RAI1retinoic acid induced 1
Autism Reports / Total Reports
16 / 38Rare Variants / Common Variants
31 / 2Aliases
RAI1, SMS, SMCR, KIAA1820, MGC12824Associated Syndromes
Smith-Magenis syndrome, Potocki-Lupski syndrome, Smith-Magenis syndrome, DD, IDChromosome Band
17p11.2Associated Disorders
ID, EPSGenetic Category
Rare Single Gene Mutation, Syndromic, Genetic Association, FunctionalRelevance to Autism
Smith-Magenis syndrome is caused either by large interstitial deletions in the 17p11.2 chromosomal region (Smith et al., 1986) or by mutations in the RAI1 gene (Slager et al., 2003), which is located within the Smith-Magenis chromosomal region. Conversely, Potocki-Lupski syndrome is caused by duplications of the same 17p11.2 chromosomal region (Potocki et al., 2007). Both syndromes share overlapping clinical features, including behavioral problems such as autistic features. RAI1 was included within a 17p11.2 duplication identified in an individual with autism and intellectual disability and showed altered gene expression (Nakamine et al., 2008); it was identified as the single gene in this interval that overlaps with the region affected in Potocki-Lupski syndrome, making it those most likely candidate. A de novo frameshift variant was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while two de novo missense variants (one of which was predicted to be damaging in silico) were identified in ASD probands from the Autism Sequencing Consortium (De Rubeis et al., 2014). A de novo protein-truncating variant in RAI1 was identified in an ASD proband from the Autism Sequencing Consortium in Satterstrom et al., 2020; three protein-truncating variants in this gene were also observed in case samples from the Danish iPSYCH study in this report. Furthermore, TADA analysis of de novo variants from the Simons Simplex Collection and the Autism Sequencing Consortium and protein-truncating variants from iPSYCH in Satterstrom et al., 2020 identified RAI1 as a candidate gene with a false discovery rate (FDR) 0.01. A de novo missense variant in the RAI1 gene that was experimentally shown to significantly reduce BDNF-enhancer-driven transcription activity was identified in a male patient diagnosed with ASD and displaying an atypical Smith-Magenis syndrome presentation in Abad et al., 2018. A two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in Zhou et al., 2022 identified RAI1 as a gene reaching exome-wide significance (P < 2.5E-06).
Molecular Function
Transcriptional regulator of the circadian clock components: CLOCK, BMAL1, BMAL2, PER1/3, CRY1/2, NR1D1/2 and RORA/C. Positively regulates the transcriptional activity of CLOCK a core component of the circadian clock. Regulates transcription through chromatin remodeling by interacting with other proteins in chromatin as well as proteins in the basic transcriptional machinery. May be important for embryonic and postnatal development. May be involved in neuronal differentiation.
External Links
SFARI Genomic Platforms
Reports related to RAI1 (38 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Highly Cited | Mutations in RAI1 associated with Smith-Magenis syndrome | Slager RE , et al. (2003) | No | - |
2 | Primary | Duplication of 17(p11.2p11.2) in a male child with autism and severe language delay | Nakamine A , et al. (2007) | Yes | - |
3 | Highly Cited | Characterization of Potocki-Lupski syndrome (dup(17)(p11.2p11.2)) and delineation of a dosage-sensitive critical interval that can convey an autism phenotype | Potocki L , et al. (2007) | No | - |
4 | Recent Recommendation | How much is too much? Phenotypic consequences of Rai1 overexpression in mice | Girirajan S , et al. (2008) | No | - |
5 | Recent Recommendation | Abnormal maternal behavior, altered sociability, and impaired serotonin metabolism in Rai1-transgenic mice | Girirajan S and Elsea SH (2009) | No | - |
6 | Support | Gene-network analysis identifies susceptibility genes related to glycobiology in autism | van der Zwaag B , et al. (2009) | Yes | - |
7 | Recent Recommendation | Array comparative genomic hybridisation of 52 subjects with a Smith-Magenis-like phenotype: identification of dosage sensitive loci also associated with schizophrenia, autism, and developmental delay | Williams SR , et al. (2009) | No | - |
8 | Recent Recommendation | Identification of uncommon recurrent Potocki-Lupski syndrome-associated duplications and the distribution of rearrangement types and mechanisms in PTLS | Zhang F , et al. (2010) | No | - |
9 | Support | Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with autism spectrum disorder | Koshimizu E , et al. (2013) | Yes | ID, epilepsy |
10 | Highly Cited | Interstitial deletion of (17)(p11.2p11.2) in nine patients | Smith AC , et al. (1986) | No | - |
11 | Support | Three rare diseases in one Sib pair: RAI1, PCK1, GRIN2B mutations associated with Smith-Magenis Syndrome, cytosolic PEPCK deficiency and NMDA receptor glutamate insensitivity | Adams DR , et al. (2014) | No | Hypoglycemia, lactic acidosis |
12 | Support | Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing | Redin C , et al. (2014) | No | - |
13 | Support | Synaptic, transcriptional and chromatin genes disrupted in autism | De Rubeis S , et al. (2014) | Yes | - |
14 | Support | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
15 | Support | Large-scale discovery of novel genetic causes of developmental disorders | Deciphering Developmental Disorders Study (2014) | No | - |
16 | Recent Recommendation | Increased expression of retinoic acid-induced gene 1 in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, and major depression | Haybaeck J , et al. (2015) | No | - |
17 | Recent Recommendation | Low load for disruptive mutations in autism genes and their biased transmission | Iossifov I , et al. (2015) | Yes | - |
18 | Recent Recommendation | Molecular and Neural Functions of Rai1, the Causal Gene for Smith-Magenis Syndrome | Huang WH , et al. (2016) | No | - |
19 | Recent Recommendation | Rai1 Haploinsufficiency Is Associated with Social Abnormalities in Mice | Rao NR , et al. (2017) | No | - |
20 | Support | Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients | Chrot E , et al. (2017) | No | Behavioral disorder (including stereotypies) |
21 | Support | A Rare De Novo RAI1 Gene Mutation Affecting BDNF-Enhancer-Driven Transcription Activity Associated with Autism and Atypical Smith-Magenis Syndrome Presentation | Abad C , et al. (2018) | Yes | - |
22 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
23 | Support | Next-Generation Sequencing in Korean Children With Autism Spectrum Disorder and Comorbid Epilepsy | Lee J et al. (2020) | Yes | - |
24 | Support | RAI1 Regulates Activity-Dependent Nascent Transcription and Synaptic Scaling | Garay PM et al. (2020) | No | - |
25 | Support | - | Ohashi K et al. (2021) | Yes | - |
26 | Support | - | Javed S et al. (2021) | No | - |
27 | Support | - | Krgovic D et al. (2022) | Yes | ADHD, DD, ID |
28 | Support | - | Sironi A et al. (2022) | No | Stereotypy |
29 | Support | - | Levchenko O et al. (2022) | No | - |
30 | Support | - | Zhou X et al. (2022) | Yes | - |
31 | Support | - | Chang YT et al. (2022) | No | - |
32 | Support | - | Turco EM et al. (2022) | No | - |
33 | Support | - | Wang J et al. (2023) | Yes | - |
34 | Support | - | Sheth F et al. (2023) | Yes | DD, ID, epilepsy/seizures |
35 | Support | - | Ya-Ting Chang et al. (2024) | No | - |
36 | Support | - | Marketa Wayhelova et al. (2024) | No | - |
37 | Positive Association | - | Xi Yuan et al. (2024) | Yes | - |
38 | Support | - | Axel Schmidt et al. (2024) | Yes | - |
Rare Variants (31)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
- | - | copy_number_gain | - | - | - | 20188345 | Zhang F , et al. (2010) | |
- | - | copy_number_loss | Unknown | - | - | 32477112 | Lee J et al. (2020) | |
- | - | copy_number_loss | - | - | - | 19492091 | van der Zwaag B , et al. (2009) | |
- | - | copy_number_gain | De novo | - | - | 17334992 | Nakamine A , et al. (2007) | |
- | - | copy_number_loss | De novo | - | Simplex | 35821519 | Sironi A et al. (2022) | |
c.5566-1G>C | - | splice_site_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.4678C>T | p.Arg1560Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.2273G>A | p.Trp758Ter | stop_gained | De novo | - | - | 24863970 | Adams DR , et al. (2014) | |
c.3649C>T | p.Arg1217Trp | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.13C>T | p.Arg5Ter | stop_gained | De novo | - | - | 38321498 | Marketa Wayhelova et al. (2024) | |
c.4710C>T | p.Pro1570%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.3265C>T | p.Arg1089Ter | stop_gained | De novo | - | Simplex | 37393044 | Wang J et al. (2023) | |
c.1664C>T | p.Thr555Ile | missense_variant | De novo | - | - | 25363760 | De Rubeis S , et al. (2014) | |
c.2347G>A | p.Asp783Asn | missense_variant | De novo | - | - | 25363760 | De Rubeis S , et al. (2014) | |
c.422A>T | p.Tyr141Phe | missense_variant | Unknown | - | Simplex | 37543562 | Sheth F et al. (2023) | |
c.3440G>A | p.Arg1147Gln | missense_variant | De novo | - | Simplex | 29794985 | Abad C , et al. (2018) | |
c.3130C>T | p.Pro1044Ser | missense_variant | Unknown | - | Simplex | 37543562 | Sheth F et al. (2023) | |
c.2879del | p.Arg960GlnfsTer104 | frameshift_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.4342dup | p.Ser1448LysfsTer42 | frameshift_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.304G>A | p.Val102Ile | missense_variant | Familial | Maternal | - | 33590427 | Ohashi K et al. (2021) | |
c.629C>G | p.Pro210Arg | missense_variant | De novo | - | Simplex | 35887114 | Levchenko O et al. (2022) | |
c.1854del | p.Ile618MetfsTer201 | frameshift_variant | De novo | - | - | 35813072 | Krgovic D et al. (2022) | |
c.1148C>T | p.Pro383Leu | missense_variant | Unknown | - | Unknown | 24066114 | Koshimizu E , et al. (2013) | |
c.4238T>C | p.Met1413Thr | missense_variant | Unknown | - | Unknown | 24066114 | Koshimizu E , et al. (2013) | |
c.2966_2969del | p.Lys989SerfsTer74 | frameshift_variant | De novo | - | - | 28708303 | Chrot E , et al. (2017) | |
c.3575del | p.Ser1192ThrfsTer8 | frameshift_variant | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) | |
c.1069_1070insC | p.Ser357ThrfsTer32 | frameshift_variant | De novo | - | - | 39039281 | Axel Schmidt et al. (2024) | |
c.2332_2336del | p.Gly778GlnfsTer7 | frameshift_variant | De novo | - | Simplex | 25167861 | Redin C , et al. (2014) | |
c.412del | p.Val138TrpfsTer8 | frameshift_variant | De novo | - | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
c.2526_2545del | p.His843LeufsTer19 | frameshift_variant | De novo | - | - | 38321498 | Marketa Wayhelova et al. (2024) | |
c.1471G>A | p.Glu491Lys | missense_variant | De novo | - | Unknown | 25533962 | Deciphering Developmental Disorders Study (2014) |
Common Variants (2)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.-149+11644G>C;c.-149+7249G>C;c.-149+9734G>C;c.-17+11644G>C | - | intron_variant | - | - | - | 38674394 | Xi Yuan et al. (2024) | |
N/A | N/A | copy_number_gain | - | - | - | 20188345 | Zhang F , et al. (2010) |
SFARI Gene score
High Confidence, Syndromic
Score Delta: Score remained at 1S
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.
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."
1/1/2021
Score remained at 1
Description
Smith-Magenis syndrome is caused either by large interstitial deletions in the 17p11.2 chromosomal region (Smith et al., 1986) or by mutations in the RAI1 gene (Slager et al., 2003), which is located within the Smith-Magenis chromosomal region. Conversely, Potocki-Lupski syndrome is caused by duplications of the same 17p11.2 chromosomal region (Potocki et al., 2007). Both syndromes share overlapping clinical features, including behavioral problems such as autistic features. RAI1 was included within a 17p11.2 duplication identified in an individual with autism and intellectual disability and showed altered gene expression (Nakamine et al., 2008); it was identified as the single gene in this interval that overlaps with the region affected in Potocki-Lupski syndrome, making it those most likely candidate. A de novo frameshift variant was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while two de novo missense variants (one of which was predicted to be damaging in silico) were identified in ASD probands from the Autism Sequencing Consortium (De Rubeis et al., 2014). A de novo missense variant in the RAI1 gene that was experimentally shown to significantly reduce BDNF-enhancer-driven transcription activity was identified in a male patient diagnosed with ASD and displaying an atypical Smith-Magenis syndrome presentation in Abad et al., 2018.
7/1/2020
Score remained at 1
Description
Smith-Magenis syndrome is caused either by large interstitial deletions in the 17p11.2 chromosomal region (Smith et al., 1986) or by mutations in the RAI1 gene (Slager et al., 2003), which is located within the Smith-Magenis chromosomal region. Conversely, Potocki-Lupski syndrome is caused by duplications of the same 17p11.2 chromosomal region (Potocki et al., 2007). Both syndromes share overlapping clinical features, including behavioral problems such as autistic features. RAI1 was included within a 17p11.2 duplication identified in an individual with autism and intellectual disability and showed altered gene expression (Nakamine et al., 2008); it was identified as the single gene in this interval that overlaps with the region affected in Potocki-Lupski syndrome, making it those most likely candidate. A de novo frameshift variant was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while two de novo missense variants (one of which was predicted to be damaging in silico) were identified in ASD probands from the Autism Sequencing Consortium (De Rubeis et al., 2014). A de novo missense variant in the RAI1 gene that was experimentally shown to significantly reduce BDNF-enhancer-driven transcription activity was identified in a male patient diagnosed with ASD and displaying an atypical Smith-Magenis syndrome presentation in Abad et al., 2018.
4/1/2020
Score remained at 1
Description
Smith-Magenis syndrome is caused either by large interstitial deletions in the 17p11.2 chromosomal region (Smith et al., 1986) or by mutations in the RAI1 gene (Slager et al., 2003), which is located within the Smith-Magenis chromosomal region. Conversely, Potocki-Lupski syndrome is caused by duplications of the same 17p11.2 chromosomal region (Potocki et al., 2007). Both syndromes share overlapping clinical features, including behavioral problems such as autistic features. RAI1 was included within a 17p11.2 duplication identified in an individual with autism and intellectual disability and showed altered gene expression (Nakamine et al., 2008); it was identified as the single gene in this interval that overlaps with the region affected in Potocki-Lupski syndrome, making it those most likely candidate. A de novo frameshift variant was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while two de novo missense variants (one of which was predicted to be damaging in silico) were identified in ASD probands from the Autism Sequencing Consortium (De Rubeis et al., 2014). A de novo missense variant in the RAI1 gene that was experimentally shown to significantly reduce BDNF-enhancer-driven transcription activity was identified in a male patient diagnosed with ASD and displaying an atypical Smith-Magenis syndrome presentation in Abad et al., 2018.
1/1/2020
Score remained at 1
Description
Smith-Magenis syndrome is caused either by large interstitial deletions in the 17p11.2 chromosomal region (Smith et al., 1986) or by mutations in the RAI1 gene (Slager et al., 2003), which is located within the Smith-Magenis chromosomal region. Conversely, Potocki-Lupski syndrome is caused by duplications of the same 17p11.2 chromosomal region (Potocki et al., 2007). Both syndromes share overlapping clinical features, including behavioral problems such as autistic features. RAI1 was included within a 17p11.2 duplication identified in an individual with autism and intellectual disability and showed altered gene expression (Nakamine et al., 2008); it was identified as the single gene in this interval that overlaps with the region affected in Potocki-Lupski syndrome, making it those most likely candidate. A de novo frameshift variant was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while two de novo missense variants (one of which was predicted to be damaging in silico) were identified in ASD probands from the Autism Sequencing Consortium (De Rubeis et al., 2014). A de novo missense variant in the RAI1 gene that was experimentally shown to significantly reduce BDNF-enhancer-driven transcription activity was identified in a male patient diagnosed with ASD and displaying an atypical Smith-Magenis syndrome presentation in Abad et al., 2018.
10/1/2019
Decreased from 3S to 1
New Scoring Scheme
Description
Smith-Magenis syndrome is caused either by large interstitial deletions in the 17p11.2 chromosomal region (Smith et al., 1986) or by mutations in the RAI1 gene (Slager et al., 2003), which is located within the Smith-Magenis chromosomal region. Conversely, Potocki-Lupski syndrome is caused by duplications of the same 17p11.2 chromosomal region (Potocki et al., 2007). Both syndromes share overlapping clinical features, including behavioral problems such as autistic features. RAI1 was included within a 17p11.2 duplication identified in an individual with autism and intellectual disability and showed altered gene expression (Nakamine et al., 2008); it was identified as the single gene in this interval that overlaps with the region affected in Potocki-Lupski syndrome, making it those most likely candidate. A de novo frameshift variant was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while two de novo missense variants (one of which was predicted to be damaging in silico) were identified in ASD probands from the Autism Sequencing Consortium (De Rubeis et al., 2014). A de novo missense variant in the RAI1 gene that was experimentally shown to significantly reduce BDNF-enhancer-driven transcription activity was identified in a male patient diagnosed with ASD and displaying an atypical Smith-Magenis syndrome presentation in Abad et al., 2018.
Reports Added
[New Scoring Scheme]7/1/2018
Increased from S to 3S
Description
Smith-Magenis syndrome is caused either by large interstitial deletions in the 17p11.2 chromosomal region (Smith et al., 1986) or by mutations in the RAI1 gene (Slager et al., 2003), which is located within the Smith-Magenis chromosomal region. Conversely, Potocki-Lupski syndrome is caused by duplications of the same 17p11.2 chromosomal region (Potocki et al., 2007). Both syndromes share overlapping clinical features, including behavioral problems such as autistic features. RAI1 was included within a 17p11.2 duplication identified in an individual with autism and intellectual disability and showed altered gene expression (Nakamine et al., 2008); it was identified as the single gene in this interval that overlaps with the region affected in Potocki-Lupski syndrome, making it those most likely candidate. A de novo frameshift variant was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while two de novo missense variants (one of which was predicted to be damaging in silico) were identified in ASD probands from the Autism Sequencing Consortium (De Rubeis et al., 2014). A de novo missense variant in the RAI1 gene that was experimentally shown to significantly reduce BDNF-enhancer-driven transcription activity was identified in a male patient diagnosed with ASD and displaying an atypical Smith-Magenis syndrome presentation in Abad et al., 2018.
7/1/2017
Increased from S to S
Description
RAI1 is included in a region that is duplicated in an individual with autism/MR, and shows altered gene expression (PMID: 17334992). It was identified as the single gene in this interval that overlaps with the region affected in Potocki-Lupski syndrome, making it those most likely candidate. There is no evidence implicating it in idiopathic autism.
4/1/2017
Increased from S to S
Description
RAI1 is included in a region that is duplicated in an individual with autism/MR, and shows altered gene expression (PMID: 17334992). It was identified as the single gene in this interval that overlaps with the region affected in Potocki-Lupski syndrome, making it those most likely candidate. There is no evidence implicating it in idiopathic autism.
Reports Added
[Duplication of 17(p11.2p11.2) in a male child with autism and severe language delay.2007] [Gene-network analysis identifies susceptibility genes related to glycobiology in autism.2009] [Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...2013] [Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014] [Identification of uncommon recurrent Potocki-Lupski syndrome-associated duplications and the distribution of rearrangement types and mechanisms in ...2010] [Array comparative genomic hybridisation of 52 subjects with a Smith-Magenis-like phenotype: identification of dosage sensitive loci also associated...2009] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Mutations in RAI1 associated with Smith-Magenis syndrome.2003] [How much is too much? Phenotypic consequences of Rai1 overexpression in mice.2008] [Abnormal maternal behavior, altered sociability, and impaired serotonin metabolism in Rai1-transgenic mice.2009] [Increased expression of retinoic acid-induced gene 1 in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, and major depression.2015] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Molecular and Neural Functions of Rai1, the Causal Gene for Smith-Magenis Syndrome.2016] [Rai1 Haploinsufficiency Is Associated with Social Abnormalities in Mice.2017]10/1/2016
Increased from S to S
Description
RAI1 is included in a region that is duplicated in an individual with autism/MR, and shows altered gene expression (PMID: 17334992). It was identified as the single gene in this interval that overlaps with the region affected in Potocki-Lupski syndrome, making it those most likely candidate. There is no evidence implicating it in idiopathic autism.
1/1/2016
Increased from S to S
Description
RAI1 is included in a region that is duplicated in an individual with autism/MR, and shows altered gene expression (PMID: 17334992). It was identified as the single gene in this interval that overlaps with the region affected in Potocki-Lupski syndrome, making it those most likely candidate. There is no evidence implicating it in idiopathic autism.
Reports Added
[Duplication of 17(p11.2p11.2) in a male child with autism and severe language delay.2007] [Gene-network analysis identifies susceptibility genes related to glycobiology in autism.2009] [Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...2013] [Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014] [Identification of uncommon recurrent Potocki-Lupski syndrome-associated duplications and the distribution of rearrangement types and mechanisms in ...2010] [Array comparative genomic hybridisation of 52 subjects with a Smith-Magenis-like phenotype: identification of dosage sensitive loci also associated...2009] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Mutations in RAI1 associated with Smith-Magenis syndrome.2003] [How much is too much? Phenotypic consequences of Rai1 overexpression in mice.2008] [Abnormal maternal behavior, altered sociability, and impaired serotonin metabolism in Rai1-transgenic mice.2009] [Increased expression of retinoic acid-induced gene 1 in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, and major depression.2015] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Low load for disruptive mutations in autism genes and their biased transmission.2015] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014]1/1/2015
Increased from S to S
Description
RAI1 is included in a region that is duplicated in an individual with autism/MR, and shows altered gene expression (PMID: 17334992). It was identified as the single gene in this interval that overlaps with the region affected in Potocki-Lupski syndrome, making it those most likely candidate. There is no evidence implicating it in idiopathic autism.
Reports Added
[Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Increased expression of retinoic acid-induced gene 1 in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, and major depression.2015]Krishnan Probability Score
Score 0.4818310536303
Ranking 7890/25841 scored genes
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ExAC Score
Score 0.99913611187699
Ranking 1035/18225 scored genes
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Iossifov Probability Score
Score 0.983
Ranking 41/239 scored genes
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Sanders TADA Score
Score 0.32388577342716
Ranking 199/18665 scored genes
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Zhang D Score
Score 0.40262137298965
Ranking 1432/20870 scored genes
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CNVs associated with RAI1(1 CNVs)
Sort By:
17p11.2 | 65 | Deletion-Duplication | 85 / 339 |