ITGA2B

Chr 17ADAR

integrin subunit alpha 2b

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

NCBI Gene: 3674 ENSG00000005961 UniProt: P08514

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]

Primary Disease Associations & Inheritance

Bleeding disorder, platelet-type, 16, autosomal dominantMIM #187800

Fetomaternal alloimmune thrombocytopenia 2MIM #621266

Glanzmann thrombasthenia 1MIM #273800

Active trials

Pathogenic / LP

489

ClinVar variants

Pubs (1 yr)

1.2

Missense Z

0.76

LOEUF

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

51 Pathogenic / Likely Pathogenic· 263 VUS of 489 total submissions

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Clinical Trials

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

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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?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.76LOEUF

pLI 0.000

Z-score 3.14

OE 0.57 (0.44–0.76)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

1.23Z-score

OE missense 0.86 (0.80–0.92)

512 obs / 596.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.57 (0.44–0.76)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.80–0.92)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91

0≤1.21.6

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

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).PMID:29090484

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