GP9

Chr 3AR

glycoprotein IX platelet

Also known as: CD42a, GPIX

NCBI Gene: 2815 ENSG00000169704 UniProt: P14770 OMIM: 173515

The protein is a small membrane glycoprotein that forms part of the GPIb-V-IX complex on platelet surfaces, functioning as the von Willebrand factor receptor that mediates platelet adhesion to injured blood vessels. Mutations cause Bernard-Soulier syndrome type C, characterized by abnormally large platelets and clinical bleeding tendency. This condition follows autosomal recessive inheritance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a small membrane glycoprotein found on the surface of human platelets. It forms a 1-to-1 noncovalent complex with glycoprotein Ib, a platelet surface membrane glycoprotein complex that functions as a receptor for von Willebrand factor. The complete receptor complex includes noncovalent association of the alpha and beta subunits with the protein encoded by this gene and platelet glycoprotein V. Defects in this gene are a cause of Bernard-Soulier syndrome, also known as giant platelet disease. These patients have unusually large platelets and have a clinical bleeding tendency. [provided by RefSeq, Oct 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Bernard-Soulier syndrome, type CMIM #231200

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Bernard-Soulier syndrome · AR · ClinGen 2019

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.46

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.46LOEUF

pLI 0.476

Z-score 1.22

OE 0.00 (0.00–1.46)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.16Z-score

OE missense 0.96 (0.82–1.12)

109 obs / 113.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.46)

0≤0.351.4

Missense OE?0.96 (0.82–1.12)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 0 / 1.7Missense obs/exp: 109 / 113.9Syn Z: -0.47

Background carrier burden — how many people carry a rare variant somewhere in GP9?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

238 rare PASS variants

Rare truncating (LoF)

1 in 20,000

21 rare PASS variants

Rare synonymous (reference)

1 in 270

123 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GP9. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 190	1 in 29,000
South Asian	~43k	1 in 110	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 140	none seen
European (Finnish)	~27k	1 in 270	none seen
Admixed American	~22k	1 in 110	none seen
African / African American	~21k	1 in 95	≈ 1 in 9,300
East Asian	~20k	1 in 260	≈ 1 in 6,500
Ashkenazi Jewish	~13k	≈ 1 in 4,300	none seen
Middle Eastern	~2,884	1 in 120	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓