NR2C2

Summary

NR2C2 (nuclear receptor subfamily 2 group C member 2, HGNC:7972) is a protein-coding gene on chromosome 3p25.1, encoding Nuclear receptor subfamily 2 group C member 2 (P49116). Orphan nuclear receptor that can act as a repressor or activator of transcription.

This gene encodes a protein that belongs to the nuclear hormone receptor family. Members of this family act as ligand-activated transcription factors and function in many biological processes such as development, cellular differentiation and homeostasis. The activated receptor/ligand complex is translocated to the nucleus where it binds to hormone response elements of target genes. The protein encoded by this gene plays a role in protecting cells from oxidative stress and damage induced by ionizing radiation. The lack of a similar gene in mouse results in growth retardation, severe spinal curvature, subfertility, premature aging, and prostatic intraepithelial neoplasia (PIN) development. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 7182 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 45 total — 1 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Transcription factor: yes — 63 downstream targets (CollecTRI)
• MANE Select transcript: NM_001291694

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7972
Approved symbol	NR2C2
Name	nuclear receptor subfamily 2 group C member 2
Location	3p25.1
Locus type	gene with protein product
Status	Approved
Aliases	TAK1, TR2R1, hTAK1
Ensembl gene	ENSG00000177463
Ensembl biotype	protein_coding
OMIM	601426
Entrez	7182

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 22 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000323373, ENST00000393102, ENST00000413118, ENST00000413194, ENST00000425241, ENST00000435454, ENST00000437120, ENST00000439011, ENST00000475707, ENST00000478572, ENST00000495282, ENST00000859246, ENST00000859247, ENST00000859248, ENST00000859249, ENST00000859250, ENST00000859251, ENST00000859252, ENST00000859253, ENST00000911529, ENST00000968197, ENST00000968198, ENST00000968199, ENST00000968200, ENST00000968201

RefSeq mRNA: 2 — MANE Select: NM_001291694 NM_001291694, NM_003298

CCDS: CCDS2621, CCDS74905

Canonical transcript exons

ENST00000425241 — 14 exons

Exon	Start	End
ENSE00003492379	15039122	15039227
ENSE00003503305	15016152	15016254
ENSE00003536358	15024115	15024208
ENSE00003547304	15023200	15023347
ENSE00003562303	15032379	15032500
ENSE00003563540	15034670	15034809
ENSE00003570854	15028586	15028719
ENSE00003612846	15030275	15030452
ENSE00003638694	15013589	15013789
ENSE00003659184	15038000	15038137
ENSE00003674077	15003876	15003986
ENSE00003675648	15020753	15020932
ENSE00003725344	15042834	15049273
ENSE00003930082	14947583	14947906

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 94.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.3790 / max 242.9265, expressed in 1811 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35484	22.1687	1807
35483	2.1574	1097
35482	0.8097	373
35480	0.6988	386
35487	0.6639	374
35481	0.5899	332
35490	0.1591	56
35486	0.1315	50

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	94.87	gold quality
upper leg skin	UBERON:0004262	93.72	gold quality
tibia	UBERON:0000979	93.69	gold quality
cortical plate	UBERON:0005343	93.53	gold quality
skin of hip	UBERON:0001554	93.48	gold quality
colonic epithelium	UBERON:0000397	92.72	gold quality
jejunal mucosa	UBERON:0000399	92.58	gold quality
superficial temporal artery	UBERON:0001614	91.78	gold quality
epithelium of nasopharynx	UBERON:0001951	91.24	gold quality
ganglionic eminence	UBERON:0004023	90.85	gold quality
germinal epithelium of ovary	UBERON:0001304	90.60	gold quality
parietal pleura	UBERON:0002400	90.60	gold quality
left lobe of thyroid gland	UBERON:0001120	90.41	gold quality
calcaneal tendon	UBERON:0003701	90.30	gold quality
trabecular bone tissue	UBERON:0002483	90.28	gold quality
right lobe of thyroid gland	UBERON:0001119	90.20	gold quality
adrenal tissue	UBERON:0018303	90.13	gold quality
adult organism	UBERON:0007023	90.10	gold quality
postcentral gyrus	UBERON:0002581	90.05	gold quality
middle temporal gyrus	UBERON:0002771	89.92	gold quality
jejunum	UBERON:0002115	89.86	gold quality
endothelial cell	CL:0000115	89.81	gold quality
visceral pleura	UBERON:0002401	89.80	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.69	gold quality
thyroid gland	UBERON:0002046	89.66	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.41	gold quality
oral cavity	UBERON:0000167	89.33	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.24	gold quality
cerebellar hemisphere	UBERON:0002245	89.20	gold quality
pleura	UBERON:0000977	89.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.25

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

63 targets.

Target	Regulation
ACOX1
ACP5
ADAM2
ADAMTS5
AKT1
APOE	Unknown
ATM
BCL2	Unknown
BGLAP
CCNA1	Repression
CCND1	Activation
CCR7
CD36	Unknown
CD44
CDKN1A	Repression
CDKN2A
CXCL8
CYP21A2	Repression
CYP24A1	Repression
DUSP14
ESR1
FGF10
GADD45A
GATA1	Activation
GSK3A
HBE1
HBG1
HGF
HLA-DRB1
IL2

JASPAR motifs

Motif	Name	Family
MA0504.1	NR2C2	RXR-related receptors (NR2)
MA0504.2	NR2C2	RXR-related receptors (NR2)
MA1536.1	NR2C2	RXR-related receptors (NR2)
MA1536.2	NR2C2	RXR-related receptors (NR2)

JASPAR matrix evidence (PMIDs): PMID:11478808

Upstream regulators (CollecTRI, top): AR, DR1, ELK4, FOXO3, NR2C1, NR2C2, STAT3, TGFB1I1

miRNA regulators (miRDB)

317 targeting NR2C2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-568	99.98	69.86	2084
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-5696	99.98	72.36	4487
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4789-5P	99.98	70.76	2721

Literature-anchored findings (GeneRIF, showing 40)

• role in modulating estrogen receptor-mediated trans-activation (PMID:11844790)
• DRED is a 540 kDa complex containing the nuclear orphan receptors TR2 and TR4, which form a heterodimer that binds to the epsilon and gamma globin promoter DR1 sites. TR2 & 4 mRNAs are expressed at all stages of murine and human erythropoiesis. (PMID:12093744)
• TR4 can serve as a negative modulator in the transcriptional regulation of HBV core gene expression (PMID:12522137)
• TR2 and TR4 can have distinct functions. Existence of differential and bi-directional regulation between PPAR alpha and TR2/TR4. Possible roles in PPAR alpha signaling pathway in human keratinocytes. (PMID:12615366)
• The binding activity of C/EBPs to the TR4 promoter is increased in response to cAMP treatment. (PMID:19618297)
• Human testicular orphan receptor 4 enhances thyroid hormone receptor signaling. (PMID:19859911)
• Activation of IRF3 and IRF3-dependent gene expressions was dependent on TAK1 and TANK-binding kinase 1 (TBK1). (PMID:19955181)
• the ADAP CARMA1 binding site is required for IKK gamma ubiquitination; both TAK1 and CARMA1 binding sites are required for IkappaB alpha phosphorylation and degradation and NF-kappaB nuclear translocation (PMID:20164171)
• Our data establish the central role of TAK1 in controlling nuclear and cytoplasmic signaling cascades in primary neutrophils (PMID:20200282)
• TAK1 is an important transcriptional modulator of cerebellar development and neurodevelopmentally regulated behavior. (PMID:20393820)
• COX-2 gene expression and prostaglandin (PG)E2 release are specific outcomes of collagen II signaling, and both depend on TAK1 mediation in primary human chondrocytes. (PMID:20604713)
• TR4 is a ligand-regulated nuclear receptor and suggest that retinoids might have a much wider regulatory role via activation of orphan receptors such as TR4. (PMID:21068381)
• TR4 binding at a subset of sites is facilitated through the ETS transcription factor ELK4. (PMID:21126370)
• Results demonstrate that USP4 serves as a critical control to downregulate TNFalpha-induced NF-kappaB activation through deubiquitinating TAK1. (PMID:21331078)
• These results demonstrated the role of TAK1 as an important upstream signaling molecule regulating RSV-induced NF-kappaB and AP-1 activation. (PMID:21835421)
• The purpose of the study was to investigate the potential contribution of HPK1, MEKK1, TAK1, p-MKK4 to the development of extramammary Paget disease (PMID:21915030)
• Testicular nuclear receptor 4 (TR4) regulates UV light-induced responses via Cockayne syndrome B protein-mediated transcription-coupled DNA repair (PMID:21918225)
• the protein associates with TGF-beta receptors and components of the TRAF6-TAK1 signaling module (PMID:21980489)
• Mycobacterium tuberculosis interacts with macrophage lipids and human host testicular receptor (TR)4 to ensure survival of the pathogen by modulating macrophage function. (PMID:22544925)
• Celastrol highlights the therapeutic potential of agents targeting TAK1 as a key node in this pro-oncogenic TGF-beta-NF-kappaB signal pathway (PMID:22641218)
• PINK1 positively regulates two key molecules, TRAF6 and TAK1, in the IL-1beta-mediated signaling pathway, consequently up-regulating their downstream inflammatory events (PMID:22643835)
• Beta-TrCP deficiency abolished the translocation TAK1-TRAF6 complex from the membrane to the cytosol, resulting in a diminishment of the IL-1-induced TAK1-dependent pathway. (PMID:22851693)
• Lys63-linked TAK1 polyubiquitination at Lys-158 is required for Dox-induced NF-kappaB activation. (PMID:22981905)
• Mice that lack the ortholog of this gene display severe spinal curvature, subfertility, premature aging, and prostatic intraepithelial neoplasia (PIN) development. (PMID:23463759)
• TR4-Oct4-IL1Ra axis may play a critical role in the development of chemoresistance in the PCa stem/progenitor cells. (PMID:23609451)
• TR4 transcriptionally activates proopiomelanocortin through binding of a direct repeat 1 response element in the promoter, and that this is enhanced by MAPK-mediated TR4 phosphorylation. (PMID:23653479)
• The results provide a proof-of-concept that TAK1 inhibition significantly increases the sensitivity of neuroblastoma cells to chemotherapy-induced cell-death. (PMID:23700229)
• These results reveal Sef-S actives Lys63-linked TAK1 polyubiquitination on lysine 209, induces TAK1-mediated JNK and p38 activation and also results apoptosis in 293T cells. (PMID:23770285)
• Findings reveal the role of TAK1 in thermoresistance and show that the mediation is independent of NF-kappaB phosphorylation but is dependent on TNFAIP3 and IL-8 induction. (PMID:24028082)
• TAK1 regulates H. pylori-mediated early JNK activation and cytokine production. (PMID:24082073)
• Small interfering RNA-mediated silencing of TRAF6 and TAK1. (PMID:24337384)
• We provide evidence for an intimate mutual control of the IKK complex by mitogen-activated protein kinase kinase kinase 3 (MEKK3) and transforming growth factor beta activated kinase 1 (TAK1). (PMID:24418622)
• miR-26b suppresses NF-kappaB signaling and sensitizes hepatocellular carcinoma cells to doxorubicin-induced apoptosis by inhibiting the expression of TAK1 and TAB3. (PMID:24565101)
• TR4 nuclear receptor functions as a tumor suppressor for prostate tumorigenesis via modulation of DNA damage/repair system. (PMID:24583925)
• our findings describe a TAK1-dependent, beta-catenin- and Sp1-mediated signaling cascade activated downstream of TGF-beta which regulates WNT-5A induction. (PMID:24728340)
• TAK1 is a key regulator of receptor crosstalk between BCR and TLR9. (PMID:24801688)
• study reveals that the TR4 regulatory network is far more complex than previously appreciated and that TR4 regulates basic, essential biological processes during the terminal differentiation of human erythroid cells. (PMID:24811540)
• TR4 binding with keto-MA features a unique association of host nuclear receptor with a bacterial lipid and adds to the presently known ligand repertoire beyond dietary lipids. (PMID:24907344)
• Knockdown of endogenous TAK1 significantly attenuated the ability of Vpr to activate NF-kappaB and AP-1. (PMID:24912525)
• Authors demonstrate that enterovirus 71 3C interacts with TAB2 and TAK1 and suppresses cytokine expression via cleavage of the TAK1 complex proteins. (PMID:24942571)

Cross-species orthologs

30 orthologs

Organism	Symbol	Gene ID
danio_rerio	nr2c2	ENSDARG00000042477
mus_musculus	Nr2c2	ENSMUSG00000005893
rattus_norvegicus	Nr2c2	ENSRNOG00000010536
drosophila_melanogaster	usp	FBGN0003964
drosophila_melanogaster	Hr78	FBGN0015239
drosophila_melanogaster	Hr83	FBGN0037436
caenorhabditis_elegans		WBGENE00003626
caenorhabditis_elegans		WBGENE00003650
caenorhabditis_elegans	nhr-69	WBGENE00003659
caenorhabditis_elegans		WBGENE00003683
caenorhabditis_elegans		WBGENE00003706
caenorhabditis_elegans		WBGENE00003719
caenorhabditis_elegans		WBGENE00003726
caenorhabditis_elegans		WBGENE00007547
caenorhabditis_elegans		WBGENE00008221
caenorhabditis_elegans		WBGENE00011097
caenorhabditis_elegans		WBGENE00011098
caenorhabditis_elegans		WBGENE00011099
caenorhabditis_elegans		WBGENE00011100
caenorhabditis_elegans		WBGENE00015395
caenorhabditis_elegans		WBGENE00015396
caenorhabditis_elegans		WBGENE00015397
caenorhabditis_elegans		WBGENE00015705
caenorhabditis_elegans		WBGENE00016975
caenorhabditis_elegans		WBGENE00017198
caenorhabditis_elegans		WBGENE00017787
caenorhabditis_elegans		WBGENE00020748
caenorhabditis_elegans		WBGENE00021848
caenorhabditis_elegans		WBGENE00022423
caenorhabditis_elegans		WBGENE00044354

Paralogs (11): HNF4A (ENSG00000101076), NR2E1 (ENSG00000112333), NR2C1 (ENSG00000120798), RXRG (ENSG00000143171), NR2F6 (ENSG00000160113), HNF4G (ENSG00000164749), NR2F1 (ENSG00000175745), NR2F2 (ENSG00000185551), RXRA (ENSG00000186350), RXRB (ENSG00000204231), NR2E3 (ENSG00000278570)

Protein

Protein identifiers

Nuclear receptor subfamily 2 group C member 2 — P49116 (reviewed: P49116)

Alternative names: Orphan nuclear receptor TAK1, Orphan nuclear receptor TR4, Testicular receptor 4

All UniProt accessions (7): C9J2Y1, C9JKS0, C9JMI6, F2YGU2, H7C3L1, H7C3R1, P49116

UniProt curated annotations — full annotation on UniProt →

Function. Orphan nuclear receptor that can act as a repressor or activator of transcription. An important repressor of nuclear receptor signaling pathways such as retinoic acid receptor, retinoid X, vitamin D3 receptor, thyroid hormone receptor and estrogen receptor pathways. May regulate gene expression during the late phase of spermatogenesis. Together with NR2C1, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription including that of GATA1. Binds to hormone response elements (HREs) consisting of two 5’-AGGTCA-3’ half site direct repeat consensus sequences. Plays a fundamental role in early embryonic development and embryonic stem cells. Required for normal spermatogenesis and cerebellum development. Appears to be important for neurodevelopmentally regulated behavior. Activates transcriptional activity of LHCG. Antagonist of PPARA-mediated transactivation.

Subunit / interactions. Homodimer; can bind DNA as homodimer. Heterodimer; binds DNA as a heterodimer with NR2C1 required for chromatin remodeling and for binding to promoter regions such as globin DR1 repeats. Interacts with PCAF; the interaction preferentially occurs on the non-phosphorylated form and induces NR2C2-mediated transactivation activity and does not require the ligand-binding domain. Interacts (MAPK-mediated phosphorylated form) with NRIP1; the interaction promotes repression of NR2C2-mediated activity. Interacts with NR2C2AP; the interaction represses selective NR2C2-mediated transcriptional activity. Interacts with NLRP10. Interacts (via ligand-binding region) with transcriptional corepressor JAZF1; the interaction promotes NR2C2-mediated transcriptional repression.

Subcellular location. Nucleus.

Post-translational modifications. Phosphorylation on Ser-19 and Ser-68 is an important regulator of NR2C2-mediated transcriptional activity. Phosphorylation on these residues recruits the corepressor, NRIP1, leading to transcripional repression, whereas the non-phosphorylated form preferentially recruits the coactivator, PCAF.

Induction. Induced by oxidative stress via FOXO3 activation.

Similarity. Belongs to the nuclear hormone receptor family. NR2 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P49116-1	1	yes
P49116-2	2

RefSeq proteins (2): NP_001278623, NP_003289 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000536	Nucl_hrmn_rcpt_lig-bd	Domain
IPR001628	Znf_hrmn_rcpt	Domain
IPR001723	Nuclear_hrmn_rcpt	Family
IPR013088	Znf_NHR/GATA	Homologous_superfamily
IPR035500	NHR-like_dom_sf	Homologous_superfamily
IPR048245	NR2C1/2-like_DBD	Domain
IPR048246	NR2C1/2-like_LBD	Domain
IPR050274	Nuclear_hormone_rcpt_NR2	Family

Pfam: PF00104, PF00105

UniProt features (48 total): helix 17, modified residue 7, sequence conflict 7, strand 6, turn 3, zinc finger region 2, chain 1, domain 1, cross-link 1, splice variant 1, mutagenesis site 1, DNA-binding region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7XV9	X-RAY DIFFRACTION	1.6
7XVA	X-RAY DIFFRACTION	1.86
7XV6	X-RAY DIFFRACTION	2.3
3P0U	X-RAY DIFFRACTION	3
7XV8	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49116-F1	66.50	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.

Post-translational modifications (8): 219, 231, 192, 19, 46, 55, 68, 98

Mutagenesis-validated functional residues (1):

Position	Phenotype
576	reduces interaction with jazf1.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-383280	Nuclear Receptor transcription pathway
R-HSA-9940951	Interaction of NuRD complexes with transcription factors

MSigDB gene sets: 300 (showing top): ACTACCT_MIR196A_MIR196B, GAANYNYGACNY_UNKNOWN, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, BROWNE_HCMV_INFECTION_16HR_UP, TGACCTY_ERR1_Q2, GOBP_MALE_GAMETE_GENERATION, FOXO1_01, GTGCCTT_MIR506, CATTTCA_MIR203, GOBP_JNK_CASCADE, MODULE_99

GO Biological Process (11): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), spermatogenesis (GO:0007283), nervous system development (GO:0007399), cell differentiation (GO:0030154), tumor necrosis factor-mediated signaling pathway (GO:0033209), positive regulation of embryonic development (GO:0040019), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of JNK cascade (GO:0046330), intracellular receptor signaling pathway (GO:0030522)

GO Molecular Function (12): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), nuclear receptor activity (GO:0004879), zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): chromatin (GO:0000785), nucleoplasm (GO:0005654), nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Generic Transcription Pathway	1
NuRD complex assembly	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
transcription by RNA polymerase II	2
transcription cis-regulatory region binding	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
negative regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
developmental process involved in reproduction	1
male gamete generation	1
system development	1
cellular developmental process	1
cytokine-mediated signaling pathway	1
cellular response to tumor necrosis factor	1
embryo development	1
regulation of embryonic development	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
positive regulation of DNA-templated transcription	1
JNK cascade	1
positive regulation of MAPK cascade	1
regulation of JNK cascade	1
intracellular signal transduction	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
regulation of DNA-templated transcription	1
transcription regulator activity	1
intracellular receptor signaling pathway	1
signaling receptor activity	1
ligand-modulated transcription factor activity	1
transition metal ion binding	1
DNA binding	1

Protein interactions and networks

STRING

4181 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NR2C2	NR2C2AP	Q86WQ0	854
NR2C2	JAZF1	Q86VZ6	697
NR2C2	TAB2	Q9NYJ8	673
NR2C2	NCOR1	O75376	667
NR2C2	BCL11A	Q9H165	659
NR2C2	NR2C1	P13056	650
NR2C2	DNMT1	P26358	646
NR2C2	KLF1	Q13351	631
NR2C2	SIN3A	Q96ST3	630
NR2C2	TNFRSF6B	O95407	608
NR2C2	TRAF6	Q9Y4K3	601
NR2C2	GATA1	P15976	591
NR2C2	DYNC2I2	Q96EX3	584
NR2C2	SOX6	P35712	581
NR2C2	ZNF827	Q17R98	561

IntAct

87 interactions, top by confidence:

A	B	Type	Score
NR2C2	JAZF1	psi-mi:“MI:0915”(physical association)	0.790
NR2C2	JAZF1	psi-mi:“MI:0403”(colocalization)	0.790
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
JAZF1	YEATS4	psi-mi:“MI:0914”(association)	0.530
NR2C2	NR2C2AP	psi-mi:“MI:0403”(colocalization)	0.460
NR2C2	NR2C2AP	psi-mi:“MI:0915”(physical association)	0.460
NR2C2	UL37	psi-mi:“MI:0915”(physical association)	0.400
CBLB	NR2C2	psi-mi:“MI:0915”(physical association)	0.400
HSP90AB1	NR2C2	psi-mi:“MI:0915”(physical association)	0.400
	NR2C2	psi-mi:“MI:0915”(physical association)	0.370
CCL24	NR2C2	psi-mi:“MI:0915”(physical association)	0.370
CXCL3	NR2C2	psi-mi:“MI:0915”(physical association)	0.370
IFNA16	NR2C2	psi-mi:“MI:0915”(physical association)	0.370
IFNA8	NR2C2	psi-mi:“MI:0915”(physical association)	0.370
IL17A	NR2C2	psi-mi:“MI:0915”(physical association)	0.370
IL17F	NR2C2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (1461): NR2C2 (Co-fractionation), S100A4 (Affinity Capture-MS), SMARCC1 (Affinity Capture-MS), EED (Affinity Capture-MS), RPP38 (Affinity Capture-MS), PATZ1 (Affinity Capture-MS), TANC2 (Affinity Capture-MS), RBMX2 (Affinity Capture-MS), PRPF40A (Affinity Capture-MS), KLHL7 (Affinity Capture-MS), NR2C2 (Affinity Capture-MS), NR2C2 (Two-hybrid), NR2C2 (Affinity Capture-MS), UBB (Affinity Capture-MS), NR2C2 (Affinity Capture-RNA)

ESM2 similar proteins: A0JNE3, A0P8Z4, O00482, O42101, P06211, P06212, P13056, P19785, P28701, P28705, P35398, P37238, P45448, P48443, P49116, P49117, P49867, P51128, P51129, P51448, P55094, P57783, P70033, P79926, P81559, Q04913, Q0GFF6, Q0VC20, Q15406, Q26622, Q28CK1, Q505F1, Q5BJR8, Q5RCZ5, Q5REL6, Q64249, Q66J63, Q66JK1, Q6GN21, Q8VIJ4

Diamond homologs: A0JNE3, A2T928, A4IIG7, G5ECR9, G5EDJ0, O02151, O45666, O76202, O97716, P10276, P10588, P10826, P10827, P10828, P11416, P12813, P13056, P13631, P16376, P18117, P18514, P18515, P18516, P18911, P20153, P22448, P22449, P22605, P22736, P22829, P28699, P31396, P33242, P33244, P41828, P41830, P43354, P45447, P49116, P49117

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
SMAD6	down-regulates	NR2C2	binding
JAZF1	down-regulates	NR2C2	binding
PRKAA1	down-regulates	NR2C2	phosphorylation
AMPK	down-regulates	NR2C2	phosphorylation
NR2C2	“up-regulates quantity by expression”	LHCGR	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 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
SARS-CoV-2 activates/modulates innate and adaptive immune responses	8	11.7×	2e-04
Interleukin-1 signaling	5	10.2×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
response to wounding	5	14.0×	2e-03
transcription by RNA polymerase II	9	8.0×	3e-04
immune response	8	4.8×	9e-03
inflammatory response	9	4.3×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	26
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3062708	GRCh37/hg19 3p26.3-22.3(chr3:61891-33946644)x3	Pathogenic

SpliceAI

4286 predictions. Top by Δscore:

Variant	Effect	Δscore
3:14959193:TCAG:T	donor_loss	1.0000
3:14959194:CAG:C	donor_loss	1.0000
3:14959195:AG:A	donor_loss	1.0000
3:14959196:GG:G	donor_loss	1.0000
3:14959197:GT:G	donor_loss	1.0000
3:14959198:T:A	donor_loss	1.0000
3:14959627:G:GG	donor_gain	1.0000
3:14959637:GAATT:G	donor_gain	1.0000
3:14959642:G:GG	donor_gain	1.0000
3:15013584:TATA:T	acceptor_loss	1.0000
3:15013585:ATAG:A	acceptor_loss	1.0000
3:15013586:TAGAT:T	acceptor_loss	1.0000
3:15013587:A:G	acceptor_loss	1.0000
3:15013588:G:GT	acceptor_loss	1.0000
3:15013588:GATT:G	acceptor_gain	1.0000
3:15016151:GATT:G	acceptor_gain	1.0000
3:15020748:TTCA:T	acceptor_loss	1.0000
3:15020749:TCA:T	acceptor_loss	1.0000
3:15020750:CA:C	acceptor_loss	1.0000
3:15020752:G:A	acceptor_loss	1.0000
3:15020752:GGCC:G	acceptor_gain	1.0000
3:15020928:GGAAT:G	donor_gain	1.0000
3:15020929:GAAT:G	donor_gain	1.0000
3:15020929:GAATG:G	donor_gain	1.0000
3:15020930:A:T	donor_gain	1.0000
3:15020930:AAT:A	donor_gain	1.0000
3:15020931:AT:A	donor_gain	1.0000
3:15020932:TG:T	donor_loss	1.0000
3:15020933:G:GG	donor_gain	1.0000
3:15020933:GTG:G	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000017575 (3:15042951 C>T), RS1000043493 (3:14973426 G>A,T), RS1000047549 (3:15006820 G>A), RS1000056973 (3:14958968 C>T), RS1000103870 (3:14971723 C>T), RS1000112613 (3:14948450 G>A,C), RS1000132741 (3:14954822 T>C,G), RS1000137784 (3:14973185 A>G), RS1000169678 (3:14970300 T>G), RS1000243179 (3:14956994 A>G), RS1000269837 (3:14979345 T>C), RS1000279901 (3:14997832 C>A,G,T), RS1000289674 (3:14997525 G>A), RS1000303337 (3:14985342 C>A,T), RS1000323582 (3:15020535 T>A)

Disease associations

OMIM: gene MIM:601426 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001471_3	Alcohol and nicotine co-dependence	4.000000e-07
GCST012490_537	Femur bone mineral density x serum urate levels interaction	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3885612 (CHIMERIC PROTEIN), CHEMBL5716 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,252 (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
CHEMBL2010872	CEP-11981	2	1,252

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: nhr — 2C. Testicular receptors

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

Ligand	Action	Affinity	Parameter
retinol	Full agonist	4.71	pEC50
tretinoin	Full agonist	4.62	pEC50

Binding affinities (BindingDB)

10 measured of 12 human assays (12 total across all organisms); most potent 10 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[5-[[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)benzoyl]amino]-2-methylphenyl]-5-(1-methylpyrazol-4-yl)pyridine-3-carboxamide	IC50	2.43 nM	US-9908872: Methods to treat lymphoplasmacytic lymphoma
N-[5-[[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)benzoyl]amino]-2-methylphenyl]-5-(1,2-oxazol-4-yl)pyridine-3-carboxamide	IC50	5.33 nM	US-9908872: Methods to treat lymphoplasmacytic lymphoma
9-(1-methylpyrazol-4-yl)-1-(1-prop-2-enoyl-2,3-dihydroindol-6-yl)benzo[h][1,6]naphthyridin-2-one	IC50	6.73 nM	US-10000483: Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof
QL-X-138	IC50	7 nM	US-10000483: Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof
N-[5-[9-[4-(methanesulfonamido)phenyl]-2-oxobenzo[h][1,	IC50	7.99 nM	US-10000483: Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof
N-[2-methyl-5-[[3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)phenyl]carbamoyl]phenyl]-5-thiophen-2-ylpyridine-3-carboxamide	IC50	22.8 nM	US-9908872: Methods to treat lymphoplasmacytic lymphoma
N-[5-[(3,5-dimorpholin-4-ylphenyl)carbamoyl]-2-methylphenyl]-5-thiophen-2-ylpyridine-3-carboxamide	IC50	56.5 nM	US-9908872: Methods to treat lymphoplasmacytic lymphoma
N-[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]carbamoyl]phenyl]-5-thiophen-2-ylpyridine-3-carboxamide	IC50	62.2 nM	US-9908872: Methods to treat lymphoplasmacytic lymphoma
N-[5-[[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)benzoyl]amino]-2-methylphenyl]-5-thiophen-2-ylpyridine-3-carboxamide	IC50	8210 nM	US-9908872: Methods to treat lymphoplasmacytic lymphoma
5-Phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine	IC50	50000 nM	US-10214511

ChEMBL bioactivities

49 potent at pChembl≥5 of 53 total, top 49 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.61	IC50	2.43	nM	CHEMBL5915826
8.27	IC50	5.33	nM	CHEMBL5827081
8.13	IC50	7.4	nM	CHEMBL5950918
8.05	IC50	9	nM	CHEMBL1077979
7.85	IC50	14	nM	CEP-11981
7.64	IC50	22.8	nM	CHEMBL6044253
7.52	IC50	30	nM	HYPOTHEMYCIN
7.52	IC50	29.9	nM	CHEMBL6014241
7.35	IC50	45	nM	CHEMBL6038355
7.27	IC50	53.8	nM	CHEMBL6006139
7.25	IC50	56.5	nM	CHEMBL5778860
7.21	IC50	61	nM	CHEMBL3426225
7.21	IC50	62.2	nM	CHEMBL5834925
7.20	IC50	63.5	nM	CHEMBL5962638
7.14	IC50	71.7	nM	CHEMBL5961742
7.12	IC50	76.2	nM	CHEMBL5887569
7.04	IC50	92	nM	CHEMBL6022481
7.00	IC50	100	nM	CHEMBL5929345
7.00	IC50	100	nM	CHEMBL5885824
6.93	IC50	117	nM	CHEMBL5994443
6.92	IC50	120	nM	CHEMBL5188433
6.90	IC50	126	nM	CHEMBL5088153
6.87	IC50	136	nM	CHEMBL5860086
6.75	IC50	180	nM	CHEMBL5184381
6.58	IC50	260	nM	CHEMBL5185000
6.44	IC50	364	nM	CHEMBL5705821
6.42	IC50	380	nM	CHEMBL5204235
6.40	IC50	400	nM	CHEMBL5903220
6.37	IC50	430	nM	CHEMBL5174288
6.35	IC50	450	nM	CHEMBL5186931
6.31	IC50	487	nM	CHEMBL5705821
6.30	IC50	500	nM	CHEMBL5207996
6.24	IC50	580	nM	CHEMBL4848326
6.23	IC50	591	nM	CHEMBL5950869
6.20	IC50	630	nM	CHEMBL5173905
6.16	IC50	700	nM	CHEMBL5185893
6.14	IC50	720	nM	CHEMBL5179846
6.14	IC50	717	nM	CHEMBL4075449
6.09	IC50	820	nM	CHEMBL5174742
6.09	IC50	820	nM	CHEMBL5186989
5.96	IC50	1100	nM	CHEMBL5185951
5.90	IC50	1260	nM	CHEMBL4848130
5.87	IC50	1360	nM	CHEMBL4863906
5.77	IC50	1700	nM	CHEMBL5186228
5.76	IC50	1750	nM	CHEMBL5829674
5.60	IC50	2520	nM	CHEMBL4861259
5.16	IC50	6870	nM	CHEMBL4869542
5.14	IC50	7310	nM	CHEMBL5798659
5.09	IC50	8210	nM	CHEMBL5950918

PubChem BioAssay actives

24 with measured affinity, of 107 total; 24 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
(4S,6Z,9S,10S,12E)-9,10,18-trihydroxy-16-methoxy-4-methyl-3-oxabicyclo[12.4.0]octadeca-1(14),6,12,15,17-pentaene-2,8-dione	1772487: Inhibition of Tak1/Tab1 (unknown origin) assessed as inhibition of Tak1 kinase activity preincubated for 30 mins followed by addition of MBP protein and ATP and measured after 2 hrs by ADP-Glo kinase assay	ic50	0.0090	uM
19-methyl-3-(2-methylpropyl)-7-(pyrimidin-2-ylamino)-3,13,19,20-tetrazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4(9),5,7,11(15),17,20-octaen-14-one	653727: Inhibition of human TAK1 using ATP as substrate	ic50	0.0140	uM
(2R,4R,6S,7S,9Z,12S)-6,7,16-trihydroxy-18-methoxy-12-methyl-3,13-dioxatricyclo[13.4.0.02,4]nonadeca-1(15),9,16,18-tetraene-8,14-dione	1870096: Inhibition of recombinant human N-terminal GST-tagged TAK1 (1 to 303 residues)/TAB1 (437 to end residues) expressed in baculovirus infected Sf9 insect cells using myelin basic protein as substrate preincubated for 10 mins followed by ATP addition and measured after 45 mins by kinase-glo luminescence assay	ic50	0.0300	uM
3-[2-(4-amino-1-ethylpyrazolo[3,4-d]pyrimidin-3-yl)ethynyl]-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide	1206232: Inhibition of human TAK1	ic50	0.0610	uM
methyl N-[4-[6-[(2S)-2-amino-2,4-dimethylpentoxy]-5-chloro-3-pyridinyl]-2-pyridinyl]carbamate	1904690: Inhibition of TAK (unknown origin)	ic50	0.1200	uM
1-[3-tert-butyl-1-(4-chlorophenyl)pyrazol-5-yl]-3-[4-[(6,6-dimethyl-7-oxo-8H-pyrimido[5,4-b][1,4]oxazin-4-yl)amino]-3-methylphenyl]urea	1822460: Inhibition of human TAK1 in presence of ATP by radiometric assay	ic50	0.1260	uM
methyl N-[4-[6-[(2S)-2-amino-2,4-dimethylpentoxy]-5-methyl-3-pyridinyl]-2-pyridinyl]carbamate	1904687: Inhibition of TAK/TAB (unknown origin)	ic50	0.1800	uM
methyl N-[4-[6-[(2S)-2-amino-2,4-dimethylpentoxy]-5-cyano-3-pyridinyl]-2-pyridinyl]carbamate	1904690: Inhibition of TAK (unknown origin)	ic50	0.2600	uM
(Z)-4-[[(2R,4R,6S,7S,9Z,12S)-7,16-dihydroxy-18-methoxy-12-methyl-8,14-dioxo-3,13-dioxatricyclo[13.4.0.02,4]nonadeca-1(15),9,16,18-tetraen-6-yl]oxy]-4-oxobut-2-enoic acid	1870096: Inhibition of recombinant human N-terminal GST-tagged TAK1 (1 to 303 residues)/TAB1 (437 to end residues) expressed in baculovirus infected Sf9 insect cells using myelin basic protein as substrate preincubated for 10 mins followed by ATP addition and measured after 45 mins by kinase-glo luminescence assay	ic50	0.3800	uM
[(2R,4R,6S,7S,9Z,12S)-7,16-dihydroxy-18-methoxy-12-methyl-8,14-dioxo-3,13-dioxatricyclo[13.4.0.02,4]nonadeca-1(15),9,16,18-tetraen-6-yl] acetate	1870096: Inhibition of recombinant human N-terminal GST-tagged TAK1 (1 to 303 residues)/TAB1 (437 to end residues) expressed in baculovirus infected Sf9 insect cells using myelin basic protein as substrate preincubated for 10 mins followed by ATP addition and measured after 45 mins by kinase-glo luminescence assay	ic50	0.4300	uM
[(2R,4R,6S,7S,9Z,12S)-6,16-dihydroxy-18-methoxy-12-methyl-8,14-dioxo-3,13-dioxatricyclo[13.4.0.02,4]nonadeca-1(15),9,16,18-tetraen-7-yl] acetate	1870096: Inhibition of recombinant human N-terminal GST-tagged TAK1 (1 to 303 residues)/TAB1 (437 to end residues) expressed in baculovirus infected Sf9 insect cells using myelin basic protein as substrate preincubated for 10 mins followed by ATP addition and measured after 45 mins by kinase-glo luminescence assay	ic50	0.4500	uM
[(2R,4R,6S,7S,9Z,12S)-7,16-dihydroxy-18-methoxy-12-methyl-8,14-dioxo-3,13-dioxatricyclo[13.4.0.02,4]nonadeca-1(15),9,16,18-tetraen-6-yl] ethyl carbonate	1870096: Inhibition of recombinant human N-terminal GST-tagged TAK1 (1 to 303 residues)/TAB1 (437 to end residues) expressed in baculovirus infected Sf9 insect cells using myelin basic protein as substrate preincubated for 10 mins followed by ATP addition and measured after 45 mins by kinase-glo luminescence assay	ic50	0.5000	uM
N-methyl-4-[4-[(4-piperidin-1-ylpyrimidin-2-yl)amino]phenoxy]pyridine-2-carboxamide	1772487: Inhibition of Tak1/Tab1 (unknown origin) assessed as inhibition of Tak1 kinase activity preincubated for 30 mins followed by addition of MBP protein and ATP and measured after 2 hrs by ADP-Glo kinase assay	ic50	0.5800	uM
[(2R,4R,6S,7S,9Z,12S)-7,16-dihydroxy-18-methoxy-12-methyl-8,14-dioxo-3,13-dioxatricyclo[13.4.0.02,4]nonadeca-1(15),9,16,18-tetraen-6-yl] methyl carbonate	1870096: Inhibition of recombinant human N-terminal GST-tagged TAK1 (1 to 303 residues)/TAB1 (437 to end residues) expressed in baculovirus infected Sf9 insect cells using myelin basic protein as substrate preincubated for 10 mins followed by ATP addition and measured after 45 mins by kinase-glo luminescence assay	ic50	0.6300	uM
[(2R,4R,6S,7S,9Z,12S)-7,16-dihydroxy-18-methoxy-12-methyl-8,14-dioxo-3,13-dioxatricyclo[13.4.0.02,4]nonadeca-1(15),9,16,18-tetraen-6-yl] prop-2-enyl carbonate	1870096: Inhibition of recombinant human N-terminal GST-tagged TAK1 (1 to 303 residues)/TAB1 (437 to end residues) expressed in baculovirus infected Sf9 insect cells using myelin basic protein as substrate preincubated for 10 mins followed by ATP addition and measured after 45 mins by kinase-glo luminescence assay	ic50	0.7000	uM
4-[[(2R,4R,6S,7S,9Z,12S)-7,16-dihydroxy-18-methoxy-12-methyl-8,14-dioxo-3,13-dioxatricyclo[13.4.0.02,4]nonadeca-1(15),9,16,18-tetraen-6-yl]oxy]-4-oxobutanoic acid	1870096: Inhibition of recombinant human N-terminal GST-tagged TAK1 (1 to 303 residues)/TAB1 (437 to end residues) expressed in baculovirus infected Sf9 insect cells using myelin basic protein as substrate preincubated for 10 mins followed by ATP addition and measured after 45 mins by kinase-glo luminescence assay	ic50	0.7200	uM
[(2R,4R,6S,7S,9Z,12S)-6,16-dihydroxy-18-methoxy-12-methyl-8,14-dioxo-3,13-dioxatricyclo[13.4.0.02,4]nonadeca-1(15),9,16,18-tetraen-7-yl] methyl carbonate	1870096: Inhibition of recombinant human N-terminal GST-tagged TAK1 (1 to 303 residues)/TAB1 (437 to end residues) expressed in baculovirus infected Sf9 insect cells using myelin basic protein as substrate preincubated for 10 mins followed by ATP addition and measured after 45 mins by kinase-glo luminescence assay	ic50	0.8200	uM
[(2R,4R,6S,7S,9Z,12S)-6,16-dihydroxy-18-methoxy-12-methyl-8,14-dioxo-3,13-dioxatricyclo[13.4.0.02,4]nonadeca-1(15),9,16,18-tetraen-7-yl] prop-2-enyl carbonate	1870096: Inhibition of recombinant human N-terminal GST-tagged TAK1 (1 to 303 residues)/TAB1 (437 to end residues) expressed in baculovirus infected Sf9 insect cells using myelin basic protein as substrate preincubated for 10 mins followed by ATP addition and measured after 45 mins by kinase-glo luminescence assay	ic50	0.8200	uM
(Z)-4-[[(2R,4R,6S,7S,9Z,12S)-7-[(Z)-3-carboxyprop-2-enoyl]oxy-16-hydroxy-18-methoxy-12-methyl-8,14-dioxo-3,13-dioxatricyclo[13.4.0.02,4]nonadeca-1(15),9,16,18-tetraen-6-yl]oxy]-4-oxobut-2-enoic acid	1870096: Inhibition of recombinant human N-terminal GST-tagged TAK1 (1 to 303 residues)/TAB1 (437 to end residues) expressed in baculovirus infected Sf9 insect cells using myelin basic protein as substrate preincubated for 10 mins followed by ATP addition and measured after 45 mins by kinase-glo luminescence assay	ic50	1.1000	uM
4-[4-[[4-(3,4-dihydro-1H-isoquinolin-2-yl)pyrimidin-2-yl]amino]phenoxy]-N-methylpyridine-2-carboxamide	1772487: Inhibition of Tak1/Tab1 (unknown origin) assessed as inhibition of Tak1 kinase activity preincubated for 30 mins followed by addition of MBP protein and ATP and measured after 2 hrs by ADP-Glo kinase assay	ic50	1.2600	uM
N-methyl-4-[4-[(4-pyrrolidin-1-ylpyrimidin-2-yl)amino]phenoxy]pyridine-2-carboxamide	1772487: Inhibition of Tak1/Tab1 (unknown origin) assessed as inhibition of Tak1 kinase activity preincubated for 30 mins followed by addition of MBP protein and ATP and measured after 2 hrs by ADP-Glo kinase assay	ic50	1.3600	uM
[(2R,4R,6S,7S,9Z,12S)-6,16-dihydroxy-18-methoxy-12-methyl-8,14-dioxo-3,13-dioxatricyclo[13.4.0.02,4]nonadeca-1(15),9,16,18-tetraen-7-yl] ethyl carbonate	1870096: Inhibition of recombinant human N-terminal GST-tagged TAK1 (1 to 303 residues)/TAB1 (437 to end residues) expressed in baculovirus infected Sf9 insect cells using myelin basic protein as substrate preincubated for 10 mins followed by ATP addition and measured after 45 mins by kinase-glo luminescence assay	ic50	1.7000	uM
4-piperidin-1-yl-N-(4-thieno[2,3-d]pyrimidin-4-yloxyphenyl)pyrimidin-2-amine	1772487: Inhibition of Tak1/Tab1 (unknown origin) assessed as inhibition of Tak1 kinase activity preincubated for 30 mins followed by addition of MBP protein and ATP and measured after 2 hrs by ADP-Glo kinase assay	ic50	2.5200	uM
4-(3,4-dihydro-1H-isoquinolin-2-yl)-N-(4-thieno[2,3-d]pyrimidin-4-yloxyphenyl)pyrimidin-2-amine	1772487: Inhibition of Tak1/Tab1 (unknown origin) assessed as inhibition of Tak1 kinase activity preincubated for 30 mins followed by addition of MBP protein and ATP and measured after 2 hrs by ADP-Glo kinase assay	ic50	6.8700	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases expression, affects expression, decreases methylation, affects cotreatment	5
methylmercuric chloride	increases expression	2
trichostatin A	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
coumarin	increases phosphorylation	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
PCI 5002	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Caffeine	affects phosphorylation	1
Dexamethasone	increases expression	1
Diazinon	increases methylation	1
Hydralazine	affects cotreatment, increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Quercetin	increases phosphorylation	1

ChEMBL screening assays

59 unique, capped per target: 58 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2352148	Binding	Inhibition of TAK1-TAB1 (unknown origin) using [gamma-33P]ATP assessed as residual activity at 3 uM	Discovery and characterization of novel allosteric FAK inhibitors. — Eur J Med Chem
CHEMBL4811105	ADMET	Inhibition of human TAK1 at 1 uM measured after 30 mins by [gamma-33P]-ATP assay	Preparation, biological & cheminformatics-based assessment of N2,N4-diphenylpyrimidine-2,4-diamine as potential Kinase-targeted antimalarials. — Bioorg Med Chem

Cellosaurus cell lines

5 cell lines: 3 embryonic stem cell, 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A4U5	SEES3-1V human NR2C2, clone1	Embryonic stem cell	Male
CVCL_A4U6	SEES3-1V human NR2C2, clone2	Embryonic stem cell	Male
CVCL_A4U7	SEES3-1V human NR2C2, clone3	Embryonic stem cell	Male
CVCL_B3CQ	Abcam HEK293T NR2C2 KO	Transformed cell line	Female
CVCL_GZ91	K562 eGFP-NR2C2	Cancer cell line	Female

Clinical trials (associated diseases)

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