ITGA2B

Chr 17ADAR

integrin subunit alpha 2b

Also known as: BDPLT16, BDPLT2, CD41, CD41B, FMAIT2, GP2B, GPIIb, GT

NCBI Gene: 3674 ENSG00000005961 UniProt: P08514 OMIM: 607759

The protein forms the alpha subunit of the alpha-IIb/beta-3 integrin receptor that binds fibrinogen and other ligands to mediate platelet aggregation during blood coagulation. Mutations cause Glanzmann thrombasthenia and other platelet-type bleeding disorders characterized by failure of platelet aggregation, with autosomal recessive inheritance. This gene is extremely intolerant to loss-of-function variants in the general population.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the integrin alpha chain family of proteins. The encoded preproprotein is proteolytically processed to generate light and heavy chains that associate through disulfide linkages to form a subunit of the alpha-IIb/beta-3 integrin cell adhesion receptor. This receptor plays a crucial role in the blood coagulation system, by mediating platelet aggregation. Mutations in this gene are associated with platelet-type bleeding disorders, which are characterized by a failure of platelet aggregation, including Glanzmann thrombasthenia. [provided by RefSeq, Jan 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismAD/ARLOEUF 0.763 OMIM phenotypes

Clinical Summary— ITGA2B

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Gene-Disease Validity (ClinGen)

platelet-type bleeding disorder 16 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

263 unique Pathogenic / Likely Pathogenic· 443 VUS of 1006 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — ITGA2B

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.76LOEUF

pLI 0.000

Z-score 3.14

OE 0.57 (0.44–0.76)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.23Z-score

OE missense 0.86 (0.80–0.92)

512 obs / 596.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.57 (0.44–0.76)

0≤0.351.4

Missense OE?0.86 (0.80–0.92)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 36 / 62.9Missense obs/exp: 512 / 596.6Syn Z: 1.14

This gene — mechanism propensity

0.6842th %ile

GOF

0.7029th %ile

LOF

0.2971th %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

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

GOFRare gain-of-function mutations within the ITGA2B or ITGB3 genes have been recognized to cause macrothrombocytopenia (MTP).1

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

References

1.PMID 29090484 ↗

ClinVar Variant Classifications

1006 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic160

Likely Pathogenic103

VUS443

Likely Benign239

Benign39

Conflicting11

160

Pathogenic

103

Likely Pathogenic

443

VUS

239

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	128	26	5	1	160
Likely Pathogenic	38	55	9	1	103
VUS	10	374	47	12	443
Likely Benign	1	2	127	109	239
Benign	0	8	25	6	39
Conflicting	—				11
Total	177	465	213	129	995

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 10) ClinVar copy-number / structural variants overlap ITGA2B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →