ITGB3

Chr 17ADAR

integrin subunit beta 3

Also known as: BDPLT16, BDPLT2, BDPLT24, CD61, FMAIT1, GP3A, GPIIIa, GT

NCBI Gene: 3690 ENSG00000259207 UniProt: P05106 OMIM: 173470

The ITGB3 protein is the integrin beta-3 subunit that combines with alpha chains to form cell surface receptors essential for platelet aggregation and hemostasis, particularly the alpha-IIb/beta-3 complex that binds fibrinogen and other clotting factors. Mutations cause Glanzmann thrombasthenia, a bleeding disorder characterized by defective platelet aggregation and mucocutaneous bleeding that typically presents in infancy or early childhood. This condition follows autosomal recessive inheritance.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

The ITGB3 protein product is the integrin beta chain beta 3. Integrins are integral cell-surface proteins composed of an alpha chain and a beta chain. A given chain may combine with multiple partners resulting in different integrins. Integrin beta 3 is found along with the alpha IIb chain in platelets. Integrins are known to participate in cell adhesion as well as cell-surface mediated signalling. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismAD/AR3 OMIM phenotypes

Clinical Summary— ITGB3

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Gene-Disease Validity (ClinGen)

Glanzmann thrombasthenia · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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ClinVar Variants

198 unique Pathogenic / Likely Pathogenic· 348 VUS of 978 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

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GeneReview available — ITGB3

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

This gene — mechanism propensity

0.6647th %ile

GOF

0.74top 25%

LOF

0.2775th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median · 1 literature citation

DNprediction above median · 1 literature citation

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

DNWe have shown the concomitant presence of both the normal and a mutated b3 protein in platelet lysates of the proband; thus, a loss-of-function hypothesis, with a dominant negative effect resulting from the p.D647_E686del mutation, can be made.1

GOFRare gain-of-function mutations within the ITGA2B or ITGB3 genes have been recognized to cause macrothrombocytopenia (MTP).2

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References

ClinVar Variant Classifications

978 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic127

Likely Pathogenic71

VUS348

Likely Benign352

Benign63

Conflicting4

127

Pathogenic

Likely Pathogenic

348

VUS

352

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	94	24	7	2	127
Likely Pathogenic	19	47	4	1	71
VUS	7	297	38	6	348
Likely Benign	0	6	139	207	352
Benign	0	6	46	11	63
Conflicting	—				4
Total	120	380	234	227	965

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

8 pathogenic / likely-pathogenic (of 10) ClinVar copy-number / structural variants overlap ITGB3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →