• Investigating Genetic Alterations in ACTL9: Unraveling the Origins of Male Infertility
  • Roya Sinaei,1,* Mehdi Hashemi,2
    1. Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
    2. Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran


  • Introduction: Infertility, which impacts approximately 9% of couples globally, is a complex condition with notable contributions from male factors. Although conventional diagnostic methods, including semen analysis and hormonal evaluations, are routinely employed, a considerable number of male infertility cases remain without a clear explanation, underscoring the necessity for more sophisticated diagnostic approaches.
  • Methods: The ACTL9 gene has been identified as a significant genetic factor in male infertility. Situated on chromosome 19, ACTL9 encodes a testis-specific actin-like protein that is crucial for the development and functionality of the sperm acrosome. Mutations in the ACTL9 gene can disrupt the localization of phospholipase C zeta (PLCz), an essential protein for oocyte activation, which can lead to failures in fertilization. Recent research has uncovered both homozygous and heterozygous pathogenic mutations in ACTL9 that adversely affect sperm functionality and contribute to infertility.
  • Results: Gaining insights into these mutations may pave the way for targeted diagnostic and therapeutic strategies, such as genetic screening and personalized treatment options. Future investigations should aim to clarify the molecular mechanisms associated with ACTL9-related infertility, assess its wider implications across different tissues, and utilize advancements in genomic technologies to enhance diagnostic and therapeutic methodologies.
  • Conclusion: Incorporating ACTL9 mutation analysis into clinical settings could significantly improve the management of male infertility and lead to better reproductive outcomes.
  • Keywords: male infertility, mutation , ACTL9