P2RY12 was first reported in relation to autosomal dominant platelet-type bleeding disorder 8 in 2007 (Remijn JA, et al., PMID: 17311506). At least seven unique missense variants have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least eight probands in six publications (PMIDs: 29117459, 17311506, 25567036, 19237732, 21937696, 36232816). This gene-disease relationship is supported by its biochemical function in the P2Y12 receptor stimulation induced rapid activation of Rap1 (PMID: 16236484), expression A evidence of P2Y12 receptor is selectively expressed in platelets (PMID: 11196645), expression B evidence of reduced P2Y12 receptor expression in patients ( PMID: 21937696), functional alteration in both patient ( PMID: 17311506) and non-patient cells ( PMID: 29117459, PMID: 23387322), and non-human model organism knock-in mouse models (PMID: 36232816). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged.
This gene-disease pair was originally evaluated by the Hemostasis Thrombosis GCEP on 08/26/2020. It was reevaluated on 04/02/2023. As a result of this reevaluation, the classification did not change.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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