HORMAD2

HORMAD2 is a human protein encoded by the HORMAD2 gene. It is a member of the HORMA-domain containing protein family and is primarily associated with meiosis in germ cells. The HORMA domain is a conserved module involved in chromosome-based signaling and checkpoint control.

During meiotic prophase I, HORMAD2 localizes to the chromosomal axes of unsynapsed homologs, where it helps mark regions that have not yet achieved synapsis. In coordination with HORMAD1, it participates in the surveillance of synapsis and recombination and contributes to meiotic silencing of unsynapsed chromatin (MSUC) and, for sex chromosomes, meiotic sex chromosome inactivation (MSCI).

HORMAD2 interacts with other components of the meiotic chromosome axis and is thought to influence the recruitment or activity of checkpoint factors such as ATR at unsynapsed chromatin. As synapsis progresses, HORMAD2 is removed from chromosomes, a process promoted by the AAA+ ATPase TRIP13 (PCH2), which remodels HORMA-domain proteins to facilitate progression through meiosis.

Expression of HORMAD2 is mainly restricted to testis, consistent with a meiosis-specific role; however, transcripts and protein have also been detected in other tissues and in certain cancer samples, leading to interest in its potential as a cancer-testis antigen and biomarker.

Structurally, HORMAD2 contains an N-terminal HORMA domain and regions likely involved in protein–protein interactions and chromosome axis association. Together with related HORMA-domain proteins, HORMAD2 contributes to proper chromosome synapsis, recombination, and genome integrity during meiosis.