ITGA2B

integrin subunit alpha 2b, the group of CD molecules|Integrin alpha subunits|Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): 17:44372180-44389649

Previous symbols: [ "GP2B" ]

Links

ENSG00000005961 ∙ NCBI:3674 ∙ OMIM:607759 ∙ HGNC:6138 ∙ Uniprot:P08514 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Glanzmann's thrombasthenia (Definitive), mode of inheritance: AR
• platelet-type bleeding disorder 16 (Moderate), mode of inheritance: AD
• Glanzmann's thrombasthenia (Supportive), mode of inheritance: AR
• autosomal dominant macrothrombocytopenia (Supportive), mode of inheritance: AD
• Glanzmann thrombasthenia 1 (Strong), mode of inheritance: AR
• platelet-type bleeding disorder 16 (Strong), mode of inheritance: AD
• platelet-type bleeding disorder 16 (Definitive), mode of inheritance: AD
• Glanzmann thrombasthenia (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bleeding disorder, platelet-type, 16, autosomal dominant; Glanzmann thrombasthenia 1	AD/AR	Hematologic	Individuals with Bleeding disorder, platelet-type, 16 may have mild disease, but awareness may allow prompt diagnosis, allowing preventive measures and rapid treatment of bleedin episodes; Individuals with Glanzmann thrombasthenia 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; Precipitating factors should be avoided	Hematologic	2014236; 8282784; 16463284; 19408193; 20020534; 21454453; 21917754; 22102273; 21487445; 22250950; 22513797

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ITGA2B gene.

• Glanzmann thrombasthenia (139 variants)
• Glanzmann thrombasthenia 1 (31 variants)
• not provided (7 variants)
• Platelet-type bleeding disorder 16 (3 variants)
• ITGA2B-related disorder (2 variants)
• Macrothrombocytopenia (1 variants)
• Abnormal platelet function (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ITGA2B 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			7	63	5	75
missense	25	48	224	3	7	307
nonsense	36	6	1			43
start loss						0
frameshift	55	15	4			74
inframe indel	1	3	6			10
splice donor/acceptor (+/-2bp)	22	9	2			33
splice region	2	6	19	18	4	49
non coding		2	18	58	17	95
Total	139	83	262	124	29

Highest pathogenic variant AF is 0.0000527

Variants in ITGA2B

This is a list of pathogenic ClinVar variants found in the ITGA2B region.

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

Position	Type	Phenotype	Significance	ClinVar
17-44372199-A-G		Glanzmann thrombasthenia	Uncertain significance (Jun 02, 2022)
17-44372214-G-T		Glanzmann thrombasthenia	Likely benign (Jan 13, 2018)
17-44372244-A-G		Glanzmann thrombasthenia	Uncertain significance (Jan 15, 2018)
17-44372313-G-A		Glanzmann thrombasthenia	Likely benign (Jan 13, 2018)
17-44372364-T-TCACTC		Glanzmann thrombasthenia	Likely pathogenic (Aug 15, 2023)
17-44372376-TTCA-T		not specified	Uncertain significance (Jun 28, 2023)
17-44372383-T-A		Glanzmann thrombasthenia	Uncertain significance (Oct 22, 2023)
17-44372385-T-A		Glanzmann thrombasthenia • ITGA2B-related disorder	Uncertain significance (May 02, 2024)
17-44372390-C-CCA		Glanzmann thrombasthenia • Platelet-type bleeding disorder 16	Uncertain significance (Jun 01, 2023)
17-44372391-CA-C		Glanzmann thrombasthenia • Glanzmann thrombasthenia 1	Likely pathogenic (Dec 02, 2021)
17-44372392-AG-A		Glanzmann thrombasthenia	Likely pathogenic (Apr 07, 2022)
17-44372394-G-C		Glanzmann thrombasthenia	Uncertain significance (Jan 12, 2018)
17-44372396-G-A			Uncertain significance (Aug 08, 2023)
17-44372401-C-T		Glanzmann thrombasthenia	Uncertain significance (Jul 20, 2022)
17-44372407-C-A		ITGA2B-related disorder	Uncertain significance (Dec 10, 2022)
17-44372407-C-T		Platelet-type bleeding disorder 16 • Thrombocytopenia • Glanzmann thrombasthenia • not specified	Uncertain significance (Sep 07, 2023)
17-44372407-CG-GC		Glanzmann thrombasthenia	Uncertain significance (Nov 02, 2023)
17-44372408-G-A		Platelet-type bleeding disorder 16 • Thrombocytopenia • Glanzmann thrombasthenia • Glanzmann thrombasthenia 1 • ITGA2B-related disorder	Uncertain significance (Jun 16, 2020)
17-44372414-A-T		Platelet-type bleeding disorder 16	Uncertain significance (-)
17-44372416-A-G		not specified	Uncertain significance (Apr 16, 2024)
17-44372421-G-A		not specified • Glanzmann thrombasthenia • Glanzmann thrombasthenia 1	Benign (Jan 31, 2024)
17-44372422-A-G		Glanzmann thrombasthenia	Uncertain significance (Sep 02, 2021)
17-44372423-C-A		Glanzmann thrombasthenia	Uncertain significance (Mar 14, 2023)
17-44372424-C-T		Glanzmann thrombasthenia	Pathogenic (Aug 05, 2022)
17-44372427-G-A		Glanzmann thrombasthenia	Conflicting classifications of pathogenicity (Mar 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ITGA2B	protein_coding	protein_coding	ENST00000262407	30	17326

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.52e-16	0.999	125666	0	82	125748	0.000326

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.23	512	597	0.858	0.0000357	6611
Missense in Polyphen		175	216.56	0.80807		2402
Synonymous	1.14	235	258	0.910	0.0000165	2157
Loss of Function	3.14	36	62.9	0.572	0.00000334	643

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000847	0.000840
Ashkenazi Jewish	0.00	0.00
East Asian	0.000654	0.000653
Finnish	0.000143	0.000139
European (Non-Finnish)	0.000230	0.000229
Middle Eastern	0.000654	0.000653
South Asian	0.000661	0.000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It 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 cell surface.
• 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:10607701, ECO:0000269|PubMed:11798398, ECO:0000269|PubMed:12083483, ECO:0000269|PubMed:12181054, ECO:0000269|PubMed:12424194, ECO:0000269|PubMed:12506038, ECO:0000269|PubMed:15099289, ECO:0000269|PubMed:15219201, ECO:0000269|PubMed:17018384, ECO:0000269|PubMed:20020534, ECO:0000269|PubMed:7508443, ECO:0000269|PubMed:7706461, ECO:0000269|PubMed:8282784, ECO:0000269|PubMed:8704171, ECO:0000269|PubMed:9215749, ECO:0000269|PubMed:9473221, ECO:0000269|PubMed:9722314, ECO:0000269|PubMed:9734640, ECO:0000269|PubMed:9763559, ECO:0000269|PubMed:9920835}. 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:21454453, ECO:0000269|PubMed:9834222}. 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);Small cell lung cancer - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Platelet Aggregation Inhibitor Pathway, Pharmacodynamics;Eptifibatide Action Pathway;Tirofiban Action Pathway;Abciximab Action Pathway;Integrin-mediated Cell Adhesion;Arrhythmogenic Right Ventricular Cardiomyopathy;Human Complement System;Hematopoietic Stem Cell Differentiation;Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;PI3K-Akt Signaling Pathway;Developmental Biology;MAP2K and MAPK activation;Disease;Signal Transduction;Gene expression (Transcription);il-7 signal transduction;Generic Transcription Pathway;Integrin cell surface interactions;RNA Polymerase II Transcription;Extracellular matrix organization;GRB2:SOS provides linkage to MAPK signaling for Integrins ;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;p130Cas linkage to MAPK signaling for integrins;Integrin alphaIIb beta3 signaling;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;Hemostasis;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Signal transduction by L1;L1CAM interactions;Axon guidance;ECM proteoglycans;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;Transcriptional regulation by RUNX1;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction;Arf6 signaling events;Signaling events mediated by PTP1B (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.500
• rvis_EVS: -0.33
• rvis_percentile_EVS: 30.9

Haploinsufficiency Scores

• pHI: 0.342
• hipred: Y
• hipred_score: 0.723
• ghis: 0.499

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.769

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Itga2b
• 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); hematopoietic system phenotype; embryo phenotype; immune system phenotype; digestive/alimentary phenotype; cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: itga2b
• Affected structure: thrombocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased functionality

Gene ontology

• Biological process: platelet degranulation;positive regulation of leukocyte migration;cell-matrix adhesion;integrin-mediated signaling pathway;extracellular matrix organization;regulation of megakaryocyte differentiation;platelet aggregation
• Cellular component: plasma membrane;focal adhesion;integrin complex;external side of plasma membrane;cell surface;platelet alpha granule membrane;extracellular exosome;blood microparticle
• Molecular function: protein binding;identical protein binding;metal ion binding;extracellular matrix binding;fibrinogen binding