F9 encodes coagulation factor FIX that forms the tenase complex with FVII to activate FX in the coagulation cascade. F9 was first reported in relation to X-linked thrombophilia due to factor 9 defect in 2009 (Simioni et al, PMID: 19846852). Evidence supporting this gene-disease relationship includes case-level data only. Just two, missense variants have been reported in relation to thrombophilia. Two siblings from 1 publication have been reported with the hemizygous missense variant, Arg384Leu (PMID: 19846852) and and additional patient with Arg384Gln (PMID: 32079698). The mechanism is reported to be gain of function. While a few other polymorphisms, including F9 Malmo have been reported in association with risk of deep vein thrombosis, the biological mechanism for the association is not known. These variants have not been included in this curation.
In summary, the level of evidence to support the gene-disease relationship of F9 and X-linked thrombophilia due to factor 9 defect is limited. 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 HT GCEP on June 24, 2020. It was reevaluated on 10/24/2023. As a result of this reevaluation one additional patient was identified (PMID: 32079698) however the classification remained Limited (SOP Version 9).
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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