ABCC4 was first reported in relation to an autosomal recessive qualitative platelet defect in 2020 (Azouzi S, et al., 2020, PMID: 31826245). This heritable platelet function defect is characterized by reduced platelet aggregation in response to low concentration ADP. ABCC4 encodes MRP4 which is thought to promote platelet aggregation by modulating the cAMP–protein kinase A signaling pathway. One variant (the GRCh38 (chr13:95018454-95085982) deletion accompanied by the insertion of an intervening 18-bp sequence of CTGTAATCCCAGCACTTT) has been reported in 4 French-Canadian probands in 1 publication (PMID: 31826245). This gene-disease association is supported by its function in cAMP transport (PMID: 11856762), which when disrupted leads to a platelet aggregation defect (PMID: 35295075), as well as its expression on the plasma membrane of platelets (PMID: 26405223), and two mouse models that recapitulate a platelet aggregation defect (PMIDs: 26405223, 26316625). 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 previously evaluated by the HT GCEP on May 25, 2022. It was reevaluated on June 3, 2024. As a result of this reevaluation no new evidence was identified and the classification remained Moderate (SOP Version 10).
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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