Human Gene Module / Chromosome 1 / DISC1

DISC1disrupted in schizophrenia 1

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
8 / 34
Rare Variants / Common Variants
16 / 14
Aliases
DISC1, SCZD9,  KIAA0457
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Syndromic, Genetic Association
Chromosome Band
1q42.2
Associated Disorders
SCZ, ASD, BPD
Relevance to Autism

Several studies have found genetic association and rare variants in the DISC1 gene that are associated with autism. Positive associations have been found in the Chinese Han population and in the Finnish population (for both autism and Asperger syndrome; Kilpinen et al., 2008). In addition, genetic association between DISC1 and a psychosis phenotype was found in a Finnish sample, and association with schizophrenia and bipolar disorder was found in some European cohorts.

Molecular Function

This gene encodes a protein with multiple coiled coil motifs and is involved in neurite outgrowth and cortical development through its interaction with other proteins.

Reports related to DISC1 (34 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of ... Morris JA , et al. (2003) No -
2 Highly Cited DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling. Millar JK , et al. (2005) No -
3 Recent Recommendation Behavioral phenotypes of Disc1 missense mutations in mice. Clapcote SJ , et al. (2007) No -
4 Primary Association of DISC1 with autism and Asperger syndrome. Kilpinen H , et al. (2007) Yes Asperger syndrome
5 Recent Recommendation Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain. Duan X , et al. (2007) No -
6 Recent Recommendation DISC1 association, heterogeneity and interplay in schizophrenia and bipolar disorder. Hennah W , et al. (2008) No -
7 Recent Recommendation Nuclear DISC1 regulates CRE-mediated gene transcription and sleep homeostasis in the fruit fly. Sawamura N , et al. (2008) No -
8 Recent Recommendation Replication study of candidate genes for cognitive abilities: the Lothian Birth Cohort 1936. Houlihan LM , et al. (2008) No -
9 Recent Recommendation Association of variants in DISC1 with psychosis-related traits in a large population cohort. Tomppo L , et al. (2009) No -
10 Recent Recommendation Association studies and gene expression analyses of the DISC1-interacting molecules, pericentrin 2 (PCNT2) and DISC1-binding zinc finger protein (D... Anitha A , et al. (2009) No -
11 Support A 1q42 deletion involving DISC1, DISC2, and TSNAX in an autism spectrum disorder. Williams JM , et al. (2009) Yes -
12 Recent Recommendation Roles of disrupted-in-schizophrenia 1-interacting protein girdin in postnatal development of the dentate gyrus. Enomoto A , et al. (2009) No -
13 Support DISC1 duplication in two brothers with autism and mild mental retardation. Crepel A , et al. (2009) Yes MR
14 Recent Recommendation Disrupted-in-Schizophrenia 1 (DISC1) regulates spines of the glutamate synapse via Rac1. Hayashi-Takagi A , et al. (2010) No -
15 Recent Recommendation Knockdown of DISC1 by in utero gene transfer disturbs postnatal dopaminergic maturation in the frontal cortex and leads to adult behavioral deficits. Niwa M , et al. (2010) No -
16 Recent Recommendation DISC1-dependent switch from progenitor proliferation to migration in the developing cortex. Ishizuka K , et al. (2011) No -
17 Positive Association Evidence for association between Disrupted-in-Schizophrenia 1 (DISC1) gene polymorphisms and autism in Chinese Han population: a family-based assoc... Zheng F , et al. (2011) Yes -
18 Recent Recommendation Interplay between DISC1 and GABA signaling regulates neurogenesis in mice and risk for schizophrenia. Kim JY , et al. (2012) No -
19 Support De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Sanders SJ , et al. (2012) Yes -
20 Support Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder. Girirajan S , et al. (2013) Yes -
21 Recent Recommendation mTOR Inhibition ameliorates cognitive and affective deficits caused by Disc1 knockdown in adult-born dentate granule neurons. Zhou M , et al. (2013) No -
22 Positive Association 708 Common and 2010 rare DISC1 locus variants identified in 1542 subjects: analysis for association with psychiatric disorder and cognitive traits. Thomson PA , et al. (2013) No SCZ, BPD
23 Support Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders. Kenny EM , et al. (2013) Yes -
24 Recent Recommendation DISC1 (disrupted-in-schizophrenia-1) regulates differentiation of oligodendrocytes. Hattori T , et al. (2014) No -
25 Support The contribution of de novo coding mutations to autism spectrum disorder. Iossifov I , et al. (2014) Yes -
26 Recent Recommendation Disrupted-in-schizophrenia 1 regulates transport of ITPR1 mRNA for synaptic plasticity. Tsuboi D , et al. (2015) No -
27 Recent Recommendation Genomic DISC1 Disruption in hiPSCs Alters Wnt Signaling and Neural Cell Fate. Srikanth P , et al. (2015) No -
28 Recent Recommendation The cortical thickness phenotype of individuals with DISC1 translocation resembles schizophrenia. Doyle OM , et al. (2015) No -
29 Recent Recommendation DISC1-dependent Regulation of Mitochondrial Dynamics Controls the Morphogenesis of Complex Neuronal Dendrites. Norkett R , et al. (2015) No -
30 Recent Recommendation Early postnatal GABAA receptor modulation reverses deficits in neuronal maturation in a conditional neurodevelopmental mouse model of DISC1. Saito A , et al. (2016) No -
31 Recent Recommendation Missense mutation in DISC1 C-terminal coiled-coil has GSK3 signaling and sex-dependent behavioral effects in mice. Dachtler J , et al. (2016) No -
32 Recent Recommendation DISC1 causes associative memory and neurodevelopmental defects in fruit flies. Furukubo-Tokunaga K , et al. (2016) No -
33 Recent Recommendation Shared effects of DISC1 disruption and elevated WNT signaling in human cerebral organoids. Srikanth P , et al. (2018) No -
34 Recent Recommendation DISC1 regulates lactate metabolism in astrocytes: implications for psychiatric disorders. Jouroukhin Y , et al. (2018) No -
Rare Variants   (16)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain Familial Paternal Multiplex 20002455 Crepel A , et al. (2009)
- - copy_number_loss Familial Maternal Simplex 19606485 Williams JM , et al. (2009)
- - copy_number_loss Familial Paternal Simplex 23375656 Girirajan S , et al. (2013)
c.112C>T p.Arg38Trp missense_variant De novo - Simplex 22495306 Sanders SJ , et al. (2012)
c.248C>T p.Ala83Val missense_variant Unknown - Unknown 23732877 Thomson PA , et al. (2013)
c.479G>T p.Trp160Leu missense_variant Unknown - Unknown 23732877 Thomson PA , et al. (2013)
c.2316delT p.Pro772fs frameshift_variant Unknown - Unknown 24126926 Kenny EM , et al. (2013)
c.1253G>A p.Arg418His missense_variant Unknown - Unknown 23732877 Thomson PA , et al. (2013)
c.1880C>G p.Ala627Gly missense_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
- p.Glu661Lys missense_variant Familial Paternal Simplex 19606485 Williams JM , et al. (2009)
c.816G>A p.(=) synonymous_variant Familial Paternal Multiplex 23732877 Thomson PA , et al. (2013)
c.698G>A p.Arg233Lys missense_variant Familial Maternal Simplex 23732877 Thomson PA , et al. (2013)
c.1819C>T p.Leu607Phe missense_variant Familial Paternal Simplex 19606485 Williams JM , et al. (2009)
c.68-1421_1690-2372del - copy_number_loss Familial Maternal Simplex 23375656 Girirajan S , et al. (2013)
c.109C>T p.Arg37Trp missense_variant Familial Maternal Multi-generational 23732877 Thomson PA , et al. (2013)
c.348G>A p.(=) synonymous_variant Familial (1 case), Unknown (1 case) Paternal (1 case) Multi-generational (1 case), unknown (1 case) 23732877 Thomson PA , et al. (2013)
Common Variants   (14)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.2242-8069T>A;c.2404-8069T>A;c.1942-8069T>A;c.2308-8069T>A - intron_variant - - - 23732877 Thomson PA , et al. (2013)
c.1981+54284A>G;c.2077+54284A>G;c.1615+54284A>G;c.1635-86027A>G - intron_variant - - - 21569632 Zheng F , et al. (2011)
c.1269-6018C>T;c.1365-6018C>T;c.1268+11046C>T;c.219-6018C>T T/C intron_variant - - - 18317464 Hennah W , et al. (2008)
c.1982-467A>G;c.2078-467A>G;c.1616-467A>G;c.1982-50424A>G;c.1635-467A>G - intron_variant - - - 19188535 Tomppo L , et al. (2009)
c.1982-315G>A;c.2078-315G>A;c.1616-315G>A;c.1982-50272G>A;c.1635-315G>A N/A intron_variant - - - 19188535 Tomppo L , et al. (2009)
c.1635-2053G>A;c.1731-2053G>A;c.1269-2053G>A;c.1634+22119G>A;c.584+22119G>A - intron_variant - - - 18317464 Hennah W , et al. (2008)
c.1819C>T;c.1915C>T;c.1453C>T;c.1716C>T;c.1634+47285C>T;c.*5C>T p.Leu607Phe missense_variant - - - 18317464 Hennah W , et al. (2008)
c.1635-2053G>A;c.1731-2053G>A;c.1269-2053G>A;c.1634+22119G>A;c.584+22119G>A - intron_variant - - - 17579608 Kilpinen H , et al. (2007)
c.1982-27517T>G;c.2078-27517T>G;c.1616-27517T>G;c.1982-77474T>G;c.1635-27517T>G G/T intron_variant - - - 18317464 Hennah W , et al. (2008)
c.1982-27517T>G;c.2078-27517T>G;c.1616-27517T>G;c.1982-77474T>G;c.1635-27517T>G N/A intron_variant - - - 19188535 Tomppo L , et al. (2009)
c.2110A>T;c.2206A>T;c.1744A>T;c.2049A>T;c.*83A>T p.Ser704Cys;p.Ser736Cys;p.Ser582Cys;p.Arg683Ser missense_variant, 3_prime_UTR_variant - - - 17579608 Kilpinen H , et al. (2007)
- - intron_variant, microsatellite - - - 17579608 Kilpinen H , et al. (2007)
c.68-23286G>C;c.67+43606G>C C/G intron_variant - - - 21569632 Zheng F , et al. (2011)
c.1047+3167T>C;c.68-51954T>C C/T intron_variant - - - 21569632 Zheng F , et al. (2011)
SFARI Gene score
3

Suggestive Evidence

3

Score Delta: Increased from 3 to 4.3 + 4.4 + acc

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

4/1/2016
3
icon
3

Increased from 3 to 3

Description

Evidence for the involvement of DISC1 in autism is suggestive. There have been two gene-based association studies (Kilpinen et al., 2008; Lim et al., 2009) with inconsistent results. In addition, two studies have identified copy number variants in DISC1 in affected individuals. Finally, DISC1 is thought to play a role in the genetic etiology of schizophrenia, a related neuropsychiatric disorder.

Reports Added
[Association of DISC1 with autism and Asperger syndrome.2007] [A 1q42 deletion involving DISC1, DISC2, and TSNAX in an autism spectrum disorder.2009] [DISC1 duplication in two brothers with autism and mild mental retardation.2009] [Evidence for association between Disrupted-in-Schizophrenia 1 (DISC1) gene polymorphisms and autism in Chinese Han population: a family-based assoc...2011] [De novo mutations revealed by whole-exome sequencing are strongly associated with autism.2012] [Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders.2013] [708 Common and 2010 rare DISC1 locus variants identified in 1542 subjects: analysis for association with psychiatric disorder and cognitive traits.2013] [DISC1 association, heterogeneity and interplay in schizophrenia and bipolar disorder.2008] [DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of ...2003] [DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling.2005] [Behavioral phenotypes of Disc1 missense mutations in mice.2007] [Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain.2007] [Nuclear DISC1 regulates CRE-mediated gene transcription and sleep homeostasis in the fruit fly.2008] [Replication study of candidate genes for cognitive abilities: the Lothian Birth Cohort 1936.2008] [Association of variants in DISC1 with psychosis-related traits in a large population cohort.2009] [Association studies and gene expression analyses of the DISC1-interacting molecules, pericentrin 2 (PCNT2) and DISC1-binding zinc finger protein (D...2009] [Roles of disrupted-in-schizophrenia 1-interacting protein girdin in postnatal development of the dentate gyrus.2009] [Disrupted-in-Schizophrenia 1 (DISC1) regulates spines of the glutamate synapse via Rac1.2010] [Knockdown of DISC1 by in utero gene transfer disturbs postnatal dopaminergic maturation in the frontal cortex and leads to adult behavioral deficits.2010] [DISC1-dependent switch from progenitor proliferation to migration in the developing cortex.2011] [Interplay between DISC1 and GABA signaling regulates neurogenesis in mice and risk for schizophrenia.2012] [mTOR Inhibition ameliorates cognitive and affective deficits caused by Disc1 knockdown in adult-born dentate granule neurons.2013] [DISC1 (disrupted-in-schizophrenia-1) regulates differentiation of oligodendrocytes.2014] [Disrupted-in-schizophrenia 1 regulates transport of ITPR1 mRNA for synaptic plasticity.2015] [The cortical thickness phenotype of individuals with DISC1 translocation resembles schizophrenia.2015] [Genomic DISC1 Disruption in hiPSCs Alters Wnt Signaling and Neural Cell Fate.2015] [DISC1-dependent Regulation of Mitochondrial Dynamics Controls the Morphogenesis of Complex Neuronal Dendrites.2015] [The contribution of de novo coding mutations to autism spectrum disorder.2014] [Early postnatal GABAA receptor modulation reverses deficits in neuronal maturation in a conditional neurodevelopmental mouse model of DISC1.2016] [Missense mutation in DISC1 C-terminal coiled-coil has GSK3 signaling and sex-dependent behavioral effects in mice.2016] [DISC1 causes associative memory and neurodevelopmental defects in fruit flies.2016]
1/1/2016
3
icon
3

Increased from 3 to 3

Description

Evidence for the involvement of DISC1 in autism is suggestive. There have been two gene-based association studies (Kilpinen et al., 2008; Lim et al., 2009) with inconsistent results. In addition, two studies have identified copy number variants in DISC1 in affected individuals. Finally, DISC1 is thought to play a role in the genetic etiology of schizophrenia, a related neuropsychiatric disorder.

Reports Added
[Association of DISC1 with autism and Asperger syndrome.2007] [A 1q42 deletion involving DISC1, DISC2, and TSNAX in an autism spectrum disorder.2009] [DISC1 duplication in two brothers with autism and mild mental retardation.2009] [Evidence for association between Disrupted-in-Schizophrenia 1 (DISC1) gene polymorphisms and autism in Chinese Han population: a family-based assoc...2011] [De novo mutations revealed by whole-exome sequencing are strongly associated with autism.2012] [Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders.2013] [708 Common and 2010 rare DISC1 locus variants identified in 1542 subjects: analysis for association with psychiatric disorder and cognitive traits.2013] [DISC1 association, heterogeneity and interplay in schizophrenia and bipolar disorder.2008] [DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of ...2003] [DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling.2005] [Behavioral phenotypes of Disc1 missense mutations in mice.2007] [Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain.2007] [Nuclear DISC1 regulates CRE-mediated gene transcription and sleep homeostasis in the fruit fly.2008] [Replication study of candidate genes for cognitive abilities: the Lothian Birth Cohort 1936.2008] [Association of variants in DISC1 with psychosis-related traits in a large population cohort.2009] [Association studies and gene expression analyses of the DISC1-interacting molecules, pericentrin 2 (PCNT2) and DISC1-binding zinc finger protein (D...2009] [Roles of disrupted-in-schizophrenia 1-interacting protein girdin in postnatal development of the dentate gyrus.2009] [Disrupted-in-Schizophrenia 1 (DISC1) regulates spines of the glutamate synapse via Rac1.2010] [Knockdown of DISC1 by in utero gene transfer disturbs postnatal dopaminergic maturation in the frontal cortex and leads to adult behavioral deficits.2010] [DISC1-dependent switch from progenitor proliferation to migration in the developing cortex.2011] [Interplay between DISC1 and GABA signaling regulates neurogenesis in mice and risk for schizophrenia.2012] [mTOR Inhibition ameliorates cognitive and affective deficits caused by Disc1 knockdown in adult-born dentate granule neurons.2013] [DISC1 (disrupted-in-schizophrenia-1) regulates differentiation of oligodendrocytes.2014] [Disrupted-in-schizophrenia 1 regulates transport of ITPR1 mRNA for synaptic plasticity.2015] [The cortical thickness phenotype of individuals with DISC1 translocation resembles schizophrenia.2015] [Genomic DISC1 Disruption in hiPSCs Alters Wnt Signaling and Neural Cell Fate.2015] [DISC1-dependent Regulation of Mitochondrial Dynamics Controls the Morphogenesis of Complex Neuronal Dendrites.2015] [The contribution of de novo coding mutations to autism spectrum disorder.2014] [Early postnatal GABAA receptor modulation reverses deficits in neuronal maturation in a conditional neurodevelopmental mouse model of DISC1.2016] [Missense mutation in DISC1 C-terminal coiled-coil has GSK3 signaling and sex-dependent behavioral effects in mice.2016]
7/1/2015
3
icon
3

Increased from 3 to 3

Description

Evidence for the involvement of DISC1 in autism is suggestive. There have been two gene-based association studies (Kilpinen et al., 2008; Lim et al., 2009) with inconsistent results. In addition, two studies have identified copy number variants in DISC1 in affected individuals. Finally, DISC1 is thought to play a role in the genetic etiology of schizophrenia, a related neuropsychiatric disorder.

Reports Added
[Association of DISC1 with autism and Asperger syndrome.2007] [A 1q42 deletion involving DISC1, DISC2, and TSNAX in an autism spectrum disorder.2009] [DISC1 duplication in two brothers with autism and mild mental retardation.2009] [Evidence for association between Disrupted-in-Schizophrenia 1 (DISC1) gene polymorphisms and autism in Chinese Han population: a family-based assoc...2011] [De novo mutations revealed by whole-exome sequencing are strongly associated with autism.2012] [Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders.2013] [708 Common and 2010 rare DISC1 locus variants identified in 1542 subjects: analysis for association with psychiatric disorder and cognitive traits.2013] [DISC1 association, heterogeneity and interplay in schizophrenia and bipolar disorder.2008] [DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of ...2003] [DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling.2005] [Behavioral phenotypes of Disc1 missense mutations in mice.2007] [Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain.2007] [Nuclear DISC1 regulates CRE-mediated gene transcription and sleep homeostasis in the fruit fly.2008] [Replication study of candidate genes for cognitive abilities: the Lothian Birth Cohort 1936.2008] [Association of variants in DISC1 with psychosis-related traits in a large population cohort.2009] [Association studies and gene expression analyses of the DISC1-interacting molecules, pericentrin 2 (PCNT2) and DISC1-binding zinc finger protein (D...2009] [Roles of disrupted-in-schizophrenia 1-interacting protein girdin in postnatal development of the dentate gyrus.2009] [Disrupted-in-Schizophrenia 1 (DISC1) regulates spines of the glutamate synapse via Rac1.2010] [Knockdown of DISC1 by in utero gene transfer disturbs postnatal dopaminergic maturation in the frontal cortex and leads to adult behavioral deficits.2010] [DISC1-dependent switch from progenitor proliferation to migration in the developing cortex.2011] [Interplay between DISC1 and GABA signaling regulates neurogenesis in mice and risk for schizophrenia.2012] [mTOR Inhibition ameliorates cognitive and affective deficits caused by Disc1 knockdown in adult-born dentate granule neurons.2013] [DISC1 (disrupted-in-schizophrenia-1) regulates differentiation of oligodendrocytes.2014] [Disrupted-in-schizophrenia 1 regulates transport of ITPR1 mRNA for synaptic plasticity.2015] [The cortical thickness phenotype of individuals with DISC1 translocation resembles schizophrenia.2015] [Genomic DISC1 Disruption in hiPSCs Alters Wnt Signaling and Neural Cell Fate.2015]
4/1/2015
3
icon
3

Increased from 3 to 3

Description

Evidence for the involvement of DISC1 in autism is suggestive. There have been two gene-based association studies (Kilpinen et al., 2008; Lim et al., 2009) with inconsistent results. In addition, two studies have identified copy number variants in DISC1 in affected individuals. Finally, DISC1 is thought to play a role in the genetic etiology of schizophrenia, a related neuropsychiatric disorder.

7/1/2014
No data
icon
3

Increased from No data to 3

Description

Evidence for the involvement of DISC1 in autism is suggestive. There have been two gene-based association studies (Kilpinen et al., 2008; Lim et al., 2009) with inconsistent results. In addition, two studies have identified copy number variants in DISC1 in affected individuals. Finally, DISC1 is thought to play a role in the genetic etiology of schizophrenia, a related neuropsychiatric disorder.

4/1/2014
No data
icon
3

Increased from No data to 3

Description

Evidence for the involvement of DISC1 in autism is suggestive. There have been two gene-based association studies (Kilpinen et al., 2008; Lim et al., 2009) with inconsistent results. In addition, two studies have identified copy number variants in DISC1 in affected individuals. Finally, DISC1 is thought to play a role in the genetic etiology of schizophrenia, a related neuropsychiatric disorder.

Krishnan Probability Score

Score 0.57209327184167

Ranking 723/25841 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.
ExAC Score

Score 0.019709883561619

Ranking 9430/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score

Score 0.87713455133219

Ranking 4677/18665 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).
Larsen Cumulative Evidence Score

Score 15

Ranking 129/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
CNVs associated with DISC1(1 CNVs)
1q42.2 19 Deletion-Duplication 35  /  75
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
AGTPBP1 ATP/GTP binding protein 1 Human Protein Binding 23287 Q9UPW5
ANKHD1 ankyrin repeat and KH domain containing 1 Human Protein Binding 54882 Q8IWZ3
ARFGEF2 ADP-ribosylation factor guanine nucleotide-exchange factor 2 (brefeldin A-inhibited) Rat Protein Binding 296380 Q7TSU1
ARIH2 ariadne homolog 2 (Drosophila) Human Protein Binding 10425 O95376
ATF4 activating transcription factor 4 (tax-responsive enhancer element B67) Human Protein Binding 468 P18848
ATF5 activating transcription factor 5 Human Protein Binding 22809 Q9Y2D1
BBS1 Bardet-Biedl syndrome 1 Human Protein Binding 582 Q8NFJ9
BBS2 Bardet-Biedl syndrome 2 Human Protein Binding 583 Q9BXC9
BBS7 Bardet-Biedl syndrome 7 Human Protein Binding 55212 Q8IWZ6
BICD1 bicaudal D homolog 1 (Drosophila) Human Protein Binding 636 Q96G01
CCDC141 coiled-coil domain containing 141 Human Protein Binding 285025 Q6ZP82
CCDC24 coiled-coil domain containing 24 Human Protein Binding 149473 Q8N4L8
CDC16 cell division cycle 16 Human Protein Binding 8881 Q13042
CDK5RAP3 CDK5 regulatory subunit associated protein 3 Human Protein Binding 80279 Q96JB5
CELA1 Chymotrypsin-like elastase family member 1 Human Protein Binding 1990 Q9UNI1
CEP290 centrosomal protein 290kDa Human Protein Binding 80184 O15078
CIT citron (rho-interacting, serine/threonine kinase 21) Human Protein Binding 11113 O14578
CRYBA4 Beta-crystallin A4 Human Protein Binding 1413 P53673
DAB1 disabled homolog 1 (Drosophila) Human Protein Binding 1600 O75553
DIXDC1 DIX domain containing 1 Mouse Protein Binding 330938 Q80Y83
DPYSL3 dihydropyrimidinase-like 3 Human Protein Binding 1809 Q14195
DTNBP1 dystrobrevin binding protein 1 Human Protein Binding 84062 Q96EV8
Dysb Dysbindin ortholog Fruit Fly Protein Binding 40052 Q9VVT5
EIF3H eukaryotic translation initiation factor 3, subunit H Human Protein Binding 8667 O15372
EPB49 erythrocyte membrane protein band 4.9 (dematin) Human Protein Binding 2039 Q08495
EXOC1 exocyst complex component 1 Human Protein Binding 55763 Q9NV70
FBXO41 F-box protein 41 Human Protein Binding 150726 Q8TF61
GNPTAB N-acetylglucosamine-1-phosphate transferase, alpha and beta subunits Human Protein Binding 79158 Q3T906
HERC2P2 hect domain and RLD 2 pseudogene 2 Human Protein Binding 400322 N/A
Itpr1 inositol 1,4,5-trisphosphate receptor 1 Mouse RNA Binding 16438 P11881
KALRN kalirin, RhoGEF kinase Human Protein Binding 8997 O60229
KATNAL1 katanin p60 subunit A-like 1 Human Protein Binding 84056 Q9BW62
KCNQ5 potassium voltage-gated channel, KQT-like subfamily, member 5 Human Protein Binding 56479 Q9NR82
KIAA1377 KIAA1377 Human Protein Binding 57562 Q9P2H0
KIF3A kinesin family member 3A Human Protein Binding 11127 Q9Y496
Kif5a kinesin family member 5A Rat Protein Binding 314906 Q6QLM7
MAP1A microtubule-associated protein 1A Human Protein Binding 4130 P78559
Mfn1 mitofusin 1 Mouse Protein Binding 67414 Q811U4
MGAT3 mannosyl (beta-1,4-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferase Human Protein Binding 4248 Q09327
MKKS McKusick-Kaufman syndrome Human Protein Binding 8195 Q9NPJ1
MLC1 megalencephalic leukoencephalopathy with subcortical cysts 1 Human Protein Binding 23209 Q15049
MPPED1 metallophosphoesterase domain containing 1 Human Protein Binding 758 O15442
MYF6 myogenic factor 6 (herculin) Human Protein Binding 4618 P23409
OLFM1 olfactomedin 1 Human Protein Binding 10439 Q99784
P4HA2 Prolyl 4-hydroxylase subunit alpha-2 Human Protein Binding 8974 O15460-2
PDE4B phosphodiesterase 4B, cAMP-specific Human Protein Binding 5142 Q07343
PGK1 phosphoglycerate kinase 1 Human Protein Binding 5230 P00558
PPFIA4 protein tyrosine phosphatase, receptor type, f polypeptide (PTPRF), interacting protein (liprin), alpha 4 Human Protein Binding 8497 O75335
RABGAP1 RAB GTPase activating protein 1 Human Protein Binding 23637 Q9Y3P9
RASSF7 Ras association (RalGDS/AF-6) domain family (N-terminal) member 7 Human Protein Binding 8045 Q02833
RIBC1 RIB43A-like with coiled-coils protein 1 Human Protein Binding 158787 Q8N443
ROGDI rogdi homolog (Drosophila) Human Protein Binding 79641 Q9GZN7
SH3BP5 SH3-domain binding protein 5 (BTK-associated) Human Protein Binding 9467 O60239
SNX6 sorting nexin 6 Human Protein Binding 58533 Q9UNH7
SPARCL1 SPARC-like 1 (hevin) Human Protein Binding 8404 Q14515
SRGAP2 SLIT-ROBO Rho GTPase activating protein 2 Human Protein Binding 23380 O75044
STX11 syntaxin 11 Human Protein Binding 8676 O75558
TCL1B T-cell leukemia/lymphoma protein 1B Human Protein Binding 9623 O95988
TIAM2 T-cell lymphoma invasion and metastasis 2 Human Protein Binding 26230 Q8IVF5
TRAF3IP1 TNF receptor-associated factor 3 interacting protein 1 Human Protein Binding 26146 Q8TDR0
TRAK1 trafficking protein, kinesin binding 1 Human Protein Binding 22906 Q9UPV9
TTC8 tetratricopeptide repeat domain 8 Human Protein Binding 123016 Q8TAM2
TUBG1 tubulin, gamma 1 Rat Protein Binding 252921 P83888
XPNPEP1 X-prolyl aminopeptidase (aminopeptidase P) 1, soluble Human Protein Binding 7511 Q9NQW7
Zfp385a zinc finger protein 385A Rat Protein Binding 685474 A0A0G2KB91
ZNF365 zinc finger protein 365 Human Protein Binding 22891 Q70YC5
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