NR4A2

nuclear receptor subfamily 4 group A member 2, the group of Nuclear receptor subfamily 4 group A

Basic information

Region (hg38): 2:156324437-156342348

Previous symbols: [ "NURR1" ]

Links

ENSG00000153234 ∙ ∙ OMIM:601828 ∙ HGNC:7981 ∙ Uniprot:P43354 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism (Strong), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
• neurodevelopmental disorder (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism	AD	Neurologic	The condition can include dystonia and movement abnormalities, which has been reported as responding to medical management (with L-dopa)	Neurologic	28544326; 29770430; 31428396; 31922365; 32366965; 33585677

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NR4A2 gene.

• not_provided (59 variants)
• Intellectual_developmental_disorder_with_language_impairment_and_early-onset_DOPA-responsive_dystonia-parkinsonism (50 variants)
• Inborn_genetic_diseases (49 variants)
• Parkinson_disease,_late-onset (21 variants)
• not_specified (7 variants)
• NR4A2-related_disorder (5 variants)
• Autism_spectrum_disorder (2 variants)
• Complex_neurodevelopmental_disorder (2 variants)
• Neurodevelopmental_disorder (1 variants)
• History_of_neurodevelopmental_disorder (1 variants)
• Epilepsy (1 variants)
• Neurodevelopmental_delay (1 variants)
• Autism (1 variants)
• Developmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NR4A2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006186.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	12	3	23
missense	5	15	96	10	1	127
nonsense	2	2	2			6
start loss	1					1
frameshift	12	5	4			21
splice donor/acceptor (+/-2bp)	2	1	1			4
Total	22	23	111	22	4

Highest pathogenic variant AF is 0.0000020526295

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NR4A2	protein_coding	protein_coding	ENST00000339562	6	17917

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000407	113255	0	1	113256	0.00000441

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.24	236	354	0.666	0.0000221	3936
Missense in Polyphen		58	138.82	0.41781		1595
Synonymous	0.0913	153	154	0.991	0.0000110	1183
Loss of Function	4.39	0	22.4	0.00	0.00000112	255

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000311	0.00000999
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development. It is crucial for expression of a set of genes such as SLC6A3, SLC18A2, TH and DRD2 which are essential for development of mdDA neurons (By similarity). {ECO:0000250, ECO:0000269|PubMed:17184956}.
• Pathway: Aldosterone synthesis and secretion - Homo sapiens (human);NHR;Nuclear Receptors;Corticotropin-releasing hormone signaling pathway;Dopaminergic Neurogenesis;VEGFA-VEGFR2 Signaling Pathway;Gene expression (Transcription);Generic Transcription Pathway;Nuclear Receptor transcription pathway;RNA Polymerase II Transcription (Consensus)

Recessive Scores

• pRec: 0.607

Intolerance Scores

• loftool: 0.0180
• rvis_EVS: -0.63
• rvis_percentile_EVS: 17.03

Haploinsufficiency Scores

• pHI: 0.647
• hipred: Y
• hipred_score: 0.775
• ghis: 0.549

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nr4a2
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: nr4a2a
• Affected structure: caudal tuberculum
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;response to hypoxia;neuron migration;response to amphetamine;transcription, DNA-templated;transcription initiation from RNA polymerase II promoter;signal transduction;adult locomotory behavior;post-embryonic development;central nervous system projection neuron axonogenesis;central nervous system neuron differentiation;habenula development;intracellular receptor signaling pathway;cellular response to extracellular stimulus;cellular response to oxidative stress;regulation of dopamine metabolic process;dopamine biosynthetic process;neuron maturation;positive regulation of catalytic activity;steroid hormone mediated signaling pathway;negative regulation of neuron apoptotic process;regulation of respiratory gaseous exchange;fat cell differentiation;positive regulation of transcription by RNA polymerase II;general adaptation syndrome;canonical Wnt signaling pathway;cellular response to corticotropin-releasing hormone stimulus;dopaminergic neuron differentiation;midbrain dopaminergic neuron differentiation;negative regulation of apoptotic signaling pathway
• Cellular component: nucleus;nucleoplasm;transcription factor complex;cytoplasm;nuclear speck
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;steroid hormone receptor activity;nuclear receptor activity;protein binding;beta-catenin binding;zinc ion binding;glucocorticoid receptor binding;protein homodimerization activity;sequence-specific DNA binding;retinoid X receptor binding;protein heterodimerization activity