CDC73（也称为HRPT2或parafibromin）是一个抑癌基因，主要编码parafibromin蛋白，该蛋白是RNA聚合酶II相关因子1（PAF1）复合物的组成部分，参与调控基因转录、组蛋白修饰和细胞周期进程。其生物学功能包括抑制细胞增殖、促进分化，并在Wnt/β-catenin信号通路中起负调控作用。主要作用位点为甲状旁腺，但也在骨骼、肾脏等组织中表达。CDC73突变会导致其功能丧失，与遗传性甲状旁腺功能亢进-颌骨肿瘤综合征（HPT-JT syndrome）密切相关，表现为甲状旁腺腺瘤、颌骨纤维性骨病变及肾囊肿等。此外，体细胞突变还见于散发性甲状旁腺癌。该基因属于PAF1复合物基因家族，家族成员共性为参与转录延伸、组蛋白甲基化（如H3K4me3）及发育调控。若CDC73过表达，可能通过异常抑制Wnt通路影响组织稳态；而表达降低则导致细胞增殖失控，促进肿瘤发生。其表达异常还可能影响其他PAF1复合物相关基因（如LEO1、CTR9）的功能，破坏转录调控网络。专业术语解释：抑癌基因（tumor suppressor gene）指抑制肿瘤发生的基因；组蛋白修饰（histone modification）是通过化学修饰改变染色质结构从而调控基因表达的过程；Wnt/β-catenin通路是调控细胞增殖和分化的关键信号途径。目前中文术语"parafibromin"无统一译名，建议保留英文原名。

此基因编码参与转录和转录后控制途径中的肿瘤抑制。该蛋白质是PAF的蛋白复合物，其与RNA聚合酶II亚基POLR2A并用组蛋白甲基络合物关联的组分。该蛋白质似乎促进的3‘mRNA加工因子与积极转录染色质的关联。在这个基因的突变已与甲状旁腺功能亢进爪肿瘤综合征，家族孤立甲状旁腺功能亢进，甲状旁腺癌。 [由RefSeq的，2009年7月提供]

CDC73, also known as HRPT2, encodes the tumor suppressor protein parafibromin, a critical component of the RNA polymerase II-associated factor 1 (PAF1) complex that plays a pivotal role in regulating transcriptional elongation, chromatin remodeling, and cell cycle progression. By mediating specific histone modifications, such as the maintenance of H3K4me3 marks, parafibromin helps establish a repressive chromatin environment that inhibits uncontrolled cellular proliferation and promotes differentiation, while simultaneously acting as a negative regulator of the Wnt/β-catenin signaling pathway to preserve tissue homeostasis. Although this gene is broadly expressed in various tissues including bone and kidney, it is most functionally significant in the parathyroid gland, where its loss-of-function germline mutations are the primary genetic cause of hyperparathyroidism-jaw tumor (HPT-JT) syndrome, a hereditary condition characterized by parathyroid adenomas, ossifying fibromas of the jaw, and renal cysts. Beyond its hereditary implications, somatic mutations in CDC73 are frequently identified in sporadic parathyroid carcinomas, underscoring its essential role in preventing malignant transformation. As a member of the PAF1 complex gene family, which includes related subunits like LEO1 and CTR9, CDC73 contributes to a coordinated transcriptional regulatory network; consequently, aberrant expression levels—whether the overexpression that disrupts Wnt signaling or the underexpression that releases proliferative brakes—can destabilize this network, leading to impaired developmental controls and increased susceptibility to tumorigenesis.

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