NR2F2

Summary

NR2F2 (nuclear receptor subfamily 2 group F member 2, HGNC:7976) is a protein-coding gene on chromosome 15q26.2, encoding COUP transcription factor 2 (P24468). Ligand-activated transcription factor.

This gene encodes a member of the steroid thyroid hormone superfamily of nuclear receptors. The encoded protein is a ligand inducible transcription factor that is involved in the regulation of many different genes. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 7026 — RefSeq curated summary.

At a glance

• Gene–disease (curated): NR2F2 related multiple congenital anomalies/dysmorphic syndrome (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 27
• Clinical variants (ClinVar): 179 total — 20 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 14
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• Transcription factor: yes — 94 downstream targets (CollecTRI)
• MANE Select transcript: NM_021005

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7976
Approved symbol	NR2F2
Name	nuclear receptor subfamily 2 group F member 2
Location	15q26.2
Locus type	gene with protein product
Status	Approved
Aliases	COUP-TFII, COUPTFB, SVP40, NF-E3, COUPTF2
Ensembl gene	ENSG00000185551
Ensembl biotype	protein_coding
OMIM	107773
Entrez	7026

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000394166, ENST00000394171, ENST00000421109, ENST00000453270, ENST00000559679, ENST00000961130

RefSeq mRNA: 4 — MANE Select: NM_021005 NM_001145155, NM_001145156, NM_001145157, NM_021005

CCDS: CCDS10375, CCDS45358, CCDS45359

Canonical transcript exons

ENST00000394166 — 3 exons

Exon	Start	End
ENSE00001517664	96330700	96332547
ENSE00003694164	96334076	96334603
ENSE00003843117	96337348	96340258

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 125.3876 / max 1659.7528, expressed in 1521 samples.

FANTOM5 promoters (33 alternative TSS)

Promoter ID	TPM avg	Samples expressed
148720	43.6294	1476
148722	19.4611	1412
148721	18.5549	1329
148719	9.8896	1459
148729	3.3352	1061
148730	3.1679	1055
148726	2.9803	925
148724	2.6397	898
148713	2.4077	803
148735	1.8586	782

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
urethra	UBERON:0000057	99.57	gold quality
cardia of stomach	UBERON:0001162	99.49	gold quality
dorsal root ganglion	UBERON:0000044	99.44	gold quality
renal medulla	UBERON:0000362	99.38	gold quality
trigeminal ganglion	UBERON:0001675	99.35	gold quality
right ovary	UBERON:0002118	99.11	gold quality
stromal cell of endometrium	CL:0002255	99.06	gold quality
decidua	UBERON:0002450	99.06	gold quality
seminal vesicle	UBERON:0000998	99.04	gold quality
left ovary	UBERON:0002119	99.02	gold quality
saphenous vein	UBERON:0007318	99.02	gold quality
endometrium	UBERON:0001295	98.95	gold quality
penis	UBERON:0000989	98.87	gold quality
ovary	UBERON:0000992	98.86	gold quality
pericardium	UBERON:0002407	98.84	gold quality
cauda epididymis	UBERON:0004360	98.77	gold quality
endometrium epithelium	UBERON:0004811	98.65	gold quality
blood vessel layer	UBERON:0004797	98.61	gold quality
pylorus	UBERON:0001166	98.57	gold quality
synovial joint	UBERON:0002217	98.50	gold quality
endocervix	UBERON:0000458	98.47	gold quality
right coronary artery	UBERON:0001625	98.46	gold quality
tibial nerve	UBERON:0001323	98.44	gold quality
germinal epithelium of ovary	UBERON:0001304	98.42	gold quality
body of uterus	UBERON:0009853	98.33	gold quality
myometrium	UBERON:0001296	98.27	gold quality
choroid plexus epithelium	UBERON:0003911	98.27	gold quality
superficial temporal artery	UBERON:0001614	98.23	gold quality
vena cava	UBERON:0004087	98.23	gold quality
tendon of biceps brachii	UBERON:0008188	98.23	gold quality

Single-cell (SCXA)

Detected in 25 experiment(s), a significant marker in 22.

Experiment	Marker?	Max mean expression
E-HCAD-36	yes	1019.65
E-MTAB-8894	yes	934.69
E-MTAB-10662	yes	630.06
E-HCAD-10	yes	595.65
E-HCAD-5	yes	590.30
E-ANND-5	yes	464.34
E-MTAB-3929	yes	388.87
E-GEOD-134144	yes	43.82
E-MTAB-8142	yes	43.75
E-MTAB-6701	yes	40.81
E-GEOD-135922	yes	35.31
E-HCAD-11	yes	22.78
E-MTAB-8410	yes	21.89
E-HCAD-1	yes	18.36
E-HCAD-9	yes	17.53

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

94 targets.

Target	Regulation
ACADM
ACTA1	Unknown
ADAM2
ALDH2
ANGPT1	Unknown
APOA1	Repression
APOA2	Repression
APOB	Unknown
APOC2	Unknown
APOC3	Unknown
BGLAP	Unknown
BMP2
CCND1	Unknown
CCNE1	Repression
CD44
CDK2
CDKN1A	Unknown
CETP	Unknown
CTNNB1	Activation
CYP19A1
CYP3A4
CYP7A1	Activation
DR1
E2F1	Unknown
EFNB2
EPO
ESR1
EYA1
F9	Unknown
FGFR3

JASPAR motifs

Motif	Name	Family
MA1111.1	NR2F2	RXR-related receptors (NR2)
MA1111.2	NR2F2	RXR-related receptors (NR2)

JASPAR matrix evidence (PMIDs): PMID:1324415

Upstream regulators (CollecTRI, top): ETS1, ETS2, FOXC1, FOXO1, GATA4, HNF4A, NCOR2, NR2F2, NR3C1, NR5A1, RARA, RUNX2, TCF3, TFAP2A, USF2, VEGFA

miRNA regulators (miRDB)

193 targeting NR2F2, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-150-5P	99.99	66.69	1976
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-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-495-3P	99.96	72.81	4197

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• COUP-TFII represses the alpha-subunit of mitochondrial F1F0 ATP synthase (ATPA) complex and inhibits the USF2-dependent transactivation of the ATPA promoter through competition for an overlapping bindng site in the ATPA cis-acting regulatory element 1. (PMID:12614160)
• DAX-1 and COUP-TFII may play a role in the modulation of Ad4BP/SF-1-dependent transcription of steroidogenic enzymes in different cell types and follicular stages in normal cycling human ovaries. (PMID:12843196)
• GR stimulates COUP-TFII-induced transactivation by attracting cofactors via its activation function-1, while COUP-TFII represses the GR-governed transcriptional activity by tethering corepressors … (PMID:15265774)
• the DR motif site of the renin gene functions as a negative regulatory element involved in a twofold repression of transcription; nucleic receptors bind the site and are important in renin gene expression; one of the binding proteins may be COUP-TFII. (PMID:17455195)
• Regulation of vascular endothelial growth factor D by hepatocyte nuclear factor-4 alpha and chicken ovalbumin upstream promoter transcription factors 1 and 2. (PMID:18199540)
• COUP-TFII antagonizes the repression of the PED/PEA-15 gene by HNF-4alpha. (PMID:18765665)
• Data demonstrate that COUP-TFII is a ligand-regulated nuclear receptor, in which ligands activate the receptor by releasing it from the autorepressed conformation. (PMID:18798693)
• venous endothelial cell fate regulator COUP-TFII is expressed in lymphatic cells throughout development and physically interacts with Prox1 to form a stable complex in various cell types (PMID:18815287)
• COUP-TFII may represent a biomarker for good prognosis in colorectal cancer. (PMID:19082449)
• COUP-TFII was investigated as a possible regulator of lymphangiogenesis via vascular endothelial growth factor-C expression. (PMID:19154418)
• The present study shows that COUP-TFII plays important roles in the regulation of the function of Prox1. (PMID:19210544)
• Novel and distinct cell-intrinsic mechanisms mediated by COUP-TF genes to direct the specification and differentiation of progenitor cells; COUP-TFs are crucial for dorsalization of the eye. (PMID:20147377)
• Results strongly suggest that NR2F2 is involved in villous CTB cell differentiation and that NR2F2 acts, at least in part, by directly activating TFAP2A gene expression and by potentiating the transactivation of TFAP2A by RARA and RXRA. (PMID:20195529)
• Data suggest a novel model that the endothelial cell fate regulators, Notch, COUP-TFII, and Prox1, are under an exquisite feedback control mechanism and dynamically regulate each other in LECs. (PMID:20351309)
• role for the TGFbeta pathway and COUP-TFII in mediating the endothelial transdifferentiating properties of retinoic acid (PMID:20386594)
• NR2F2 plays a crucial role in the activation of neural genes during early differentiation in humans. (PMID:21151097)
• In summary, COUP-TFII is expressed in the human fetal forebrain in GABAergic cells, according to its possible role in migration of cortical interneurons. (PMID:22178710)
• COUP-TFII negatively regulates osteoblast differentiation via interaction with Runx2, and during the differentiation state, BMP2-induced Runx2 represses COUP-TFII expression and promotes osteoblast differentiation. (PMID:22493443)
• The C-allele at rs3743462 was associated with increased NR2F2 binding and decreased NR2F2 gene expression. (PMID:22606236)
• nucleolin plays a coregulatory role in transcriptional regulation of the tumor suppressor RARB2 by COUP-TFII (PMID:22693611)
• COUP-TFII regulates vein identity by suppressing the Notch signal pathway. (PMID:22734039)
• MiR-302 inhibits NR2F2 and promotes pluripotency through indirect positive regulation of OCT4. (PMID:23136034)
• findings reveal that the destruction of the TGF-beta-dependent barrier by COUP-TFII is crucial for the progression of PTEN-mutant prostate cancer into a life-threatening disease (PMID:23201680)
• COUP-TFII orchestrates venous and lymphatic endothelial identity by homo- or hetero-dimerisation with PROX1 (PMID:23345397)
• COUP-TFII-V2 negatively regulates the function of COUP-TFII by inhibiting its binding to DNA, decreasing Cyp7a1 expression. (PMID:23458092)
• Data suggest that NR2F2 is expressed in stromal cells of healthy ovary with little/no expression in epithelial cells; this pattern is markedly disrupted in ovarian cancers with decreased NR2F2 in stroma and ectopic NR2F2 expression in epithelium. (PMID:23690307)
• Data suggest that NR2F2 and CTNNB1 (catenin beta-1) are aberrantly expressed in uterine fibroid tissue compared with matched myometrium, with strong blood vessel-specific localization. (PMID:23704310)
• Hey2 and COUP-TFII have an important role in arteriovenous differentiation of human endothelial cells. (PMID:23744056)
• COUP-TFII and related NRs such as the COUPTFs and PNR can selectively associate with the developmental corepressor BCL11A via a conserved motif F/YSXXLXXL/Y within the RID1 and RID2 domains. The interaction with BCL11A facilitates COUP-TFII-mediated repression of the RARb2 gene. (PMID:23975195)
• Interaction of NSD1 with the NR2E/F subfamily including COUP-TFI, COUP-TFII, EAR2 and TLX requires a F/YSXXLXXL/Y motif. NSD1 interaction with liganded NRs is mediated by an overlapping LXXLL motif. (PMID:23975195)
• Using several human red opsin enhancer/promoter-luciferase reporter constructs, the study found that COUPTFII suppressed intron 3-4 region-dependent luciferase activities. (PMID:24058409)
• In vitro silencing of COUP-TFII reduces the cell growth. (PMID:24122412)
• These data indicate a novel role for COUP-TFII in suppression of NFkappaB activity. (PMID:24141032)
• COUP-TFII plays a role in controlling the expression of inflammatory cytokines. (PMID:24176914)
• showed that all six coding sequence variants observed in individuals significantly alter the activity of NR2F2 on target promoters (PMID:24702954)
• Overexpression of COUP-TFII was required for cancer cells to metastasise in vivo. (PMID:25032732)
• TGF-beta inhibited the expression of NR2F2. (PMID:25129343)
• These data demonstrate that Nr2f2 is a direct target of POU4F3 in vitro and that this regulatory relationship may be relevant to hair cell development and survival. (PMID:25372459)
• COUP-TFII (NR2F2) induces down-regulation of cadherin-6 and up-regulation of cadherin-11 in cultured cell lines.high expression of COUP-TFII in some gastric and oesophageal adenocarcinomas, correlated with abnormal cadherin-11 expression. (PMID:25687954)
• Positive COUP-TF II expression levels has significant value in determining CRC stage and metastasis and cooperates with negative Smad4 expression contributing to assess prognosis in patients with colorectal cancer. (PMID:26261604)

Cross-species orthologs

30 orthologs

Organism	Symbol	Gene ID
danio_rerio	nr2f2	ENSDARG00000040926
mus_musculus	Nr2f2	ENSMUSG00000030551
rattus_norvegicus	Nr2f2	ENSRNOG00000010308
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), NR2C2 (ENSG00000177463), RXRA (ENSG00000186350), RXRB (ENSG00000204231), NR2E3 (ENSG00000278570)

Protein

Protein identifiers

COUP transcription factor 2 — P24468 (reviewed: P24468)

Alternative names: Apolipoprotein A-I regulatory protein 1, COUP transcription factor II, Nuclear receptor subfamily 2 group F member 2

All UniProt accessions (3): P24468, F1D8R0, H3BTC2

UniProt curated annotations — full annotation on UniProt →

Function. Ligand-activated transcription factor. Activated by high concentrations of 9-cis-retinoic acid and all-trans-retinoic acid, but not by dexamethasone, cortisol or progesterone (in vitro). Regulation of the apolipoprotein A-I gene transcription. Binds to DNA site A. May be required to establish ovary identity during early gonad development.

Subunit / interactions. Interacts with SQSTM1. Binds DNA as a dimer; homodimer or heterodimer with NR2F6. Interacts with NCOA1, NCOA2, NCOA3 and PPARGC1A. Interacts with ZFPM2.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous. Expressed in the stromal cells of developing fetal ovaries.

Disease relevance. Congenital heart defects, multiple types, 4 (CHTD4) [MIM:615779] A disorder characterized by congenital developmental abnormalities involving structures of the heart. Common defects include transposition of the great arteries, aortic stenosis, atrial septal defect, ventricular septal defect, pulmonic stenosis, and patent ductus arteriosus. Some patients also have cardiac arrhythmias, which may be due to the anatomic defect itself or to surgical interventions. The disease is caused by variants affecting the gene represented in this entry. 46,XX sex reversal 5 (SRXX5) [MIM:618901] A condition in which male gonads develop in a genetic female (female to male sex reversal). Additional features in SRXX5 patients are congenital heart disease, congenital diaphragmatic hernia, and blepharophimosis-ptosis-epicanthus inversus syndrome. SRXX5 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P24468-1	1	yes
P24468-2	2
P24468-3	3

RefSeq proteins (4): NP_001138627, NP_001138628, NP_001138629, NP_066285* (*=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
IPR050274	Nuclear_hormone_rcpt_NR2	Family

Pfam: PF00104, PF00105

UniProt features (42 total): helix 13, mutagenesis site 8, sequence variant 6, compositionally biased region 3, region of interest 3, splice variant 2, zinc finger region 2, chain 1, domain 1, modified residue 1, DNA-binding region 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3CJW	X-RAY DIFFRACTION	1.48

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P24468-F1	77.94	0.53

Functional residue map

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

Post-translational modifications (1): 51

Mutagenesis-validated functional residues (8):

Position	Phenotype
228	reduces transcription activation by 40%; when associated with r-398.
249	reduces transcription activation by 50%; when associated with a-250.
250	reduces transcription activation by 50%; when associated with a-249.
250	reduces transcription activation by 50%.
253–254	reduces transcription activation by 50%.
269–270	reduces transcription activation by 50%.
364–365	reduces transcription activation by 80%.
398	reduces transcription activation by 40%; when associated with e-228.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-9940951	Interaction of NuRD complexes with transcription factors

MSigDB gene sets: 487 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, CREL_01, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, WANG_CLIM2_TARGETS_UP, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, WWTAAGGC_UNKNOWN, GOBP_REGULATION_OF_BLOOD_PRESSURE, TGCGCANK_UNKNOWN, PID_TELOMERASE_PATHWAY

GO Biological Process (28): negative regulation of transcription by RNA polymerase II (GO:0000122), maternal placenta development (GO:0001893), negative regulation of endothelial cell proliferation (GO:0001937), positive regulation of systemic arterial blood pressure (GO:0003084), regulation of transcription by RNA polymerase II (GO:0006357), nervous system development (GO:0007399), skeletal muscle tissue development (GO:0007519), female gonad development (GO:0008585), fertilization (GO:0009566), anterior/posterior pattern specification (GO:0009952), radial pattern formation (GO:0009956), negative regulation of endothelial cell migration (GO:0010596), cell differentiation (GO:0030154), forebrain development (GO:0030900), response to estradiol (GO:0032355), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), blood vessel morphogenesis (GO:0048514), placenta blood vessel development (GO:0060674), trophoblast giant cell differentiation (GO:0060707), lymphatic endothelial cell fate commitment (GO:0060838), negative regulation of vascular endothelial growth factor signaling pathway (GO:1900747), interneuron migration (GO:1904936), in utero embryonic development (GO:0001701), neuron migration (GO:0001764), lymph vessel development (GO:0001945), regulation of DNA-templated transcription (GO:0006355), intracellular receptor signaling pathway (GO:0030522)

GO Molecular Function (11): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), retinoic acid binding (GO:0001972), DNA-binding transcription factor activity (GO:0003700), nuclear receptor activity (GO:0004879), zinc ion binding (GO:0008270), protein homodimerization activity (GO:0042803), sequence-specific DNA binding (GO:0043565), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Adipogenesis	1
NuRD complex assembly	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
regulation of transcription by RNA polymerase II	2
placenta development	2
anatomical structure development	2
regionalization	2
blood vessel development	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
developmental process involved in reproduction	1
maternal process involved in female pregnancy	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
negative regulation of epithelial cell proliferation	1
regulation of systemic arterial blood pressure	1
positive regulation of blood pressure	1
system development	1
striated muscle tissue development	1
skeletal muscle organ development	1
gonad development	1
development of primary female sexual characteristics	1
sexual reproduction	1
reproductive process	1
regulation of endothelial cell migration	1
negative regulation of cell migration	1
endothelial cell migration	1
cellular developmental process	1
brain development	1
response to lipid	1
response to oxygen-containing compound	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
tube morphogenesis	1
cell differentiation involved in embryonic placenta development	1
cis-regulatory region sequence-specific DNA binding	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription repressor activity	1

Protein interactions and networks

STRING

2358 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NR2F2	BCL11A	Q9H165	902
NR2F2	BCL11B	Q9C0K0	897
NR2F2	RERE	Q9P2R6	881
NR2F2	EP300	Q09472	840
NR2F2	SOX18	P35713	789
NR2F2	ZFPM2	Q8WW38	787
NR2F2	NCOR1	O75376	766
NR2F2	MEF2C	Q06413	759
NR2F2	PROX1	Q92786	737
NR2F2	DLL4	Q9NR61	694
NR2F2	HNF1B	P35680	656
NR2F2	NCOR2	Q9Y618	649
NR2F2	RARS1	P54136	648
NR2F2	SMAD4	Q13485	631
NR2F2	EFNB2	P52799	626

IntAct

183 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
MPPED1	TXNDC9	psi-mi:“MI:0914”(association)	0.640
SCN2B	EXOC5	psi-mi:“MI:0914”(association)	0.640
NR2F2	NR2F6	psi-mi:“MI:0915”(physical association)	0.620
NR2F2	SMAD4	psi-mi:“MI:0915”(physical association)	0.590
SMAD4	NR2F2	psi-mi:“MI:0915”(physical association)	0.590
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC2A12	METTL15	psi-mi:“MI:0914”(association)	0.530
NR2F2	GC	psi-mi:“MI:0914”(association)	0.530
HYCC1	GC	psi-mi:“MI:0914”(association)	0.530
SPPL2B	UQCRQ	psi-mi:“MI:0914”(association)	0.530
NT5E	SCAMP1	psi-mi:“MI:0914”(association)	0.530
SLC39A9	B4GALT5	psi-mi:“MI:0914”(association)	0.530
SALL2	GFPT2	psi-mi:“MI:0914”(association)	0.530
WNT16	WNT11	psi-mi:“MI:0914”(association)	0.530
TOR1AIP2	TMEM223	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
CD79A	METTL15	psi-mi:“MI:0914”(association)	0.530
VASN	AP3B1	psi-mi:“MI:0914”(association)	0.530
EPHA1	EXOC5	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530

BioGRID (200): NR2F2 (Affinity Capture-MS), NR2F2 (Affinity Capture-MS), NR2F2 (Affinity Capture-MS), NR2F2 (Affinity Capture-MS), NR2F2 (Affinity Capture-MS), NR2F2 (Affinity Capture-MS), NR2F2 (Affinity Capture-MS), NR2F2 (Affinity Capture-MS), NR2F2 (Affinity Capture-MS), NR2F2 (Affinity Capture-MS), NR2F2 (Affinity Capture-MS), NR2F2 (Affinity Capture-MS), NR2F2 (Affinity Capture-MS), RPGR (Affinity Capture-MS), AKT1 (Affinity Capture-MS)

ESM2 similar proteins: A2T929, F1QLY4, O00482, O09018, O42101, O95718, P11475, P19793, P22449, P24468, P28700, P28701, P28705, P31396, P41235, P43135, P48443, P49698, P49700, P49743, P51128, P51129, P54779, P62508, P62509, P62510, P79926, Q05343, Q06725, Q06726, Q0GFF6, Q0VC20, Q14541, Q5BJR8, Q5I7G2, Q5RAM2, Q5REL6, Q60632, Q61539, Q6DHP9

Diamond homologs: A0JNE3, A0P8Z4, A2T928, A4IIG7, F1QJF4, F1QLY4, O01639, O09018, O18924, O18971, O35507, O62807, O77245, O88275, P10276, P10589, P10826, P11416, P13055, P13056, P13631, P16375, P16376, P17671, P18514, P18515, P18516, P18911, P22448, P22605, P24468, P28699, P31396, P33244, P35398, P37231, P37233, P37238, P41828, P41829

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
NR2F2	“up-regulates quantity by expression”	NR3C1	“transcriptional regulation”
NR3C1	“up-regulates quantity by expression”	NR2F2	“transcriptional regulation”
NR2F2	down-regulates	MYOD1	binding
NR2F2	up-regulates	NR2F1	binding
NR2F2	up-regulates	RXRA	binding
RXRB	up-regulates	NR2F2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 187 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.

GO biological processes:

GO term	Partners	Fold	FDR
humoral immune response	7	11.6×	1e-03
chemokine-mediated signaling pathway	6	11.4×	4e-03
cell chemotaxis	7	7.6×	7e-03
adaptive immune response	12	6.0×	6e-04
immune response	20	5.5×	9e-07
inflammatory response	16	3.5×	4e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	14
Uncertain significance	78
Likely benign	47
Benign	11

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
128233	NM_021005.4(NR2F2):c.614A>T (p.Asn205Ile)	Pathogenic
128235	NM_021005.4(NR2F2):c.970+1G>A	Pathogenic
1452069	NM_021005.4(NR2F2):c.604C>T (p.Gln202Ter)	Pathogenic
1710861	NM_021005.4(NR2F2):c.442+1G>T	Pathogenic
2276040	NM_021005.4(NR2F2):c.775C>T (p.Gln259Ter)	Pathogenic
280543	NM_021005.4(NR2F2):c.856dup (p.Val286fs)	Pathogenic
3062062	NM_021005.4(NR2F2):c.576del (p.Thr193fs)	Pathogenic
3376906	NM_021005.4(NR2F2):c.232G>T (p.Glu78Ter)	Pathogenic
3777741	NM_021005.4(NR2F2):c.368T>A (p.Ile123Asn)	Pathogenic
3895676	NM_021005.4(NR2F2):c.896_903del (p.Val299fs)	Pathogenic
3898685	NM_021005.4(NR2F2):c.486dup (p.Gln163fs)	Pathogenic
4085859	NM_021005.4(NR2F2):c.394C>T (p.Gln132Ter)	Pathogenic
446122	NM_021005.4(NR2F2):c.247G>T (p.Gly83Ter)	Pathogenic
4722378	NM_021005.4(NR2F2):c.139_155dup (p.Thr55fs)	Pathogenic
4813242	NM_021005.4(NR2F2):c.971-12A>G	Pathogenic
521133	NM_021005.4(NR2F2):c.1097G>C (p.Arg366Pro)	Pathogenic
521441	NM_021005.4(NR2F2):c.64C>T (p.Gln22Ter)	Pathogenic
817184	NM_021005.4(NR2F2):c.1029_1035del (p.Cys343fs)	Pathogenic
848589	NM_021005.4(NR2F2):c.217C>T (p.Gln73Ter)	Pathogenic
916034	NM_021005.4(NR2F2):c.97_103del (p.Pro33fs)	Pathogenic
1805610	NM_021005.4(NR2F2):c.558dup (p.Arg187fs)	Likely pathogenic
2429770	NM_021005.4(NR2F2):c.1019del (p.Lys340fs)	Likely pathogenic
2443196	NM_021005.4(NR2F2):c.931G>A (p.Glu311Lys)	Likely pathogenic
2570647	NM_021005.4(NR2F2):c.1133_1134dup (p.Glu379Ter)	Likely pathogenic
2570648	NM_021005.4(NR2F2):c.23G>A (p.Trp8Ter)	Likely pathogenic
2683753	NM_021005.4(NR2F2):c.737G>A (p.Arg246His)	Likely pathogenic
3062234	NM_021005.4(NR2F2):c.1164dup (p.Lys389Ter)	Likely pathogenic
3062322	NM_021005.4(NR2F2):c.684del (p.Asn229fs)	Likely pathogenic
3773829	NM_021005.4(NR2F2):c.263G>A (p.Gly88Asp)	Likely pathogenic
3897577	NM_021005.4(NR2F2):c.305T>G (p.Phe102Cys)	Likely pathogenic

SpliceAI

486 predictions. Top by Δscore:

Variant	Effect	Δscore
15:96332544:G:GT	donor_gain	1.0000
15:96332544:G:T	donor_gain	1.0000
15:96334074:A:AG	acceptor_gain	1.0000
15:96334074:AGC:A	acceptor_gain	1.0000
15:96334074:AGCG:A	acceptor_gain	1.0000
15:96334075:G:GC	acceptor_gain	1.0000
15:96334075:GCG:G	acceptor_gain	1.0000
15:96334075:GCGG:G	acceptor_gain	1.0000
15:96334075:GCGGT:G	acceptor_gain	1.0000
15:96334561:GCCGA:G	donor_gain	1.0000
15:96334599:CTCAG:C	donor_loss	1.0000
15:96334601:CAG:C	donor_loss	1.0000
15:96334602:AGGTA:A	donor_loss	1.0000
15:96334603:GG:G	donor_loss	1.0000
15:96334604:GTAG:G	donor_loss	1.0000
15:96334605:T:A	donor_loss	1.0000
15:96332497:GCC:G	donor_gain	0.9900
15:96332501:G:GG	donor_gain	0.9900
15:96332545:A:T	donor_gain	0.9900
15:96334071:CGCA:C	acceptor_loss	0.9900
15:96334073:CAG:C	acceptor_loss	0.9900
15:96334074:A:C	acceptor_loss	0.9900
15:96334075:GC:G	acceptor_gain	0.9900
15:96332529:G:GG	donor_gain	0.9800
15:96332545:AAGG:A	donor_loss	0.9800
15:96332546:AG:A	donor_loss	0.9800
15:96332547:GG:G	donor_loss	0.9800
15:96332548:G:T	donor_loss	0.9800
15:96334071:C:CA	acceptor_gain	0.9800
15:96334604:G:GG	donor_gain	0.9800

AlphaMissense

2720 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:96332340:T:A	C79S	1.000
15:96332340:T:C	C79R	1.000
15:96332341:G:A	C79Y	1.000
15:96332341:G:C	C79S	1.000
15:96332341:G:T	C79F	1.000
15:96332342:C:G	C79W	1.000
15:96332346:G:A	V81M	1.000
15:96332347:T:A	V81E	1.000
15:96332349:T:A	C82S	1.000
15:96332349:T:C	C82R	1.000
15:96332349:T:G	C82G	1.000
15:96332350:G:A	C82Y	1.000
15:96332350:G:C	C82S	1.000
15:96332350:G:T	C82F	1.000
15:96332351:C:G	C82W	1.000
15:96332355:G:C	D84H	1.000
15:96332356:A:C	D84A	1.000
15:96332356:A:G	D84G	1.000
15:96332356:A:T	D84V	1.000
15:96332364:A:C	S87R	1.000
15:96332366:C:A	S87R	1.000
15:96332366:C:G	S87R	1.000
15:96332367:G:A	G88S	1.000
15:96332367:G:C	G88R	1.000
15:96332367:G:T	G88C	1.000
15:96332368:G:A	G88D	1.000
15:96332368:G:T	G88V	1.000
15:96332370:A:G	K89E	1.000
15:96332372:G:C	K89N	1.000
15:96332372:G:T	K89N	1.000

dbSNP variants (sampled 300 via entrez): RS1000005234 (15:96340618 CTCTT>C), RS1000101256 (15:96332126 G>A), RS1000113165 (15:96335083 G>A,T), RS1000396925 (15:96330432 C>G,T), RS1000439790 (15:96340207 G>A), RS1000545452 (15:96336227 A>G), RS1000695447 (15:96331282 G>C), RS1000762660 (15:96325833 G>A), RS1001064404 (15:96328554 T>C), RS1001129116 (15:96331139 G>A), RS1001166348 (15:96340013 A>G), RS1001218439 (15:96339752 G>A), RS1001478307 (15:96339370 T>A,C), RS1001729842 (15:96333049 C>T), RS1001736053 (15:96325108 T>C)

Disease associations

OMIM: gene MIM:107773 | disease phenotypes: MIM:615779, MIM:618901

GenCC curated gene-disease

Disease	Classification	Inheritance
NR2F2 related multiple congenital anomalies/dysmorphic syndrome	Definitive	Autosomal dominant
46,xx sex reversal 5	Definitive	Autosomal dominant
congenital heart defects, multiple types, 4	Strong	Autosomal dominant
syndromic disease	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
NR2F2 related multiple congenital anomalies/dysmorphic syndrome	Definitive	AD

Mondo (6): congenital heart defects, multiple types, 4 (MONDO:0014344), neurodevelopmental disorder (MONDO:0700092), 46 XY differences of sex development (MONDO:0020040), 46,xx sex reversal 5 (MONDO:0030049), NR2F2 related multiple congenital anomalies/dysmorphic syndrome (MONDO:0800458), syndromic disease (MONDO:0002254)

Orphanet (1): 46,XY difference of sex development (Orphanet:98085)

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000062	Ambiguous genitalia
HP:0001629	Ventricular septal defect
HP:0001636	Tetralogy of Fallot
HP:0001650	Aortic valve stenosis
HP:0001680	Coarctation of aorta
HP:0001684	Secundum atrial septal defect
HP:0003577	Congenital onset
HP:0004383	Hypoplastic left ventricle
HP:0006695	Atrioventricular canal defect
HP:0009112	Aplasia of the left hemidiaphragm
HP:0030088	Increased serum testosterone level
HP:0032092	Left ventricular outflow tract obstruction
HP:0100779	Urogenital sinus anomaly

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST001510_1	Response to TNF-alpha inhibitors in rheumatoid arthritis	6.000000e-07
GCST001612_23	Sex hormone-binding globulin levels	8.000000e-12
GCST001612_6	Sex hormone-binding globulin levels	5.000000e-06
GCST001612_7	Sex hormone-binding globulin levels	8.000000e-08
GCST002441_6	Immune response to measles-mumps-rubella vaccine	2.000000e-07
GCST002688_3	Very long-chain saturated fatty acid levels (fatty acid 22:0)	2.000000e-06
GCST002759_20	Motion sickness	1.000000e-10
GCST002763_8	Optic disc area	3.000000e-08
GCST003075_21	Cognitive decline rate in late mild cognitive impairment	4.000000e-06
GCST003075_55	Cognitive decline rate in late mild cognitive impairment	9.000000e-07
GCST003382_1	Cannabis use	2.000000e-06
GCST003992_27	Photic sneeze reflex	4.000000e-73
GCST006992_4	Cerebrospinal fluid p-tau levels in Alzheimer’s disease dementia	1.000000e-07
GCST007324_115	Adventurousness	1.000000e-08
GCST007576_208	Chronotype	8.000000e-09
GCST007576_400	Chronotype	9.000000e-07
GCST008311_1	Lymphangioleiomyomatosis (sporadic)	3.000000e-08
GCST008362_82	Birth weight	2.000000e-16
GCST009391_1526	Metabolite levels	9.000000e-06
GCST009391_1952	Metabolite levels	5.000000e-06
GCST009391_760	Metabolite levels	6.000000e-06
GCST009391_783	Metabolite levels	8.000000e-06
GCST009391_807	Metabolite levels	7.000000e-06
GCST009462_84	Optic disc size	2.000000e-15
GCST010320_138	PR interval	3.000000e-12
GCST010321_48	PR interval	4.000000e-13
GCST90011900_120	Serum alkaline phosphatase levels	3.000000e-09

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0004653	response to TNF antagonist
EFO:0004696	sex hormone-binding globulin measurement
EFO:0004645	response to vaccine
EFO:0006796	very long-chain saturated fatty acid measurement
EFO:0006928	motion sickness
EFO:0007710	cognitive decline measurement
EFO:0007585	Cannabis use
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome
EFO:0004763	p-tau measurement
EFO:0008579	risk-taking behaviour
EFO:0008328	chronotype measurement
EFO:0004344	birth weight
EFO:0010508	malate measurement
EFO:0010423	triacylglycerol 54:5 measurement
EFO:0010391	sphingomyelin 16:0 measurement
EFO:0010394	sphingomyelin 18:1 measurement
EFO:0010396	sphingomyelin 22:1 measurement
EFO:0004462	PR interval
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D058490	Disorder of Sex Development, 46,XY	C12.050.351.875.253.096; C12.200.706.316.096; C12.800.316.096; C16.131.939.316.096; C19.391.119.096
D065886	Neurodevelopmental Disorders	F03.625
D013577	Syndrome	C23.550.288.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1961790 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 54,311 (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
CHEMBL95431	CARBOXYAMIDOTRIAZOLE	3	12,804
CHEMBL123292	CYCLOHEXIMIDE	2	39,732
CHEMBL152649	CHLORMIDAZOLE	2	1,775

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: nhr — 2F. COUP-TF-like receptors

ChEMBL bioactivities

169 potent at pChembl≥5 of 218 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.12	IC50	7.64	nM	CHEMBL1699691
7.65	IC50	22.34	nM	CHEMBL1702665
7.21	IC50	61.93	nM	PYRIDABEN
6.68	IC50	208.5	nM	CHEMBL1567944
6.44	IC50	360	nM	RESACTIN A
6.29	IC50	518.6	nM	CHEMBL1721226
6.25	IC50	568	nM	CHEMBL1423004
6.21	IC50	616.8	nM	CHEMBL1323872
6.20	IC50	628.3	nM	CHEMBL1415184
6.13	IC50	737.1	nM	CHEMBL1523841
6.09	IC50	807.1	nM	CHEMBL1320669
5.99	IC50	1032	nM	CHEMBL1358722
5.95	IC50	1134	nM	CHEMBL1519955
5.90	IC50	1253	nM	CHEMBL1461631
5.88	IC50	1315	nM	CYCLOHEXIMIDE
5.83	IC50	1465	nM	CHEMBL1878609
5.82	IC50	1506	nM	CHEMBL1531328
5.81	IC50	1548	nM	CHEMBL1575502
5.75	IC50	1786	nM	CHEMBL1404493
5.75	IC50	1772	nM	CHEMBL3184181
5.71	IC50	1969	nM	CHEMBL1423660
5.70	IC50	2016	nM	CHEMBL1569724
5.70	IC50	2009	nM	CHEMBL2136916
5.69	IC50	2048	nM	CHEMBL1437030
5.66	IC50	2212	nM	CHEMBL1603001
5.64	IC50	2272	nM	CHEMBL1372292
5.64	IC50	2287	nM	CHEMBL1490503
5.62	IC50	2405	nM	CHEMBL1550278
5.60	IC50	2538	nM	CHEMBL1513705
5.59	IC50	2579	nM	CHEMBL1387401
5.58	IC50	2663	nM	CHEMBL3194760
5.58	IC50	2608	nM	CHEMBL1401965
5.57	IC50	2680	nM	CHEMBL1388241
5.57	IC50	2705	nM	CHEMBL1711360
5.56	IC50	2750	nM	CHEMBL1382917
5.51	IC50	3111	nM	CHEMBL1344838
5.51	IC50	3068	nM	CHEMBL1386344
5.49	IC50	3214	nM	CHEMBL1441604
5.49	IC50	3249	nM	CHEMBL1377607
5.48	IC50	3333	nM	CHEMBL1366727
5.48	IC50	3283	nM	CHEMBL1434450
5.47	IC50	3378	nM	CHEMBL1406208
5.47	IC50	3379	nM	CHEMBL1491621
5.45	IC50	3519	nM	CHEMBL530291
5.44	IC50	3662	nM	CHEMBL1503651
5.42	IC50	3820	nM	CHEMBL1435226
5.41	IC50	3875	nM	CHEMBL1708045
5.38	IC50	4191	nM	CHEMBL1497024
5.38	IC50	4184	nM	CHEMBL3182910
5.38	IC50	4166	nM	CHEMBL1893675

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases methylation	7
Tretinoin	increases expression, decreases expression	6
methylmercuric chloride	decreases expression, increases expression, affects cotreatment	5
trichostatin A	decreases expression, affects expression, affects cotreatment	4
Tobacco Smoke Pollution	decreases expression, increases methylation	4
Benzo(a)pyrene	decreases expression, increases methylation	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
Cyclosporine	decreases expression	3
Aflatoxin B1	decreases expression, decreases methylation, increases methylation	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
bisphenol A	decreases expression, increases expression	2
entinostat	decreases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Acetaminophen	decreases expression	2
Air Pollutants	decreases expression, increases abundance, affects response to substance	2
Cisplatin	affects cotreatment, decreases expression	2
Estradiol	increases expression, decreases expression, decreases reaction	2
Particulate Matter	decreases expression, increases abundance, affects response to substance	2
aristolochic acid I	decreases expression	1
dicrotophos	increases expression	1
ascorbate-2-phosphate	affects binding, affects cotreatment, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
cupric oxide	decreases expression	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	affects cotreatment, increases expression	1
mercuric bromide	affects cotreatment, decreases expression	1
brequinar	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 1 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1961853	Binding	Effect on TFCOUP2(NR2F2) dependent reporter activity in HEK293 cells at 20 uM	Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. — Nature
CHEMBL3214816	Functional	PubChem BioAssay. Luminescence-based cell-based high throughput dose response assay to identify inhibitors of COUP-TFII (NR2F2). (Class of assay: confirmatory)	PubChem BioAssay data set

Cellosaurus cell lines

8 cell lines: 3 embryonic stem cell, 3 cancer cell line, 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4V7	SEES3-1V human NR2F2, clone1	Embryonic stem cell	Male
CVCL_A4V8	SEES3-1V human NR2F2, clone2	Embryonic stem cell	Male
CVCL_A4V9	SEES3-1V human NR2F2, clone3	Embryonic stem cell	Male
CVCL_B1DX	Abcam HCT 116 NR2F2 KO	Cancer cell line	Male
CVCL_B1YZ	Abcam HeLa NR2F2 KO	Cancer cell line	Female
CVCL_D6PH	MCRIi030-A-1	Induced pluripotent stem cell	Female
CVCL_D6PI	MCRIi030-A-2	Induced pluripotent stem cell	Female
CVCL_TB00	HAP1 NR2F2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00027456	PHASE2	COMPLETED	Leptin to Treat Severe Insulin Resistance - Pilot Study
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT00213447	Not specified	COMPLETED	T Cell Response in Hypersensitivity Syndrome
NCT02240888	Not specified	COMPLETED	Vaccination in Inflammatory Rheumatic Disease (VACCIMIL). The Impact of Antirheumatic Treatment on Antibody Response
NCT02526082	Not specified	ACTIVE_NOT_RECRUITING	Long-term Follow-up of the Helsinki Businessmen Study
NCT02637518	Not specified	UNKNOWN	Comprehensive Validation of Frailty Assessment Tools in Older Adults in Different Clinical and Social Settings
NCT02971072	Not specified	COMPLETED	Neurophysiology of Weakness and Exercise in Rotator Cuff Tendinopathy
NCT02974569	Not specified	COMPLETED	Improving Symptom Self-management in Adolescents & Young Adults With Cancer
NCT03265561	Not specified	COMPLETED	Spinal Infection Management With Structural Allograft
NCT04190342	Not specified	COMPLETED	Effects of a Traditional Chinese Exercise Program on Symptom Cluster in Breast Cancer Patients
NCT04874584	Not specified	COMPLETED	Culturally Tailored Nurse Coaching Study for Cancer Symptom Management
NCT04909489	Not specified	UNKNOWN	PDR and SKYD of Dyslipidemia’s Characteristics From the Oxidative Stress Enhancement Caused by Inhibition of Serine Metabolic Pathway
NCT05218122	Not specified	UNKNOWN	Characteristics of LKDS and PBSS of KOA Based on the Enhancement of Inflammatory Response by TGF-β/Smad Pathway Inhibited
NCT05266118	Not specified	COMPLETED	Patient Reported Symptoms the First Week After Intensive Care Unit Discharge and up to Hospital Discharge
NCT05321966	Not specified	COMPLETED	The Effect of Video Training on Symptom Burden Patients Undergoing Hemodialysis Treatment
NCT05818748	Not specified	UNKNOWN	Effect Of Virtual Reality Distraction on Symptom Control and Anxiety in Children With Leukemia
NCT05837988	Not specified	UNKNOWN	Construction of Symptom Network in Maintenance Hemodialysis Patients
NCT06143436	Not specified	UNKNOWN	TCM Constitution, Pattern Types, and Disease Factors in Primary Lung Cancer.
NCT06222008	Not specified	UNKNOWN	Study on Symptom Clusters During Chemotherapy in Ovarian Cancer Patients With Different Chinese Medicine Constitution
NCT06412107	Not specified	COMPLETED	Somatic Acupressure for Symptom Cluster Management in Breast Cancer Survivors
NCT06847360	Not specified	RECRUITING	Home-based Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) for IBS Pain
NCT07281300	Not specified	RECRUITING	Mindfulness-Oriented Respiratory Distress Symptom Intervention for Lung Cancer
NCT07315672	Not specified	RECRUITING	Acupressure for Cough in Lung Cancer Survivors
NCT07479654	Not specified	NOT_YET_RECRUITING	AI-Enabled Frailty Risk Prediction in Adult Congenital Heart Disease
NCT07495358	Not specified	NOT_YET_RECRUITING	Development and Usability Evaluation of a Knowledge Graph-Based Symptom Management System for Patients With Breast Cancer Undergoing Chemotherapy
NCT07576114	Not specified	RECRUITING	Comparison of Gluteal Muscle Activation and Core Strengthening in Dead Butt Syndrome Syndrome
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy