Biallelic Variants in ATP1A4 Are Associated with Oligoasthenoteratozoospermia and Male Infertility.

Biallelic ATP1A4 variants (testis-specific Na+,K+-ATPase isoform) impairing flagellar architecture

ATP1A4 encodes a testis-specific Na+,K+-ATPase isoform essential for ionic homeostasis. The authors identify compound biallelic variants, a missense (p.Tyr860Asn) and a frameshift (p.Gly861Aspfs5), in a patient with severe oligoasthenoteratozoospermia. Both variants markedly reduce ATP1A4 protein expression, with coiled and folded flagella, disorganized mitochondrial sheaths and irregular sperm heads. ATP1A4* is enriched in post-meiotic spermatids and localizes along the flagellum; ICSI yielded low fertilization and failed implantation, suggesting a role beyond motility.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A first human case supported by expression and morphology data consistent with Atp1a4-KO mouse models, broadening the genetic spectrum of male infertility. The single-patient cohort limits scope: replication is needed before diagnostic use. The possible impact on post-ICSI fertilization is a prognostic lead to confirm.

Analysis by Dr Thibaut Benquey