NR4A2
Chr 2ADnuclear receptor subfamily 4 group A member 2
Also known as: HZF-3, IDLDP, NOT, NURR1, RNR1, TINUR
The protein functions as a transcriptional regulator essential for the differentiation and maintenance of midbrain dopaminergic neurons during development, controlling expression of genes critical for dopaminergic neuron function including dopamine transporter, vesicular monoamine transporter, tyrosine hydroxylase, and dopamine D2 receptor. Mutations cause autosomal dominant intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism. This gene is extremely intolerant to loss-of-function variation (pLI 1.0, LOEUF 0.13), reflecting its critical role in neurodevelopment.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
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
NR4A2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools