GP9 was first reported in relation to autosomal recessive Bernard-Soulier syndrome in 1993 Wright SD, et al., 1993, PMID: 8481514). At least 32 unique variants (primarily missense, with some nonsense, and frameshifts) have been reported in humans. The unifying feature of all of the mutations is the ability of the mutation to disrupt the assembly and/or function of a surface-expressed GP Ib-IX-V complex. How individual mutations affect complex assembly or surface expression can be variable. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least 36 probands in 12 publications (PMIDs: 8481514, 23143686, 9432024, 21699652, 21173099, 21113250, 9886312, 12100158, 10583255, 16916536, 15609295, 23995613). Variants in this gene segregated with disease in 6 additional family members. More evidence is available in the literature, but the maximum score for genetic and experimental evidence has been reached. This gene-disease association is supported by its reduced expression in patient cells (PMID: 9432024), its protein interactions with GP1BB (PMID: 808914), functional alteration in non-patient cells (PMID: 10527407, PMID: 8608225), and a knock-out animal model (PMID: 28650483). In summary, GP9 is definitively associated with autosomal recessive Bernard-Soulier syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.
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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