GP5

Chr 3

glycoprotein V platelet

Also known as: CD42d, GPV

NCBI Gene: 2814 ENSG00000178732 UniProt: P40197 OMIM: 173511

Human platelet glycoprotein V (GP5) is a part of the Ib-V-IX system of surface glycoproteins that constitute the receptor for von Willebrand factor (VWF; MIM 613160) and mediate the adhesion of platelets to injured vascular surfaces in the arterial circulation, a critical initiating event in hemostasis. The main portion of the receptor is a heterodimer composed of 2 polypeptide chains, an alpha chain (GP1BA; MIM 606672) and a beta chain (GP1BB; MIM 138720), that are linked by disulfide bonds. The complete receptor complex includes noncovalent association of the alpha and beta subunits with platelet glycoprotein IX (GP9; MIM 173515) and GP5. Mutations in GP1BA, GP1BB, and GP9 have been shown to cause Bernard-Soulier syndrome (MIM 231200), a bleeding disorder (review by Lopez et al., 1998 [PubMed 9616133]).[supplied by OMIM, Nov 2010]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

127

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.63

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.63LOEUF

pLI 0.000

Z-score 0.34

OE 0.86 (0.47–1.63)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.11Z-score

OE missense 0.83 (0.75–0.92)

283 obs / 340.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.86 (0.47–1.63)

0≤0.351.4

Missense OE?0.83 (0.75–0.92)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 6 / 7.0Missense obs/exp: 283 / 340.9Syn Z: 0.83

Background carrier burden — how many people carry a rare variant somewhere in GP5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 92

812 rare PASS variants

Rare truncating (LoF)

1 in 1,100

111 rare PASS variants

Rare synonymous (reference)

1 in 130

395 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GP5. 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 140	1 in 1,300
South Asian	~43k	1 in 94	1 in 830
Remaining (unassigned)	~30k	1 in 74	1 in 710
European (Finnish)	~27k	1 in 350	1 in 1,600
Admixed American	~22k	1 in 69	1 in 1,000
African / African American	~21k	1 in 97	1 in 850
East Asian	~20k	1 in 88	1 in 650
Ashkenazi Jewish	~13k	1 in 520	1 in 1,700
Middle Eastern	~2,884	1 in 110	1 in 340

Each group is summed over the variants that are rare in that group. 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 ↓