NR4A3

Chr 9

nuclear receptor subfamily 4 group A member 3

Also known as: CHN, CSMF, MINOR, NOR1

NCBI Gene: 8013ENSG00000119508UniProt: Q92570OMIM: 600542

The protein is a transcriptional activator that binds to specific DNA sequences to regulate gene expression controlling cell proliferation, survival, differentiation, metabolism, and inflammation across multiple tissue types. Mutations cause extraskeletal myxoid chondrosarcoma as a somatic cancer. This gene is highly constrained against loss-of-function mutations (pLI 0.91, LOEUF 0.36), suggesting intolerance to complete protein loss.

OMIMResearchSummary from OMIM, UniProt
LOFmechanismLOEUF 0.361 OMIM phenotype
Clinical Summary— NR4A3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.91). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
34 unique Pathogenic / Likely Pathogenic· 49 VUS of 91 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.36LOEUF
pLI 0.913
Z-score 3.94
OE 0.16 (0.08–0.36)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.81Z-score
OE missense 0.56 (0.50–0.64)
186 obs / 329.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.16 (0.08–0.36)
0≤0.351.4
Missense OE0.56 (0.50–0.64)
0≤0.61.4
Synonymous OE0.82
0≤1.21.6
LoF obs/exp: 4 / 25.5Missense obs/exp: 186 / 329.3Syn Z: 1.70
DN
0.3793th %ile
GOF
0.2994th %ile
LOF
0.79top 5%

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

LOFprediction above median · LOEUF 0.36

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

91 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic3
VUS49
Likely Benign4
31
Pathogenic
3
Likely Pathogenic
49
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
0
3
0
3
VUS
0
45
4
0
49
Likely Benign
0
3
1
0
4
Benign
0
0
0
0
0
Total04839087

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

View in ClinVar →

Protein Context — Lollipop Plot

NR4A3 · 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