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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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NR2F1
nuclear receptor subfamily 2 group F member 1
Chromosome 5 Β· 5q15
NCBI Gene: 7025Ensembl: ENSG00000175745.15HGNC: HGNC:7975UniProt: A0A8V8TQQ6
99PubMed Papers
21Diseases
0Drugs
118Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedReceptorTranscription Factor
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
sequence-specific double-stranded DNA bindingnegative regulation of transcription by RNA polymerase IIprotein bindingDNA-binding transcription repressor activity, RNA polymerase II-specificBosch-Boonstra-Schaaf optic atrophy syndromeOptic atrophy-intellectual disability syndromegenetic disorderneurodegenerative disease
✦AI Summary

NR2F1 (nuclear receptor subfamily 2 group F member 1) is a steroid/thyroid hormone receptor superfamily transcription factor that functions as a sequence-specific DNA-binding regulator of gene expression 1. As a transcriptional repressor, NR2F1 binds to direct repeats and palindromes of specific DNA motifs and negatively regulates RNA polymerase II-dependent transcription 1. Mechanistically, NR2F1 plays critical roles in neurodevelopment, governing neural progenitor proliferation and differentiation, neocortical neuron migration, cortical area specification, and visual system assembly 1. In cancer biology, NR2F1 activation induces dormancy programs that suppress metastasis by inhibiting cell cycle progression and mTOR signaling while maintaining neural crest lineage programs 2. Conversely, NR2F1 upregulation can drive phenotypic transitions from dormancy to proliferation in drug-resistant prostate and breast cancers 34. The associated lncRNA NR2F1-AS1 regulates NR2F1 expression and acts as an oncogene in multiple malignancies including breast, lung, gastric, and pancreatic cancers, though it suppresses cervical cancer progression 56. Clinically, NR2F1 haploinsufficiency causes Bosch-Boonstra-Schaaf Optic Atrophy Syndrome, characterized by intellectual disability, visual impairment, epilepsy, and autistic traits 1. NR2F1 represents a promising therapeutic target for both preventing cancer metastasis through agonist-induced dormancy and managing drug-resistant cancers.

Sources cited
1
NR2F1 agonist activation induces cancer cell dormancy, growth arrest, and metastasis suppression through inhibition of cell cycle progression and mTOR signaling
PMID: 34812843
2
NR2F1 is a transcriptional regulator of the steroid/thyroid hormone receptor superfamily with roles in neural progenitor proliferation/differentiation, neuronal migration, cortical specification, and visual system assembly; NR2F1 haploinsufficiency causes Bosch-Boonstra-Schaaf Optic Atrophy Syndrome
PMID: 34975398
3
NR2F1-AS1 lncRNA is abnormally expressed in multiple malignancies and acts as an oncogene regulating proliferation, invasion, migration, and apoptosis
PMID: 35552086
4
NR2F1 overexpression drives phenotypic transition from dormancy to proliferation in enzalutamide-resistant prostate cancer; exosomal NR2F1 and NR2F1-AS1 promote reawakening of dormant drug-resistant cancer cells
PMID: 39695778
5
NR2F1-AS1 promotes NR2F1 translation and suppresses Ξ”Np63 transcription, leading to epithelial-mesenchymal transition and metastatic dormancy in breast cancer
PMID: 34475402
6
NR2F1-AS1 acts as an oncogene in esophageal, lung, breast, neuroblastoma, endometrial, and gastric cancers but inhibits cervical cancer progression
PMID: 36644870
7
NR2F1 acts as a transcription factor regulating marker genes in metastatic epithelial cell subtypes of breast cancer pre-nodal metastases
PMID: 39210391
Disease Associationsβ“˜21
Bosch-Boonstra-Schaaf optic atrophy syndromeOpen Targets
0.80Strong
Optic atrophy-intellectual disability syndromeOpen Targets
0.66Moderate
genetic disorderOpen Targets
0.53Moderate
neurodegenerative diseaseOpen Targets
0.50Moderate
intelligenceOpen Targets
0.42Moderate
Neurodevelopmental delayOpen Targets
0.41Moderate
type 2 diabetes mellitusOpen Targets
0.36Weak
mathematical abilityOpen Targets
0.36Weak
autism spectrum disorderOpen Targets
0.35Weak
SeizureOpen Targets
0.33Weak
systemic lupus erythematosusOpen Targets
0.32Weak
benign urinary system neoplasmOpen Targets
0.32Weak
major depressive disorderOpen Targets
0.31Weak
attention deficit hyperactivity disorderOpen Targets
0.31Weak
post-traumatic stress disorderOpen Targets
0.29Weak
Abnormality of refractionOpen Targets
0.29Weak
optic atrophyOpen Targets
0.26Weak
smoking initiationOpen Targets
0.24Weak
androgenetic alopeciaOpen Targets
0.24Weak
benign prostatic hyperplasiaOpen Targets
0.22Weak
Bosch-Boonstra-Schaaf optic atrophy syndromeUniProt
Pathogenic Variants118
NM_005654.6(NR2F1):c.2T>C (p.Met1Thr)Pathogenic
not provided|Bosch-Boonstra-Schaaf optic atrophy syndrome|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 1
NM_005654.6(NR2F1):c.1205_1206del (p.Leu402fs)Likely pathogenic
Bosch-Boonstra-Schaaf optic atrophy syndrome|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 402
NM_005654.6(NR2F1):c.452T>C (p.Met151Thr)Likely pathogenic
Bosch-Boonstra-Schaaf optic atrophy syndrome|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 151
NM_005654.6(NR2F1):c.256T>C (p.Cys86Arg)Pathogenic
Bosch-Boonstra-Schaaf optic atrophy syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 86
NM_005654.6(NR2F1):c.424C>T (p.Arg142Cys)Pathogenic
not provided|Bosch-Boonstra-Schaaf optic atrophy syndrome
β˜…β˜…β˜†β˜†2024β†’ Residue 142
NM_005654.6(NR2F1):c.1096C>T (p.Arg366Cys)Likely pathogenic
Bosch-Boonstra-Schaaf optic atrophy syndrome
β˜…β˜…β˜†β˜†2024β†’ Residue 366
NM_005654.6(NR2F1):c.313G>A (p.Gly105Ser)Pathogenic
not provided|Bosch-Boonstra-Schaaf optic atrophy syndrome
β˜…β˜…β˜†β˜†2024β†’ Residue 105
NM_005654.6(NR2F1):c.755T>C (p.Leu252Pro)Likely pathogenic
Bosch-Boonstra-Schaaf optic atrophy syndrome|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 252
NM_005654.6(NR2F1):c.317G>A (p.Cys106Tyr)Pathogenic
not provided|Inborn genetic diseases
β˜…β˜…β˜†β˜†2023β†’ Residue 106
NM_005654.6(NR2F1):c.320A>G (p.Lys107Arg)Pathogenic
See cases|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 107
NM_005654.6(NR2F1):c.365G>A (p.Cys122Tyr)Likely pathogenic
Inborn genetic diseases|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 122
NM_005654.6(NR2F1):c.425G>A (p.Arg142His)Pathogenic
Inborn genetic diseases|Bosch-Boonstra-Schaaf optic atrophy syndrome|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 142
NM_005654.6(NR2F1):c.327C>A (p.Phe109Leu)Likely pathogenic
Bosch-Boonstra-Schaaf optic atrophy syndrome
β˜…β˜…β˜†β˜†2020β†’ Residue 109
NM_005654.6(NR2F1):c.382T>C (p.Cys128Arg)Likely pathogenic
Bosch-Boonstra-Schaaf optic atrophy syndrome
β˜…β˜…β˜†β˜†2017β†’ Residue 128
NM_005654.6(NR2F1):c.1036_1038del (p.Glu346del)Pathogenic
Bosch-Boonstra-Schaaf optic atrophy syndrome
β˜…β˜†β˜†β˜†2026β†’ Residue 346
NM_005654.6(NR2F1):c.292T>C (p.Tyr98His)Likely pathogenic
Bosch-Boonstra-Schaaf optic atrophy syndrome
β˜…β˜†β˜†β˜†2026β†’ Residue 98
NM_005654.6(NR2F1):c.166_182dup (p.Thr63fs)Pathogenic
Bosch-Boonstra-Schaaf optic atrophy syndrome
β˜…β˜†β˜†β˜†2026β†’ Residue 63
NM_005654.6(NR2F1):c.609C>A (p.Tyr203Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2026β†’ Residue 203
NM_005654.6(NR2F1):c.835_844dup (p.Leu282fs)Pathogenic
Bosch-Boonstra-Schaaf optic atrophy syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 282
NM_005654.6(NR2F1):c.667del (p.Ala223fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 223
View on ClinVar β†—
Related Genes
ESR1Protein interaction100%BCL11BProtein interaction99%BCL11AProtein interaction79%NR2F6Shared pathway75%ISL1Protein interaction72%GTF2BProtein interaction71%
Tissue Expression6 tissues
Brain
100%
Ovary
45%
Liver
12%
Lung
12%
Bone Marrow
2%
Heart
2%
Gene Interaction Network
Click a node to explore
NR2F1ESR1BCL11BBCL11ANR2F6ISL1GTF2B
PROTEIN STRUCTURE
Preparing viewer…
PDB2EBL Β· NMR
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.13Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.03 [0.01–0.13]
RankingsWhere NR2F1 stands among ~20K protein-coding genes
  • #4,848of 20,598
    Most Researched99 Β· top quartile
  • #657of 5,498
    Most Pathogenic Variants118 Β· top quartile
  • #150of 17,882
    Most Constrained (LOEUF)0.13 Β· top 1%
Genes detectedNR2F1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
An NR2F1-specific agonist suppresses metastasis by inducing cancer cell dormancy.
PMID: 34812843
J Exp Med Β· 2022
1.00
2
Structural and Functional Aspects of the Neurodevelopmental Gene
PMID: 34975398
Front Mol Neurosci Β· 2021
0.90
3
The emerging role of NR2F1-AS1 in the tumorigenesis and progression of human cancer.
PMID: 35552086
Pathol Res Pract Β· 2022
0.80
4
PMID: 36508512
0.70
5
Loss of CHD1 Promotes Heterogeneous Mechanisms of Resistance to AR-Targeted Therapy via Chromatin Dysregulation.
PMID: 32220301
Cancer Cell Β· 2020
0.60