geno logo
     HELP     Sign In

Quick Links

TOOLS
Search

Relevance to Autism

Rare variants in the ERBB4 gene have been identified with autism (Pinto et al., 2010) as well as schizophrenia (Walsh et al., 2008).

Molecular Function

A transmembrane receptor tyrosine kinase that regulates cell proliferation and differentiation

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Functional impact of global rare copy number variation in autism spectrum disorders.
ASD
Support
Genome-wide characteristics of de novo mutations in autism
ASD
Support
Psychosis
Support
A new single gene deletion on 2q34: ERBB4 is associated with intellectual disability.
ID
Support
Integrating de novo and inherited variants in 42
ASD
Support
Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.
ASD
Support
Developmental Disruption of Erbb4 in Pet1+ Neurons Impairs Serotonergic Sub-System Connectivity and Memory Formation
Support
A discovery resource of rare copy number variations in individuals with autism spectrum disorder.
ASD
Support
Both rare and common genetic variants contribute to autism in the Faroe Islands.
ASD
Support
Whole-Genome Sequencing of Cytogenetically Balanced Chromosome Translocations Identifies Potentially Pathological Gene Disruptions and Highlights t...
ASD, ID, epilepsy/seizures
Support
Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.
ASD
Highly Cited
Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor.
Highly Cited
Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases.
Highly Cited
A neu acquaintance for erbB3 and erbB4: a role for receptor heterodimerization in growth signaling.
Recent Recommendation
Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling.
Recent Recommendation
Neuregulin1/ErbB4 signaling induces cardiomyocyte proliferation and repair of heart injury.
Recent Recommendation
Neuregulin-1/ErbB signaling serves distinct functions in myelination of the peripheral and central nervous system.
Recent Recommendation
Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia.
SCZ

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN081R001 
 copy_number_loss 
  
  
  
  
  
 GEN081R002 
 copy_number_loss 
  
  
  
  
  
 GEN081R003 
 copy_number_loss 
  
  
  
  
  
 GEN081R004 
 copy_number_loss 
  
  
  
  
  
 GEN081R005 
 copy_number_loss 
  
  
  
  
  
 GEN081R006 
 copy_number_loss 
  
  
 Familial 
 Maternal 
 Unknown 
 GEN081R007 
 copy_number_loss 
  
  
 Unknown 
  
 Unknown 
 GEN081R008 
 copy_number_loss 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN081R009 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN081R010 
 intron_variant 
 c.2487+50157A>G 
  
 De novo 
  
 Simplex 
 GEN081R011 
 intron_variant 
 c.421+38882T>C 
  
  
  
 Unknown 
 GEN081R012 
 translocation 
  
  
 De novo 
  
  
 GEN081R013 
 frameshift_variant 
 c.2743_2744insGTTCCCATATAGTAACTCCTATATTGGAGAAAAA 
 p.Thr915SerfsTer19 
 Familial 
 Paternal 
 Simplex 
 GEN081R014 
 synonymous_variant 
 c.1938A>G 
 p.Gln646%3D 
 De novo 
  
  
 GEN081R015 
 missense_variant 
 c.328C>G 
 p.Leu110Val 
 De novo 
  
  

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
2
Duplication
 1
 
2
Duplication
 1
 
2
Duplication
 1
 
2
Deletion
 3
 
2
Deletion
 1
 
2
Deletion
 3
 
2
Deletion-Duplication
 25
 
2
Duplication
 3
 

Model Summary

First plausible link between NRG-1/ErbB4 signaling and rhythmic network activity that may be altered in persons with schizophrenia.

References

Type
Title
Author, Year
Primary
Neuregulin-1 modulates hippocampal gamma oscillations: implications for schizophrenia.
Additional
Selective populations of hippocampal interneurons express ErbB4 and their number and distribution is altered in ErbB4 knockout mice.
Additional
Neuregulin 1 regulates pyramidal neuron activity via ErbB4 in parvalbumin-positive interneurons.

M_ERBB4_1_KO_CN_TG

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Transgenic mice expressing human ErbB4 cDNA under the control of the cardiac-specific alpha-MHC promoter in knockout mice.
Allele Type: Targeted (Transgenic)
Strain of Origin: C57BL/6
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_ERBB4_2_CKO_HM_PVALBN

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Conditional deletion of exon 2 of ErbB4 gene using Pvalb-cre, in parvalbumin expressing interneurons
Allele Type: Conditional loss-of-function
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_ERBB4_1_KO_CN_TG

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuronal number: purkinje cells1
Decreased
Description: Decreased numerical density of parvalbumin (pv)-positive neurons in cornu ammonis
Exp Paradigm: Double immunofluorescene analysis using anti-parvalbumin and anti-erbb4 antibodies of hippocampal slices
 Immunohistochemistry
 9-12 weeks
Neuronal number: interneurons2
Decreased
Description: Decreased density of cck-positive cells in all areas of the hippocampus
Exp Paradigm: Cck
 Immunohistochemistry
 12-16 weeks
Neuronal number: interneurons2
Decreased
Description: Decreased number of gabaergic cells demonstrated by decrease in gad67-immunoreactivity throught the hippocampus
Exp Paradigm: Gad67
 Immunohistochemistry
 12-16 weeks
Neuronal number: interneurons2
Decreased
Description: Decreased neuronal density of nnos-positive cells across the dorsoventral axis, dentate gyrus, and subiculum of the hippocampus
Exp Paradigm: Nnos
 Immunohistochemistry
 12-16 weeks
Neuronal number: interneurons2
Decreased
Description: Decreased density of parvalbumin (pv) positive cells in the hippocampus
Exp Paradigm: Pv
 Immunohistochemistry
 12-16 weeks
Synaptic transmission1
Decreased
Description: Decreased gamma oscillation power in hippocampal slices in response to nrg-1beta
Exp Paradigm: Extracellular field recordings in stratum pyramidale of ca3 of hippocampal slices after nrg1beta administration
 Field potential recordings
 9-12 weeks
Synaptic transmission1
Decreased
Description: Decreased gamma oscillation power in hippocampal slices in response to kainate
Exp Paradigm: Extracellular field recordings in stratum pyramidale of ca3 of hippocampal slices after kainate administration
 Field potential recordings
 9-12 weeks
Brain cytoarchitecture1
 No change
 Immunohistochemistry
 9-12 weeks
Neuronal number: purkinje cells2
 No change
 Immunohistochemistry
 12-16 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_ERBB4_2_CKO_HM_PVALBN

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity1
Increased
Description: Increased locomotor activity demonstrating hyperactivity
Exp Paradigm: Open field test
 Open field test
 Unreported
Synaptic transmission1
Decreased
Description: Decreased attenuation of spontaenous firing rate of pyramidal neurons in response to nrg1
Exp Paradigm: NA
 NA
 Unreported
Synaptic transmission1
Decreased
Description: Decreased amplitude of evoked inhibitory postsynaptic currents
Exp Paradigm: NA
 NA
 Unreported
Sensorimotor gating1
Decreased
Description: Decreased pre-pulse inhibition of auditory evoked startle stimulus
Exp Paradigm: Pre-pulse inhibition of auditory evoked startle with three levels of pre-pulse
 Prepulse inhibition
 Unreported
Sensorimotor gating1
Increased
Description: Increased pre-pulse inhibition after administration of diazepam
Exp Paradigm: Pre-pulse inhibition of auditory evoked startle with three levels of pre-pulse after administration of diazepam (3 mg/kg)
 Prepulse inhibition
 Unreported
Spatial working memory1
Decreased
Description: Decreased working memory demonstrated by increased number of total errors
Exp Paradigm: Performance on an automated radial arm maze
 Radial maze test
 Unreported
Size/growth1
 No change
 General observations
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Maternal behavior, Molecular profile, Neuroanatomy / ultrastructure / cytoarchitecture, Physiological parameters, Repetitive behavior, Seizure, Social behavior





Download ERBB4's Cytoscape file

Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
DLG4 DLG4discs, large homolog 4 (Drosophila) 1742 P78352 IP/WB
Seshadri S , et al. 2015
WAC WW domain containing adaptor with coiled-coil 51322 Q9BTA9 IP; LC-MS/MS
Joachim J , et al. 2015

HELP
Copyright © 2017 MindSpec, Inc.