NR2F6

Summary

NR2F6 (nuclear receptor subfamily 2 group F member 6, HGNC:7977) is a protein-coding gene on chromosome 19p13.11, encoding Nuclear receptor subfamily 2 group F member 6 (P10588). Transcription factor predominantly involved in transcriptional repression.

Enables DNA-binding transcription factor activity and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleus.

Source: NCBI Gene 2063 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 56 total
• Druggable target: yes
• Transcription factor: yes — 16 downstream targets (CollecTRI)
• MANE Select transcript: NM_005234

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7977
Approved symbol	NR2F6
Name	nuclear receptor subfamily 2 group F member 6
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	EAR-2, EAR2
Ensembl gene	ENSG00000160113
Ensembl biotype	protein_coding
OMIM	132880
Entrez	2063

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000291442, ENST00000596878, ENST00000871950, ENST00000943527

RefSeq mRNA: 1 — MANE Select: NM_005234 NM_005234

CCDS: CCDS12352

Canonical transcript exons

ENST00000291442 — 4 exons

Exon	Start	End
ENSE00001049890	17235499	17236065
ENSE00001049891	17244943	17245919
ENSE00001049893	17231883	17232626
ENSE00003629164	17240671	17240765

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 96.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.1380 / max 133.7210, expressed in 1680 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179846	15.5298	1675
179845	1.3546	721
179844	1.2537	566

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	96.66	gold quality
mucosa of transverse colon	UBERON:0004991	96.51	gold quality
nasal cavity epithelium	UBERON:0005384	96.16	gold quality
jejunal mucosa	UBERON:0000399	95.91	gold quality
palpebral conjunctiva	UBERON:0001812	94.83	gold quality
colonic mucosa	UBERON:0000317	94.70	gold quality
right lobe of liver	UBERON:0001114	94.57	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.11	gold quality
apex of heart	UBERON:0002098	93.88	gold quality
corpus epididymis	UBERON:0004359	93.75	gold quality
tongue squamous epithelium	UBERON:0006919	93.65	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.32	gold quality
eye	UBERON:0000970	93.26	gold quality
triceps brachii	UBERON:0001509	93.18	gold quality
lower esophagus mucosa	UBERON:0035834	93.12	gold quality
jejunum	UBERON:0002115	93.05	gold quality
pylorus	UBERON:0001166	92.86	gold quality
epithelium of esophagus	UBERON:0001976	92.82	gold quality
liver	UBERON:0002107	92.71	gold quality
pharyngeal mucosa	UBERON:0000355	92.66	gold quality
esophagus squamous epithelium	UBERON:0006920	92.61	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.53	gold quality
oviduct epithelium	UBERON:0004804	92.49	gold quality
ileal mucosa	UBERON:0000331	92.10	gold quality
gluteal muscle	UBERON:0002000	92.08	gold quality
placenta	UBERON:0001987	92.06	gold quality
duodenum	UBERON:0002114	92.05	gold quality
cervix squamous epithelium	UBERON:0006922	91.76	gold quality
renal medulla	UBERON:0000362	91.71	gold quality
body of tongue	UBERON:0011876	91.66	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	243.51
E-ANND-3	yes	10.90

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

16 targets.

Target	Regulation
APOA1	Repression
APOA2	Unknown
APOB	Unknown
APOC2	Repression
APOC3	Unknown
CD44
CYP19A1	Unknown
EEF1A2
IL17A	Activation
IL2	Activation
LHCGR	Repression
NPPA
OXT	Repression
PER1	Repression
POU5F1	Repression
REN	Repression

JASPAR motifs

Motif	Name	Family
MA1539.1	NR2F6	RXR-related receptors (NR2)

JASPAR matrix evidence (PMIDs): PMID:14559106

Upstream regulators (CollecTRI, top): CREB1, ESRRA

miRNA regulators (miRDB)

28 targeting NR2F6, 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-513A-5P	100.00	69.77	2465
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3120-5P	100.00	65.56	965
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-433-3P	99.98	69.37	1203
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-937-5P	97.43	68.39	667
HSA-MIR-3690	96.44	65.18	737
HSA-MIR-6774-3P	89.14	65.20	68

Literature-anchored findings (GeneRIF, showing 18)

• Ear2 ligand binding domain is required for Rasd1 to alleviate Ear2-mediated repression of renin transcription. (PMID:21247419)
• study demonstrated that expression of EAR2 was elevated in colorectal cancer and knockdown of EAR2 reduced survivability and tumor growth of colon cancer cells (PMID:21696885)
• EAR2/NR2F6 and related NRs such as the COUPTFs, TLX 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)
• high NR2F6 expression predicts pelvic lymph node metastasis, tumor recurrence and poor prognosis in early-stage cervical cancer. NR2F6 might be a novel prognostic biomarker and potential therapeutic target of cervical cancer. (PMID:27775588)
• Results identified rs2288539 in NR2F6 gene to be associated with poor overall and disease-free survival of patients with an early-stage non-small cell lung cancer. (PMID:28922562)
• NR2F6 is an intracellular immune checkpoint that suppresses adaptive anti-cancer immune responses (PMID:29670099)
• Results demonstrate that NR2F6 promotes the stem cell-like phenotype and induces cisplatin resistance in epithelial ovarian cancer (EOC) cells by activating the Notch3 pathway. (PMID:30895619)
• NR2F6 is identified as a direct target of miR-142-3p, which was negatively correlated with miR-142-3p expression. (PMID:31168689)
• circRHOT1 inhibits HCC development and progression via recruiting TIP60 to initiate NR2F6 expression, indicating that circRHOT1 and NR2F6 may be potential biomarkers for HCC prognosis. (PMID:31324186)
• Regulation of docetaxel chemosensitivity by NR2F6 in breast cancer. (PMID:32203934)
• NR2F6 as a Prognostic Biomarker in HNSCC. (PMID:32752295)
• Incomplete thermal ablation-induced up-regulation of transcription factor nuclear receptor subfamily 2, group F, member 6 (NR2F6) contributes to the rapid progression of residual liver tumor in hepatoblastoma. (PMID:34304715)
• [The role of nuclear receptor transcription factor NR2F6 in tumor]. (PMID:34472280)
• Overexpression of the orphan nuclear receptor NR2F6 is associated with improved survival across molecular subgroups in endometrial cancer patients. (PMID:36884115)
• NR2F6, a new immune checkpoint that acts as a potential biomarker of immunosuppression and contributes to poor clinical outcome in human glioma. (PMID:37575237)
• UPK3A[+] umbrella cell damage mediated by TLR3-NR2F6 triggers programmed destruction of urothelium in Hunner-type interstitial cystitis/painful bladder syndrome. (PMID:38551071)
• Concerted regulation of skeletal muscle metabolism and contractile properties by the orphan nuclear receptor Nr2f6. (PMID:38682559)

Cross-species orthologs

31 orthologs

Organism	Symbol	Gene ID
danio_rerio	nr2f6b	ENSDARG00000003165
danio_rerio	nr2f6a	ENSDARG00000003607
mus_musculus	Nr2f6	ENSMUSG00000002393
rattus_norvegicus	Nr2f6	ENSRNOG00000016892
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), HNF4G (ENSG00000164749), NR2F1 (ENSG00000175745), NR2C2 (ENSG00000177463), NR2F2 (ENSG00000185551), RXRA (ENSG00000186350), RXRB (ENSG00000204231), NR2E3 (ENSG00000278570)

Protein

Protein identifiers

Nuclear receptor subfamily 2 group F member 6 — P10588 (reviewed: P10588)

Alternative names: V-erbA-related protein 2

All UniProt accessions (3): P10588, F1D8R3, M0R175

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor predominantly involved in transcriptional repression. Binds to promoter/enhancer response elements that contain the imperfect 5’-AGGTCA-3’ direct or inverted repeats with various spacings which are also recognized by other nuclear hormone receptors. Involved in modulation of hormonal responses. Represses transcriptional activity of the lutropin-choriogonadotropic hormone receptor/LHCGR gene, the renin/REN gene and the oxytocin-neurophysin/OXT gene. Represses the triiodothyronine-dependent and -independent transcriptional activity of the thyroid hormone receptor gene in a cell type-specific manner. The corepressing function towards thyroid hormone receptor beta/THRB involves at least in part the inhibition of THRB binding to triiodothyronine response elements (TREs) by NR2F6. Inhibits NFATC transcription factor DNA binding and subsequently its transcriptional activity. Acts as transcriptional repressor of IL-17 expression in Th-17 differentiated CD4(+) T cells and may be involved in induction and/or maintenance of peripheral immunological tolerance and autoimmunity. Involved in development of forebrain circadian clock; is required early in the development of the locus coeruleus (LC).

Subunit / interactions. Binds DNA as dimer; homodimer and heterodimer with NR2F2 and probably NR2F1. Interacts with THRB.

Subcellular location. Nucleus.

Tissue specificity. Expressed in heart, placenta, liver, skeletal muscle, kidney and pancreas.

Induction. Inhibited by gonadotropin in granulosa cells.

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

RefSeq proteins (1): NP_005225* (*=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 (16 total): modified residue 3, sequence conflict 3, zinc finger region 2, region of interest 2, compositionally biased region 2, chain 1, domain 1, mutagenesis site 1, DNA-binding region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8C5L	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10588-F1	79.46	0.55

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 (3): 40, 83, 34

Mutagenesis-validated functional residues (1):

Position	Phenotype
74–78	loss of dna (tre) binding. reduces the corepressor activity towards thrb.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-383280	Nuclear Receptor transcription pathway

MSigDB gene sets: 189 (showing top): GOBP_CIRCADIAN_RHYTHM, ELVIDGE_HYPOXIA_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_SENSORY_PERCEPTION_OF_TEMPERATURE_STIMULUS, GOBP_PHOTOPERIODISM, GENTILE_RESPONSE_CLUSTER_D3, GOBP_NEUROGENESIS, PRAMOONJAGO_SOX4_TARGETS_DN, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A5, GOBP_REGULATION_OF_CIRCADIAN_RHYTHM, GOBP_SENSORY_PERCEPTION_OF_PAIN, GOBP_DETECTION_OF_TEMPERATURE_STIMULUS, BLALOCK_ALZHEIMERS_DISEASE_UP, HNF4_DR1_Q3, GENTILE_UV_HIGH_DOSE_DN

GO Biological Process (8): negative regulation of transcription by RNA polymerase II (GO:0000122), nervous system development (GO:0007399), cell differentiation (GO:0030154), entrainment of circadian clock by photoperiod (GO:0043153), neuron development (GO:0048666), detection of temperature stimulus involved in sensory perception of pain (GO:0050965), 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 factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), 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), nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
cellular anatomical structure	2
intracellular membrane-bounded organelle	2
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
system development	1
cellular developmental process	1
photoperiodism	1
entrainment of circadian clock	1
neuron differentiation	1
cell development	1
sensory perception of pain	1
detection of temperature stimulus involved in sensory perception	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
intracellular signal transduction	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
transcription cis-regulatory region binding	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
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
cation binding	1
chromosome	1
nuclear lumen	1
cytoplasm	1

Protein interactions and networks

STRING

706 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NR2F6	MYO9B	Q13459	770
NR2F6	PHOX2A	O14813	673
NR2F6	PHOX2B	Q99453	561
NR2F6	KAT5	Q92993	532
NR2F6	ASCL1	P50553	510
NR2F6	REN	P00797	494
NR2F6	MAF	O75444	452
NR2F6	BCL6	P41182	426
NR2F6	MYO1A	Q9UBC5	426
NR2F6	IRF7	Q92985	425
NR2F6	NSD1	Q96L73	425
NR2F6	ARFGEF1	Q9Y6D6	423
NR2F6	DNAJC22	Q8N4W6	365
NR2F6	GTF2I	P78347	357
NR2F6	THRA	P10827	351

IntAct

88 interactions, top by confidence:

A	B	Type	Score
MPPED1	TXNDC9	psi-mi:“MI:0914”(association)	0.640
MPPED1	CLUH	psi-mi:“MI:0914”(association)	0.640
NR2F2	NR2F6	psi-mi:“MI:0915”(physical association)	0.620
JUN	NFATC1	psi-mi:“MI:0914”(association)	0.610
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
NR2F2	GC	psi-mi:“MI:0914”(association)	0.530
RXRG	NR2F6	psi-mi:“MI:0914”(association)	0.530
DCAF4	CLUH	psi-mi:“MI:0914”(association)	0.530
MPPED2	NR2F6	psi-mi:“MI:0914”(association)	0.530
NAP1L1	NR2F6	psi-mi:“MI:0915”(physical association)	0.520
NR2F6	CBX1	psi-mi:“MI:0915”(physical association)	0.520
NR2F6	RASD1	psi-mi:“MI:0915”(physical association)	0.400
	NR2F6	psi-mi:“MI:0915”(physical association)	0.370
CCL22	NR2F6	psi-mi:“MI:0915”(physical association)	0.370
CCL24	NR2F6	psi-mi:“MI:0915”(physical association)	0.370
CXCL3	NR2F6	psi-mi:“MI:0915”(physical association)	0.370
IFNA16	NR2F6	psi-mi:“MI:0915”(physical association)	0.370
IFNA17	NR2F6	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (57): NR2F6 (Affinity Capture-RNA), NR2F6 (Affinity Capture-MS), NR2F6 (Affinity Capture-MS), NR2F6 (Affinity Capture-MS), NR2F6 (Affinity Capture-MS), NR2F6 (Affinity Capture-MS), NR2F6 (Affinity Capture-MS), NR2F6 (Affinity Capture-MS), NR2F6 (Affinity Capture-MS), NR2F6 (Affinity Capture-MS), NR2F6 (Affinity Capture-MS), NR2F6 (Affinity Capture-MS), NR2F6 (Affinity Capture-MS), RASD1 (Affinity Capture-Western), NR2F6 (Two-hybrid)

ESM2 similar proteins: A6NE02, A8MY62, C9JR72, D3Z7H8, D3ZU57, O09017, O15197, O19179, O95382, P0C0K6, P10588, P43136, P55203, Q02846, Q08DG4, Q15628, Q2KHV9, Q3U0S6, Q3UH93, Q5BK61, Q5U651, Q5W7P8, Q5ZMM1, Q6ZNJ1, Q6ZQA0, Q6ZVZ8, Q80ZD5, Q86WK7, Q8BH02, Q8BH83, Q8C828, Q8CIG9, Q8IUL8, Q8IYS2, Q8JGM4, Q8K2J9, Q8N239, Q8VHA6, Q91X21, Q96CD0

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

4 interactions.

A	Effect	B	Mechanism
PRKCD	down-regulates	NR2F6	phosphorylation
CREB1	“down-regulates quantity by repression”	NR2F6	“transcriptional regulation”
ESRRA	“down-regulates quantity by repression”	NR2F6	“transcriptional regulation”
NR2F6	“down-regulates quantity by repression”	LHCGR	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 68 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
natural killer cell activation involved in immune response	5	81.2×	2e-06
defense response to virus	6	6.8×	9e-03
inflammatory response	8	4.9×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

527 predictions. Top by Δscore:

Variant	Effect	Δscore
19:17232624:CGT:C	acceptor_gain	1.0000
19:17232626:TC:T	acceptor_loss	1.0000
19:17232627:C:CC	acceptor_gain	1.0000
19:17240669:AC:A	donor_gain	1.0000
19:17240669:ACCCT:A	donor_gain	1.0000
19:17240670:CC:C	donor_gain	1.0000
19:17240670:CCCTC:C	donor_gain	1.0000
19:17240701:T:TA	donor_gain	1.0000
19:17232622:GGCGT:G	acceptor_gain	0.9900
19:17232623:GCGT:G	acceptor_gain	0.9900
19:17232624:CGTC:C	acceptor_gain	0.9900
19:17232625:GT:G	acceptor_gain	0.9900
19:17235493:GCTCA:G	donor_loss	0.9900
19:17235494:CTCAC:C	donor_loss	0.9900
19:17235495:TCA:T	donor_loss	0.9900
19:17235496:CA:C	donor_loss	0.9900
19:17235498:C:G	donor_loss	0.9900
19:17235498:CCGGG:C	donor_gain	0.9900
19:17240677:T:TA	donor_gain	0.9900
19:17232623:GCGTC:G	acceptor_gain	0.9800
19:17232624:CGTCT:C	acceptor_gain	0.9800
19:17232625:GTCTA:G	acceptor_gain	0.9800
19:17235497:A:AC	donor_gain	0.9800
19:17235498:C:CC	donor_gain	0.9800
19:17240665:ACTC:A	donor_loss	0.9800
19:17240666:C:CA	donor_loss	0.9800
19:17240666:C:CG	donor_loss	0.9800
19:17240667:TCA:T	donor_loss	0.9800
19:17240668:CAC:C	donor_loss	0.9800
19:17240669:A:AA	donor_loss	0.9800

AlphaMissense

2588 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:17232410:A:T	I386N	1.000
19:17232413:A:G	L385P	1.000
19:17232413:A:T	L385Q	1.000
19:17232448:G:C	F373L	1.000
19:17232448:G:T	F373L	1.000
19:17232449:A:G	F373S	1.000
19:17232450:A:G	F373L	1.000
19:17232450:A:T	F373I	1.000
19:17232451:G:C	F372L	1.000
19:17232451:G:T	F372L	1.000
19:17232453:A:G	F372L	1.000
19:17232503:A:G	L355P	1.000
19:17232506:A:G	L354P	1.000
19:17232509:A:G	L353P	1.000
19:17232563:A:G	L335P	1.000
19:17232563:A:T	L335H	1.000
19:17235521:C:A	K306N	1.000
19:17235521:C:G	K306N	1.000
19:17235525:A:G	L305P	1.000
19:17235525:A:T	L305H	1.000
19:17235538:C:T	E301K	1.000
19:17235705:A:G	L245P	1.000
19:17235711:A:G	F243S	1.000
19:17235714:A:G	L242P	1.000
19:17235724:A:G	W239R	1.000
19:17235724:A:T	W239R	1.000
19:17235735:A:G	L235P	1.000
19:17235738:A:G	L234P	1.000
19:17235791:C:A	W216C	1.000
19:17235791:C:G	W216C	1.000

dbSNP variants (sampled 300 via entrez): RS1000144965 (19:17246105 G>A,C,T), RS1000229357 (19:17232278 T>A,G), RS1000298473 (19:17237414 T>C,G), RS1000412418 (19:17237569 G>A), RS1000622758 (19:17236324 G>A), RS1000738442 (19:17236678 C>A,G), RS1000915703 (19:17235389 C>CT), RS1001131158 (19:17241093 C>A), RS1001345537 (19:17235230 C>A,T), RS1001348808 (19:17241611 C>A,T), RS1001363895 (19:17232235 A>C,G), RS1001414451 (19:17235741 G>A), RS1001739549 (19:17235993 G>A,C), RS1001814936 (19:17232015 G>A), RS1002005321 (19:17240990 G>A)

Disease associations

OMIM: gene MIM:132880 | 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
GCST003542_158	Night sleep phenotypes	9.000000e-07
GCST007394_2	Mitochondrial DNA copy number	1.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006312	mitochondrial DNA measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1961791 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
Acetaminophen	decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Cadmium Chloride	decreases expression	2
tert-Butylhydroperoxide	decreases expression	2
Raloxifene Hydrochloride	affects expression, affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol A	increases expression	1
arsenite	increases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
4-hydroxy-2-nonenal	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
nickel sulfate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
bisphenol S	increases methylation	1
MT19c compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	decreases reaction, increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	decreases expression, increases abundance	1
Cadmium	increases expression	1
Caffeine	increases phosphorylation	1
Carbamazepine	affects expression	1
Coumestrol	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1961854	Binding	Effect on EAR2(NR2F6) dependent reporter activity in HEK293 cells at 20 uM	Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. — Nature

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4W0	SEES3-1V human NR2F6, clone1	Embryonic stem cell	Male
CVCL_A4W1	SEES3-1V human NR2F6, clone2	Embryonic stem cell	Male
CVCL_A4W2	SEES3-1V human NR2F6, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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