They demonstrated that neither the presence of HIF nor the absence of PHDs is required for hyperplastic renal cysts formation (typical hallmark of HLRCC) in a kidney-specific Fh1 (the ortholog of human FH) knockout mice that recapitulates many features of the human disease [39], suggesting that alternative oncogenic actions of fumarate could be responsible for HLRCC generation (see next paragraph). Here, FH is linked to hereditary leiomyomatosis and renal cell cancer.