NR4A2nuclear receptor subfamily 4 group A member 2
Autism Reports / Total Reports
8 / 11Rare Variants / Common Variants
19 / 0Aliases
NR4A2, HZF-3, NOT, NURR1, RNR1, TINURAssociated Syndromes
-Chromosome Band
2q24.1Associated Disorders
ASDGenetic Category
Rare Single Gene Mutation, SyndromicRelevance to Autism
De novo deletions encompassing the NR4A2 gene were identified in three unrelated individuals with developmental delay/intellectual disability and language delay/impairment, two of whom also met DSM-5 criteria for a diagnosis of ASD, in Levy et al., 2018; in contrast, no CNVs encompassing this gene were reported in the Database of Genomic Variants (DGV). De novo deletions affecting this gene had previously been identified in individuals with intellectual disability and language delay/impairment (one of whom was also diagnosed with ASD) in three separate reports (Barge-Schaapveld et al., 2013; Leppa et al., 2016; Reuter et al., 2017). A de novo damaging missense variant in the NR4A2 gene was observed in an ASD proband from the Simons Simplex Collection (O'Roak et al., 2012).
Molecular Function
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.
External Links
SFARI Genomic Platforms
Reports related to NR4A2 (11 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Support | Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations | O'Roak BJ , et al. (2012) | Yes | - |
2 | Support | Intellectual disability and hemizygous GPD2 mutation | Barge-Schaapveld DQ , et al. (2013) | No | - |
3 | Support | Rare Inherited and De Novo CNVs Reveal Complex Contributions to ASD Risk in Multiplex Families | Leppa VM , et al. (2016) | Yes | - |
4 | Support | Haploinsufficiency of NR4A2 is associated with a neurodevelopmental phenotype with prominent language impairment | Reuter MS , et al. (2017) | No | - |
5 | Primary | NR4A2 haploinsufficiency is associated with intellectual disability and autism spectrum disorder | Lvy J , et al. (2018) | Yes | - |
6 | Support | Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes | Guo H , et al. (2018) | Yes | - |
7 | Support | Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes | Feliciano P et al. (2019) | Yes | - |
8 | Recent Recommendation | De novo variants of NR4A2 are associated with neurodevelopmental disorder and epilepsy | Singh S et al. (2020) | No | ASD |
9 | Support | - | Krgovic D et al. (2022) | Yes | ID |
10 | Support | - | Zhou X et al. (2022) | Yes | - |
11 | Support | - | Suhua Chang et al. () | Yes | - |
Rare Variants (19)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
- | - | copy_number_loss | De novo | - | - | 32366965 | Singh S et al. (2020) | |
- | - | copy_number_loss | De novo | - | - | 28544326 | Reuter MS , et al. (2017) | |
- | - | copy_number_loss | De novo | - | Simplex | 29770430 | Lvy J , et al. (2018) | |
- | - | copy_number_loss | De novo | - | Simplex | 27569545 | Leppa VM , et al. (2016) | |
- | - | copy_number_loss | De novo | - | - | 23554088 | Barge-Schaapveld DQ , et al. (2013) | |
c.571C>T | p.Gln191Ter | stop_gained | De novo | - | - | 35813072 | Krgovic D et al. (2022) | |
c.839G>A | p.Cys280Tyr | missense_variant | De novo | - | - | 32366965 | Singh S et al. (2020) | |
c.857T>C | p.Phe286Ser | missense_variant | De novo | - | - | 32366965 | Singh S et al. (2020) | |
c.1175A>G | p.Asp392Gly | missense_variant | De novo | - | - | 32366965 | Singh S et al. (2020) | |
c.914G>A | p.Cys305Tyr | missense_variant | De novo | - | Simplex | 32366965 | Singh S et al. (2020) | |
c.968G>T | p.Cys323Phe | missense_variant | De novo | - | Simplex | 32366965 | Singh S et al. (2020) | |
c.1576G>T | p.Glu526Ter | stop_gained | Unknown | Not maternal | - | 32366965 | Singh S et al. (2020) | |
c.325dup | p.Gln109ProfsTer3 | frameshift_variant | De novo | - | - | 32366965 | Singh S et al. (2020) | |
c.823T>C | p.Tyr275His | missense_variant | De novo | - | Simplex | 22495309 | O'Roak BJ , et al. (2012) | |
c.865-1_865delinsAAAAAGGAGT | - | splice_site_variant | De novo | - | - | 32366965 | Singh S et al. (2020) | |
c.693del | p.Phe232SerfsTer69 | frameshift_variant | De novo | - | - | 31452935 | Feliciano P et al. (2019) | |
c.598_599insGTCC | p.Val200GlyfsTer83 | frameshift_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.860_864del | p.Phe287SerfsTer15 | frameshift_variant | De novo | - | Simplex | 39126614 | Suhua Chang et al. () | |
c.354_355insGTCC | p.Ser119ValfsTer62 | frameshift_variant | De novo | - | Simplex | 30504930 | Guo H , et al. (2018) |
Common Variants
No common variants reported.
SFARI Gene score
High Confidence
Score Delta: Score remained at 1
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
4/1/2020
Score remained at 1
Description
De novo deletions encompassing the NR4A2 gene were identified in three unrelated individuals with developmental delay/intellectual disability and language delay/impairment, two of whom also met DSM-5 criteria for a diagnosis of ASD, in Levy et al., 2018; in contrast, no CNVs encompassing this gene were reported in the Database of Genomic Variants (DGV). De novo deletions affecting this gene had previously been identified in individuals with intellectual disability and language delay/impairment (one of whom was also diagnosed with ASD) in three separate reports (Barge-Schaapveld et al., 2013; Leppa et al., 2016; Reuter et al., 2017). A de novo damaging missense variant in the NR4A2 gene was observed in an ASD proband from the Simons Simplex Collection (O'Roak et al., 2012).
10/1/2019
Decreased from 4 to 1
New Scoring Scheme
Description
De novo deletions encompassing the NR4A2 gene were identified in three unrelated individuals with developmental delay/intellectual disability and language delay/impairment, two of whom also met DSM-5 criteria for a diagnosis of ASD, in Levy et al., 2018; in contrast, no CNVs encompassing this gene were reported in the Database of Genomic Variants (DGV). De novo deletions affecting this gene had previously been identified in individuals with intellectual disability and language delay/impairment (one of whom was also diagnosed with ASD) in three separate reports (Barge-Schaapveld et al., 2013; Leppa et al., 2016; Reuter et al., 2017). A de novo damaging missense variant in the NR4A2 gene was observed in an ASD proband from the Simons Simplex Collection (O'Roak et al., 2012).
10/1/2018
Decreased from 4 to 4
Description
De novo deletions encompassing the NR4A2 gene were identified in three unrelated individuals with developmental delay/intellectual disability and language delay/impairment, two of whom also met DSM-5 criteria for a diagnosis of ASD, in Levy et al., 2018; in contrast, no CNVs encompassing this gene were reported in the Database of Genomic Variants (DGV). De novo deletions affecting this gene had previously been identified in individuals with intellectual disability and language delay/impairment (one of whom was also diagnosed with ASD) in three separate reports (Barge-Schaapveld et al., 2013; Leppa et al., 2016; Reuter et al., 2017). A de novo damaging missense variant in the NR4A2 gene was observed in an ASD proband from the Simons Simplex Collection (O'Roak et al., 2012).
7/1/2018
Increased from to 4
Description
De novo deletions encompassing the NR4A2 gene were identified in three unrelated individuals with developmental delay/intellectual disability and language delay/impairment, two of whom also met DSM-5 criteria for a diagnosis of ASD, in Levy et al., 2018; in contrast, no CNVs encompassing this gene were reported in the Database of Genomic Variants (DGV). De novo deletions affecting this gene had previously been identified in individuals with intellectual disability and language delay/impairment (one of whom was also diagnosed with ASD) in three separate reports (Barge-Schaapveld et al., 2013; Leppa et al., 2016; Reuter et al., 2017). A de novo damaging missense variant in the NR4A2 gene was observed in an ASD proband from the Simons Simplex Collection (O'Roak et al., 2012).
Krishnan Probability Score
Score 0.57232097632821
Ranking 713/25841 scored genes
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ExAC Score
Score 0.99143286550823
Ranking 1744/18225 scored genes
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Sanders TADA Score
Score 0.75828136767205
Ranking 1640/18665 scored genes
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Zhang D Score
Score 0.47752191524009
Ranking 678/20870 scored genes
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