HIF is strongly upregulated, both in HLRCC-associated human pRCC and in the hyperplastic renal cysts that develop in mice following targeted inactivation of Fh1 (the murine homolog of FH), and studies of gene expression patterns in these tissues have revealed strong signatures of HIF activation (Ashrafian et al., 2010; Isaacs et al., 2005; Pollard et al., 2005; Pollard et al., 2007). Here, FH is linked to cystic kidney disease.