NR2F2

Chr 15AD

nuclear receptor subfamily 2 group F member 2

Also known as: ARP-1, ARP1, CHTD4, COUPTF2, COUPTFB, COUPTFII, NF-E3, SRXX5

NCBI Gene: 7026ENSG00000185551UniProt: P24468OMIM: 107773

This highly constrained gene encodes a ligand-activated transcription factor that regulates gene expression and is required for establishing ovary identity during early gonad development. Autosomal dominant mutations cause 46,XX sex reversal and multiple types of congenital heart defects. The gene has a GeneReviews entry available for additional clinical guidance.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.222 OMIM phenotypes
Clinical Summary— NR2F2
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Gene-Disease Validity (ClinGen)
NR2F2 related multiple congenital anomalies/dysmorphic syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
66 unique Pathogenic / Likely Pathogenic· 31 VUS of 139 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — NR2F2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.22LOEUF
pLI 0.990
Z-score 3.44
OE 0.00 (0.00–0.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.60Z-score
OE missense 0.34 (0.28–0.41)
79 obs / 233.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.22)
0≤0.351.4
Missense OE0.34 (0.28–0.41)
0≤0.61.4
Synonymous OE1.30
0≤1.21.6
LoF obs/exp: 0 / 13.8Missense obs/exp: 79 / 233.7Syn Z: -2.38
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveNR2F2-related congenital heart defects and 46XX sex reversalLOFAD
DN
0.2698th %ile
GOF
0.2795th %ile
LOF
0.88top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 21% of P/LP variants are LoF · LOEUF 0.22

Literature Evidence

LOFThe results pinpoint haploinsufficiency of NR2F2 as a cause of CDH and cardiovascular malformations.PMID:24122781

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

139 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic56
Likely Pathogenic10
VUS31
Likely Benign28
Benign12
Conflicting2
56
Pathogenic
10
Likely Pathogenic
31
VUS
28
Likely Benign
12
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
2
44
0
56
Likely Pathogenic
4
3
3
0
10
VUS
2
26
3
0
31
Likely Benign
0
0
6
22
28
Benign
0
0
11
1
12
Conflicting
—2
Total16316723139

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NR2F2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients