Tabriz University of Medical Sciences BioImpacts 2228-5652 16 1 2026 01 04 Identifying a CATSPERB Variant in Unexplained Male Infertility Through Familial Exome Sequencing 31358 31358 10.34172/bi.31358 EN Seyedeh Zahra Mousavi https://orcid.org/0000-0001-8298-2770 Pegah Kouhi Vahid Esmaeili Zeynab Rokhsattalab Abdolreza Esmaeilzadeh Navid Almadani Bahram Mohammad Soltani https://orcid.org/0000-0003-2468-901X Mehdi Totonchi https://orcid.org/0000-0002-7285-3155 Journal Article 10.34172/bi.31358 2025 04 05 2026 05 31 Introduction: Unexplained male infertility (UMI) refers to a situation where no underlying cause of male infertility is defined during investigations of the couple. Methods: Whole exome sequencing (WES) was performed to identify variants associated with UMI in a consanguineous Iranian family. Results: WES revealed a rare homozygous missense variant (chr14:g.92088086C>T; NM_024764.4:c.2126G>A; p.Arg709Gln) located in the extracellular region of CATSPERB in three affected siblings. This mutation resulted in the substitution of arginine 709 (R) with glutamine (Q) and co-segregated with the phenotype in other available family members. The kinematic parameters of sperm motility indicated abnormal hyperactivated movement. In-silico protein stability analysis suggests that the Arg709Gln (R709Q) alteration reduces the stability of the CATSPERB protein, potentially compromising causing defects in the overall stability of the CatSper complex. Conclusions: Our findings provide initial evidence supporting the involvement of CATSPERB variants in UMI. This is the first reported genetic variant within the CATSPERB gene associated with UMI.