GP1BA

Chr 17ARAD

glycoprotein Ib platelet subunit alpha

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismAR/ADLOEUF 1.664 OMIM phenotypes
Clinical SummaryGP1BA
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Gene-Disease Validity (ClinGen)
Bernard-Soulier syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.66LOEUF
pLI 0.003
Z-score 0.46
OE 0.78 (0.381.66)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.30Z-score
OE missense 1.05 (0.961.14)
368 obs / 352.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.78 (0.381.66)
00.351.4
Missense OE1.05 (0.961.14)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 4 / 5.1Missense obs/exp: 368 / 352.0Syn Z: -0.81
DN
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.PMID:23934752

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GP1BA · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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