FH
小结
FH是抑癌基因，编码编码一种将三羧酸（TCA）循环中的延胡索酸转化为苹果酸的酶。FH存在于线粒体和胞浆形式中，前者在TCA循环中发挥FH的典型作用，后者可能参与氨基酸代谢。FH的线粒体形式由C端信号序列决定。FH的杂合胚系突变，导致遗传性平滑肌瘤病和肾细胞癌（HLRCC），这是一种常染色体显性遗传综合征，以多发性皮肤平滑肌瘤、子宫平滑肌瘤和乳头状2型肾癌为特征。在HLRCC，肿瘤形成发生在野生型等位基因失活之后，因此FH被归类为肿瘤抑制因子。体细胞FH突变在其他癌症类型比较罕见。
FH (fumarate hydratase, also known as fumarase) encodes an enzyme that converts fumarate to malate as part of the tricarboxylic acid (TCA) cycle. FH exists in a mitochondrial and a cytosolic form, the former of which carries out FH's canonical role in the TCA cycle and the latter of which is likely involved in amino acid metabolism. The mitochondrial form of FH is determined by a C-terminal signal sequence. Heterozygous germline mutations of FH cause hereditary leiomyomatosis and renal cell cancer (HLRCC), an autosomal dominant syndrome characterized by multiple cutaneous piloleiomyomas, uterine leiomyomas and papillary type 2 renal cancer. Individuals with this disease are at risk for developing cutaneous and uterine leiomyomas, a form kidney cancer. In HLRCC, tumor formation occurs following the inactivation of the wildtype allele, and therefore FH is classified as a tumor suppressor. Somatic FH mutations are sporadically found in other cancer types. The mechanism underlying FH-deficient disease is attributed to reduced or ablated FH enzymatic activity.