Human Gene Module / Chromosome 5 / MEGF10

MEGF10multiple EGF like domains 10

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
6 / 8
Rare Variants / Common Variants
4 / 5
Aliases
MEGF10, EMARDD
Associated Syndromes
-
Chromosome Band
5q23.2
Associated Disorders
-
Relevance to Autism

Three SNPs in the transcription regulatory region of the MEGF10 gene were found to associate with autism in a family-based association study of a Chinese Han cohort; one of these SNPs showed reduced protein binding activity in an electrophoretic mobility shift assay. Furthermore, the risk haplotype of these three SNPs was preferentially transmitted from parents to affected offspring and demonstrated reduced transcriptional activity in a luciferase reporter assay (Wu et al., 2017). MEGF10 has been shown to associate with schizophrenia in an Irish case-control study (Chen et al., 2008), but not in a Chinese case-control study (Yun et al., 2011).

Molecular Function

This gene encodes a member of the multiple epidermal growth factor-like domains protein family. The encoded protein plays a role in cell adhesion, motility and proliferation, and is a critical mediator of apoptotic cell phagocytosis as well as amyloid-beta peptide uptake in the brain. Mutations in this gene are a cause of early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD) as well as congenital myopathy with minicores

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to MEGF10 (8 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Positive Association MEGF10 association with schizophrenia Chen X , et al. (2008) No -
2 Negative Association No association between schizophrenia and rs27388 of the MEGF10 gene in Chinese case-control sample Yun L , et al. (2010) No -
3 Primary Genetic variants in the transcription regulatory region of MEGF10 are associated with autism in Chinese Han population Wu Z , et al. (2017) Yes -
4 Positive Association Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017) Yes -
5 Support Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder Lim ET , et al. (2017) Yes -
6 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
7 Support - Woodbury-Smith M et al. (2022) Yes -
8 Support - Zhou X et al. (2022) Yes -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1853G>T p.Gly618Val missense_variant De novo - Simplex 28714951 Lim ET , et al. (2017)
c.1434C>T p.His478%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.2296G>A p.Asp766Asn missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.3224_3232del p.Tyr1075_Glu1078delinsTer splice_site_variant Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
Common Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.-70+16451C>G;c.-19+16451C>G;c.92+16451C>G - intron_variant - - - 28540026 Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017)
c.319+7487G>A - intron_variant - - - 18179784 Chen X , et al. (2008)
c.-19+1127T>G;c.-70+1127T>G - intron_variant - - - 28536440 Wu Z , et al. (2017)
c.-19+1350A>G;c.-70+1350A>G - intron_variant - - - 28536440 Wu Z , et al. (2017)
c.-19+2023G>T;c.-70+2023G>T - intron_variant - - - 28536440 Wu Z , et al. (2017)
SFARI Gene score
2

Strong Candidate

Three SNPs in the transcription regulatory region of the MEGF10 gene were found to associate with autism in a family-based association study of a Chinese Han cohort; one of these SNPs showed reduced protein binding activity in an electrophoretic mobility shift assay. Furthermore, the risk haplotype of these three SNPs was preferentially transmitted from parents to affected offspring and demonstrated reduced transcriptional activity in a luciferase reporter assay (Wu et al., 2017). MEGF10 has been shown to associate with schizophrenia in an Irish case-control study (Chen et al., 2008), but not in a Chinese case-control study (Yun et al., 2011).

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

Three SNPs in the transcription regulatory region of the MEGF10 gene were found to associate with autism in a family-based association study of a Chinese Han cohort; one of these SNPs showed reduced protein binding activity in an electrophoretic mobility shift assay. Furthermore, the risk haplotype of these three SNPs was preferentially transmitted from parents to affected offspring and demonstrated reduced transcriptional activity in a luciferase reporter assay (Wu et al., 2017). MEGF10 has been shown to associate with schizophrenia in an Irish case-control study (Chen et al., 2008), but not in a Chinese case-control study (Yun et al., 2011).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Three SNPs in the transcription regulatory region of the MEGF10 gene were found to associate with autism in a family-based association study of a Chinese Han cohort; one of these SNPs showed reduced protein binding activity in an electrophoretic mobility shift assay. Furthermore, the risk haplotype of these three SNPs was preferentially transmitted from parents to affected offspring and demonstrated reduced transcriptional activity in a luciferase reporter assay (Wu et al., 2017). MEGF10 has been shown to associate with schizophrenia in an Irish case-control study (Chen et al., 2008), but not in a Chinese case-control study (Yun et al., 2011).

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

Decreased from 4 to 4

Description

Three SNPs in the transcription regulatory region of the MEGF10 gene were found to associate with autism in a family-based association study of a Chinese Han cohort; one of these SNPs showed reduced protein binding activity in an electrophoretic mobility shift assay. Furthermore, the risk haplotype of these three SNPs was preferentially transmitted from parents to affected offspring and demonstrated reduced transcriptional activity in a luciferase reporter assay (Wu et al., 2017). MEGF10 has been shown to associate with schizophrenia in an Irish case-control study (Chen et al., 2008), but not in a Chinese case-control study (Yun et al., 2011).

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
4/1/2017
icon
4

Increased from to 4

Description

Three SNPs in the transcription regulatory region of the MEGF10 gene were found to associate with autism in a family-based association study of a Chinese Han cohort; one of these SNPs showed reduced protein binding activity in an electrophoretic mobility shift assay. Furthermore, the risk haplotype of these three SNPs was preferentially transmitted from parents to affected offspring and demonstrated reduced transcriptional activity in a luciferase reporter assay (Wu et al., 2017). MEGF10 has been shown to associate with schizophrenia in an Irish case-control study (Chen et al., 2008), but not in a Chinese case-control study (Yun et al., 2011).

Krishnan Probability Score

Score 0.50030120459282

Ranking 2087/25841 scored genes


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

Score 0.99432494508164

Ranking 1579/18225 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
Original Source
Sanders TADA Score

Score 0.77377058240991

Ranking 1820/18665 scored genes


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

Score -0.035917033270273

Ranking 9895/20870 scored genes


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