ITGB3

integrin subunit beta 3, the group of Integrin beta subunits|CD molecules

Basic information

Region (hg38): 17:47253826-47313743

Previous symbols: [ "GP3A" ]

Links

ENSG00000259207 ∙ NCBI:3690 ∙ OMIM:173470 ∙ HGNC:6156 ∙ Uniprot:P05106 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Glanzmann's thrombasthenia (Supportive), mode of inheritance: AR
• autosomal dominant macrothrombocytopenia (Supportive), mode of inheritance: AD
• Glanzmann thrombasthenia 2 (Strong), mode of inheritance: AR
• bleeding disorder, platelet-type, 24 (Strong), mode of inheritance: AD
• Glanzmann thrombasthenia (Definitive), mode of inheritance: AR
• platelet-type bleeding disorder 16 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bleeding disorder, platelet-type, 24, autosomal dominant; Glanzmann thrombasthenia 2; Thrombocytopenia, neonatal alloimmune	AD/AR	Hematologic	Individuals with dominant disease may demonstrate moderate to severe bleeding, and awareness may allow preventive measures and prompt management; Precipitating factors for bleeding episodes should be avoided (for both dominant and recessive disease forms); Individuals with bi-allelic variants can have severe bleeding diatheses, and preventive measures as well as rapid treatment (which can include local measures as well as platelet transfusions, recombinant activated factor VII, and octreotide for GI bleeding) can be beneficial; Variants may be relevant to potential reactions from platelet transfusion, and knowledge may have relevance to related treatment	Hematologic	7193688; 2257303; 2428841; 2565345; 1967954; 2257303; 2392682; 2014236; 1371279; 1438206; 1602006; 1430225; 8093349; 8471765; 7694683; 8878424; 9160670; 9351872; 9845537; 9700201; 10583927; 10559451; 11425767; 11723016; 16721604; 16463284; 18065693; 19336737; 19408193; 20020534; 20081061; 20345392; 21917754; 22102273; 22250950; 22890234; 23146053; 23253071; 23929305
Bi-allelic variants have been described as resulting in a more severe phenotype; Specific variants may also be important in neonatal alloimune thrombocytopenia (as relates to platelet transfusions)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ITGB3 gene.

• Glanzmann thrombasthenia (285 variants)
• not provided (271 variants)
• not specified (26 variants)
• Glanzmann thrombasthenia 2 (24 variants)
• Inborn genetic diseases (20 variants)
• Bleeding disorder, platelet-type, 24 (10 variants)
• Glanzmann thrombasthenia 1 (7 variants)
• Platelet-type bleeding disorder 16 (6 variants)
• ITGB3-related condition (6 variants)
• Macrothrombocytopenia (3 variants)
• Abnormal bleeding;Prolonged bleeding time (2 variants)
• Abnormal bleeding (2 variants)
• Bleeding disorder, platelet-type, 24;Myocardial infarction, susceptibility to;Glanzmann thrombasthenia 2 (1 variants)
• Abnormal platelet aggregation;Thrombocytopenia (1 variants)
• See cases (1 variants)
• Ca/Tu ALLOANTIGEN POLYMORPHISM (1 variants)
• Mo ALLOANTIGEN POLYMORPHISM (1 variants)
• Myocardial infarction, susceptibility to (1 variants)
• Abnormal platelet aggregation (1 variants)
• Thrombocytopenia (1 variants)
• Thrombocytopenia;Abnormal bleeding (1 variants)
• PEN(a)/PEN(b) ALLOANTIGEN POLYMORPHISM (1 variants)
• PL(A1)/(A2) ALLOANTIGEN POLYMORPHISM (1 variants)
• Fetal and neonatal alloimmune thrombocytopenia (1 variants)
• Glanzmann thrombasthenia;Platelet-type bleeding disorder 16 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ITGB3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			10	65	11	86
missense	15	43	138	6	6	208
nonsense	26	1				27
start loss			1			1
frameshift	36	5				41
inframe indel		2	4			6
splice donor/acceptor (+/-2bp)	11	4	1			16
splice region		3	3	8	1	15
non coding			35	32	43	110
Total	88	55	189	103	60

Highest pathogenic variant AF is 0.000151

Variants in ITGB3

This is a list of pathogenic ClinVar variants found in the ITGB3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-47253855-G-C		not specified • Glanzmann thrombasthenia	Benign (Jan 13, 2018)
17-47253862-A-T			Uncertain significance (Dec 27, 2023)
17-47253863-T-C		Glanzmann thrombasthenia	Uncertain significance (Apr 06, 2023)
17-47253865-C-A			Likely benign (Jan 24, 2024)
17-47253868-G-C			Uncertain significance (Dec 27, 2023)
17-47253877-C-T		Glanzmann thrombasthenia	Uncertain significance (Sep 27, 2022)
17-47253878-G-A		Inborn genetic diseases	Uncertain significance (Jul 29, 2023)
17-47253878-G-T			Uncertain significance (Sep 29, 2023)
17-47253879-G-A			Likely benign (Jan 07, 2024)
17-47253879-G-T			Likely benign (Oct 17, 2023)
17-47253880-C-T		Glanzmann thrombasthenia	Uncertain significance (Jan 13, 2018)
17-47253881-C-T			Uncertain significance (Dec 16, 2023)
17-47253882-C-G			Likely benign (Jun 23, 2023)
17-47253884-G-A		Inborn genetic diseases	Uncertain significance (Feb 17, 2022)
17-47253884-G-C			Uncertain significance (Aug 24, 2023)
17-47253888-G-A		ITGB3-related disorder	Likely benign (Jan 17, 2023)
17-47253891-C-G			Likely benign (Jan 27, 2024)
17-47253892-T-C		Glanzmann thrombasthenia	Pathogenic (Nov 02, 2023)
17-47253896-C-A		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
17-47253897-G-T			Likely benign (Jan 02, 2024)
17-47253900-T-C			Likely benign (Oct 22, 2023)
17-47253901-G-A		Glanzmann thrombasthenia	Benign (Jun 04, 2020)
17-47253910-C-T			Likely benign (Nov 11, 2022)
17-47253911-TG-T			Pathogenic (May 18, 2023)
17-47253911-T-TG		Glanzmann thrombasthenia	Pathogenic (Mar 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ITGB3	protein_coding	protein_coding	ENST00000559488	15	90447

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00172	0.998	125672	0	76	125748	0.000302

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.16	371	440	0.844	0.0000268	5172
Missense in Polyphen		147	202.59	0.72562		2394
Synonymous	0.395	168	175	0.962	0.0000107	1515
Loss of Function	3.85	12	37.4	0.320	0.00000218	455

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00179	0.00179
Ashkenazi Jewish	0.00	0.00
East Asian	0.000381	0.000381
Finnish	0.0000472	0.0000462
European (Non-Finnish)	0.000168	0.000158
Middle Eastern	0.000381	0.000381
South Asian	0.0000653	0.0000653
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 (ITGA2B:ITGB3) is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha- IIb/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha- IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. Fibrinogen binding enhances SELP expression in activated platelets (By similarity). ITGAV:ITGB3 binds to fractalkine (CX3CL1) and acts as its coreceptor in CX3CR1-dependent fractalkine signaling (PubMed:23125415, PubMed:24789099). ITGAV:ITGB3 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGAV:ITGB3 binds to FGF1 and this binding is essential for FGF1 signaling (PubMed:18441324). ITGAV:ITGB3 binds to FGF2 and this binding is essential for FGF2 signaling (PubMed:28302677). ITGAV:ITGB3 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:19578119). ITGAV:ITGB3 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464). ITGAV:ITGB3 binds to IL1B and this binding is essential for IL1B signaling (PubMed:29030430). ITGAV:ITGB3 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:18635536, PubMed:25398877). ITGAV:ITGB3 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1 (PubMed:12807887). {ECO:0000250|UniProtKB:O54890, ECO:0000269|PubMed:12807887, ECO:0000269|PubMed:18441324, ECO:0000269|PubMed:18635536, ECO:0000269|PubMed:19578119, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:24789099, ECO:0000269|PubMed:25398877, ECO:0000269|PubMed:28302677, ECO:0000269|PubMed:28873464, ECO:0000269|PubMed:29030430, ECO:0000269|PubMed:9195946, ECO:0000303|PubMed:16322781, ECO:0000303|PubMed:17635696}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Coxsackievirus A9. {ECO:0000269|PubMed:7519807}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Cytomegalovirus/HHV-5. {ECO:0000269|PubMed:15834425}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB3 acts aP05556s a receptor for Human parechovirus 1. {ECO:0000269|PubMed:11160695}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. {ECO:0000269|PubMed:10397733}.
• Disease: DISEASE: Glanzmann thrombasthenia (GT) [MIM:273800]: A common inherited disease of platelet aggregation. It is characterized by mucocutaneous bleeding of mild-to-moderate severity. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb-IIIa complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the GPIIb-IIIa complex at reduced levels, have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. {ECO:0000269|PubMed:10233432, ECO:0000269|PubMed:11588040, ECO:0000269|PubMed:11897046, ECO:0000269|PubMed:12083483, ECO:0000269|PubMed:12353082, ECO:0000269|PubMed:1371279, ECO:0000269|PubMed:1438206, ECO:0000269|PubMed:15583747, ECO:0000269|PubMed:15634267, ECO:0000269|PubMed:15748237, ECO:0000269|PubMed:1602006, ECO:0000269|PubMed:20020534, ECO:0000269|PubMed:2392682, ECO:0000269|PubMed:8781422, ECO:0000269|PubMed:9215749, ECO:0000269|PubMed:9376589, ECO:0000269|PubMed:9684783, ECO:0000269|PubMed:9790984}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Bleeding disorder, platelet-type 16 (BDPLT16) [MIM:187800]: An autosomal dominant form of congenital macrothrombocytopenia associated with platelet anisocytosis. It is a disorder of platelet production. Affected individuals may have no or only mildly increased bleeding tendency. In vitro studies show mild platelet functional abnormalities. {ECO:0000269|PubMed:18065693}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Platelet activation - Homo sapiens (human);ECM-receptor interaction - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Phagosome - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Platelet Aggregation Inhibitor Pathway, Pharmacodynamics;VEGF Signaling Pathway;Eptifibatide Action Pathway;Tirofiban Action Pathway;Abciximab Action Pathway;Osteoclast Signaling;Osteopontin Signaling;Serotonin Transporter Activity;Integrin-mediated Cell Adhesion;Arrhythmogenic Right Ventricular Cardiomyopathy;Primary Focal Segmental Glomerulosclerosis FSGS;Human Complement System;Hematopoietic Stem Cell Differentiation;Focal Adhesion;Osteoblast Signaling;MFAP5-mediated ovarian cancer cell motility and invasiveness;TGF-beta Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;Monoamine Transport;Developmental Biology;MAP2K and MAPK activation;Disease;Signal Transduction;phospholipids as signalling intermediaries;VEGFA-VEGFR2 Pathway;Integrin cell surface interactions;Extracellular matrix organization;GRB2:SOS provides linkage to MAPK signaling for Integrins ;p130Cas linkage to MAPK signaling for integrins;Integrin alphaIIb beta3 signaling;Molecules associated with elastic fibres;Elastic fibre formation;Fibroblast growth factor-1;Platelet Aggregation (Plug Formation);Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Beta3 integrin cell surface interactions;Integrin;Integrin signaling;PECAM1 interactions;Cell surface interactions at the vascular wall;Hemostasis;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Signal transduction by L1;Signaling by VEGF;L1CAM interactions;Syndecan interactions;Non-integrin membrane-ECM interactions;Axon guidance;ECM proteoglycans;Signaling by Receptor Tyrosine Kinases;Signaling by RAS mutants;Signaling by high-kinase activity BRAF mutants;Signaling by moderate kinase activity BRAF mutants;Paradoxical activation of RAF signaling by kinase inactive BRAF;Osteopontin-mediated events;Nectin adhesion pathway;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction;Arf6 signaling events;Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling;PDGFR-beta signaling pathway;IL4-mediated signaling events;Signaling events mediated by PTP1B;Signaling events mediated by VEGFR1 and VEGFR2;Integrins in angiogenesis (Consensus)

Recessive Scores

• pRec: 0.861

Intolerance Scores

• loftool: 0.127
• rvis_EVS: -1.02
• rvis_percentile_EVS: 8.1

Haploinsufficiency Scores

• pHI: 0.544
• hipred: N
• hipred_score: 0.389
• ghis: 0.515

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.685

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Itgb3
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; vision/eye phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; neoplasm; embryo phenotype; respiratory system phenotype; liver/biliary system phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: positive regulation of protein phosphorylation;positive regulation of endothelial cell proliferation;platelet degranulation;cell adhesion;cell-matrix adhesion;integrin-mediated signaling pathway;blood coagulation;positive regulation of endothelial cell migration;negative regulation of macrophage derived foam cell differentiation;negative regulation of lipid storage;smooth muscle cell migration;cell migration;platelet activation;extracellular matrix organization;positive regulation of vascular endothelial growth factor receptor signaling pathway;cell-substrate adhesion;activation of protein kinase activity;negative regulation of lipid transport;cell adhesion mediated by integrin;heterotypic cell-cell adhesion;substrate adhesion-dependent cell spreading;tube development;apolipoprotein A-I-mediated signaling pathway;wound healing;apoptotic cell clearance;regulation of bone resorption;negative regulation of low-density lipoprotein particle receptor biosynthetic process;viral entry into host cell;vascular endothelial growth factor receptor signaling pathway;mesodermal cell differentiation;positive regulation of peptidyl-tyrosine phosphorylation;negative regulation of lipoprotein metabolic process;leukocyte migration;negative chemotaxis;angiogenesis involved in wound healing;platelet aggregation;regulation of postsynaptic neurotransmitter receptor internalization
• Cellular component: nucleus;plasma membrane;integral component of plasma membrane;focal adhesion;integrin complex;cell surface;platelet alpha granule membrane;lamellipodium membrane;filopodium membrane;microvillus membrane;ruffle membrane;integrin alphav-beta3 complex;alphav-beta3 integrin-PKCalpha complex;alphav-beta3 integrin-IGF-1-IGF1R complex;alphav-beta3 integrin-HMGB1 complex;melanosome;receptor complex;extracellular exosome;alphav-beta3 integrin-vitronectin complex;glutamatergic synapse
• Molecular function: virus receptor activity;fibronectin binding;protease binding;protein disulfide isomerase activity;platelet-derived growth factor receptor binding;integrin binding;protein binding;coreceptor activity;fibroblast growth factor binding;enzyme binding;C-X3-C chemokine binding;insulin-like growth factor I binding;neuregulin binding;identical protein binding;vascular endothelial growth factor receptor 2 binding;cell adhesion molecule binding;extracellular matrix binding;fibrinogen binding