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 gene was one de novo loss-of-function (LoF) variant.
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.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Integrated systems analysis reveals a molecular network underlying autism spectrum disorders.
Both Erbin null and the PDZ-domain truncation mutants display decreased myelination in PNS but not in CNS. The nonmyelinating axon ensheathment of sciatic nerves is also affected in these mutants. These abnormalities can be reflected by the decreased tail nerve motor conduction and pain sensitivity.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Exons 1 and 2 of erbin gene were replaced in erbin-targeting vector by a neomycin-resistant marker flanked with LoxP sites.
Allele Type: Targeted (Knock Out)
Strain of Origin: Not specified
Genetic Background: Not specified
ES Cell Line: 129 Ola
Mutant ES Cell Line: Not specified
Model Source: Not specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Erbin gene disrupted by gene trapping using the pGT2Lxf vector resulted in a C-terminal PDZ motif truncated product (truncated form missing exon 21 to 24).
Allele Type: Gene trapped
Strain of Origin: Not specified
Genetic Background: C57/Bl6; Bga258
ES Cell Line: Bga258
Mutant ES Cell Line: Not specified
Model Source: Not specified
Description: The number of unmyelinated axons was significantly increased in remak bundles where axons were small and were compacted to each other and not completely segregated in the mutant sciatic nerves
Exp Paradigm: Electron microscopy
Description: The myelin of sciatic nerve axons was significantly thinner with normal myelination initiation, radial sorting, and compaction in mutant mice compared to that of littermate controls
Exp Paradigm: Axon diameters/fiber diameters (g-ratio) of myelinated axons
G-ratio measurement (axon diameters/fiber diameters of myelinated axons)
Description: Increased sensory threshold (the smallest strength of von frey hair) in the mutant mice compared to the littermate controls
Exp Paradigm: Hindpaws were stimulated by von frey hair
Description: Decreased conduction velocity in the tail nerve of mutant mice
Exp Paradigm: 2 ring electrodes at different proximal tail locations were used as stimuli. an electrode placed at the distal region was used to record the conduction, with tail tips grounded by a clip electrod
Description: Decreased protein levels of p0 (mpz), erbb2, or erbb3 in mutant sciatic nerves compared to littermate controls
Exp Paradigm: Western blot: p0 (mpz), erbb2, erbb3
Description: The myelin of sciatic nerve axons was significantly thinner with normal myelination initiation, radial sorting, and compaction in mutant mice compared to that of littermate controls
Exp Paradigm: Axon diameters/fiber diameters (g-ratio) of myelinated axons
G-ratio measurement (axon diameters/fiber diameters of myelinated axons)
Description: The number of unmyelinated axons was significantly increased in remak bundles where axons were small and were compacted to each other and not completely segregated in the mutant sciatic nerves
Exp Paradigm: Electron microscopy
Description: Decreased conduction velocity in the tail nerve of mutant mice
Exp Paradigm: 2 ring electrodes at different proximal tail locations were used as stimuli. an electrode placed at the distal region was used to record the conduction, with tail tips grounded by a clip electrod
Description: Increased sensory threshold (the smallest strength of von frey hair) in the mutant mice compared to the littermate controls
Exp Paradigm: Hindpaws were stimulated by von frey hair
Description: Decreased protein levels of p0 (mpz), erbb2, or erbb3 in mutant sciatic nerves relative to littermate controls
Exp Paradigm: Western blot: p0 (mpz), erbb2, erbb3
