetic acid | 1066185: Inhibition of recombinant JMJD1A (unknown origin) incubated for 15 mins prior to substrate addition by AlphaScreen method | ic50 | 0.1400 | uM |
| 8-hydroxyquinoline-5-carboxylic acid | 1249065: Inhibition of KDM3A (unknown origin) | ic50 | 0.1585 | uM |
| 2-(carboxymethylamino)-2-oxoacetic acid | 1801992: Demethylase AlphaScreen Assay from Article 10.1038/nchembio.2087: “Structural analysis of human KDM5B guides histone demethylase inhibitor development.” | ic50 | 0.2900 | uM |
| (E)-4-[2-(4-benzylpyridine-3-carbonyl)hydrazinyl]-4-oxobut-2-enoic acid | 1916584: Inhibition of human KDM3A preincubated for 15 mins followed by substrate addition and measured after 5 mins using H3(1-21)K9Me2-GGK-Biotin peptide as substrate by AlphaScreen-based assay | ic50 | 0.4000 | uM |
| 2-[[[2-[2-(dimethylamino)ethyl-ethylamino]-2-oxoethyl]amino]methyl]pyridine-4-carboxylic acid | 1801992: Demethylase AlphaScreen Assay from Article 10.1038/nchembio.2087: “Structural analysis of human KDM5B guides histone demethylase inhibitor development.” | ic50 | 0.7800 | uM |
| 2-(4-methoxycarbonyl-2-pyridinyl)pyridine-4-carboxylic acid | 1066185: Inhibition of recombinant JMJD1A (unknown origin) incubated for 15 mins prior to substrate addition by AlphaScreen method | ic50 | 1.1000 | uM |
| 2-pyridin-2-ylpyridine-4-carboxylic acid | 1249055: Inhibition of KDM3A (unknown origin) using H3(1-21)K9Me2-GGK-biotin substrate incubated for 5 mins by alpha screen assay | ic50 | 1.2589 | uM |
| 8-[4-[2-[4-[3-(pyrrolidin-1-ylmethyl)phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one | 1556106: Inhibition of KDM3A (unknown origin) by Alphascreen assay | ic50 | 1.8500 | uM |
| 8-[4-[2-[4-[4-[2-(dimethylamino)ethyl]phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one | 1556106: Inhibition of KDM3A (unknown origin) by Alphascreen assay | ic50 | 2.0200 | uM |
| 2-[2-hydroxy-5-[(4-hydroxybenzoyl)amino]phenyl]pyridine-4-carboxylic acid | 1282316: Inhibition of KDM3A (unknown origin) expressed in Escherichia coli using H3 (1 to 21 residues) K9Me2-GGK-Biotin KDM3A Cognate Ligand/10 uM alpha-ketoglutarate as substrate/cofactor preincubated for 5 mins followed by substrate addition measured after 20 mins by alphascreen assay | ic50 | 2.3000 | uM |
| 2-[5-[(4-chloro-2-methylphenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid | 1391735: Inhibition of KDM3A (unknown origin) | ic50 | 2.3000 | uM |
| ethyl 2-[[[2-[2-(dimethylamino)ethyl-ethylamino]-2-oxoethyl]amino]methyl]pyridine-4-carboxylate | 1802660: AlphaScreen Assay from Article 10.1016/j.chembiol.2017.02.006: “Potent and Selective KDM5 Inhibitor Stops Cellular Demethylation of H3K4me3 at Transcription Start Sites and Proliferation of MM1S Myeloma Cells.” | ic50 | 3.0000 | uM |
| 2-[1-(2-phenylethyl)triazol-4-yl]pyridine-4-carboxylic acid | 1249055: Inhibition of KDM3A (unknown origin) using H3(1-21)K9Me2-GGK-biotin substrate incubated for 5 mins by alpha screen assay | ic50 | 3.1623 | uM |
| pyridine-2,4-dicarboxylic acid | 1282316: Inhibition of KDM3A (unknown origin) expressed in Escherichia coli using H3 (1 to 21 residues) K9Me2-GGK-Biotin KDM3A Cognate Ligand/10 uM alpha-ketoglutarate as substrate/cofactor preincubated for 5 mins followed by substrate addition measured after 20 mins by alphascreen assay | ic50 | 3.3000 | uM |
| 8-[4-[2-[4-[(4-chlorophenyl)methyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one | 1282553: Inhibition of KDM3A (unknown origin) using biotin-H3K9me2 (1 to 21 residues) as substrate preincubated for 15 mins followed by substrate addition measured after 5 mins by alphascreen assay | ic50 | 4.8000 | uM |
| 8-[4-[2-[4-(3-chlorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one | 1282553: Inhibition of KDM3A (unknown origin) using biotin-H3K9me2 (1 to 21 residues) as substrate preincubated for 15 mins followed by substrate addition measured after 5 mins by alphascreen assay | ic50 | 5.3000 | uM |
| 8-[4-[2-[4-[3-(pyrrolidin-1-ylmethyl)-5-(trifluoromethyl)phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one | 1556106: Inhibition of KDM3A (unknown origin) by Alphascreen assay | ic50 | 5.6800 | uM |
| 2-[2-hydroxy-5-[(5-methyl-1,2-oxazole-3-carbonyl)amino]phenyl]pyridine-4-carboxylic acid | 1282316: Inhibition of KDM3A (unknown origin) expressed in Escherichia coli using H3 (1 to 21 residues) K9Me2-GGK-Biotin KDM3A Cognate Ligand/10 uM alpha-ketoglutarate as substrate/cofactor preincubated for 5 mins followed by substrate addition measured after 20 mins by alphascreen assay | ic50 | 5.7000 | uM |
| 8-[4-(2-spiro[1,2-dihydroindene-3,4’-piperidine]-1’-ylethyl)pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one | 1556106: Inhibition of KDM3A (unknown origin) by Alphascreen assay | ic50 | 5.7800 | uM |
| 8-[4-[2-[4-(3,5-dichlorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one | 1282553: Inhibition of KDM3A (unknown origin) using biotin-H3K9me2 (1 to 21 residues) as substrate preincubated for 15 mins followed by substrate addition measured after 5 mins by alphascreen assay | ic50 | 6.1000 | uM |
| 8-[4-[1-(cyclobutylmethyl)piperidin-4-yl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one | 1556106: Inhibition of KDM3A (unknown origin) by Alphascreen assay | ic50 | 6.1300 | uM |
| 8-[4-[2-[4-(3-fluorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one | 1556106: Inhibition of KDM3A (unknown origin) by Alphascreen assay | ic50 | 6.4200 | uM |
| potassium 2-(1-ethyltriazol-4-yl)pyridine-4-carboxylate | 1249055: Inhibition of KDM3A (unknown origin) using H3(1-21)K9Me2-GGK-biotin substrate incubated for 5 mins by alpha screen assay | ic50 | 7.9433 | uM |
| potassium 2-[1-(3-methylphenyl)triazol-4-yl]pyridine-4-carboxylate | 1249055: Inhibition of KDM3A (unknown origin) using H3(1-21)K9Me2-GGK-biotin substrate incubated for 5 mins by alpha screen assay | ic50 | 7.9433 | uM |
| 8-[4-[2-(4-thiophen-2-ylpiperidin-1-yl)ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one | 1282553: Inhibition of KDM3A (unknown origin) using biotin-H3K9me2 (1 to 21 residues) as substrate preincubated for 15 mins followed by substrate addition measured after 5 mins by alphascreen assay | ic50 | 8.3000 | uM |
| ethyl 3-[[2-pyridin-2-yl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]amino]propanoate | 2145035: Inhibition of KDM3A (2 to 1322 residues)(unknown origin) by Alphalisa assay | ic50 | 8.5000 | uM |
| 2-[2-hydroxy-5-[[2-(3-methoxyphenyl)acetyl]amino]phenyl]pyridine-4-carboxylic acid | 1282316: Inhibition of KDM3A (unknown origin) expressed in Escherichia coli using H3 (1 to 21 residues) K9Me2-GGK-Biotin KDM3A Cognate Ligand/10 uM alpha-ketoglutarate as substrate/cofactor preincubated for 5 mins followed by substrate addition measured after 20 mins by alphascreen assay | ic50 | 9.0000 | uM |
| N-[6-[4-[(1R,2S)-2-aminocyclopropyl]anilino]-6-oxohexyl]-8-hydroxyquinoline-5-carboxamide;hydrochloride | 1066185: Inhibition of recombinant JMJD1A (unknown origin) incubated for 15 mins prior to substrate addition by AlphaScreen method | ic50 | 9.1000 | uM |
| N-[5-[4-[(1R,2S)-2-aminocyclopropyl]anilino]-5-oxopentyl]-8-hydroxyquinoline-5-carboxamide;hydrochloride | 1066185: Inhibition of recombinant JMJD1A (unknown origin) incubated for 15 mins prior to substrate addition by AlphaScreen method | ic50 | 9.7000 | uM |
| 2-[1-(2-phenoxyethyl)triazol-4-yl]pyridine-4-carboxylic acid | 1249055: Inhibition of KDM3A (unknown origin) using H3(1-21)K9Me2-GGK-biotin substrate incubated for 5 mins by alpha screen assay | ic50 | 10.0000 | uM |
CTD chemical–gene interactions
86 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Oxygen | increases reaction, increases expression, affects binding | 7 |
| sodium arsenite | increases expression, affects expression, decreases expression | 5 |
| cobaltous chloride | increases expression, decreases reaction | 4 |
| Valproic Acid | affects expression, decreases expression, increases expression | 4 |
| nickel chloride | decreases reaction, increases expression | 3 |
| Air Pollutants | decreases expression, affects expression, increases abundance | 2 |
| Cisplatin | decreases expression, affects cotreatment | 2 |
| Ozone | affects cotreatment, increases oxidation, affects expression, increases abundance | 2 |
| 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide | increases expression, decreases expression | 2 |
| Cadmium Chloride | increases expression, decreases expression | 2 |
| aristolochic acid I | decreases expression | 1 |
| GSK-J4 | increases expression | 1 |
| FR900359 | affects phosphorylation | 1 |
| dicrotophos | decreases expression | 1 |
| bufotalin | increases expression | 1 |
| chloroacetaldehyde | decreases expression | 1 |
| bisphenol A | affects expression | 1 |
| lead acetate | decreases expression | 1 |
| quercitrin | increases expression | 1 |
| arsenite | affects binding, decreases reaction | 1 |
| sodium bichromate | increases expression | 1 |
| zinc chloride | decreases reaction, increases expression | 1 |
| butyraldehyde | decreases expression | 1 |
| gossypol acetic acid | increases expression | 1 |
| cupric chloride | increases expression | 1 |
| nickel sulfate | increases expression | 1 |
| methacrylaldehyde | affects cotreatment, increases oxidation | 1 |
| testosterone-3-carboxymethyloxime-bovine serum albumin conjugate | decreases expression | 1 |
| cobalt oxide | increases expression | 1 |
| di-n-butylphosphoric acid | affects expression | 1 |
ChEMBL screening assays
25 unique, capped per target: 25 binding
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1942534 | Binding | Inhibition of KDM3A | Lysine demethylases inhibitors. — J Med Chem |
Cellosaurus cell lines
8 cell lines: 5 cancer cell line, 3 embryonic stem cell
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_A3L6 | SEES3-1V human KDM3A, clone1 | Embryonic stem cell | Male |
| CVCL_A3L7 | SEES3-1V human KDM3A, clone2 | Embryonic stem cell | Male |
| CVCL_A3L8 | SEES3-1V human KDM3A, clone3 | Embryonic stem cell | Male |
| CVCL_B8J4 | Abcam HCT 116 KDM3A KO | Cancer cell line | Male |
| CVCL_B8XY | Abcam MCF-7 KDM3A KO | Cancer cell line | Female |
| CVCL_B9LF | Abcam A-549 KDM3A KO | Cancer cell line | Male |
| CVCL_SU22 | HAP1 KDM3A (-) 1 | Cancer cell line | Male |
| CVCL_SU23 | HAP1 KDM3A (-) 2 | Cancer cell line | Male |
Clinical trials (associated diseases)
300 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT00029224 | PHASE4 | COMPLETED | Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions |
| NCT00035997 | PHASE4 | COMPLETED | Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis |
| NCT00063609 | PHASE4 | COMPLETED | The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy |
| NCT00103623 | PHASE4 | SUSPENDED | The Plenaxis® Experience Study |
| NCT00106392 | PHASE4 | COMPLETED | A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy |
| NCT00185029 | PHASE4 | UNKNOWN | MR-Lymphography and Lymph Node Staging in Prostate Cancer |
| NCT00199485 | PHASE4 | COMPLETED | Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer |
| NCT00219219 | PHASE4 | COMPLETED | Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases |
| NCT00219271 | PHASE4 | COMPLETED | Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer |
| NCT00237146 | PHASE4 | COMPLETED | Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy |
| NCT00242554 | PHASE4 | COMPLETED | Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases |
| NCT00280098 | PHASE4 | COMPLETED | Docetaxel in the Treatment of Hormone Refractory Prostate Cancer |
| NCT00293696 | PHASE4 | COMPLETED | Casodex/Zoladex Biomarkers in Localised Prostate Cancer |
| NCT00334139 | PHASE4 | COMPLETED | Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer |
| NCT00375765 | PHASE4 | COMPLETED | Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer |
| NCT00391690 | PHASE4 | COMPLETED | Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer |
| NCT00422708 | PHASE4 | COMPLETED | Local Anesthesia for Prostate Biopsy |
| NCT00526331 | PHASE4 | COMPLETED | Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy |
| NCT00590213 | PHASE4 | COMPLETED | Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX |
| NCT00629330 | PHASE4 | TERMINATED | Dissemination of Prostate Cancer Screening to PCP’s in African American Communities |
| NCT00771966 | PHASE4 | COMPLETED | Radical Prostatectomy and Perioperative Fluid Therapy |
| NCT00805701 | PHASE4 | COMPLETED | Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation |
| NCT00859027 | PHASE4 | COMPLETED | Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer |
| NCT00906269 | PHASE4 | UNKNOWN | Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer |
| NCT00953277 | PHASE4 | COMPLETED | Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer |
| NCT00982800 | PHASE4 | COMPLETED | Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy? |
| NCT01083199 | PHASE4 | COMPLETED | Global Performance Evaluation of the AMS CONTINUUM™ Device |
| NCT01136226 | PHASE4 | COMPLETED | Evaluate Recovery of Testosterone for Patients Using Eligard |
| NCT01161563 | PHASE4 | COMPLETED | Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration |
| NCT01230905 | PHASE4 | COMPLETED | Study to Monitor the Effects of Androgen Suppression Treatment on the Heart |
| NCT01296672 | PHASE4 | COMPLETED | 3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer |
| NCT01365143 | PHASE4 | TERMINATED | Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy |
| NCT01379742 | PHASE4 | UNKNOWN | Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy |
| NCT01486563 | PHASE4 | COMPLETED | Hydroxyethyl Starch and Renal Function After Radical Prostatectomy |
| NCT01511874 | PHASE4 | COMPLETED | Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer |
| NCT01512472 | PHASE4 | TERMINATED | Firmagon (Degarelix) Intermittent Therapy |
| NCT01547416 | PHASE4 | COMPLETED | The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function |
| NCT01571544 | PHASE4 | COMPLETED | The Use of Thermal Suits as Preventing Hypothermia During Surgery |
| NCT01581749 | PHASE4 | UNKNOWN | Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer |
| NCT01649635 | PHASE4 | COMPLETED | Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer |
Related Atlas pages
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): ovarian carcinoma, susceptibility to respiratory infections associated with CD8alpha chain mutation