KDR was first reported in relation to autosomal dominant pulmonary arterial hypertension in 2018 by Graf et al., (PMID29650961). At least 6 loss of function variants have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data, case-control data and experimental data.
Summary of case level data: 3 points. Variants in this gene have been reported in at least 2 probands with a predicted or proven null variant (PMID: 31980491). Variants in this gene segregated with the disease in 2 additional family members with PAH.
Summary of Case-Control Data: 3.5 points This gene-disease relationship has been studied in at least 1 case control study at the aggregate variant level. (PMID29650961). Protein truncating variants were reported in 4 out of 838 PAH cases versus 0 in 6385 controls. Both the case and the control group were analysed using whole genome sequencing. The gene-disease association is supported by animal models and expression studies. In summary, there is strong evidence to support the relationship between KDR and autosomal dominant pulmonary arterial hypertension. Three years must elapse from the first proposal of the association to reach a definitive classification.
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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