Human Gene Module / Chromosome 5 / ERBIN

ERBINerbb2 interacting protein

Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 5
Rare Variants / Common Variants
3 / 0
Aliases
ERBIN, ERBB2IP,  HEL-S-78,  LAP2
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
5q12.3
Associated Disorders
-
Relevance to Autism

This gene, formerly known as ERBB2IP, was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015); among the variants identified in this ge

Molecular Function

This gene is a member of the leucine-rich repeat and PDZ domain (LAP) family that binds to the unphosphorylated form of the ERBB2 protein and regulates ERBB2 function and localization. It has also been shown to affect the Ras signaling pathway by disrupting Ras-Raf interaction.

Reports related to ERBIN (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Synaptic, transcriptional and chromatin genes disrupted in autism. De Rubeis S , et al. (2014) Yes -
2 Primary Integrated systems analysis reveals a molecular network underlying autism spectrum disorders. Li J , et al. (2015) Yes -
3 Support Excess of rare, inherited truncating mutations in autism. Krumm N , et al. (2015) Yes -
4 Recent recommendation Low load for disruptive mutations in autism genes and their biased transmission. Iossifov I , et al. (2015) Yes -
5 Recent recommendation Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci. Sanders SJ , et al. (2015) Yes -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
A/T - splice_site_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.821C>T p.Ser274Leu missense_variant Unknown - Unknown 25549968 Li J , et al. (2015)
c.1292C>T p.Pro431Leu missense_variant De novo - Simplex 25961944 Krumm N , et al. (2015)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

This gene, formerly known as ERBB2IP, was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). This gene was subsequently identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant that was not present in dbSNP or ESP.

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.

04-01-2017
2

Initial score established: 2

Description

This gene, formerly known as ERBB2IP, was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). This gene was subsequently identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant that was not present in dbSNP or ESP.

CNVs associated with ERBIN(1 CNVs)
5q12.3 8 Deletion-Duplication 15  /  18
Animal Models associated with ERBIN(2 Models)
ERBIN_1_KO_HM Genetic
ERBIN_2_KO_HM Genetic
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