GP1BA

glycoprotein Ib platelet subunit alpha, the group of CD molecules

Basic information

Region (hg38): 17:4932276-4935023

Previous symbols: [ "GP1B" ]

Links

ENSG00000185245 ∙ NCBI:2811 ∙ OMIM:606672 ∙ HGNC:4439 ∙ Uniprot:P07359 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bernard-Soulier syndrome (Definitive), mode of inheritance: Semidominant
• Bernard-Soulier syndrome (Supportive), mode of inheritance: AD
• platelet-type von Willebrand disease (Supportive), mode of inheritance: AD
• autosomal dominant macrothrombocytopenia (Supportive), mode of inheritance: AD
• Bernard-Soulier syndrome, type A2, autosomal dominant (Strong), mode of inheritance: AD
• platelet-type von Willebrand disease (Strong), mode of inheritance: AD
• Bernard-Soulier syndrome (Strong), mode of inheritance: AR
• Bernard-Soulier syndrome (Definitive), mode of inheritance: AR
• platelet-type von Willebrand disease (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bernard-Soulier syndrome, type A2; Bernard-Soulier syndrome, type A1; Pseudo-von Willebrand disease	AD/AR	Hematologic; Pharmacogenomic	Preventive measures (eg, in the case of surgery) and treatment of bleeding episodes can be beneficial; Specific medications (eg, certain anesthetics) that interfere with platelet function should be avoided	Hematologic	18116504; 14081293; 6019024; 6286015; 6798442; 6333901; 2308962; 2052556; 1901273; 1730088; 8384898; 9616133; 11222377; 14711733; 21173099; 22102188; 23014764

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GP1BA gene.

• not provided (49 variants)
• not specified (30 variants)
• Inborn genetic diseases (28 variants)
• Bernard-Soulier syndrome, type A2, autosomal dominant (22 variants)
• Bernard Soulier syndrome (15 variants)
• GP1BA-related condition (12 variants)
• Pseudo von Willebrand disease (8 variants)
• Macrothrombocytopenia (7 variants)
• Thrombocytopenia (6 variants)
• Bernard-Soulier syndrome, type A1 (3 variants)
• Thrombocytopenia;Abnormal bleeding (2 variants)
• Pseudo von Willebrand disease;Bernard Soulier syndrome;Bernard-Soulier syndrome, type A2, autosomal dominant (1 variants)
• Impaired ristocetin-induced platelet aggregation (1 variants)
• CIC-DUX Sarcoma (1 variants)
• Bernard Soulier syndrome;Bernard-Soulier syndrome, type A2, autosomal dominant;Nonarteritic anterior ischemic optic neuropathy, susceptibility to;Pseudo von Willebrand disease (1 variants)
• Pseudo von Willebrand disease;Bernard Soulier syndrome;Bernard-Soulier syndrome, type A2, autosomal dominant;Nonarteritic anterior ischemic optic neuropathy, susceptibility to (1 variants)
• Pseudo von Willebrand disease;Bernard-Soulier syndrome, type A2, autosomal dominant;Bernard Soulier syndrome;Nonarteritic anterior ischemic optic neuropathy, susceptibility to (1 variants)
• Bernard-Soulier syndrome, type A2, autosomal dominant;Bernard Soulier syndrome;Pseudo von Willebrand disease;Nonarteritic anterior ischemic optic neuropathy, susceptibility to (1 variants)
• Nonarteritic anterior ischemic optic neuropathy, susceptibility to;Bernard-Soulier syndrome, type A2, autosomal dominant;Pseudo von Willebrand disease;Bernard Soulier syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GP1BA gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	11	3	15
missense	6	12	60	5	2	85
nonsense	2	1	1			4
start loss						0
frameshift	7	6	1	2		16
inframe indel	1	1	1	4		7
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					1	1
Total	16	20	64	22	6

Highest pathogenic variant AF is 0.000118

Variants in GP1BA

This is a list of pathogenic ClinVar variants found in the GP1BA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-4932557-A-T			Benign (May 12, 2021)
17-4932600-T-C		not specified	Benign (May 05, 2021)
17-4932636-C-T		Inborn genetic diseases	Uncertain significance (Dec 16, 2022)
17-4932662-T-G		Bernard-Soulier syndrome, type A2, autosomal dominant	Pathogenic (Aug 15, 2023)
17-4932668-G-T		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
17-4932696-T-A		Bernard-Soulier syndrome, type A2, autosomal dominant • GP1BA-related disorder	Uncertain significance (Jun 13, 2023)
17-4932696-T-C		Pseudo von Willebrand disease;Bernard Soulier syndrome;Bernard-Soulier syndrome, type A2, autosomal dominant	not provided (-)
17-4932701-T-C		Bernard Soulier syndrome	Uncertain significance (-)
17-4932702-G-A		Bernard-Soulier syndrome, type A2, autosomal dominant	Likely pathogenic (-)
17-4932702-G-C		Macrothrombocytopenia	Likely pathogenic (Feb 01, 2019)
17-4932706-CA-C		Bernard Soulier syndrome	Pathogenic (Oct 04, 2020)
17-4932710-A-G		not specified • Nonarteritic anterior ischemic optic neuropathy, susceptibility to;Bernard-Soulier syndrome, type A2, autosomal dominant;Pseudo von Willebrand disease;Bernard Soulier syndrome	Benign/Likely benign (Apr 01, 2023)
17-4932741-C-T		Bernard Soulier syndrome • Bernard-Soulier syndrome, type A2, autosomal dominant • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 31, 2024)
17-4932742-G-A		GP1BA-related disorder	Likely benign (Feb 10, 2021)
17-4932751-AAC-A		Macrothrombocytopenia	Pathogenic (Feb 01, 2019)
17-4932764-CTGAG-C			Pathogenic (Mar 03, 2023)
17-4932773-A-G		Bernard-Soulier syndrome, type A2, autosomal dominant • GP1BA-related disorder	Likely pathogenic (Aug 01, 2023)
17-4932775-C-A		Macrothrombocytopenia • not specified • GP1BA-related disorder	Conflicting classifications of pathogenicity (Jan 05, 2024)
17-4932776-C-T		Inborn genetic diseases	Uncertain significance (Apr 05, 2023)
17-4932780-T-C		GP1BA-related disorder	Uncertain significance (Feb 21, 2023)
17-4932795-T-C		Bernard-Soulier syndrome, type A2, autosomal dominant	Uncertain significance (-)
17-4932798-C-T		GP1BA-related disorder	Uncertain significance (Oct 12, 2022)
17-4932804-T-G		Macrothrombocytopenia	Uncertain significance (Feb 01, 2019)
17-4932810-C-T		not specified • Bernard Soulier syndrome • Bernard-Soulier syndrome, type A2, autosomal dominant	Uncertain significance (Nov 17, 2022)
17-4932819-G-A		not specified	Benign (Mar 29, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GP1BA	protein_coding	protein_coding	ENST00000329125	1	2734

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00323	0.620	124505	0	148	124653	0.000594

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.303	368	352	1.05	0.0000208	4149
Missense in Polyphen		68	73.815	0.92122		941
Synonymous	-0.811	178	165	1.08	0.0000105	1501
Loss of Function	0.463	4	5.13	0.779	2.67e-7	55

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000401	0.000400
Ashkenazi Jewish	0.00	0.00
East Asian	0.000503	0.000445
Finnish	0.000790	0.000789
European (Non-Finnish)	0.00105	0.000974
Middle Eastern	0.000503	0.000445
South Asian	0.0000997	0.0000980
Other	0.000687	0.000495

dbNSFP

Source: dbNSFP

• Function: FUNCTION: GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium.
• Disease: DISEASE: Non-arteritic anterior ischemic optic neuropathy (NAION) [MIM:258660]: An ocular disease due to ischemic injury to the optic nerve. It usually affects the optic disk and leads to visual loss and optic disk swelling of a pallid nature. Visual loss is usually sudden, or over a few days at most and is usually permanent, with some recovery possibly occurring within the first weeks or months. Patients with small disks having smaller or non- existent cups have an anatomical predisposition for non-arteritic anterior ischemic optic neuropathy. As an ischemic episode evolves, the swelling compromises circulation, with a spiral of ischemia resulting in further neuronal damage. {ECO:0000269|PubMed:14711733}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Bernard-Soulier syndrome (BSS) [MIM:231200]: A coagulation disorder characterized by a prolonged bleeding time, unusually large platelets, thrombocytopenia, and impaired prothrombin consumption. {ECO:0000269|PubMed:10089893, ECO:0000269|PubMed:1730088, ECO:0000269|PubMed:7690774, ECO:0000269|PubMed:7819107, ECO:0000269|PubMed:7873390, ECO:0000269|PubMed:9639514}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Bernard-Soulier syndrome A2, autosomal dominant (BSSA2) [MIM:153670]: A coagulation disorder characterized by mild to moderate bleeding tendency, thrombocytopenia, and an increased mean platelet volume. Some individuals have no symptoms. Mild bleeding tendencies manifest as epistaxis, gingival bleeding, menorrhagia, easy bruising, or prolonged bleeding after dental surgery. {ECO:0000269|PubMed:11222377}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Pseudo-von Willebrand disease (VWDP) [MIM:177820]: A bleeding disorder characterized by abnormally enhanced binding of von Willebrand factor by the platelet glycoprotein Ib (GP Ib) receptor complex. Hemostatic function is impaired due to the removal of VWF multimers from the circulation. {ECO:0000269|PubMed:14521605, ECO:0000269|PubMed:2052556, ECO:0000269|PubMed:8384898, ECO:0000269|PubMed:8486780}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Platelet activation - Homo sapiens (human);ECM-receptor interaction - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;GP1b-IX-V activation signalling;Platelet Adhesion to exposed collagen;Platelet Aggregation (Plug Formation);Platelet activation, signaling and aggregation;Intrinsic Pathway of Fibrin Clot Formation;Hemostasis;Formation of Fibrin Clot (Clotting Cascade);Transcriptional regulation by RUNX1;Beta2 integrin cell surface interactions (Consensus)

Recessive Scores

• pRec: 0.550

Intolerance Scores

• loftool: 0.630
• rvis_EVS: 0.14
• rvis_percentile_EVS: 63.62

Haploinsufficiency Scores

• pHI: 0.109
• hipred: N
• hipred_score: 0.327
• ghis: 0.412

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.883

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gp1ba
• Phenotype: hematopoietic system phenotype; homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: cell morphogenesis;cell adhesion;cell surface receptor signaling pathway;blood coagulation;blood coagulation, intrinsic pathway;platelet activation;regulation of blood coagulation;fibrinolysis;regulation of megakaryocyte differentiation;thrombin-activated receptor signaling pathway;platelet aggregation
• Cellular component: extracellular space;plasma membrane;integral component of plasma membrane;cell surface;membrane;extracellular matrix;anchored component of external side of plasma membrane;extracellular exosome
• Molecular function: protein binding;thrombin-activated receptor activity