On this page
GP9
glycoprotein IX platelet
The GP9 gene provides instructions for glycoprotein IX (GPIX), a protein essential for normal blood clotting by facilitating platelet adhesion at injury sites. The GP9 gene encodes glycoprotein IX (GPIX), a key component of the GPIb-IX-V protein complex found on the surface of platelets.
GP9 is located on the long (q) arm of chromosome 3, at band 3q21.3. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 3 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The GP9 gene is responsible for producing glycoprotein IX (GPIX), a protein that plays a crucial role in haemostasis, the process of stopping bleeding. GPIX is an integral part of the GPIb-IX-V complex, located on the surface of platelets. These small blood cells are essential for forming clots to repair damaged blood vessels.
Disruptions in the GP9 gene's function can lead to impaired platelet activity, which is associated with conditions like Bernard-Soulier syndrome, characterised by bleeding abnormalities.
What the gene does
The GP9 gene provides the blueprint for glycoprotein IX (GPIX), a subunit within the larger GPIb-IX-V protein complex. This complex is expressed on the surface of platelets and is critical for their ability to adhere to damaged blood vessel walls. GPIX is necessary for the proper assembly and stability of the entire GPIb-IX-V complex on the platelet surface.
The GPIb-IX-V complex functions by binding to von Willebrand factor, a protein found at sites of vascular injury. This interaction is akin to a lock-and-key mechanism, enabling platelets to stick to the injury site and initiate the formation of a clot. Without functional GPIX, the complex cannot properly form or operate, leading to impaired platelet adhesion and a compromised clotting response.
Video: Genetics 101
Chromosome location
The GP9 gene is situated on chromosome 3 at position 3q21.3. This specific location indicates its precise address within the human genome. The gene contains the genetic instructions for a protein comprising 177 amino acids.
Protein structure
The glycoprotein IX (GPIX) protein, encoded by the GP9 gene, consists of 177 amino acids and features a distinct domain organisation. It includes a Leucine-rich repeat N-terminal (LRRNT) domain located from amino acids 17 to 51. Additionally, it contains a Leucine-rich repeat (LRR) spanning amino acids 60 to 83, and a Leucine-rich repeat C-terminal (LRRCT) domain from amino acids 85 to 137. These domains are structurally important for the protein's interactions within the GPIb-IX-V complex.
Key variants
Variants within the GP9 gene can affect the structure and function of the GPIX protein. These genetic changes may lead to a non-functional or unstable protein, or one that cannot be properly incorporated into the GPIb-IX-V complex on the platelet surface. Such alterations can impair normal platelet function.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.182A>G | p.Asn61Ser | Pathogenic | ★★★☆ | Bernard Soulier syndrome |
c.212T>C | p.Phe71Ser | Pathogenic | ★★★☆ | Bernard Soulier syndrome |
c.266G>A | p.Cys89Tyr | Pathogenic | ★★★☆ | Bernard Soulier syndrome |
g.129058767_129062425del | - | Pathogenic | ★☆☆☆ | Bernard Soulier syndrome |
g.(?_129061730)_(129062283_?)del | - | Pathogenic | ★☆☆☆ | not provided |
c.-210_*133del | p.Met1fs | Pathogenic | ★☆☆☆ | Bernard Soulier syndrome |
c.2T>C | p.Met1Thr | Pathogenic | ★☆☆☆ | not provided |
c.34del | p.Ala12fs | Pathogenic | ★☆☆☆ | not provided |
c.46dup | p.Ala16fs | Pathogenic | ★☆☆☆ | Bernard Soulier syndrome |
c.8_11dup | p.Trp4fs | Pathogenic | ★☆☆☆ | Bernard Soulier syndrome |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the GP9 gene are associated with Bernard-Soulier syndrome, an inherited bleeding disorder. This condition is characterised by abnormally large platelets and a reduced platelet count (macrothrombocytopenia). Individuals with Bernard-Soulier syndrome typically experience excessive bleeding due to the impaired function of their platelets.
Inheritance pattern
Conditions caused by pathogenic GP9 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The GP9 gene is included in several NHS Genomic Medicine Service approved panels for genetic testing. It is listed on the 'Bleeding and platelet disorders' panel (R90) and the 'Inherited bleeding disorders' panel, both classified as 'green' indicating they are routinely considered for testing.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main role of the GP9 gene?
The GP9 gene provides instructions for making glycoprotein IX (GPIX), a protein crucial for normal blood clotting. GPIX is part of a complex on platelets that helps them stick to injured blood vessels.
What condition is associated with variants in the GP9 gene?
Variants in the GP9 gene are associated with Bernard-Soulier syndrome. This is an inherited bleeding disorder characterised by large, dysfunctional platelets and a tendency for excessive bleeding.
How does GP9 relate to platelet function?
GPIX, the protein encoded by GP9, is essential for the assembly and stability of the GPIb-IX-V complex on the surface of platelets. This complex allows platelets to bind to von Willebrand factor at injury sites, initiating the formation of blood clots.
References
- Xu G, Shang D, Zhang Z. The Transmembrane Domains of β and IX Subunits Mediate the Localization of the Platelet Glycoprotein Ib-IX Complex to the Glycosphingolipid-enriched Membrane Domain. The Journal of biological chemistry. 2015. PMID: 26203189
- Savoia A, Kunishima S, De Rocco D. Spectrum of the mutations in Bernard-Soulier syndrome. Human mutation. 2014. PMID: 24934643
- Li R, Emsley J. The organizing principle of the platelet glycoprotein Ib-IX-V complex. Journal of thrombosis and haemostasis : JTH. 2013. PMID: 23336709
- Geng H, Xu G, Ran Y. Platelet glycoprotein Ib beta/IX mediates glycoprotein Ib alpha localization to membrane lipid domain critical for von Willebrand factor interaction at high shear. The Journal of biological chemistry. 2011. PMID: 21507943
- McEwan PA, Yang W, Carr KH. Quaternary organization of GPIb-IX complex and insights into Bernard-Soulier syndrome revealed by the structures of GPIbβ and a GPIbβ/GPIX chimera. Blood. 2011. PMID: 21908432