NR4A2

Chr 2

nuclear receptor subfamily 4 group A member 2

Also known as: HZF-3, IDLDP, NOT, NURR1, RNR1, TINUR

NCBI Gene: 4929 ENSG00000153234 UniProt: P43354

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.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the steroid-thyroid hormone-retinoid receptor superfamily. The encoded protein may act as a transcription factor. Mutations in this gene have been associated with disorders related to dopaminergic dysfunction, including Parkinson disease, schizophernia, and manic depression. Misregulation of this gene may be associated with rheumatoid arthritis. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

117

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.13

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)