GP1BA

Chr 17ARAD

glycoprotein Ib platelet subunit alpha

Also known as: BDPLT1, BDPLT3, BSS, CD42B, CD42b-alpha, DBPLT3, GP1B, GPIbA

NCBI Gene: 2811 ENSG00000185245 OMIM: 606672

Glycoprotein Ib alpha forms part of the platelet surface receptor complex that binds von Willebrand factor to initiate platelet adhesion and activation during hemostasis. Mutations cause Bernard-Soulier syndrome (both autosomal recessive and dominant forms) and platelet-type von Willebrand disease, presenting with bleeding disorders due to impaired platelet function. The gene shows low constraint to loss-of-function variation (pLI 0.003, LOEUF 1.66), consistent with its association with both recessive and dominant inheritance patterns.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Glycoprotein Ib (GP Ib) is a platelet surface membrane glycoprotein composed of a heterodimer, an alpha chain and a beta chain, that is linked by disulfide bonds. The Gp Ib functions as a receptor for von Willebrand factor (VWF). The complete receptor complex includes noncovalent association of the alpha and beta subunits with platelet glycoprotein IX and platelet glycoprotein V. The binding of the GP Ib-IX-V complex to VWF facilitates initial platelet adhesion to vascular subendothelium after vascular injury, and also initiates signaling events within the platelet that lead to enhanced platelet activation, thrombosis, and hemostasis. This gene encodes the alpha subunit. Mutations in this gene result in Bernard-Soulier syndromes and platelet-type von Willebrand disease. The coding region of this gene is known to contain a polymophic variable number tandem repeat (VNTR) domain that is associated with susceptibility to nonarteritic anterior ischemic optic neuropathy. [provided by RefSeq, Oct 2013]

OMIM ResearchGenerating clinical summary…

MultiplemechanismAR/ADLOEUF 1.664 OMIM phenotypes

Clinical Summary— GP1BA

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Gene-Disease Validity (ClinGen)

Bernard-Soulier syndrome · ARDefinitive

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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.66LOEUF

pLI 0.003

Z-score 0.46

OE 0.78 (0.38–1.66)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.30Z-score

OE missense 1.05 (0.96–1.14)

368 obs / 352.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.78 (0.38–1.66)

0≤0.351.4

Missense OE?1.05 (0.96–1.14)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 4 / 5.1Missense obs/exp: 368 / 352.0Syn Z: -0.81

This gene — mechanism propensity

0.74top 25%

GOF

0.78top 25%

LOF

0.2968th %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

GOFThe disease is caused by gain-of-function mutations in the platelet GP1BA gene, which codes for the platelet von Willebrand factor (VWF) receptor, GPIba.1

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

References