NR4A3

Chr 9

nuclear receptor subfamily 4 group A member 3

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 SummaryNR4A3
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.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.36LOEUF
pLI 0.913
Z-score 3.94
OE 0.16 (0.080.36)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.81Z-score
OE missense 0.56 (0.500.64)
186 obs / 329.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.16 (0.080.36)
00.351.4
Missense OE0.56 (0.500.64)
00.61.4
Synonymous OE0.82
01.21.6
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

0 submitted variants 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

No active trials found for this gene.

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Clinical Literature
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