Human Gene Module / Chromosome 5 / NR2F1

NR2F1nuclear receptor subfamily 2 group F member 1

SFARI Gene Score
2S
Strong Candidate, Syndromic Criteria 2.1, Syndromic
Autism Reports / Total Reports
10 / 27
Rare Variants / Common Variants
78 / 1
Aliases
NR2F1, BBOAS,  BBSOAS,  COUP-TFI,  EAR-3,  EAR3,  ERBAL3,  NR2F2,  SVP44,  TCFCOUP1,  TFCOUP1
Associated Syndromes
Bosch-Boonstra-Schaaf optic atrophy syndrome, Bosch-Boonstra-Schaaf optic atrophy syndrome, DD, Tourette syndrome
Chromosome Band
5q15
Associated Disorders
DD/NDD, ADHD, ID, EPS, ASD
Relevance to Autism

One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).

Molecular Function

The protein encoded by this gene is a nuclear hormone receptor and transcriptional regulator that binds to 5'-AGGTCA-3' repeats. Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome Informatics
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to NR2F1 (27 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support De novo mutations revealed by whole-exome sequencing are strongly associated with autism Sanders SJ , et al. (2012) Yes -
2 Primary NR2F1 mutations cause optic atrophy with intellectual disability Bosch DG , et al. (2014) No ID, ASD
3 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
4 Recent Recommendation The expanding clinical phenotype of Bosch-Boonstra-Schaaf optic atrophy syndrome: 20 new cases and possible genotype-phenotype correlations Chen CA , et al. (2016) No ID, ASD, epilepsy/seizures, ADHD
5 Support Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability Lelieveld SH et al. (2016) No -
6 Support The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies Redin C , et al. (2016) No Multiple congenital anomalies
7 Support Lessons learned from additional research analyses of unsolved clinical exome cases Eldomery MK , et al. (2017) Yes -
8 Support A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology Vissers LE , et al. (2017) No -
9 Support Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism Chen R , et al. (2017) Yes -
10 Support Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder Lim ET , et al. (2017) Yes -
11 Support The combination of whole-exome sequencing and copy number variation sequencing enables the diagnosis of rare neurological disorders Jiao Q , et al. (2019) No DD, ID
12 Support Increased diagnostic and new genes identification outcome using research reanalysis of singleton exome sequencing Bruel AL , et al. (2019) No -
13 Support Autism risk in offspring can be assessed through quantification of male sperm mosaicism Breuss MW , et al. (2019) Yes -
14 Support Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use Husson T , et al. (2020) Yes -
15 Recent Recommendation Phenotypic expansion of Bosch-Boonstra-Schaaf optic atrophy syndrome and further evidence for genotype-phenotype correlations Rech ME et al. (2020) No ASD or autistic features, ADHD
16 Recent Recommendation Imbalance of Excitatory/Inhibitory Neuron Differentiation in Neurodevelopmental Disorders with an NR2F1 Point Mutation Zhang K et al. (2020) Yes -
17 Support Missense NR2F1 variant in monozygotic twins affected with the Bosch-Boonstra-Schaaf optic atrophy syndrome Mio C et al. (2020) No -
18 Support NR2F1 regulates regional progenitor dynamics in the mouse neocortex and cortical gyrification in BBSOAS patients Bertacchi M et al. (2020) No -
19 Support Novel dominant-negative NR2F1 frameshift mutation and a phenotypic expansion of the Bosch-Boonstra-Schaaf optic atrophy syndrome Walsh S et al. (2020) No ASD, DD, epilepsy/seizures
20 Recent Recommendation - Jurkute N et al. (2021) No ASD, ADHD, learning disability, epilepsy/seizures
21 Support - Billiet B et al. (2021) No -
22 Support - Zhou X et al. (2022) Yes -
23 Positive Association - Tsetsos F et al. (2023) No -
24 Support - Yuan B et al. (2023) Yes -
25 Support - Spataro N et al. (2023) No -
26 Support - Bonzano S et al. (2023) No -
27 Support - et al. () No -
Rare Variants   (78)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Unknown - - 32275123 Rech ME et al. (2020)
- - copy_number_loss De novo - - 26986877 Chen CA , et al. (2016)
- - copy_number_loss Unknown - - 26986877 Chen CA , et al. (2016)
- - copy_number_loss De novo - - 24462372 Bosch DG , et al. (2014)
- - copy_number_loss Unknown - - 24462372 Bosch DG , et al. (2014)
- - copy_number_loss De novo - - 34466801 Jurkute N et al. (2021)
- - copy_number_loss Familial Maternal - 32275123 Rech ME et al. (2020)
- - complex_structural_alteration De novo - - 27841880 Redin C , et al. (2016)
c.1117C>T p.Arg373Ter stop_gained De novo - - 32275123 Rech ME et al. (2020)
c.115G>T p.Glu39Ter stop_gained De novo - - 34466801 Jurkute N et al. (2021)
c.353T>G p.Leu118Ter stop_gained De novo - - 34466801 Jurkute N et al. (2021)
c.513G>C p.Tyr171Ter stop_gained Unknown - - 34466801 Jurkute N et al. (2021)
c.698G>A p.Trp233Ter stop_gained De novo - - 34466801 Jurkute N et al. (2021)
- - copy_number_loss Familial Paternal Simplex 26986877 Chen CA , et al. (2016)
c.1198G>T p.Glu400Ter stop_gained De novo - - 34466801 Jurkute N et al. (2021)
c.766T>G p.Trp256Gly missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.256T>C p.Cys86Arg missense_variant De novo - - 32275123 Rech ME et al. (2020)
c.262G>A p.Val88Met missense_variant De novo - - 32275123 Rech ME et al. (2020)
c.284G>T p.Gly95Val missense_variant Unknown - - 32275123 Rech ME et al. (2020)
c.290A>C p.His97Pro missense_variant Unknown - - 32275123 Rech ME et al. (2020)
c.293A>G p.Tyr98Cys missense_variant De novo - - 32275123 Rech ME et al. (2020)
c.124C>T p.Gln42Ter stop_gained De novo - Simplex 35982159 Zhou X et al. (2022)
c.311A>G p.Glu104Gly missense_variant De novo - - 32275123 Rech ME et al. (2020)
c.323G>T p.Ser108Ile missense_variant Unknown - - 32275123 Rech ME et al. (2020)
c.365G>C p.Cys122Ser missense_variant Unknown - - 32275123 Rech ME et al. (2020)
c.417A>T p.Gln139His missense_variant De novo - - 32275123 Rech ME et al. (2020)
c.931G>C p.Ala311Pro missense_variant Unknown - - 32275123 Rech ME et al. (2020)
c.954G>C p.Glu318Asp missense_variant De novo - - 32275123 Rech ME et al. (2020)
c.82C>T p.Gln28Ter stop_gained De novo - Simplex 28344757 Chen R , et al. (2017)
c.993C>T p.Asp331%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.1217T>C p.Met406Thr missense_variant De novo - - 32275123 Rech ME et al. (2020)
c.2T>C p.Met1? initiator_codon_variant De novo - - 30945278 Jiao Q , et al. (2019)
c.1A>G p.Met1? initiator_codon_variant De novo - - 32275123 Rech ME et al. (2020)
c.2T>C p.Met1? initiator_codon_variant De novo - - 32275123 Rech ME et al. (2020)
c.382T>C p.Cys128Arg missense_variant De novo - - 26986877 Chen CA , et al. (2016)
c.403C>A p.Arg135Ser missense_variant De novo - - 26986877 Chen CA , et al. (2016)
c.413G>A p.Cys138Tyr missense_variant De novo - - 26986877 Chen CA , et al. (2016)
c.425G>T p.Arg142Leu missense_variant De novo - - 26986877 Chen CA , et al. (2016)
c.436T>C p.Cys146Arg missense_variant De novo - - 26986877 Chen CA , et al. (2016)
c.463G>A p.Ala155Thr missense_variant De novo - - 26986877 Chen CA , et al. (2016)
c.289C>T p.His97Tyr missense_variant De novo - - 31231135 Bruel AL , et al. (2019)
c.290A>C p.His97Pro missense_variant De novo - - 34466801 Jurkute N et al. (2021)
c.1103G>A p.Gly368Asp missense_variant De novo - - 26986877 Chen CA , et al. (2016)
c.2T>G p.Met1? initiator_codon_variant De novo - - 26986877 Chen CA , et al. (2016)
c.339C>A p.Ser113Arg missense_variant De novo - - 24462372 Bosch DG , et al. (2014)
c.344G>C p.Arg115Pro missense_variant De novo - - 24462372 Bosch DG , et al. (2014)
c.755T>C p.Leu252Pro missense_variant De novo - - 24462372 Bosch DG , et al. (2014)
c.366C>G p.Cys122Trp missense_variant De novo - - 34466801 Jurkute N et al. (2021)
c.463G>A p.Ala155Thr missense_variant De novo - - 34466801 Jurkute N et al. (2021)
c.599C>G p.Thr200Arg missense_variant De novo - - 34466801 Jurkute N et al. (2021)
c.320A>G p.Lys107Arg missense_variant De novo - - 36980980 Spataro N et al. (2023)
c.1024G>A p.Glu342Lys missense_variant De novo - - 34466801 Jurkute N et al. (2021)
c.1183G>A p.Gly395Ser missense_variant De novo - - 34466801 Jurkute N et al. (2021)
c.403C>T p.Arg135Cys missense_variant De novo - - 31873310 Breuss MW , et al. (2019)
c.91_93dup p.Arg31dup inframe_insertion Unknown - - 34466801 Jurkute N et al. (2021)
c.359dup p.Tyr120Ter frameshift_variant Unknown - - 34466801 Jurkute N et al. (2021)
c.314G>A p.Gly105Asp missense_variant De novo - - 28333917 Vissers LE , et al. (2017)
c.1036_1038del p.Glu346del inframe_deletion De novo - - 35982159 Zhou X et al. (2022)
c.328_330del p.Phe110del inframe_deletion De novo - - 26986877 Chen CA , et al. (2016)
c.305C>T p.Thr102Ile missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.314G>A p.Gly105Asp missense_variant De novo - - 27479843 Lelieveld SH et al. (2016)
c.4del p.Ala2GlnfsTer3 frameshift_variant De novo - - 34466801 Jurkute N et al. (2021)
c.531C>G p.Asp177Glu missense_variant De novo - Simplex 28714951 Lim ET , et al. (2017)
c.21_43del p.Trp8GlyfsTer381 frameshift_variant De novo - - 36881370 Yuan B et al. (2023)
c.291del p.Tyr98ThrfsTer21 frameshift_variant De novo - - 26986877 Chen CA , et al. (2016)
c.335G>A p.Arg112Lys missense_variant De novo - Simplex 24462372 Bosch DG , et al. (2014)
c.380dup p.Asn127LysfsTer270 frameshift_variant Unknown - - 32275123 Rech ME et al. (2020)
c.1184G>C p.Gly395Ala missense_variant De novo - Simplex 32094338 Husson T , et al. (2020)
c.1211G>A p.Arg404His missense_variant De novo - Simplex 22495306 Sanders SJ , et al. (2012)
c.413G>A p.Cys138Tyr missense_variant De novo - Simplex 28327206 Eldomery MK , et al. (2017)
c.51_69dup p.Asn24GlyfsTer379 frameshift_variant Unknown - - 34466801 Jurkute N et al. (2021)
c.2_4delinsGGA p.MetAla1_?2 initiator_codon_variant De novo - - 26986877 Chen CA , et al. (2016)
c.1036_1047del p.Glu346_Gln349del inframe_deletion Unknown - - 34466801 Jurkute N et al. (2021)
c.1083del p.Asn362ThrfsTer33 frameshift_variant De novo - Simplex 32712214 Walsh S et al. (2020)
c.1115T>C p.Leu372Pro missense_variant Familial Maternal Multiplex 34466801 Jurkute N et al. (2021)
c.103_113delinsCGCCGCCGC p.Gly35ArgfsTer361 frameshift_variant De novo - - 26986877 Chen CA , et al. (2016)
c.313G>A p.Gly105Ser missense_variant De novo - Multiplex (monozygotic twins) 32412696 Mio C et al. (2020)
c.1118_1123del p.Arg373_Leu374del inframe_deletion Familial Maternal Simplex 34466801 Jurkute N et al. (2021)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
T>A - intergenic_variant - - - 36738982 Tsetsos F et al. (2023)
SFARI Gene score
2S

Strong Candidate, Syndromic

Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).

Score Delta: Score remained at 2S

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We 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.

S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

4/1/2022
3S
icon
2S

Decreased from 3S to 2S

Description

Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).

7/1/2020
3S
icon
3S

Decreased from 3S to 3S

Description

Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).

Reports Added
[Novel dominant-negative NR2F1 frameshift mutation and a phenotypic expansion of the Bosch-Boonstra-Schaaf optic atrophy syndrome2020]
4/1/2020
3S
icon
3S

Decreased from 3S to 3S

Description

Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).

Reports Added
[Phenotypic expansion of Bosch-Boonstra-Schaaf optic atrophy syndrome and further evidence for genotype-phenotype correlations2020] [Imbalance of Excitatory/Inhibitory Neuron Differentiation in Neurodevelopmental Disorders with an NR2F1 Point Mutation2020] [Missense NR2F1 variant in monozygotic twins affected with the Bosch-Boonstra-Schaaf optic atrophy syndrome2020] [NR2F1 regulates regional progenitor dynamics in the mouse neocortex and cortical gyrification in BBSOAS patients2020]
1/1/2020
3S
icon
3S

Decreased from 3S to 3S

Description

Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).

Reports Added
[Autism risk in offspring can be assessed through quantification of male sperm mosaicism.2019] [Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use.2020]
10/1/2019
4S
icon
3S

Decreased from 4S to 3S

New Scoring Scheme
Description

Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).

Reports Added
[New Scoring Scheme]
7/1/2019
4S
icon
4S

Decreased from 4S to 4S

Description

Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).

Reports Added
[Increased diagnostic and new genes identification outcome using research reanalysis of singleton exome sequencing.2019]
4/1/2019
4S
icon
4S

Decreased from 4S to 4S

Description

Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).

Reports Added
[The combination of whole-exome sequencing and copy number variation sequencing enables the diagnosis of rare neurological disorders.2019]
7/1/2017
4S
icon
4S

Decreased from 4S to 4S

Description

Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).

Reports Added
[Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder.2017]
4/1/2017
4S
icon
4S

Decreased from 4S to 4S

Description

Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).

Reports Added
[NR2F1 mutations cause optic atrophy with intellectual disability.2014] [The expanding clinical phenotype of Bosch-Boonstra-Schaaf optic atrophy syndrome: 20 new cases and possible genotype-phenotype correlations.2016] [De novo mutations revealed by whole-exome sequencing are strongly associated with autism.2012] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016] [The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016] [Lessons learned from additional research analyses of unsolved clinical exome cases.2017] [Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism.2017] [A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology.2017]
10/1/2016
4S
icon
4S

Decreased from 4S to 4S

Description

Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).

Reports Added
[The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016]
7/1/2016
4S
icon
4S

Decreased from 4S to 4S

Description

Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).

Reports Added
[Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016]
4/1/2016
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4S

Increased from to 4S

Description

Heterozygous mutations in this gene are a cause of Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIM 615722), an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy (Bosch et al., 2014). One of the six patients with Bosch-Boonstra-Schaaf optic atrophy syndrome described in Bosch et al., 2014 presented with autism spectrum disorder with marked obsessive-compulsive behaviors. Evaluation of the clinical features of 20 individuals with novel pathogenic NR2F1 variants demonstrated that, in addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), repetitive behavior (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%) (Chen et al., 2016). De novo probably damaging missense variants in NR2F1 have also been observed in two ASD probands: one from the Simons Simplex Collection (Sanders et al., 2012), the other from the Autism Sequencing Consortium (De Rubeis et al., 2014).

Krishnan Probability Score

Score 0.56619311657082

Ranking 1220/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
Sanders TADA Score

Score 0.40393677506562

Ranking 284/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score 0.2346314388017

Ranking 3695/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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