DNAJB13 polymorphisms and association with idiopathic asthenozoospermia in Sichuan, China

The axonemal co-chaperone gene DNAJB13 is essential for sperm motility and structural integrity. This study aimed to investigate the association between coding variants in DNAJB13 and idiopathic asthenozoospermia (IAZS) in a cohort from Sichuan, China.

Sanger sequencing of all DNAJB13 exons was performed in 130 patients with IAZS and 120 fertile controls with strictly normal semen parameters according to World Health Organization (WHO) 5th edition criteria. Detected variants were analyzed for genotype and allele frequencies. The potential impact of a novel missense variant was assessed using evolutionary conservation analysis across mammalian orthologs and in silico prediction tools for structural and splicing effects.

Six coding variants were identified. Three variants (c.T279C, c.C882T, c.G927A) were common single nucleotide polymorphisms (SNPs ) with no significant differences between cases and controls. A novel missense variant, c.T272G (p.V91G), was detected exclusively in patients. Genotype distribution and allele frequency of this variant differed significantly between groups. Valine 91 was highly conserved, and computational modeling predicted that the p.V91G substitution would destabilize protein structure, disrupt hydrophobic core architecture, potentially interfere with RNA splicing regulatory elements, and impair DNAJB13 co-chaperone function in axonemal assembly.

The c.T272G (p.V91G) in DNAJB13 is significantly associated with IAZS in the studied cohort and represents a potential high-risk genetic factor. Predicted detrimental effects on protein structure and function suggest a novel genetic mechanism underlying impaired sperm motility. Functional validation and replication studies in diverse populations are necessary to confirm its pathogenic role.