On this page
GP1BA
glycoprotein Ib platelet subunit alpha
The GP1BA gene encodes a subunit of a platelet protein complex vital for blood clotting, playing a key role in the initial adhesion of platelets at sites of vascular injury. The GP1BA gene provides instructions for the glycoprotein Ib-alpha (GPIbα) protein, a crucial component of the GPIb-IX-V complex found on platelet surfaces.
GP1BA is located on the short (p) arm of chromosome 17, at band 17p13.2. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 17 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The GP1BA gene, or glycoprotein Ib platelet subunit alpha, is central to the process of blood clotting. It codes for the GPIbα protein, which forms part of a larger protein complex called GPIb-IX-V, situated on the surface of platelets.
This complex is essential for platelets to adhere to injured blood vessel walls, a critical first step in forming a blood clot. Pathogenic variants in GP1BA can disrupt this process, leading to bleeding disorders.
What the gene does
The GP1BA gene produces the glycoprotein Ib-alpha (GPIbα) subunit, which is indispensable for the assembly of the GPIb-IX-V protein complex on the surface of platelets. This complex functions as a receptor, specifically binding to von Willebrand factor (VWF), a protein present in the lining of blood vessels.
When a blood vessel is damaged, VWF is exposed, and the GPIb-IX-V complex's interaction with VWF allows platelets to adhere to the injury site. This initial platelet adhesion is a vital step in haemostasis, preventing excessive blood loss. The GPIbα subunit is the primary site of interaction with VWF and also participates in interactions with other coagulation proteins, further contributing to the clotting cascade.
Video: Genetics 101
Chromosome location
The GP1BA gene is located on chromosome 17 at position 13.2 (17p13.2). This chromosomal band houses the genetic instructions for the GPIbα protein, which is 652 amino acids in length.
Protein structure
The GPIbα protein exhibits a complex structure with several distinct domains. It includes an LRRNT domain (amino acids 17-47) followed by seven leucine-rich repeats: LRR 1 (amino acids 48-68), LRR 2 (amino acids 72-93), LRR 3 (amino acids 94-115), LRR 4 (amino acids 117-137), LRR 5 (amino acids 141-162), LRR 6 (amino acids 165-186), and LRR 7 (amino acids 189-210). A LRRCT domain is found between amino acids 221-282. Additionally, the protein contains a Disordered region spanning amino acids 336-459, which often indicates flexibility or involvement in multiple protein interactions.
Key variants
Genetic variations within the GP1BA gene can impact the structure and function of the GPIbα protein. These variants may lead to an altered protein that is either unstable, unable to properly integrate into the GPIb-IX-V complex, or incapable of effectively binding to von Willebrand factor. The consequences of such changes can range from mild platelet dysfunction to severe bleeding disorders.
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.1454dup | p.Ser486fs | Pathogenic | ★★★☆ | Bernard Soulier syndrome |
c.1480del | p.Thr494fs | Pathogenic | ★★★☆ | Bernard Soulier syndrome |
c.1562_1563del | p.Leu521fs | Pathogenic | ★★★☆ | Bernard Soulier syndrome |
c.1601_1602del | p.Tyr534fs | Pathogenic | ★★★☆ | Bernard Soulier syndrome |
c.1620G>A | p.Trp540Ter | Pathogenic | ★★★☆ | Bernard Soulier syndrome |
c.241T>C | p.Cys81Arg | Pathogenic | ★★★☆ | Bernard Soulier syndrome |
c.673T>A | p.Cys225Ser | Pathogenic | ★★★☆ | Bernard Soulier syndrome |
c.58T>G | p.Cys20Gly | Pathogenic | ★★☆☆ | Bernard-Soulier syndrome, type A2, autosomal dominant |
c.745G>A | p.Gly249Ser | Pathogenic/Likely pathogenic | ★★☆☆ | Thrombocytopenia |
c.97T>C | p.Cys33Arg | Pathogenic/Likely pathogenic | ★★☆☆ | Bernard-Soulier syndrome, type A2, autosomal dominant |
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 GP1BA gene are primarily associated with inherited bleeding disorders. One such condition is Bernard-Soulier syndrome, an autosomal recessive disorder characterised by abnormally large platelets (macrothrombocytopenia) and a reduced platelet count, leading to excessive bleeding. Some GP1BA mutations result in a dysfunctional GPIbα subunit that is either rapidly degraded or fails to reach the platelet surface, impairing the GPIb-IX-V complex's formation and function.
Inheritance pattern
Conditions caused by pathogenic GP1BA 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 GP1BA gene is included in the NHS Genomic Medicine Service clinical panels for "Bleeding and platelet disorders" (R90) and "Inherited bleeding disorders", both of which are categorised as green, indicating that there is strong evidence for the gene's association with these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary role of the GP1BA gene?
The GP1BA gene provides instructions for the GPIbα protein, a crucial part of the GPIb-IX-V complex on platelets. This complex is essential for platelets to adhere to injured blood vessels, initiating the blood clotting process.
What health conditions are associated with GP1BA gene variants?
Variants in the GP1BA gene are primarily linked to inherited bleeding disorders, most notably Bernard-Soulier syndrome. This condition involves abnormal platelets and an increased tendency for bleeding.
How is Bernard-Soulier syndrome inherited?
Bernard-Soulier syndrome is inherited in an autosomal recessive pattern. This means an individual must inherit two copies of the altered GP1BA gene (one from each parent) to develop the condition.
References
- 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
- Othman M, Kaur H, Emsley J. Platelet-type von Willebrand disease: new insights into the molecular pathophysiology of a unique platelet defect. Seminars in thrombosis and hemostasis. 2013. PMID: 23934752
- Schade AJ, Arya M, Gao S. Cytoplasmic truncation of glycoprotein Ib alpha weakens its interaction with von Willebrand factor and impairs cell adhesion. Biochemistry. 2003. PMID: 12590614
- Cauwenberghs N, Vanhoorelbeke K, Vauterin S. Structural determinants within platelet glycoprotein Ibalpha involved in its binding to von Willebrand factor. Platelets. 2000. PMID: 11132103