GP6

glycoprotein VI platelet, the group of Ig-like cell adhesion molecule family|Immunoglobulin like domain containing

Basic information

Region (hg38): 19:55013705-55038264

Links

ENSG00000088053 ∙ NCBI:51206 ∙ OMIM:605546 ∙ HGNC:14388 ∙ Uniprot:Q9HCN6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• platelet-type bleeding disorder 11 (Strong), mode of inheritance: AR
• platelet-type bleeding disorder 11 (Supportive), mode of inheritance: AR
• platelet-type bleeding disorder 11 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bleeding disorder, platelet-type, 11	AR	Hematologic	Individuals may demonstrate a bleeding diathesis (including postraumatic/postsurgical), and surveillance and prompt treatment of bleeding episodes may reduce morbidity	Hematologic	19549989; 19552682

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GP6 gene.

• not provided (7 variants)
• Platelet-type bleeding disorder 11 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GP6 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				29	12	41
missense			68	18	18	104
nonsense	5		2	2		9
start loss						0
frameshift	3	1	2	1	1	8
inframe indel			1	1		2
splice donor/acceptor (+/-2bp)		1				1
splice region				1	1	2
non coding				11	24	35
Total	8	2	73	62	55

Highest pathogenic variant AF is 0.0000788

Variants in GP6

This is a list of pathogenic ClinVar variants found in the GP6 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-55013969-G-A			Benign (Jun 20, 2021)
19-55014020-G-T			Benign (Nov 12, 2018)
19-55014086-ATCAGGGTAATTGACATAT-A			Uncertain significance (Aug 27, 2022)
19-55014101-A-G			Uncertain significance (Jun 26, 2022)
19-55014129-A-G		not specified • Platelet-type bleeding disorder 11	Benign (Jan 31, 2024)
19-55014133-A-G			Likely benign (Sep 27, 2022)
19-55014139-C-T		GP6-related disorder	Benign (Oct 22, 2023)
19-55014140-G-A		not specified	Benign (Jan 29, 2024)
19-55014146-C-T			Uncertain significance (Apr 06, 2022)
19-55014156-T-G			Benign (Jan 19, 2024)
19-55014192-C-CGGGA		GP6-related disorder	Benign (Jan 18, 2024)
19-55014200-C-A		GP6-related disorder	Uncertain significance (Aug 31, 2023)
19-55014215-C-T			Uncertain significance (Oct 04, 2022)
19-55014218-C-T		not specified	Benign (Jan 31, 2024)
19-55014228-T-C		not specified • Platelet-type bleeding disorder 11	Benign (Jan 31, 2024)
19-55014228-TG-CA			Likely benign (Oct 13, 2023)
19-55014229-G-A		GP6-related disorder	Benign (Apr 26, 2024)
19-55014263-C-G		Inborn genetic diseases	Uncertain significance (Jul 06, 2021)
19-55014278-G-GT			Uncertain significance (Mar 26, 2022)
19-55014288-T-C			Uncertain significance (Jul 23, 2022)
19-55014296-T-C		Inborn genetic diseases	Uncertain significance (Aug 12, 2021)
19-55014317-T-C		Inborn genetic diseases	Uncertain significance (Jan 31, 2024)
19-55014322-C-T		not specified • GP6-related disorder	Likely benign (Oct 14, 2023)
19-55014324-G-A		not specified	Likely benign (May 22, 2024)
19-55014344-G-A			Uncertain significance (Mar 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GP6	protein_coding	protein_coding	ENST00000310373	8	24560

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.64e-11	0.0309	124745	0	51	124796	0.000204

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.415	379	357	1.06	0.0000227	3880
Missense in Polyphen		80	78.532	1.0187		794
Synonymous	-1.21	178	159	1.12	0.0000116	1341
Loss of Function	-0.241	16	15.0	1.07	7.37e-7	169

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000419	0.000419
Ashkenazi Jewish	0.00	0.00
East Asian	0.000445	0.000445
Finnish	0.0000465	0.0000464
European (Non-Finnish)	0.0000795	0.0000794
Middle Eastern	0.000445	0.000445
South Asian	0.000654	0.000654
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Collagen receptor involved in collagen-induced platelet adhesion and activation. Plays a key role in platelet procoagulant activity and subsequent thrombin and fibrin formation. This procoagulant function may contribute to arterial and venous thrombus formation. The signaling pathway involves the FcR gamma- chain, the Src kinases (likely FYN or LYN) and SYK, the adapter protein LAT and leads to the activation of PLCG2. {ECO:0000269|PubMed:10961879, ECO:0000269|PubMed:18955485}.
• Disease: DISEASE: Bleeding disorder, platelet-type 11 (BDPLT11) [MIM:614201]: A mild to moderate bleeding disorder caused by defective platelet activation and aggregation in response to collagen. {ECO:0000269|PubMed:19549989, ECO:0000269|PubMed:19552682}. 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);Platelet Aggregation Inhibitor Pathway, Pharmacodynamics;Platelet Adhesion to exposed collagen;GPVI-mediated activation cascade;Platelet activation, signaling and aggregation;Cell surface interactions at the vascular wall;Hemostasis (Consensus)

Intolerance Scores

• loftool: 0.957
• rvis_EVS: 2.13
• rvis_percentile_EVS: 97.94

Haploinsufficiency Scores

• pHI: 0.0493
• hipred: N
• hipred_score: 0.327
• ghis: 0.415

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.607

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gp6
• Phenotype: hematopoietic system phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype; immune system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype

Gene ontology

• Biological process: enzyme linked receptor protein signaling pathway;blood coagulation;platelet activation;leukocyte migration
• Cellular component: plasma membrane;integral component of plasma membrane;cell surface;extracellular exosome;tetraspanin-enriched microdomain
• Molecular function: transmembrane signaling receptor activity;protein binding;collagen binding;signaling receptor activity