HORMA domain-containing protein 1 (HORMAD1) also known as cancer/testis antigen 46 (CT46) is a protein that in humans is encoded by the HORMAD1gene.[5][6][7]
HORMAD1 is a cancer/testis antigen that plays a key role in meiotic progression.[6] It has shown to regulate 3 different functions during meiosis. Specifically, it:
Ensures that sufficient numbers of processed DNA double-strand breaks (DSBs) are available for successful homology search by increasing the steady-state numbers of single-stranded DSB ends
Promotes synaptonemal-complex formation independently of its role in homology search.
Plays a key role in the male mid-pachytene checkpoint and the female meiotic prophase checkpoint: required for efficient build-up of ATR activity on unsynapsed chromosome regions, a process believed to form the basis of meiotic silencing of unsynapsed chromatin (MSUC) and meiotic prophase quality control in both sexes (By similarity) [8]
HORMAD1 has been shown to have a role in Triple-Negative Breast Cancers [9] and in Lung Adenocarcinomas.[10] In particular, the Watkins et al., paper suggested that overexpression of HORMAD1 is a driver of homologous recombination repair deficiency in these types of breast cancers, and induced widespread allelic imbalances in the genome with implications for platinum and PARP inhibitor sensitivity.
^ abChen YT, Venditti CA, Theiler G, Stevenson BJ, Iseli C, Gure AO, et al. (July 2005). "Identification of CT46/HORMAD1, an immunogenic cancer/testis antigen encoding a putative meiosis-related protein". Cancer Immunity. 5: 9. PMID15999985.
Pangas SA, Yan W, Matzuk MM, Rajkovic A (December 2004). "Restricted germ cell expression of a gene encoding a novel mammalian HORMA domain-containing protein". Gene Expression Patterns. 5 (2): 257–63. doi:10.1016/j.modgep.2004.07.008. PMID15567723.
