METmet proto-oncogene (hepatocyte growth factor receptor)
Autism Reports / Total Reports
17 / 42Rare Variants / Common Variants
10 / 13Aliases
MET, HGFR, RCCP2, Oncogene MET, met proto-oncogeneAssociated Syndromes
-Chromosome Band
7q31.2Associated Disorders
-Relevance to Autism
A number of studies have focused on the genetic association of the MET gene with autism. Positive associations have been found in the Caucasian, Japanese and Italian populations as well as in AGRE family cohorts from multiple studies. Interestingly, a positive association with MET and schizophrenia has also been found, but no association was found with PDD. In addition, biochemical studies have been performed that show a reduction in MET protein levels and general disruption of MET signaling in ASD patients.
Molecular Function
The encoded protein is the hepatocyte growth factor receptor with tyrosine-kinase activity. The primary single chain precursor protein is post-translationally cleaved to produce the alpha and beta subunits, which are disulfide linked to form the mature receptor.
External Links
SFARI Genomic Platforms
Reports related to MET (42 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Highly Cited | Met receptor tyrosine kinase: enhanced signaling through adapter proteins | Furge KA , et al. (2000) | No | - |
| 2 | Highly Cited | Coupling Met to specific pathways results in distinct developmental outcomes | Maina F , et al. (2001) | No | - |
| 3 | Recent Recommendation | Disruption of interneuron development | Levitt P (2005) | No | - |
| 4 | Primary | A genetic variant that disrupts MET transcription is associated with autism | Campbell DB , et al. (2006) | Yes | - |
| 5 | Recent Recommendation | Hepatocyte growth factor-induced Ras activation requires ERM proteins linked to both CD44v6 and F-actin | Orian-Rousseau V , et al. (2006) | No | - |
| 6 | Recent Recommendation | Disruption of cerebral cortex MET signaling in autism spectrum disorder | Campbell DB , et al. (2007) | Yes | - |
| 7 | Recent Recommendation | Signalling by neurotrophins and hepatocyte growth factor regulates axon morphogenesis by differential beta-catenin phosphorylation | David MD , et al. (2008) | No | - |
| 8 | Positive Association | MET and autism susceptibility: family and case-control studies | Sousa I , et al. (2008) | Yes | - |
| 9 | Recent Recommendation | Dynamic gene and protein expression patterns of the autism-associated met receptor tyrosine kinase in the developing mouse forebrain | Judson MC , et al. (2009) | No | - |
| 10 | Positive Association | Distinct genetic risk based on association of MET in families with co-occurring autism and gastrointestinal conditions | Campbell DB , et al. (2009) | Yes | - |
| 11 | Positive Association | Genetic evidence implicating multiple genes in the MET receptor tyrosine kinase pathway in autism spectrum disorder | Campbell DB , et al. (2009) | Yes | - |
| 12 | Positive Association | Association of MET with social and communication phenotypes in individuals with autism spectrum disorder | Campbell DB , et al. (2009) | Yes | - |
| 13 | Recent Recommendation | Disease-dependent reciprocal phosphorylation of serine and tyrosine residues of c-Met/HGF receptor contributes disease retardation of a transgenic mouse model of ALS | Kadoyama K , et al. (2009) | No | - |
| 14 | Positive Association | Further evidence that the rs1858830 C variant in the promoter region of the MET gene is associated with autistic disorder | Jackson PB , et al. (2009) | Yes | - |
| 15 | Recent Recommendation | The autism susceptibility gene met regulates zebrafish cerebellar development and facial motor neuron migration | Elsen GE , et al. (2009) | Yes | - |
| 16 | Recent Recommendation | Association of genetic variation in the MET proto-oncogene with schizophrenia and general cognitive ability | Burdick KE , et al. (2010) | No | - |
| 17 | Positive Association | Further evidence for the role of MET in autism susceptibility | Thanseem I , et al. (2010) | Yes | - |
| 18 | Recent Recommendation | Evidence of cell-nonautonomous changes in dendrite and dendritic spine morphology in the met-signaling-deficient mouse forebrain | Judson MC , et al. (2010) | No | - |
| 19 | Recent Recommendation | Circuit-specific intracortical hyperconnectivity in mice with deletion of the autism-associated Met receptor tyrosine kinase | Qiu S , et al. (2011) | No | - |
| 20 | Recent Recommendation | Regulation of MET by FOXP2, genes implicated in higher cognitive dysfunction and autism risk | Mukamel Z , et al. (2011) | No | - |
| 21 | Recent Recommendation | MET and AKT genetic influence on facial emotion perception | Lin MT , et al. (2012) | No | - |
| 22 | Recent Recommendation | Autism-associated promoter variant in MET impacts functional and structural brain networks | Rudie JD , et al. (2012) | Yes | - |
| 23 | Recent Recommendation | Autism risk gene MET variation and cortical thickness in typically developing children and adolescents | Hedrick A , et al. (2012) | No | - |
| 24 | Support | Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder | Girirajan S , et al. (2013) | Yes | - |
| 25 | Recent Recommendation | Synaptic and extrasynaptic location of the receptor tyrosine kinase met during postnatal development in the mouse neocortex and hippocampus | Eagleson KL , et al. (2013) | No | - |
| 26 | Recent Recommendation | Transcriptional regulation of the MET receptor tyrosine kinase gene by MeCP2 and sex-specific expression in autism and Rett syndrome | Plummer JT , et al. (2013) | No | - |
| 27 | Recent Recommendation | Autism spectrum disorder: interaction of air pollution with the MET receptor tyrosine kinase gene | Volk HE , et al. (2013) | No | - |
| 28 | Recent Recommendation | A familial heterozygous null mutation of MET in autism spectrum disorder | Lambert N , et al. (2014) | Yes | - |
| 29 | Support | Large-scale discovery of novel genetic causes of developmental disorders | Deciphering Developmental Disorders Study (2014) | No | - |
| 30 | Recent Recommendation | The autism-associated MET receptor tyrosine kinase engages early neuronal growth mechanism and controls glutamatergic circuits development in the forebrain | Peng Y , et al. (2016) | No | - |
| 31 | Recent Recommendation | Hepatocyte Growth Factor Modulates MET Receptor Tyrosine Kinase and ?-Catenin Functional Interactions to Enhance Synapse Formation | Xie Z , et al. (2016) | No | - |
| 32 | Recent Recommendation | Autism spectrum disorders and autistic traits share genetics and biology | Bralten J , et al. (2017) | No | - |
| 33 | Support | Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder | Lim ET , et al. (2017) | Yes | - |
| 34 | Support | Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder | Takata A , et al. (2018) | Yes | - |
| 35 | Support | Disruption of MET Receptor Tyrosine Kinase, an Autism Risk Factor, Impairs Developmental Synaptic Plasticity in the Hippocampus | Ma X , et al. (2018) | No | - |
| 36 | Recent recommendation | Time-delimited signaling of MET receptor tyrosine kinase regulates cortical circuit development and critical period plasticity | Chen K , et al. (2020) | No | - |
| 37 | Support | - | Ohashi K et al. (2021) | Yes | - |
| 38 | Support | - | Zhou X et al. (2022) | Yes | - |
| 39 | Support | - | Wang J et al. (2023) | Yes | - |
| 40 | Support | - | Tamam Khalaf et al. (2024) | No | - |
| 41 | Highly Cited | Uncoupling of Grb2 from the Met receptor in vivo reveals complex roles in muscle development | Maina F , et al. (1996) | No | - |
| 42 | Highly Cited | Interaction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis | Weidner KM , et al. (1996) | No | - |
Rare Variants (10)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | copy_number_gain | Familial | Maternal | Simplex | 23375656 | Girirajan S , et al. (2013) | |
| c.3108C>T | p.Asn1036%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| - | - | copy_number_loss | Unknown | Not maternal | Multiplex | 24909855 | Lambert N , et al. (2014) | |
| c.2192G>A | p.Arg731Gln | missense_variant | De novo | - | Simplex | 28714951 | Lim ET , et al. (2017) | |
| c.2192G>A | p.Arg731Gln | missense_variant | De novo | - | Simplex | 29346770 | Takata A , et al. (2018) | |
| c.4141G>A | p.Ala1381Thr | missense_variant | Familial | Maternal | - | 33590427 | Ohashi K et al. (2021) | |
| c.1551del | p.Leu518TrpfsTer35 | frameshift_variant | De novo | - | Simplex | 37393044 | Wang J et al. (2023) | |
| c.3557T>G | p.Leu1186Arg | missense_variant | Familial | Both parents | Multiplex | 38438125 | Tamam Khalaf et al. (2024) | |
| c.3272G>A | p.Cys1091Tyr | missense_variant | De novo | - | Unknown | 25533962 | Deciphering Developmental Disorders Study (2014) | |
| c.3751G>T | p.Glu1251Ter | missense_variant | De novo | - | Unknown | 25533962 | Deciphering Developmental Disorders Study (2014) |
Common Variants (13)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.-15+9171A>G;c.-8+9171A>G;c.-91+9171A>G | G to A | intron_variant | - | - | - | 19002214 | Sousa I , et al. (2008) | |
| c.-15+7295A>G;c.-8+7295A>G;c.-91+7295A>G | A to G | intron_variant | - | - | - | 20615438 | Thanseem I , et al. (2010) | |
| c.1200+14187T>A;c.1257+14187T>A;c.-90-17197T>A | A | intron_variant | - | - | - | 20080979 | Burdick KE , et al. (2010) | |
| c.-207C>G;c.-200C>G;c.-283C>G | G/C | 2KB_upstream_variant, 5_prime_UTR_variant | - | - | - | 19681062 | Jackson PB , et al. (2009) | |
| c.-207C>G;c.-200C>G;c.-283C>G | G/C | 2KB_upstream_variant, 5_prime_UTR_variant | - | - | - | 17053076 | Campbell DB , et al. (2006) | |
| c.-207C>G;c.-200C>G;c.-283C>G | G/C | 2KB_upstream_variant, 5_prime_UTR_variant | - | - | - | 19255034 | Campbell DB , et al. (2009) | |
| c.-207C>G;c.-200C>G;c.-283C>G | C/G | 2KB_upstream_variant, 5_prime_UTR_variant | - | - | - | 19360663 | Campbell DB , et al. (2009) | |
| c.-207C>G;c.-200C>G;c.-283C>G | G/C | 2KB_upstream_variant, 5_prime_UTR_variant | - | - | - | 19548256 | Campbell DB , et al. (2009) | |
| c.3799-293G>A;c.3853-293G>A;c.3910-293G>A;c.2509-293G>A;c.3856-293G>A | C | intron_variant | - | - | - | 20080979 | Burdick KE , et al. (2010) | |
| c.2583+2065T>C;c.2637+2065T>C;c.2694+2065T>C;c.1293+2065T>C;c.2640+2065T>C | - | intron_variant | - | - | - | 20080979 | Burdick KE , et al. (2010) | |
| - | A | intergenic_variant | - | - | - | 20080979 | Burdick KE , et al. (2010) | |
| - | T | intergenic_variant | - | - | - | 20080979 | Burdick KE , et al. (2010) | |
| c.*2262+71G>T;c.*2333G>T | C | 500B_downstream_variant | - | - | - | 20080979 | Burdick KE , et al. (2010) |
SFARI Gene score
2
Strong Candidate
Under a linkage peak. At least 4 positive association studies (PMID: 17053076, 19255034, 19681062, 19360663), though not always the same findings (PMID: 19002214). One of the associated variants (rs1858830) is functional. Altered expression in autism brains vs controls (PMID: 17696172). Association with schizophrenia (PMID: 20080979).
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.
1/1/2021
2
2
Score remained at 2
Description
Under a linkage peak. At least 4 positive association studies (PMID: 17053076, 19255034, 19681062, 19360663), though not always the same findings (PMID: 19002214). One of the associated variants (rs1858830) is functional. Altered expression in autism brains vs controls (PMID: 17696172). Association with schizophrenia (PMID: 20080979).
1/1/2020
2
2
Score remained at 2
Description
Under a linkage peak. At least 4 positive association studies (PMID: 17053076, 19255034, 19681062, 19360663), though not always the same findings (PMID: 19002214). One of the associated variants (rs1858830) is functional. Altered expression in autism brains vs controls (PMID: 17696172). Association with schizophrenia (PMID: 20080979).
10/1/2019
2
2
Score remained at 2
New Scoring Scheme
Description
Under a linkage peak. At least 4 positive association studies (PMID: 17053076, 19255034, 19681062, 19360663), though not always the same findings (PMID: 19002214). One of the associated variants (rs1858830) is functional. Altered expression in autism brains vs controls (PMID: 17696172). Association with schizophrenia (PMID: 20080979).
Reports Added
[New Scoring Scheme]10/1/2018
2
2
Score remained at 2
Description
Under a linkage peak. At least 4 positive association studies (PMID: 17053076, 19255034, 19681062, 19360663), though not always the same findings (PMID: 19002214). One of the associated variants (rs1858830) is functional. Altered expression in autism brains vs controls (PMID: 17696172). Association with schizophrenia (PMID: 20080979).
7/1/2017
2
2
Score remained at 2
Description
Under a linkage peak. At least 4 positive association studies (PMID: 17053076, 19255034, 19681062, 19360663), though not always the same findings (PMID: 19002214). One of the associated variants (rs1858830) is functional. Altered expression in autism brains vs controls (PMID: 17696172). Association with schizophrenia (PMID: 20080979).
4/1/2017
2
2
Score remained at 2
Description
Under a linkage peak. At least 4 positive association studies (PMID: 17053076, 19255034, 19681062, 19360663), though not always the same findings (PMID: 19002214). One of the associated variants (rs1858830) is functional. Altered expression in autism brains vs controls (PMID: 17696172). Association with schizophrenia (PMID: 20080979).
Reports Added
[A genetic variant that disrupts MET transcription is associated with autism.2006] [Disruption of cerebral cortex MET signaling in autism spectrum disorder.2007] [MET and autism susceptibility: family and case-control studies.2008] [Distinct genetic risk based on association of MET in families with co-occurring autism and gastrointestinal conditions.2009] [Genetic evidence implicating multiple genes in the MET receptor tyrosine kinase pathway in autism spectrum disorder.2009] [Association of MET with social and communication phenotypes in individuals with autism spectrum disorder.2009] [Further evidence that the rs1858830 C variant in the promoter region of the MET gene is associated with autistic disorder.2009] [The autism susceptibility gene met regulates zebrafish cerebellar development and facial motor neuron migration.2009] [Further evidence for the role of MET in autism susceptibility.2010] [Autism-associated promoter variant in MET impacts functional and structural brain networks.2012] [Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [A familial heterozygous null mutation of MET in autism spectrum disorder.2014] [Association of genetic variation in the MET proto-oncogene with schizophrenia and general cognitive ability.2010] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Uncoupling of Grb2 from the Met receptor in vivo reveals complex roles in muscle development.1996] [Interaction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis.1996] [Met receptor tyrosine kinase: enhanced signaling through adapter proteins.2000] [Coupling Met to specific pathways results in distinct developmental outcomes.2001] [Disruption of interneuron development.2005] [Hepatocyte growth factor-induced Ras activation requires ERM proteins linked to both CD44v6 and F-actin.2006] [Signalling by neurotrophins and hepatocyte growth factor regulates axon morphogenesis by differential beta-catenin phosphorylation.2008] [Dynamic gene and protein expression patterns of the autism-associated met receptor tyrosine kinase in the developing mouse forebrain.2009] [Disease-dependent reciprocal phosphorylation of serine and tyrosine residues of c-Met/HGF receptor contributes disease retardation of a transgenic ...2009] [Evidence of cell-nonautonomous changes in dendrite and dendritic spine morphology in the met-signaling-deficient mouse forebrain.2010] [Circuit-specific intracortical hyperconnectivity in mice with deletion of the autism-associated Met receptor tyrosine kinase.2011] [Regulation of MET by FOXP2, genes implicated in higher cognitive dysfunction and autism risk.2011] [MET and AKT genetic influence on facial emotion perception.2012] [Autism risk gene MET variation and cortical thickness in typically developing children and adolescents.2012] [Synaptic and extrasynaptic location of the receptor tyrosine kinase met during postnatal development in the mouse neocortex and hippocampus.2013] [Transcriptional regulation of the MET receptor tyrosine kinase gene by MeCP2 and sex-specific expression in autism and Rett syndrome.2013] [Autism spectrum disorder: interaction of air pollution with the MET receptor tyrosine kinase gene.2013] [The autism-associated MET receptor tyrosine kinase engages early neuronal growth mechanism and controls glutamatergic circuits development in the f...2016] [Hepatocyte Growth Factor Modulates MET Receptor Tyrosine Kinase and -Catenin Functional Interactions to Enhance Synapse Formation.2016] [Autism spectrum disorders and autistic traits share genetics and biology.2017]7/1/2016
2
2
Score remained at 2
Description
Under a linkage peak. At least 4 positive association studies (PMID: 17053076, 19255034, 19681062, 19360663), though not always the same findings (PMID: 19002214). One of the associated variants (rs1858830) is functional. Altered expression in autism brains vs controls (PMID: 17696172). Association with schizophrenia (PMID: 20080979).
1/1/2016
2
2
Score remained at 2
Description
Under a linkage peak. At least 4 positive association studies (PMID: 17053076, 19255034, 19681062, 19360663), though not always the same findings (PMID: 19002214). One of the associated variants (rs1858830) is functional. Altered expression in autism brains vs controls (PMID: 17696172). Association with schizophrenia (PMID: 20080979).
Reports Added
[A genetic variant that disrupts MET transcription is associated with autism.2006] [Disruption of cerebral cortex MET signaling in autism spectrum disorder.2007] [MET and autism susceptibility: family and case-control studies.2008] [Distinct genetic risk based on association of MET in families with co-occurring autism and gastrointestinal conditions.2009] [Genetic evidence implicating multiple genes in the MET receptor tyrosine kinase pathway in autism spectrum disorder.2009] [Association of MET with social and communication phenotypes in individuals with autism spectrum disorder.2009] [Further evidence that the rs1858830 C variant in the promoter region of the MET gene is associated with autistic disorder.2009] [The autism susceptibility gene met regulates zebrafish cerebellar development and facial motor neuron migration.2009] [Further evidence for the role of MET in autism susceptibility.2010] [Autism-associated promoter variant in MET impacts functional and structural brain networks.2012] [Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [A familial heterozygous null mutation of MET in autism spectrum disorder.2014] [Association of genetic variation in the MET proto-oncogene with schizophrenia and general cognitive ability.2010] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Uncoupling of Grb2 from the Met receptor in vivo reveals complex roles in muscle development.1996] [Interaction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis.1996] [Met receptor tyrosine kinase: enhanced signaling through adapter proteins.2000] [Coupling Met to specific pathways results in distinct developmental outcomes.2001] [Disruption of interneuron development.2005] [Hepatocyte growth factor-induced Ras activation requires ERM proteins linked to both CD44v6 and F-actin.2006] [Signalling by neurotrophins and hepatocyte growth factor regulates axon morphogenesis by differential beta-catenin phosphorylation.2008] [Dynamic gene and protein expression patterns of the autism-associated met receptor tyrosine kinase in the developing mouse forebrain.2009] [Disease-dependent reciprocal phosphorylation of serine and tyrosine residues of c-Met/HGF receptor contributes disease retardation of a transgenic ...2009] [Evidence of cell-nonautonomous changes in dendrite and dendritic spine morphology in the met-signaling-deficient mouse forebrain.2010] [Circuit-specific intracortical hyperconnectivity in mice with deletion of the autism-associated Met receptor tyrosine kinase.2011] [Regulation of MET by FOXP2, genes implicated in higher cognitive dysfunction and autism risk.2011] [MET and AKT genetic influence on facial emotion perception.2012] [Autism risk gene MET variation and cortical thickness in typically developing children and adolescents.2012] [Synaptic and extrasynaptic location of the receptor tyrosine kinase met during postnatal development in the mouse neocortex and hippocampus.2013] [Transcriptional regulation of the MET receptor tyrosine kinase gene by MeCP2 and sex-specific expression in autism and Rett syndrome.2013] [Autism spectrum disorder: interaction of air pollution with the MET receptor tyrosine kinase gene.2013] [The autism-associated MET receptor tyrosine kinase engages early neuronal growth mechanism and controls glutamatergic circuits development in the f...2016]1/1/2015
2
2
Score remained at 2
Description
Under a linkage peak. At least 4 positive association studies (PMID: 17053076, 19255034, 19681062, 19360663), though not always the same findings (PMID: 19002214). One of the associated variants (rs1858830) is functional. Altered expression in autism brains vs controls (PMID: 17696172). Association with schizophrenia (PMID: 20080979).
7/1/2014
No data
2
Increased from No data to 2
Description
Under a linkage peak. At least 4 positive association studies (PMID: 17053076, 19255034, 19681062, 19360663), though not always the same findings (PMID: 19002214). One of the associated variants (rs1858830) is functional. Altered expression in autism brains vs controls (PMID: 17696172). Association with schizophrenia (PMID: 20080979).
Reports Added
[Uncoupling of Grb2 from the Met receptor in vivo reveals complex roles in muscle development.1996] [Interaction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis.1996] [Met receptor tyrosine kinase: enhanced signaling through adapter proteins.2000] [Coupling Met to specific pathways results in distinct developmental outcomes.2001] [Disruption of interneuron development.2005] [A genetic variant that disrupts MET transcription is associated with autism.2006] [Hepatocyte growth factor-induced Ras activation requires ERM proteins linked to both CD44v6 and F-actin.2006] [Disruption of cerebral cortex MET signaling in autism spectrum disorder.2007] [Signalling by neurotrophins and hepatocyte growth factor regulates axon morphogenesis by differential beta-catenin phosphorylation.2008] [MET and autism susceptibility: family and case-control studies.2008] [Dynamic gene and protein expression patterns of the autism-associated met receptor tyrosine kinase in the developing mouse forebrain.2009] [Distinct genetic risk based on association of MET in families with co-occurring autism and gastrointestinal conditions.2009] [Genetic evidence implicating multiple genes in the MET receptor tyrosine kinase pathway in autism spectrum disorder.2009] [Association of MET with social and communication phenotypes in individuals with autism spectrum disorder.2009] [Disease-dependent reciprocal phosphorylation of serine and tyrosine residues of c-Met/HGF receptor contributes disease retardation of a transgenic ...2009] [Further evidence that the rs1858830 C variant in the promoter region of the MET gene is associated with autistic disorder.2009] [The autism susceptibility gene met regulates zebrafish cerebellar development and facial motor neuron migration.2009] [Association of genetic variation in the MET proto-oncogene with schizophrenia and general cognitive ability.2010] [Further evidence for the role of MET in autism susceptibility.2010] [Evidence of cell-nonautonomous changes in dendrite and dendritic spine morphology in the met-signaling-deficient mouse forebrain.2010] [Circuit-specific intracortical hyperconnectivity in mice with deletion of the autism-associated Met receptor tyrosine kinase.2011] [Regulation of MET by FOXP2, genes implicated in higher cognitive dysfunction and autism risk.2011] [MET and AKT genetic influence on facial emotion perception.2012] [Autism-associated promoter variant in MET impacts functional and structural brain networks.2012] [Autism risk gene MET variation and cortical thickness in typically developing children and adolescents.2012] [Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.2013] [Synaptic and extrasynaptic location of the receptor tyrosine kinase met during postnatal development in the mouse neocortex and hippocampus.2013] [Transcriptional regulation of the MET receptor tyrosine kinase gene by MeCP2 and sex-specific expression in autism and Rett syndrome.2013] [Autism spectrum disorder: interaction of air pollution with the MET receptor tyrosine kinase gene.2013] [A familial heterozygous null mutation of MET in autism spectrum disorder.2014]4/1/2014
No data
2
Increased from No data to 2
Description
Under a linkage peak. At least 4 positive association studies (PMID: 17053076, 19255034, 19681062, 19360663), though not always the same findings (PMID: 19002214). One of the associated variants (rs1858830) is functional. Altered expression in autism brains vs controls (PMID: 17696172). Association with schizophrenia (PMID: 20080979).
Krishnan Probability Score
Score 0.49451513277543
Ranking 3618/25841 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 0.9964128637655
Ranking 1413/18225 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 0.94462809955764
Ranking 16150/18665 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 85
Ranking 12/461 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.
Zhang D Score
Score 0.33786637716386
Ranking 2166/20870 scored genes
[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures),
or D score, was developed to combine evidence from de novo loss-of- function mutation with
evidence from cell-type- specific gene expression in the mouse brain (specifically translational
profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with
positive D scores are more likely to be associated with autism risk, with higher-confidence genes
having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204-
215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in
supplementary table 2 from that paper.
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 |
|---|---|---|---|---|---|
| CEACAM21 | Carcinoembryonic antigen-related cell adhesion molecule 21 | Human | Protein Binding | 90273 | Q3KPI0-2 |
| Elmod1 | ELMO/CED-12 domain containing 1 | Mouse | Protein Binding | 270162 | Q3V1U8 |
| Eng | ROBO1 | Human | Protein Binding | 2022 | P17813 |
| Erc2 | ELKS/RAB6-interacting/CAST family member 2 | Mouse | Protein Binding | 238988 | Q6PH08 |
| HGF | hepatocyte growth factor (hepapoietin A; scatter factor) | Human | Protein Binding | 3082 | P14210 |
| INPP5D | inositol polyphosphate-5-phosphatase D | Rat | Protein Binding | 54259 | P97573 |
| ITGB4 | integrin, beta 4 | Human | Protein Modification | 3691 | P16144 |
| Klf8 | Kruppel-like factor 8 | Zebrafish | Direct Regulation | 562805 | A0S0R1 |
| MACC1 | metastasis associated in colon cancer 1 | Human | RNA Binding | 346389 | Q6ZN28 |
| miR-148a | microRNA 148a | Mouse | RNA Binding | 387166 | N/A |
| miR-340 | microRNA 340 | Mouse | RNA Binding | 723845 | N/A |
| miR-34b | microRNA 34b | Mouse | RNA Binding | 723849 | N/A |
| miR-34c | microRNA 34c | Human | RNA Binding | 407042 | N/A |
| miR185 | microRNA 185 | Human | RNA Binding | 406961 | N/A |
| MUC20 | mucin 20, cell surface associated | Human | Protein Binding | 200958 | Q8N307 |
| Pcdhgc5 | protocadherin gamma subfamily C, 5 | Mouse | Protein Binding | 93708 | Q91XW9 |
| Pea3 | ETS translocation variant 4 | Mouse | Direct Regulation | 18612 | P28322 |
| PTPRB | protein tyrosine phosphatase, receptor type, B | Human | Protein Modification | 5787 | P23467 |
| Rack1 | receptor for activated C kinase 1 | Mouse | Protein Binding | 14694 | P68040 |
| SCGB1D1 | Secretoglobin family 1D member 1 | Human | Protein Binding | 10648 | O95968 |
| Scn2a1 | sodium channel, voltage-gated, type II, alpha 1 | Mouse | Protein Binding | 110876 | B1AWN6 |
| Snx20 | sorting nexin 20 | Mouse | Protein Binding | 71607 | Q9D2Y5 |
| SPSB1 | splA/ryanodine receptor domain and SOCS box containing 1 | Human | Protein Binding | 80176 | Q96BD6 |
| SPSB4 | splA/ryanodine receptor domain and SOCS box containing 4 | Human | Protein Binding | 92369 | Q96A44 |
| Tenm4 | teneurin transmembrane protein 4 | Mouse | Protein Binding | 23966 | Q3UHK6 |