HORMAD1
Description
The HORMAD1 (HORMA domain containing 1) is a protein-coding gene located on chromosome 1.
HORMAD1, also known as cancer/testis antigen 46 (CT46), is a protein encoded by the HORMAD1 gene in humans. It is a cancer/testis antigen that plays a critical role in meiotic progression. HORMAD1 regulates three functions during meiosis: 1) ensuring sufficient processed DNA double-strand breaks (DSBs) for homology search, 2) promoting synaptonemal-complex formation, and 3) participating in the male mid-pachytene checkpoint and the female meiotic prophase checkpoint. In cancer, HORMAD1 has been linked to Triple-Negative Breast Cancers and Lung Adenocarcinomas. Overexpression of HORMAD1 is thought to drive homologous recombination repair deficiency in these breast cancers, leading to widespread allelic imbalances and sensitivity to platinum and PARP inhibitors.
HORMAD1 plays a crucial role in meiotic progression by regulating three key functions. First, it ensures that enough processed DNA double-strand breaks (DSBs) are available for successful homology search by increasing the number of single-stranded DSB ends. Second, it promotes synaptonemal-complex formation independently of its role in homology search. Finally, it 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. This process is believed to form the basis of meiotic silencing of unsynapsed chromatin (MSUC) and meiotic prophase quality control in both sexes.
HORMAD1 is also known as CT46, NOHMA.
Associated Diseases
- cancer
- partial chromosome Y deletion
- male infertility with teratozoospermia due to single gene mutation
