Fig. 6.

Examples by which two of the prognostic germline variants may be associated with patient outcome. a–c rs55796947 in MAP2K3/MKK3 is associated with favorable patient outcome in KIRC and results in complete loss of MAP2K3’s protein kinase domain due to a Q73* amino acid change. MAP2K3 inhibition has previously been reported to result in cell cycle arrest and response to chemotherapy drugs. Tumors with the variant show upregulation of genes involved with apoptotic cleavage (a), genes in the apoptotic execution phase (b), and downregulation of E2F targets (c) in a Gene Set Enrichment Analysis (GSEA) of RNAseq data. d–f rs77903511 in the apoptosis inhibitor BIRC5 is predictive of poor patient outcome in UVM (d). This variant is associated with increased BIRC5 expression (e). Elevated BIRC5 expression is associated with poor patient outcome (f)