NR2C1

Summary

NR2C1 (nuclear receptor subfamily 2 group C member 1, HGNC:7971) is a protein-coding gene on chromosome 12q22, encoding Nuclear receptor subfamily 2 group C member 1 (P13056). Orphan nuclear receptor.

This gene encodes a nuclear hormone receptor characterized by a highly conserved DNA binding domain (DBD), a variable hinge region, and a carboxy-terminal ligand binding domain (LBD) that is typical for all members of the steroid/thyroid hormone receptor superfamily. This protein also belongs to a large family of ligand-inducible transcription factors that regulate gene expression by binding to specific DNA sequences within promoters of target genes. Multiple alternatively spliced transcript variants have been described, but the full-length nature of some of these variants has not been determined.

Source: NCBI Gene 7181 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 94 total — 1 likely-pathogenic
• Druggable target: yes
• Transcription factor: yes — 22 downstream targets (CollecTRI)
• MANE Select transcript: NM_003297

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7971
Approved symbol	NR2C1
Name	nuclear receptor subfamily 2 group C member 1
Location	12q22
Locus type	gene with protein product
Status	Approved
Aliases	TR2-11
Ensembl gene	ENSG00000120798
Ensembl biotype	protein_coding
OMIM	601529
Entrez	7181

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 22 protein_coding, 7 protein_coding_CDS_not_defined, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000330677, ENST00000333003, ENST00000393101, ENST00000545833, ENST00000546367, ENST00000546416, ENST00000547469, ENST00000547594, ENST00000548252, ENST00000548966, ENST00000549482, ENST00000549617, ENST00000551386, ENST00000551647, ENST00000552417, ENST00000552484, ENST00000552791, ENST00000552861, ENST00000622476, ENST00000877188, ENST00000877189, ENST00000877190, ENST00000877191, ENST00000877192, ENST00000877193, ENST00000877194, ENST00000877195, ENST00000877196, ENST00000877197, ENST00000922902, ENST00000922903, ENST00000922904, ENST00000942590, ENST00000942591, ENST00000942592

RefSeq mRNA: 3 — MANE Select: NM_003297 NM_001032287, NM_001127362, NM_003297

CCDS: CCDS41821, CCDS44953, CCDS9051

Canonical transcript exons

ENST00000333003 — 14 exons

Exon	Start	End
ENSE00002412304	95073380	95073618
ENSE00003484841	95025150	95025255
ENSE00003523247	95062508	95062738
ENSE00003538563	95040476	95040597
ENSE00003544459	95058310	95058489
ENSE00003546530	95031349	95031488
ENSE00003570142	95020229	95022403
ENSE00003578172	95028387	95028524
ENSE00003580791	95049068	95049233
ENSE00003616657	95051762	95051943
ENSE00003620687	95057731	95057878
ENSE00003623547	95059906	95059984
ENSE00003638681	95067331	95067391
ENSE00003653608	95057553	95057643

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 97.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.9632 / max 624.6226, expressed in 1810 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132720	15.4586	1754
132721	12.1538	1782
132719	0.3507	150

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	97.43	gold quality
cerebellar cortex	UBERON:0002129	97.32	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.23	gold quality
cerebellum	UBERON:0002037	95.98	gold quality
left lobe of thyroid gland	UBERON:0001120	94.78	gold quality
right lung	UBERON:0002167	94.75	gold quality
tibial nerve	UBERON:0001323	94.70	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.67	gold quality
sural nerve	UBERON:0015488	94.59	gold quality
right lobe of thyroid gland	UBERON:0001119	94.54	gold quality
right lobe of liver	UBERON:0001114	94.51	gold quality
mucosa of stomach	UBERON:0001199	94.21	gold quality
body of uterus	UBERON:0009853	94.11	gold quality
right testis	UBERON:0004534	94.03	gold quality
endocervix	UBERON:0000458	93.99	gold quality
left testis	UBERON:0004533	93.97	gold quality
thyroid gland	UBERON:0002046	93.90	gold quality
metanephros cortex	UBERON:0010533	93.79	gold quality
right adrenal gland cortex	UBERON:0035827	93.79	gold quality
right ovary	UBERON:0002118	93.77	gold quality
right uterine tube	UBERON:0001302	93.67	gold quality
body of pancreas	UBERON:0001150	93.63	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.46	gold quality
lower esophagus	UBERON:0013473	93.44	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.44	gold quality
left ovary	UBERON:0002119	93.35	gold quality
gastrocnemius	UBERON:0001388	93.27	gold quality
calcaneal tendon	UBERON:0003701	93.08	gold quality
right adrenal gland	UBERON:0001233	92.90	gold quality
left adrenal gland cortex	UBERON:0035825	92.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.51

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

22 targets.

Target	Regulation
AGT	Repression
ALDOA	Activation
CRABP1
EIF3K
EPO
ESR1
GATA1
GHRHR
HBE1
HBG1
HLA-DRB1
HRH1	Repression
KLK3
MYC	Activation
NANOG	Repression
NR2C2
POU5F1	Unknown
RARB	Activation
RGR
TNFSF14
TRIM28
TXNRD2

JASPAR motifs

Motif	Name	Family
MA1535.1	NR2C1	RXR-related receptors (NR2)
MA1535.2	NR2C1	RXR-related receptors (NR2)

JASPAR matrix evidence (PMIDs): PMID:23354101

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

159 targeting NR2C1, 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-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 6)

• 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)
• TR2 that may exert an important repressor in regulating ER activity in mammary glands. (PMID:12093804)
• 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)
• TR2 may function as a negative modulator to suppress androgen receptor function in prostate cancer. Further studies on how to control TR2 function may result in the ability to modulate AR function in prostate cancer. (PMID:12949936)
• The NF1-A transcription factor plays an important role in the transcriptional activation of the TR2 gene expression via a promoter activating cis-element. (PMID:17010934)
• NamiRNA-enhancer network of miR-492 activates the NR2C1-TGF-beta/Smad3 pathway to promote epithelial-mesenchymal transition of pancreatic cancer. (PMID:36591938)

Cross-species orthologs

30 orthologs

Organism	Symbol	Gene ID
danio_rerio	nr2c1	ENSDARG00000045527
mus_musculus	Nr2c1	ENSMUSG00000005897
rattus_norvegicus	Nr2c1	ENSRNOG00000006983
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), RXRG (ENSG00000143171), NR2F6 (ENSG00000160113), HNF4G (ENSG00000164749), NR2F1 (ENSG00000175745), NR2C2 (ENSG00000177463), NR2F2 (ENSG00000185551), RXRA (ENSG00000186350), RXRB (ENSG00000204231), NR2E3 (ENSG00000278570)

Protein

Protein identifiers

Nuclear receptor subfamily 2 group C member 1 — P13056 (reviewed: P13056)

Alternative names: Orphan nuclear receptor TR2, Testicular receptor 2

All UniProt accessions (7): A0A087WUK4, P13056, F8W1Q1, H0YHC6, H0YIV1, H9NIM2, H9NIM3

UniProt curated annotations — full annotation on UniProt →

Function. Orphan nuclear receptor. Binds the IR7 element in the promoter of its own gene in an autoregulatory negative feedback mechanism. Primarily repressor of a broad range of genes. Binds to hormone response elements (HREs) consisting of two 5’-AGGTCA-3’ half site direct repeat consensus sequences. Together with NR2C2, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription. Also activator of OCT4 gene expression. May be involved in stem cell proliferation and differentiation. Mediator of retinoic acid-regulated preadipocyte proliferation.

Subunit / interactions. Homodimer. Heterodimer; binds DNA as a heterodimer with NR2C2 required for chromatin remodeling and for binding to promoter regions such as globin DR1 repeats. Interacts with NRIP1 (via its LXXLL motifs); the interaction provides corepressor activity. Interacts with HDAC3 (via the DNA-binding domain). Interacts with HDAC4 (via the DNA-binding domain). Interacts with PIAS1; the interaction is required for sumoylation of NR2C1. Interacts with UBE2I; the interaction is required for sumoylation of NR2C1. Interacts with KAT2B; the interaction acts as a corepressor of gene expression. Interacts with ESR1; the interaction prevents homodimerization of ESR1 and suppresses its transcriptional activity and cell growth.

Subcellular location. Nucleus. PML body.

Post-translational modifications. Sumoylation requires both PIAS1 and UBE2I. Sumoylation appears to dissociate NR2C1 from the PML nuclear bodies. Enhances the interaction with NRIP1 but inhibits interaction with KAT2B. In proliferating cells, stimulation by all-trans retinoic acid, activation of MAPK1-mediated phosphorylation and recruitment to PML bodies with subsequent sumoylation, suppresses OCT4 expression. Phosphorylated on several serine and threonine residues. Phosphorylation on Thr-222, stimulated by all-trans retinoic acid (atRA) mediates PML location and sumoylation in proliferating cells which then modulates its association with effector molecules, KAT2B and NRIP1. Phosphorylation on Ser-581 by PKC is important for protein stability and function as activator of RARB.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P13056-1	1, TR2-11	yes
P13056-2	2, TR2-9
P13056-3	3, TR2-7

RefSeq proteins (3): NP_001027458, NP_001120834, NP_003288* (*=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 (21 total): modified residue 5, splice variant 4, sequence conflict 3, cross-link 2, zinc finger region 2, region of interest 2, chain 1, domain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13056-F1	65.48	0.33

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 (7): 222, 581, 250, 588, 197, 215, 220

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-383280	Nuclear Receptor transcription pathway
R-HSA-4090294	SUMOylation of intracellular receptors

MSigDB gene sets: 231 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, PID_HDAC_CLASSI_PATHWAY, TGCGCANK_UNKNOWN, MORF_MSH3, GOBP_CELLULAR_RESPONSE_TO_LIPID, MORF_BRCA1, MORF_ATRX, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_REGULATION_OF_RETINOIC_ACID_RECEPTOR_SIGNALING_PATHWAY, TGACCTY_ERR1_Q2, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, MORF_PPP5C, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_DN

GO Biological Process (8): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), cell differentiation (GO:0030154), positive regulation of retinoic acid receptor signaling pathway (GO:0048386), regulation of DNA-templated transcription (GO:0006355), nuclear receptor-mediated steroid hormone signaling pathway (GO:0030518), intracellular receptor signaling pathway (GO:0030522), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (15): 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 repressor activity, RNA polymerase II-specific (GO:0001227), DNA binding (GO:0003677), nuclear steroid receptor activity (GO:0003707), nuclear receptor activity (GO:0004879), zinc ion binding (GO:0008270), signaling receptor activity (GO:0038023), protein homodimerization activity (GO:0042803), histone deacetylase binding (GO:0042826), sequence-specific double-stranded DNA binding (GO:1990837), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (4): chromatin (GO:0000785), nucleoplasm (GO:0005654), PML body (GO:0016605), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Generic Transcription Pathway	1
SUMO E3 ligases SUMOylate target proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
DNA-templated transcription	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
cellular developmental process	1
retinoic acid receptor signaling pathway	1
regulation of retinoic acid receptor signaling pathway	1
positive regulation of intracellular signal transduction	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
steroid hormone receptor signaling pathway	1
nuclear receptor-mediated signaling pathway	1
intracellular signal transduction	1
negative regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription repressor activity	1
nucleic acid binding	1
nuclear receptor activity	1
nuclear receptor-mediated steroid hormone signaling pathway	1
intracellular receptor signaling pathway	1
signaling receptor activity	1
ligand-modulated transcription factor activity	1
transition metal ion binding	1
molecular transducer activity	1
identical protein binding	1
protein dimerization activity	1
enzyme binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
binding	1
DNA binding	1

Protein interactions and networks

STRING

1226 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NR2C1	NRIP1	P48552	906
NR2C1	NR2C2	P49116	650
NR2C1	FKBP9	O95302	560
NR2C1	NCOR1	O75376	514
NR2C1	KDM1A	O60341	505
NR2C1	HDAC4	P56524	474
NR2C1	OTOP3	Q7RTS5	467
NR2C1	ZNF827	Q17R98	460
NR2C1	UBE2I	P50550	429
NR2C1	RGR	P47804	423
NR2C1	SLX4	Q8IY92	409
NR2C1	NRL	P54845	409
NR2C1	ZNF276	Q8N554	399
NR2C1	FBXL20	Q96IG2	398
NR2C1	SP1	P08047	397

IntAct

43 interactions, top by confidence:

A	B	Type	Score
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
ETV7	NFIB	psi-mi:“MI:2364”(proximity)	0.470
NR2C1	ESR1	psi-mi:“MI:0915”(physical association)	0.400
NUDT3	NR2C1	psi-mi:“MI:0915”(physical association)	0.370
JAZF1	NR2C1	psi-mi:“MI:0914”(association)	0.350
TP53BP1	PSMD14	psi-mi:“MI:2364”(proximity)	0.270
TBXT	BCL9	psi-mi:“MI:2364”(proximity)	0.270
ELF1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
ELF2	SETD1A	psi-mi:“MI:2364”(proximity)	0.270
ELK3	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
ETV3	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
FEV	TAF4	psi-mi:“MI:2364”(proximity)	0.270
HNF1B	BCL9	psi-mi:“MI:2364”(proximity)	0.270
HNF4A	TAF4	psi-mi:“MI:2364”(proximity)	0.270
KLF12		psi-mi:“MI:2364”(proximity)	0.270
KLF16	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
KLF3	MCRIP1	psi-mi:“MI:2364”(proximity)	0.270
KLF5	BCL9	psi-mi:“MI:2364”(proximity)	0.270
KLF8	USP27X	psi-mi:“MI:2364”(proximity)	0.270
KLF9	SEC16A	psi-mi:“MI:2364”(proximity)	0.270
LHX2	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
LHX3	BCL9	psi-mi:“MI:2364”(proximity)	0.270
LHX4	BCL9	psi-mi:“MI:2364”(proximity)	0.270
MYB	KMT2D	psi-mi:“MI:2364”(proximity)	0.270
MYOD1	BCL9	psi-mi:“MI:2364”(proximity)	0.270
NFIA	BCL9	psi-mi:“MI:2364”(proximity)	0.270
NFIB	BCL9	psi-mi:“MI:2364”(proximity)	0.270
NFIX	TAF4	psi-mi:“MI:2364”(proximity)	0.270
NFYC	ASDURF	psi-mi:“MI:2364”(proximity)	0.270
PAX6	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (129): NR2C1 (Affinity Capture-Western), AR (Affinity Capture-Western), AR (Two-hybrid), NR2C1 (Proximity Label-MS), HDAC3 (Reconstituted Complex), HDAC3 (Affinity Capture-Western), HDAC3 (Reconstituted Complex), HDAC4 (Reconstituted Complex), HDAC3 (Two-hybrid), NR2C1 (Proximity Label-MS), NR2C1 (Proximity Label-MS), NR2C1 (Affinity Capture-Western), NR2C1 (Affinity Capture-Western), NR2C1 (Two-hybrid), HDAC3 (Reconstituted Complex)

ESM2 similar proteins: A0A1L8GWK2, A0A571BF63, A0JMA8, A0JNE3, A2BGA0, A4IIG7, O00443, P13056, P24781, P28701, P28705, P43354, P45448, P48443, P51128, P51129, Q04913, Q06219, Q07917, Q08E53, Q09555, Q0GFF6, Q0IHW3, Q0VC20, Q1LVF3, Q26622, Q33E94, Q505F1, Q5BJR8, Q5FWP2, Q5R5Y4, Q5RAY1, Q5RCZ5, Q5REL6, Q5RJH6, Q61194, Q64287, Q68F67, Q6DHP9, Q7TNK1

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

1 interactions.

A	Effect	B	Mechanism
MAPK1	“down-regulates activity”	NR2C1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 53 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
transcription by RNA polymerase II	9	12.2×	4e-06
neuron differentiation	5	9.7×	4e-03
brain development	6	9.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	63
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
816803	NM_003297.4(NR2C1):c.544+1G>C	Likely pathogenic

SpliceAI

2857 predictions. Top by Δscore:

Variant	Effect	Δscore
12:95022400:TAAC:T	acceptor_gain	1.0000
12:95022401:AAC:A	acceptor_gain	1.0000
12:95022402:AC:A	acceptor_gain	1.0000
12:95022403:CC:C	acceptor_gain	1.0000
12:95022404:C:CC	acceptor_gain	1.0000
12:95022405:T:A	acceptor_loss	1.0000
12:95025139:A:C	donor_gain	1.0000
12:95025145:GATAC:G	donor_loss	1.0000
12:95025146:ATACC:A	donor_loss	1.0000
12:95025147:TACCT:T	donor_loss	1.0000
12:95025149:CC:C	donor_loss	1.0000
12:95025256:C:CC	acceptor_gain	1.0000
12:95025256:CT:C	acceptor_loss	1.0000
12:95025257:TGAAA:T	acceptor_loss	1.0000
12:95031344:TTTA:T	donor_loss	1.0000
12:95031346:TACCT:T	donor_loss	1.0000
12:95031347:ACCTT:A	donor_loss	1.0000
12:95031348:C:A	donor_loss	1.0000
12:95031484:CTTGC:C	acceptor_gain	1.0000
12:95031486:TGCCT:T	acceptor_loss	1.0000
12:95031487:GCCTA:G	acceptor_loss	1.0000
12:95031489:C:CC	acceptor_gain	1.0000
12:95049066:AC:A	donor_gain	1.0000
12:95049067:CC:C	donor_gain	1.0000
12:95051756:CCTTA:C	donor_loss	1.0000
12:95051757:CTTA:C	donor_loss	1.0000
12:95051760:ACC:A	donor_loss	1.0000
12:95051761:C:G	donor_loss	1.0000
12:95057557:T:C	donor_gain	1.0000
12:95057876:CAG:C	acceptor_gain	1.0000

AlphaMissense

3983 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:95028413:A:G	L502P	1.000
12:95057862:T:A	R187S	1.000
12:95057862:T:G	R187S	1.000
12:95057863:C:G	R187T	1.000
12:95057875:A:T	V183D	1.000
12:95058320:C:A	M178I	1.000
12:95058320:C:G	M178I	1.000
12:95058320:C:T	M178I	1.000
12:95058321:A:C	M178R	1.000
12:95058321:A:G	M178T	1.000
12:95058335:A:C	C173W	1.000
12:95058336:C:A	C173F	1.000
12:95058336:C:G	C173S	1.000
12:95058336:C:T	C173Y	1.000
12:95058337:A:G	C173R	1.000
12:95058337:A:T	C173S	1.000
12:95058347:C:A	R169S	1.000
12:95058347:C:G	R169S	1.000
12:95058348:C:A	R169M	1.000
12:95058348:C:G	R169T	1.000
12:95058349:T:C	R169G	1.000
12:95058350:G:C	C168W	1.000
12:95058351:C:A	C168F	1.000
12:95058351:C:G	C168S	1.000
12:95058351:C:T	C168Y	1.000
12:95058352:A:G	C168R	1.000
12:95058352:A:T	C168S	1.000
12:95058356:T:A	Q166H	1.000
12:95058356:T:G	Q166H	1.000
12:95058359:A:C	C165W	1.000

dbSNP variants (sampled 300 via entrez): RS1000043150 (12:95051983 C>T), RS1000052195 (12:95030799 T>C), RS1000071948 (12:95045320 G>A,T), RS1000109595 (12:95043290 A>C), RS1000119195 (12:95035590 G>A), RS1000174280 (12:95059429 G>A), RS1000217476 (12:95067315 C>A,T), RS1000264665 (12:95057673 G>C), RS1000351861 (12:95065675 G>T), RS1000362096 (12:95064530 G>A,C), RS1000387423 (12:95037353 A>G), RS1000414584 (12:95064290 A>C,G), RS1000487047 (12:95020565 A>G), RS1000608805 (12:95046994 A>G), RS1000650967 (12:95027663 G>C)

Disease associations

OMIM: gene MIM:601529 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST008154_15	Trunk fat mass	1.000000e-06
GCST008157_7	Body fat mass	6.000000e-06
GCST008944_4	Chromosomal aberration frequency (chromosome type)	4.000000e-06
GCST010480_11	Coronary artery disease	2.000000e-09
GCST011020_6	Intracranial aneurysm	3.000000e-12
GCST011021_11	Intracranial aneurysm	5.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009861	chromosome-type aberration frequency

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1961787 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: nhr — 2C. Testicular receptors

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	4
trichostatin A	affects cotreatment, decreases expression	2
entinostat	decreases expression, affects cotreatment	2
Acetaminophen	decreases expression	2
Benzo(a)pyrene	affects methylation	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	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, increases expression	1
dorsomorphin	increases expression, affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	increases methylation	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Coumestrol	decreases expression	1
Doxorubicin	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methapyrilene	decreases methylation	1
Methyl Methanesulfonate	increases expression	1
Selenium	decreases expression	1
Tretinoin	decreases expression	1

ChEMBL screening assays

74 unique, capped per target: 74 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1961848	Binding	Effect on TR2(NR2C1) dependent reporter activity in HEK293 cells at 20 uM	Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. — Nature

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_AW36	K562 eGFP-NR2C1	Cancer cell line	Female

Clinical trials (associated diseases)

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