HORMAD1


HORMA domain-containing protein 1 also known as cancer/testis antigen 46 is a protein that in humans is encoded by the HORMAD1 gene.

Function

HORMAD1 is a cancer/testis antigen that plays a key role in meiotic progression. It has shown to regulate 3 different functions during meiosis. Specifically, it:
  1. Ensures that sufficient numbers of processed DNA double-strand breaks are available for successful homology search by increasing the steady-state numbers of single-stranded DSB ends
  2. Promotes synaptonemal-complex formation independently of its role in homology search.
  3. 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 and meiotic prophase quality control in both sexes

Role in cancer

HORMAD1 has been shown to have a role in Triple-Negative Breast Cancers and in Lung Adenocarcinomas. 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.