NR2F1

nuclear receptor subfamily 2 group F member 1, the group of Nuclear receptor subfamily 2 group F

Basic information

Region (hg38): 5:93583222-93594611

Previous symbols: [ "ERBAL3", "TFCOUP1" ]

Links

ENSG00000175745 ∙ NCBI:7025 ∙ OMIM:132890 ∙ HGNC:7975 ∙ Uniprot:P10589 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bosch-Boonstra-Schaaf optic atrophy syndrome (Definitive), mode of inheritance: AD
• Bosch-Boonstra-Schaaf optic atrophy syndrome (Strong), mode of inheritance: AD
• Bosch-Boonstra-Schaaf optic atrophy syndrome (Supportive), mode of inheritance: AD
• Bosch-Boonstra-Schaaf optic atrophy syndrome (Definitive), mode of inheritance: AR
• Bosch-Boonstra-Schaaf optic atrophy syndrome (Definitive), mode of inheritance: AD
• Bosch-Boonstra-Schaaf optic atrophy syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bosch-Boonstra optic atrophy syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic; Ophthalmologic	24462372

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NR2F1 gene.

• not_provided (311 variants)
• Bosch-Boonstra-Schaaf_optic_atrophy_syndrome (85 variants)
• Inborn_genetic_diseases (35 variants)
• not_specified (22 variants)
• NR2F1-related_disorder (9 variants)
• Seizure (2 variants)
• Neurodevelopmental_delay (2 variants)
• See_cases (2 variants)
• Retinal_dystrophy (1 variants)
• Epilepsy (1 variants)
• Optic_atrophy (1 variants)
• Autism_spectrum_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NR2F1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005654.6. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	99	2	108
missense	13	56	127	13	3	212
nonsense	14	7	1			22
start loss	5					5
frameshift	15	9	2			26
splice donor/acceptor (+/-2bp)	1	1	1			3
Total	48	73	138	112	5

Highest pathogenic variant AF is 0.000024346

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NR2F1	protein_coding	protein_coding	ENST00000327111	3	11279

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.995	0.00518	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.17	63	247	0.255	0.0000138	2735
Missense in Polyphen		18	102.52	0.17558		1048
Synonymous	0.632	105	114	0.925	0.00000681	874
Loss of Function	3.66	0	15.6	0.00	7.59e-7	154

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Coup (chicken ovalbumin upstream promoter) transcription factor binds to the ovalbumin promoter and, in conjunction with another protein (S300-II) stimulates initiation of transcription. Binds to both direct repeats and palindromes of the 5'-AGGTCA-3' motif. Represses transcriptional activity of LHCG. {ECO:0000269|PubMed:10644740, ECO:0000269|PubMed:11682620}.
• Disease: DISEASE: Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) [MIM:615722]: An autosomal dominant disorder characterized by optic atrophy associated with developmental delay and intellectual disability. Most patients also have evidence of cerebral visual impairment. {ECO:0000269|PubMed:24462372}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: NHR;Nuclear Receptors;Adipogenesis;Gene expression (Transcription);mechanism of gene regulation by peroxisome proliferators via ppara;Generic Transcription Pathway;Nuclear Receptor transcription pathway;RNA Polymerase II Transcription (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.07

Haploinsufficiency Scores

• pHI: 0.750
• ghis: 0.645

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Low	Low
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Medium	Low	Medium

Mouse Genome Informatics

• Gene name: Nr2f1
• Phenotype: cellular phenotype; vision/eye phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); pigmentation phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: nr2f1a
• Affected structure: axial blood vessel
• Phenotype tag: abnormal
• Phenotype quality: disrupted

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;transcription initiation from RNA polymerase II promoter;signal transduction;negative regulation of neuron projection development;intracellular receptor signaling pathway;steroid hormone mediated signaling pathway;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus;nucleoplasm;cytosol
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;steroid hormone receptor activity;transcription coactivator activity;nuclear receptor activity;protein binding;zinc ion binding;sequence-specific DNA binding;retinoic acid-responsive element binding