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Relevance to Autism

Several studies have found genetic association between the ITGB3 gene and autism in a number of population cohorts, and a rare mutation in the ITGB3 gene has been identified in an individual with ASD (ORoak et al., 2012).

Molecular Function

The encoded protein is the integrin beta chain beta 3 that participates in cell adhesions and cell-surface mediated signalling.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Variation in ITGB3 is associated with whole-blood serotonin level and autism susceptibility.
ASD
Positive Association
Association and gene-gene interaction of SLC6A4 and ITGB3 in autism.
ASD
Positive Association
Multifactor dimensionality reduction-phenomics: a novel method to capture genetic heterogeneity with use of phenotypic variables.
ASD
Positive Association
Evidence for epistasis between SLC6A4 and ITGB3 in autism etiology and in the determination of platelet serotonin levels.
ASD
Positive Association
Genome-wide association study identifies ITGB3 as a QTL for whole blood serotonin.
Whole blood serotonin levels
Positive Association
Phenome-wide association study (PheWAS) in EMR-linked pediatric cohorts, genetically links PLCL1 to speech language development and IL5-IL13 to Eos...
PDD
Positive Association
Genetic association and gene-gene interaction analyses suggest likely involvement of ITGB3 and TPH2 with autism spectrum disorder (ASD) in the Indi...
ASD
Positive Association
Family-based association study of ITGB3 in autism spectrum disorder and its endophenotypes.
ASD
Support
Exploring the biological role of postzygotic and germinal de novo mutations in ASD
ASD
Support
Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
ASD
Support
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.
ASD
Support
CRISPR-mediated activation of autism gene Itgb3 restores cortical network excitability via mGluR5 signaling
Support
Integrating de novo and inherited variants in 42
ASD
Support
Integrin β3 in forebrain Emx1-expressing cells regulates repetitive self-grooming and sociability in mice
ASD
Support
Mutational Landscape of Autism Spectrum Disorder Brain Tissue
ASD
Highly Cited
Increased platelet aggregability associated with platelet GPIIIa PlA2 polymorphism: the Framingham Offspring Study.
Recent Recommendation
The Gain-of-Function Integrin 3 Pro33 Variant Alters the Serotonin System in the Mouse Brain.
ASD
ADHD
Recent Recommendation
AlphaIIbbeta3 integrin: new allelic variants in Glanzmann thrombasthenia, effects on ITGA2B and ITGB3 mRNA splicing, expression, and structure-func...
Recent Recommendation
The Foxc2 transcription factor regulates angiogenesis via induction of integrin beta3 expression.
Recent Recommendation
A nonsynonymous SNP in the ITGB3 gene disrupts the conserved membrane-proximal cytoplasmic salt bridge in the alphaIIbbeta3 integrin and cosegregat...

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN137R001 
 missense_variant 
 c.1133G>A 
 p.Arg378His 
 De novo 
  
 Simplex 
 GEN137R002 
 frameshift_variant 
 c.206dup 
 p.Asn69LysfsTer6 
 Familial 
 Maternal 
 Multiplex 
 GEN137R003 
 splice_site_variant 
 c.615-1G>C 
  
 Familial 
 Paternal 
 Multiplex 
 GEN137R004 
 missense_variant 
 c.62C>T 
 p.Ala21Val 
 De novo 
  
 Simplex 
 GEN137R005 
 synonymous_variant 
 c.72C>T 
 p.Gly24%3D 
 Unknown 
  
  
 GEN137R006 
 missense_variant 
 c.20C>T 
 p.Pro7Leu 
 De novo 
  
  
 GEN137R007 
 missense_variant 
 c.1664T>C 
 p.Val555Ala 
 De novo 
  
  
 GEN137R008 
 frameshift_variant 
 c.1700_1701del 
 p.Gln567LeufsTer9 
 De novo 
  
  
 GEN137R009 
 synonymous_variant 
 c.1469C>T 
 p.Pro490Leu 
 De novo 
  
  

Common

Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
 GEN137C001 
 missense_variant 
  
 T 
 p.Leu33Pro 
 Vanderbilt autism sample: 1255 affected individuals from 564 multiplex families and 79 trios from AGRE, Tufts-Vanderbilt University consortium, Iowa and Stanford. Combined sample: Vanderbilt autism sample and 87 outbred Caucasian ASD trios from the University of Chicago. 
 Discovery 
 GEN137C002 
 3_prime_UTR_variant 
 rs3809865 
 c.*1016T>A 
 N/A 
 Caucasian 
 Discovery 
 GEN137C003 
 intron_variant 
 rs12603582 
 c.1914-267G>T 
  
  
 Discovery 
 GEN137C004 
 missense_variant 
 rs5918 
 c.176T>C 
 p.Leu59Pro 
 India; 633 subjects including autistic families (140 trios, 23 duos & 2 singles) and healthy controls (n=165) 
 Discovery 
 GEN137C005 
 intron_variant 
 rs8074094 
 c.80-3764T>C 
 Minor allele, C 
 1141 cases, 1840 controls 
 Discovery 
 GEN137C006 
 missense_variant 
 rs5918 
  
 p.Leu33Pro 
 61 adult male ASD cases and 11371 adult male controls (from BioVU/Vanderbilt University Medical Center) 
 Replication 
 GEN137C007 
 missense_variant 
 rs5918 
  
 p.Leu33Pro 
 46 adult male ADHD cases and 11371 adult male controls (from BioVU/Vanderbilt University Medical Center) 
 Discovery 
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
17
Duplication
 1
 
17
Duplication
 1
 
17
Duplication
 1
 

Model Summary

Altered social and repetitive behavior which suggests that the integrin beta3 subunit may be involved in brain systems relevant to ASD.

References

Type
Title
Author, Year
Primary
Absence of preference for social novelty and increased grooming in integrin 3 knockout mice: initial studies and future directions.
Additional
Neuroanatomical Assessment of the Integrin 3 Mouse Model Related to Autism and the Serotonin System Using High Resolution MRI.

M_ITGB3_1_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Targeted knockout of Itgb3 gene.
Allele Type: Targeted (Knock Out)
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_ITGB3_2_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Targeted knockout of Itgb3 gene.
Allele Type: Targeted (Knock Out)
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_ITGB3_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Brain size2
Decreased
Description: Decreased total brain volume reflected in 53 of 62 regions being significantly smaller
Exp Paradigm: Brain volumetry
 Magnetic resonance imaging (mri)
 2 months
Brain morphology2
Abnormal
Description: Abnormal brain morphology indicated by specific changes in cerebellum specifically the fastigial nuclei and nucleus interpositus
Exp Paradigm: Voxel based morphometry
 Voxel based morphometry
 8 weeks
Brain morphology2
Abnormal
Description: Abnormal brain morphology indicated by drastic bilateral changes around midline hippocampus specific to ca1 region and followed the dentate gyrus and stratum granulosum and bilateral decrease in dorsal raphe nucleus
Exp Paradigm: Voxel based morphometry
 Voxel based morphometry
 8 weeks
Brain morphology2
Abnormal
Description: Abnormal brain morphology demonstrated by difference in absolute and relative volumes of corpus callosum and periaqueductal gray matter
Exp Paradigm: Voxel based morphometry
 Voxel based morphometry
 8 weeks
Self grooming: perseveration1
Increased
Description: Increased time spent grooming in novel environment
Exp Paradigm: General 10 minute observation
 General observations
 Unreported
Social interaction1
Decreased
Description: Decreased preference for social novelty
Exp Paradigm: Three-chambered test for social novelty
 Three-chamber social approach test
 Unreported
Anxiety1
 No change
 Elevated plus maze test
 Unreported
Object recognition memory1
 No change
 General observations
 Unreported
General locomotor activity1
 No change
 Open field test
 Unreported
Olfaction1
 No change
 Olfactory habituation-dishabituation test
 Unreported
Social interaction1
 No change
 Three-chamber social approach test
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_ITGB3_2_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Anxiety1
 No change
 Elevated plus maze test
 Unreported
Object recognition memory1
 No change
 General observations
 Unreported
Object recognition memory1
 No change
 General observations
 Unreported
General locomotor activity1
 No change
 Open field test
 Unreported
Olfaction1
 No change
 Olfactory habituation-dishabituation test
 Unreported
Social interaction1
 No change
 Three-chamber social approach test
 Unreported
Social interaction1
 No change
 Three-chamber social approach test
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Immune response, Maternal behavior, Molecular profile, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure





Download ITGB3's Cytoscape file

Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
AKT1 v-akt murine thymoma viral oncogene homolog 1 207 P31749 IP/WB
Kirk RI , et al. 2000
ANGPTL3 angiopoietin-like 3 27329 Q9Y5C1 IP/WB
Camenisch G , et al. 2002
APP amyloid beta (A4) precursor protein 351 P05067 IP/WB; Biolayer interferometry; Co-localization
Donner L , et al. 2016
c-SRC v-src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog 6714 P41240 IP/WB
Datta A , et al. 2001
CD36 CD36 molecule (thrombospondin receptor) 948 P16671 IP/WB
Miao WM , et al. 2001
CIB1 calcium and integrin binding 1 (calmyrin) 10519 Q99828 Y2H; GST
Naik UP , et al. 1997
COL1A2 collagen, type I, alpha 2 1278 P08123 IP/WB
Dedhar S and Gray V 1990
DAB1 disabled homolog 1 (Drosophila) 1600 O75553 GST; IP/WB
Calderwood DA , et al. 2003
DAB2 disabled homolog 2, mitogen-responsive phosphoprotein (Drosophila) 1601 P98082 GST; IP/WB
Calderwood DA , et al. 2003
DOK1 docking protein 1, 62kDa (downstream of tyrosine kinase 1) 1796 Q99704 GST; IP/WB
Calderwood DA , et al. 2003
EPS8 epidermal growth factor receptor pathway substrate 8 2059 B4E3T6 GST; IP/WB
Calderwood DA , et al. 2003
FGA fibrinogen alpha chain 2243 P02671 Clot retraction assay
Bennett JS 2001
FGG fibrinogen gamma chain 2266 P02679 Ligand binding assay
Yokoyama K , et al. 2000
FLNA filamin A, alpha 2316 P21333 Y2H; IP/WB
van der Flier A , et al. 2002
FLNB filamin B, beta 2317 O75369 Y2H
van der Flier A , et al. 2002
FN1 fibronectin 1 2335 P02751 IP/WB
Smith JW , et al. 1990
HOXA10 homeobox A10 3206 P31260 EMSA
Bei L , et al. 2007
ILK integrin-linked kinase 3611 Q13418 IP/WB
Yamaji S , et al. 2002
ITGA2B integrin, alpha 2b (platelet glycoprotein IIb of IIb/IIIa complex, antigen CD41) 3674 P08514 GALLEX
Schneider D and Engelman DM 2003
ITGA5 integrin, alpha 5 (fibronectin receptor, alpha polypeptide) 3678 P08648 IP/WB
Akimov SS , et al. 2000
ITGAV integrin, alpha V 3685 B7ZLX0 Co-crystal structure
Xiong JP , et al. 2002
ITGB3BP integrin beta 3 binding protein (beta3-endonexin) 23421 Q13352 Y2H
Fujimoto TT , et al. 2002
KDR kinase insert domain receptor (a type III receptor tyrosine kinase) 3791 P35968 IP/WB
Soldi R , et al. 1999
MIR30 microRNA 30a 407029 N/A: miRNA Luciferase reporter assay; IP/WB
Yu F , et al. 2010
MIRLET7A1 microRNA let-7a-1 406881 N/A: miRNA Luciferase reporter assay
Mller DW and Bosserhoff AK 2008
NID1 nidogen 1 4811 P14543 Co-localization
Yang Y , et al. 1996
NRIF3 integrin beta 3 binding protein (beta3-endonexin) 23421 Q13352 IP/WB
Shattil SJ , et al. 1995
NUMB numb homolog (Drosophila) 8650 P49757 GST; IP/WB
Calderwood DA , et al. 2003
P2RY2 purinergic receptor P2Y, G-protein coupled, 2 5029 P41231 IP/WB
Erb L , et al. 2001
PBX2 pre-B-cell leukemia homeobox 2 5089 P40425 EMSA
Bei L , et al. 2007
PDGFRA platelet-derived growth factor receptor, alpha polypeptide 5156 P16234 IP/WB
Baron W , et al. 2002
PDPK1 3-phosphoinositide dependent protein kinase-1 5170 O15530 IP/WB
Kirk RI , et al. 2000
PLAUR plasminogen activator, urokinase receptor 5329 Q03405 IP/WB
Cao DJ , et al. 2004
PTK2B PTK2B protein tyrosine kinase 2 beta 2185 Q14289 IP/WB
Eliceiri BP , et al. 2002
SHC1 SHC (Src homology 2 domain containing) transforming protein 1 6464 P29353 IP/WB
Kirk RI , et al. 2000
SYK spleen tyrosine kinase 6850 P43405 IP/WB
Saci A , et al. 2000
TENC1 tensin like C1 domain containing phosphatase (tensin 2) 23371 Q63HR2 GST; IP/WB
Calderwood DA , et al. 2003
TGM2 transglutaminase 2 7052 P21980 IP/WB
Akimov SS , et al. 2000
THBS1 thrombospondin 1 7057 P07996 Reconstituted complex
Lawler J and Hynes RO 1989
THY1 Thy-1 cell surface antigen 7070 P04216 Biotinylation assay
Saalbach A , et al. 2005
TLN1 talin 1 7094 Q9Y490 IP/WB
Patil S , et al. 1999
VTN vitronectin 7448 D9ZGG2 IP/WB
Maile LA , et al. 2005
ARNT2 aryl hydrocarbon receptor nuclear translocator 2 11864 Q61324 Gene microarray
Liu C , et al. 2003
CD31 platelet/endothelial cell adhesion molecule 1 18613 Q08481 Cocapping assay
Wong CW , et al. 2000
FBLN2 fibulin 2 14115 P37889 IP/WB
Gu YC , et al. 2000
FOXC2 forkhead box C2 14234 Q61850 ChIP; Luciferase reporter assay
Hayashi H , et al. 2008
PDGFRB platelet-derived growth factor receptor, beta polypeptide 5159 P09619 IP/WB
Borges E , et al. 2000
FAK PTK2 protein tyrosine kinase 2 396416 Q00944 IP/WB
Hildebrand JD , et al. 1996
PTK2 PTK2 protein tyrosine kinase 2 396416 Q00944 IP/WB
Pfaff M and Jurdic P 2001
PXN paxillin 395832 P49024 IP/WB
Pfaff M and Jurdic P 2001
CAPN1 Calpain-1 catalytic subunit 100009089 P06815 IP/WB; MS
Du X , et al. 1995

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