DISC1disrupted in schizophrenia 1
Autism Reports / Total Reports
11 / 38Rare Variants / Common Variants
20 / 14Chromosome Band
1q42.2Associated Disorders
SCZ, BPD, ASDGenetic Category
Rare Single Gene Mutation, Syndromic, Genetic Association, FunctionalRelevance 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.
External Links
SFARI Genomic Platforms
Reports related to DISC1 (38 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 interaction with mutation | 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 (DBZ), with schizophrenia and with bipolar disorder | 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 association study | 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 | - |
| 35 | Support | - | Zhou X et al. (2022) | Yes | - |
| 36 | Support | - | Yuan B et al. (2023) | Yes | - |
| 37 | Support | - | Cirnigliaro M et al. (2023) | Yes | - |
| 38 | Support | - | Johanna Heider et al. (2024) | No | - |
Rare Variants (20)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.2241+68T>G | - | splice_site_variant | De novo | - | - | 36881370 | Yuan B et al. (2023) | |
| c.991A>G | p.Arg331Gly | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| - | - | 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 | Maternal | Simplex | 23375656 | Girirajan S , et al. (2013) | |
| - | - | 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.1880C>G | p.Ala627Gly | missense_variant | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) | |
| c.479G>T | p.Trp160Leu | missense_variant | Unknown | - | Unknown | 23732877 | Thomson PA , et al. (2013) | |
| c.1253G>A | p.Arg418His | missense_variant | Unknown | - | Unknown | 23732877 | Thomson PA , et al. (2013) | |
| c.2220del | p.Asp740GlufsTer7 | frameshift_variant | Unknown | - | Unknown | 24126926 | Kenny EM , et al. (2013) | |
| c.698G>A | p.Arg233Lys | missense_variant | Familial | Maternal | Simplex | 23732877 | Thomson PA , et al. (2013) | |
| c.109C>T | p.Arg37Trp | missense_variant | Familial | Maternal | Multiplex | 23732877 | Thomson PA , et al. (2013) | |
| c.816G>A | p.Arg272= | synonymous_variant | Familial | Paternal | Multiplex | 23732877 | Thomson PA , et al. (2013) | |
| c.1819C>T | p.Leu607Phe | missense_variant | Familial | Paternal | Simplex | 19606485 | Williams JM , et al. (2009) | |
| c.1981G>A | p.Glu661Lys | missense_variant | Familial | Paternal | Simplex | 19606485 | Williams JM , et al. (2009) | |
| c.2358_2359+2del | - | frameshift_variant | Familial | Maternal | Multiplex | 37506195 | Cirnigliaro M et al. (2023) | |
| c.2358_2359+2del | - | frameshift_variant | Familial | Paternal | Multiplex | 37506195 | Cirnigliaro M et al. (2023) | |
| c.348G>A | p.Ala116= | 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
2
Strong Candidate
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.
Score Delta: Score remained at 2
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.
10/1/2019
3
2
Decreased from 3 to 2
New Scoring Scheme
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
[New Scoring Scheme]4/1/2016
3
3
Decreased 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 disorder2014] [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
3
Decreased 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 disorder2014] [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
3
Decreased 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
3
Decreased 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
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
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.
External PIN Data
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
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 |