P2RY12

purinergic receptor P2Y12, the group of P2Y receptors

Basic information

Region (hg38): 3:151336842-151384753

Links

ENSG00000169313 ∙ ∙ OMIM:600515 ∙ HGNC:18124 ∙ Uniprot:Q9H244 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• platelet-type bleeding disorder 8 (Supportive), mode of inheritance: AR
• platelet-type bleeding disorder 8 (Strong), mode of inheritance: AR
• platelet-type bleeding disorder 8 (Moderate), mode of inheritance: AR
• platelet-type bleeding disorder 8 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bleeding disorder, platelet-type, 8	AD/AR	Hematologic	Affected individuals can have excessive posttraumatic/postsurgical blood loss, as well as life-threatening bleeding episodes, and awareness may allow preventive measures and prompt treatment	Hematologic	1333302; 7706468; 11196645; 12578987; 19229056; 20966167

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the P2RY12 gene.

• not provided (62 variants)
• Inborn genetic diseases (36 variants)
• Nizon-Isidor syndrome (15 variants)
• not specified (8 variants)
• Platelet-type bleeding disorder 8 (7 variants)
• MED12L-related condition (5 variants)
• Impaired ADP-induced platelet aggregation (3 variants)
• Developmental disorder (2 variants)
• Neurodevelopmental disorder (2 variants)
• Thrombocytopenia;Abnormal bleeding (1 variants)
• MED12L-related neurodevelopmental disorder (1 variants)
• Abnormal platelet function (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the P2RY12 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				10	5	15
missense		2	31	1	4	38
nonsense						0
start loss			1			1
frameshift		2	1			3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding	2	4	51	7	7	71
Total	2	8	84	18	16

Variants in P2RY12

This is a list of pathogenic ClinVar variants found in the P2RY12 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-151337842-T-G			Uncertain significance (Nov 27, 2023)
3-151337857-T-C		P2RY12-related disorder	Benign (Jan 22, 2024)
3-151337858-C-T		not specified	Uncertain significance (Jul 06, 2021)
3-151337864-T-C			Uncertain significance (Nov 27, 2023)
3-151337868-A-G			Likely benign (Jan 25, 2023)
3-151337878-G-A			Uncertain significance (Jun 14, 2023)
3-151337896-T-C			Uncertain significance (Oct 13, 2023)
3-151337925-A-T			Uncertain significance (Oct 26, 2023)
3-151337928-T-G		not specified	Uncertain significance (Dec 12, 2022)
3-151337953-T-C		not specified	Uncertain significance (Dec 27, 2023)
3-151337998-G-A			Uncertain significance (Jun 26, 2022)
3-151338010-A-G		not specified	Uncertain significance (Dec 09, 2023)
3-151338011-C-T			Uncertain significance (Aug 11, 2023)
3-151338038-A-G		not specified	Uncertain significance (Feb 13, 2024)
3-151338041-C-T		not specified	Uncertain significance (Jun 30, 2022)
3-151338050-C-T			Uncertain significance (May 27, 2023)
3-151338052-C-G		Platelet-type bleeding disorder 8 • Impaired ADP-induced platelet aggregation	Pathogenic/Likely pathogenic (May 04, 2022)
3-151338053-G-A		Platelet-type bleeding disorder 8 • not specified	Uncertain significance (Jul 10, 2022)
3-151338074-G-T		Thrombocytopenia;Abnormal bleeding • Platelet-type bleeding disorder 8	Pathogenic/Likely pathogenic (May 01, 2020)
3-151338079-C-T		Platelet-type bleeding disorder 8 • not specified	Uncertain significance (May 04, 2022)
3-151338108-A-G			Likely benign (Nov 08, 2022)
3-151338116-C-T		not specified	Uncertain significance (Jul 12, 2023)
3-151338127-ATG-A		Platelet-type bleeding disorder 8	Pathogenic (Jan 11, 2001)
3-151338144-C-T			Likely benign (Nov 04, 2022)
3-151338173-C-A			Uncertain significance (Jun 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
P2RY12	protein_coding	protein_coding	ENST00000302632	1	47433

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00169	0.720	125709	0	25	125734	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.863	152	185	0.821	0.00000973	2258
Missense in Polyphen		42	62.544	0.67153		781
Synonymous	0.181	70	72.0	0.973	0.00000396	683
Loss of Function	0.819	5	7.40	0.675	3.98e-7	98

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.000381	0.000381
Finnish	0.00	0.00
European (Non-Finnish)	0.0000882	0.0000879
Middle Eastern	0.000381	0.000381
South Asian	0.000163	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation. {ECO:0000269|PubMed:11104774, ECO:0000269|PubMed:11196645, ECO:0000269|PubMed:11502873, ECO:0000269|PubMed:12578987, ECO:0000269|PubMed:24670650, ECO:0000269|PubMed:24784220}.
• Disease: DISEASE: Bleeding disorder, platelet-type 8 (BDPLT8) [MIM:609821]: A condition characterized by mild to moderate mucocutaneous bleeding, and excessive bleeding after surgery or trauma. The defect is due to severe impairment of platelet response to ADP resulting in defective platelet aggregation. {ECO:0000269|PubMed:11196645, ECO:0000269|PubMed:12578987, ECO:0000269|PubMed:25428217}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Platelet activation - Homo sapiens (human);Clopidogrel Pathway, Pharmacokinetics;Platelet Aggregation Inhibitor Pathway, Pharmacodynamics;Ticlopidine Metabolism Pathway;Clopidogrel Metabolism Pathway;Clopidogrel Action Pathway;Ticlopidine Action Pathway;GPCRs, Class A Rhodopsin-like;Signaling by GPCR;Signal Transduction;P2Y receptors;ADP signalling through P2Y purinoceptor 12;Signal amplification;Nucleotide-like (purinergic) receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;Platelet activation, signaling and aggregation;Hemostasis;G alpha (i) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.161

Intolerance Scores

• loftool: 0.600
• rvis_EVS: -0.18
• rvis_percentile_EVS: 40.16

Haploinsufficiency Scores

• pHI: 0.0696
• hipred: Y
• hipred_score: 0.510
• ghis: 0.492

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.187

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: P2ry12
• Phenotype: homeostasis/metabolism phenotype; normal phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: adenosine receptor signaling pathway;substrate-dependent cell migration, cell extension;G protein-coupled receptor signaling pathway;adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway;phospholipase C-activating G protein-coupled receptor signaling pathway;activation of phospholipase C activity;hemostasis;negative regulation of norepinephrine secretion;calcium-mediated signaling;cytosolic calcium signaling involved in initiation of cell movement in glial-mediated radial cell migration;cell projection organization;lamellipodium assembly;positive regulation of integrin activation by cell surface receptor linked signal transduction;positive regulation of cell adhesion mediated by integrin;calcium-mediated signaling using extracellular calcium source;G protein-coupled purinergic nucleotide receptor signaling pathway;positive regulation of ion transport;protein kinase B signaling;positive regulation of phosphatidylinositol 3-kinase activity;negative regulation of cell differentiation;response to axon injury;regulation of chemotaxis;positive regulation of chemotaxis;positive regulation of protein kinase B signaling;regulation of calcium ion transport;platelet aggregation;calcium ion transmembrane transport;cellular response to ATP;potassium ion transmembrane transport;positive regulation of ruffle assembly;regulation of microglial cell migration;positive regulation of microglial cell migration
• Cellular component: mitochondrion;plasma membrane;caveola;external side of plasma membrane;basal plasma membrane;cell surface;integral component of membrane;intrinsic component of membrane
• Molecular function: G protein-coupled adenosine receptor activity;ADP receptor activity;guanyl-nucleotide exchange factor activity;G protein-coupled purinergic nucleotide receptor activity