GP1BB

glycoprotein Ib platelet subunit beta, the group of CD molecules

Basic information

Region (hg38): 22:19723538-19724771

Links

ENSG00000203618 ∙ NCBI:2812 ∙ OMIM:138720 ∙ HGNC:4440 ∙ Uniprot:P13224 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bernard-Soulier syndrome (Supportive), mode of inheritance: AD
• autosomal dominant macrothrombocytopenia (Supportive), mode of inheritance: AD
• Bernard-Soulier syndrome (Strong), mode of inheritance: AR
• Bernard-Soulier syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bernard-Soulier syndrome; Giant platelet disorder, isolated	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; 1901273; 8703016; 9116284; 9616133; 21173099; 21800012; 22102188

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GP1BB gene.

• Bernard Soulier syndrome (28 variants)
• not provided (24 variants)
• Thrombocytopenia (9 variants)
• Macrothrombocytopenia (8 variants)
• not specified (6 variants)
• Inborn genetic diseases (6 variants)
• GP1BB-related condition (3 variants)
• Abnormal bleeding (2 variants)
• Bernard-Soulier syndrome, type B (2 variants)
• Mild macrothrombocytopenia (1 variants)
• Increased mean platelet volume (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GP1BB 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				8	1	9
missense	1	9	26	1		37
nonsense	2	3				5
start loss	2	1				3
frameshift	3	6				9
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			2		1	3
Total	8	20	29	9	2

Highest pathogenic variant AF is 0.00000664

Variants in GP1BB

This is a list of pathogenic ClinVar variants found in the GP1BB region.

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

Position	Type	Phenotype	Significance	ClinVar
22-19723556-G-A		GP1BB-related disorder	Likely benign (Feb 07, 2024)
22-19723570-A-G			Pathogenic (Feb 21, 2019)
22-19723570-A-T		Mild macrothrombocytopenia • Bernard Soulier syndrome	Pathogenic (-)
22-19723571-T-C		Bernard Soulier syndrome	Likely pathogenic (Sep 01, 2022)
22-19723572-G-C		Macrothrombocytopenia	Likely pathogenic (-)
22-19723861-C-CG		Bernard Soulier syndrome	Pathogenic (-)
22-19723867-G-T		GP1BB-related disorder	Likely benign (Jul 14, 2021)
22-19723890-T-C		Thrombocytopenia • Macrothrombocytopenia • Bernard Soulier syndrome	Pathogenic/Likely pathogenic (Feb 16, 2023)
22-19723891-GGCCCCGCCGAGCC-G		Bernard Soulier syndrome	Likely pathogenic (Mar 29, 2024)
22-19723904-CGCCCGGCCGCAGGTT-C		Macrothrombocytopenia	Likely pathogenic (-)
22-19723923-C-T		Bernard Soulier syndrome	Likely pathogenic (-)
22-19723937-T-C		GP1BB-related disorder	Uncertain significance (Jun 13, 2023)
22-19723945-G-A		GP1BB-related disorder	Likely benign (Dec 31, 2019)
22-19723949-C-T		Abnormal bleeding	Uncertain significance (Feb 01, 2019)
22-19723955-G-C			Uncertain significance (May 09, 2019)
22-19723962-G-A		Bernard Soulier syndrome	Benign/Likely benign (Jan 01, 2024)
22-19723963-GCGCCGCGGGCTGACTTGGGCCT-G		Bernard Soulier syndrome	Pathogenic (-)
22-19723970-G-T		Macrothrombocytopenia	Conflicting classifications of pathogenicity (-)
22-19723980-G-A		Thrombocytopenia • Macrothrombocytopenia • Increased mean platelet volume • Bernard Soulier syndrome • Bernard-Soulier syndrome, type B	Likely pathogenic (Feb 01, 2019)
22-19723983-C-T		not specified	Uncertain significance (Sep 20, 2023)
22-19723986-C-A		Thrombocytopenia	Pathogenic (Feb 01, 2019)
22-19723986-C-T		Bernard Soulier syndrome	Uncertain significance (May 04, 2022)
22-19723987-G-T			Likely benign (Aug 01, 2020)
22-19723991-C-A		Bernard Soulier syndrome	Uncertain significance (Aug 23, 2022)
22-19724013-C-T		Bernard Soulier syndrome	Uncertain significance (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GP1BB	protein_coding	protein_coding	ENST00000366425	2	1827

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.512	0.425	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.459	53	63.3	0.838	0.00000341	1195
Missense in Polyphen		10	14.602	0.68482		381
Synonymous	-0.641	41	36.1	1.14	0.00000198	540
Loss of Function	1.33	0	2.05	0.00	8.84e-8	28

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Gp-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to von Willebrand factor, which is already bound to the subendothelium.
• Pathway: Platelet activation - Homo sapiens (human);ECM-receptor interaction - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);Platelet Aggregation Inhibitor Pathway, Pharmacodynamics;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) (Consensus)

Haploinsufficiency Scores

• pHI: 0.161
• hipred: Y
• hipred_score: 0.553
• ghis: 0.567

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gp1bb
• Phenotype: homeostasis/metabolism phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: cell adhesion;cell surface receptor signaling pathway;blood coagulation;blood coagulation, intrinsic pathway;platelet activation
• Cellular component: plasma membrane;integral component of plasma membrane
• Molecular function: transmembrane signaling receptor activity;protein binding;identical protein binding