NR2F2

nuclear receptor subfamily 2 group F member 2, the group of Nuclear receptor subfamily 2 group F|MicroRNA protein coding host genes

Basic information

Region (hg38): 15:96325937-96340263

Previous symbols: [ "ARP1", "TFCOUP2" ]

Links

ENSG00000185551 ∙ NCBI:7026 ∙ OMIM:107773 ∙ HGNC:7976 ∙ Uniprot:P24468 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital heart defects, multiple types, 4 (Moderate), mode of inheritance: AD
• congenital heart defects, multiple types, 4 (Strong), mode of inheritance: AD
• NR2F2 related multiple congenital anomalies/dysmorphic syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital heart defects, multiple types; 46 XX sex reversal 5	AD	Cardiovascular	The conditions can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Endocrine; Genitourinary; Ophthalmologic	18371933; 24702954; 29478779; 31687637

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NR2F2 gene.

• Congenital heart defects, multiple types, 4 (52 variants)
• not provided (25 variants)
• Inborn genetic diseases (9 variants)
• NR2F2-related condition (2 variants)
• not specified (1 variants)
• NR2F2-related congenital heart defects (1 variants)
• Asplenia (1 variants)
• Congenital heart defects, multiple types, 4;46,xx sex reversal 5 (1 variants)
• Neurodevelopmental disorder (1 variants)
• 46,xx sex reversal 5 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NR2F2 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	21	1	23
missense	1	2	34	1		38
nonsense	4		2			6
start loss						0
frameshift	2	4				6
inframe indel						0
splice donor/acceptor (+/-2bp)	1		1			2
splice region				1	1	2
non coding				1	9	10
Total	8	6	38	23	10

Variants in NR2F2

This is a list of pathogenic ClinVar variants found in the NR2F2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-96326353-G-A			Uncertain significance (Apr 06, 2017)
15-96326466-G-T			Benign (Nov 12, 2018)
15-96331144-C-T			Benign (Jun 20, 2021)
15-96332041-C-T			Benign (Jun 20, 2021)
15-96332109-G-T		Congenital heart defects, multiple types, 4	Uncertain significance (Nov 08, 2019)
15-96332124-A-G		Congenital heart defects, multiple types, 4	Uncertain significance (Dec 02, 2022)
15-96332128-G-A		NR2F2 associated disorders	Likely pathogenic (Jun 02, 2023)
15-96332141-G-A		Congenital heart defects, multiple types, 4	Likely benign (Apr 06, 2020)
15-96332153-C-T		NR2F2-related disorder	Likely benign (Nov 28, 2022)
15-96332169-C-T		Inborn genetic diseases	Pathogenic (Jan 03, 2017)
15-96332181-G-C		Inborn genetic diseases	Uncertain significance (Nov 08, 2021)
15-96332186-G-GCC		Congenital heart defects, multiple types, 4	Likely pathogenic (Nov 07, 2016)
15-96332196-GGCCCGCC-G		46,xx sex reversal 5 • Congenital heart defects, multiple types, 4	Pathogenic (Jun 02, 2020)
15-96332200-C-G		Congenital heart defects, multiple types, 4 • Inborn genetic diseases	Uncertain significance (Feb 26, 2024)
15-96332202-CCGCCCGG-C		46,xx sex reversal 5	Likely pathogenic (Dec 05, 2019)
15-96332205-C-T		Inborn genetic diseases	Uncertain significance (Apr 27, 2023)
15-96332234-C-G		Congenital heart defects, multiple types, 4	Likely benign (Aug 16, 2022)
15-96332251-C-A		Inborn genetic diseases	Uncertain significance (Jan 10, 2023)
15-96332255-C-T		Congenital heart defects, multiple types, 4	Likely benign (Sep 21, 2023)
15-96332267-G-C		Inborn genetic diseases	Uncertain significance (Oct 26, 2021)
15-96332277-G-C		NR2F2-related congenital heart defects	Uncertain significance (May 30, 2019)
15-96332302-C-T		NR2F2-related disorder	Uncertain significance (Dec 09, 2022)
15-96332307-A-G		Inborn genetic diseases	Likely benign (Apr 07, 2023)
15-96332308-G-A		Congenital heart defects, multiple types, 4	Uncertain significance (Aug 10, 2022)
15-96332309-C-G		Congenital heart defects, multiple types, 4	Uncertain significance (Oct 16, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NR2F2	protein_coding	protein_coding	ENST00000394166	3	14326

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.990	0.0103	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.60	79	234	0.338	0.0000126	2705
Missense in Polyphen		15	105.28	0.14248		1142
Synonymous	-2.38	132	101	1.30	0.00000591	838
Loss of Function	3.44	0	13.8	0.00	5.95e-7	155

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: 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. {ECO:0000269|PubMed:18798693, ECO:0000269|PubMed:1899293, ECO:0000269|PubMed:9343308}.
• Pathway: NHR;Nuclear Receptors;White fat cell differentiation;Ectoderm Differentiation;White fat cell differentiation;FOXA1 transcription factor network;Regulation of Telomerase (Consensus)

Recessive Scores

• pRec: 0.292

Intolerance Scores

• rvis_EVS: -0.41
• rvis_percentile_EVS: 26.23

Haploinsufficiency Scores

• pHI: 0.871
• hipred: Y
• hipred_score: 0.717
• ghis: 0.623

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.944

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nr2f2
• Phenotype: immune system 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); digestive/alimentary phenotype; vision/eye phenotype; reproductive system 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); pigmentation phenotype; embryo phenotype; homeostasis/metabolism phenotype; muscle phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: nr2f2
• Affected structure: thoracic duct
• Phenotype tag: abnormal
• Phenotype quality: immature

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;neuron migration;maternal placenta development;negative regulation of endothelial cell proliferation;positive regulation of systemic arterial blood pressure;regulation of transcription by RNA polymerase II;lipid metabolic process;signal transduction;skeletal muscle tissue development;fertilization;anterior/posterior pattern specification;radial pattern formation;negative regulation of endothelial cell migration;intracellular receptor signaling pathway;forebrain development;response to estradiol;steroid hormone mediated signaling pathway;negative regulation of cyclin-dependent protein serine/threonine kinase activity;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;blood vessel morphogenesis;limb development;placenta blood vessel development;trophoblast giant cell differentiation;regulation of transcription involved in lymphatic endothelial cell fate commitment
• Cellular component: nucleus;nucleoplasm;cytosol
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;retinoic acid binding;DNA-binding transcription factor activity;steroid hormone receptor activity;transcription corepressor activity;nuclear receptor activity;protein binding;zinc ion binding;protein homodimerization activity;sequence-specific DNA binding