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…

GOFmechanismARLOEUF 1.461 OMIM phenotype

Clinical Summary— GP9

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Gene-Disease Validity (ClinGen)

Bernard-Soulier syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.

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ClinVar Variants

29 unique Pathogenic / Likely Pathogenic· 59 VUS of 169 total submissions

Explore recent and relevant literature in Research Assistant →

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

This gene — mechanism propensity

0.5770th %ile

GOF

0.73top 25%

LOF

0.3941th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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.

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

ClinVar Variant Classifications

169 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11

Likely Pathogenic18

VUS59

Likely Benign63

Benign10

Conflicting8

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	4	5	2	0	11
Likely Pathogenic	9	9	0	0	18
VUS	1	53	5	0	59
Likely Benign	0	4	2	57	63
Benign	0	3	4	3	10
Conflicting	—				8
Total	14	74	13	60	169

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap GP9 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →