ArticleAmerican journal of human genetics2013
Missense mutations in SLC26A8, encoding a sperm-specific activator of CFTR, are associated with human asthenozoospermia.
Article in American journal of human genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- Sperm Ion Transporters and Channels in Human Asthenozoospermia: Genetic Etiology, Lessons from Animal Models, and Clinical Perspectives.International journal of molecular sciences · 2022Pooled it
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- The ZBTB16/CUL3/ROC1 ubiquitin ligase drives the degradation of pathogenic pendrin (SLC26A4) protein variants.Journal of biomedical science · 2026Article
- Beyond obstructive azoospermia: emerging insights into reproductive health in men with cystic fibrosis.Journal of assisted reproduction and genetics · 2026Review
- The systems that transport ions and their impact on sperm function and male fertility.Function (Oxford, England) · 2026Review
- Exploration of shared biomarkers and mechanisms in systemic lupus erythematous and lung cancer via bioinformatics analysis.Journal of translational autoimmunity · 2025Article
- Human asthenozoospermia: Update on genetic causes, patient management, and clinical strategies.Andrology · 2025Review
- Comparative genomics reveals common diversity and adaptation to harsh environments in the Arabian Peninsula indigenous chickens.Animal genetics · 2025Article
- Bovine serum albumin-induced calcium influx triggers soluble adenylyl cyclase activation and cyclic AMP signalling pathways in mouse sperm capacitation.The Journal of physiology · 2025Article
- The annulus: composition, role and importance in sperm flagellum biogenesis and male fertility.Basic and clinical andrology · 2024Review
- The role of SLC26A8 homozygous variants in male infertility and flagellum abnormalities.Asian journal of andrology · 2024Article
- Review
- Review
- Large-scale genomic and transcriptomic analyses elucidate the genetic basis of high meat yield in chickens.Journal of advanced research · 2024Article
- SLC26 Anion Transporters.Handbook of experimental pharmacology · 2024Review
- A robust mRNA signature obtained via recursive ensemble feature selection predicts the responsiveness of omalizumab in moderate-to-severe asthma.Clinical and translational allergy · 2023Article
- A novel mutation in PCD-associated gene DNAAF3 causes male infertility due to asthenozoospermia.Journal of cellular and molecular medicine · 2023Article
- Control of intracellular pH and bicarbonate by CONature communications · 2023Article
- Article
- The Role of Sperm Membrane Potential and Ion Channels in Regulating Sperm Function.International journal of molecular sciences · 2023Review
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) is present in mature sperm and is required for sperm motility and capacitation. Both these processes are controlled by ions fluxes and are essential for fertilization. We have shown that SLC26A8, a sperm-specific member of the SLC26 family of anion exchangers, associates with the CFTR channel and strongly stimulates its activity. This suggests that the two proteins cooperate to regulate the anion fluxes required for correct sperm motility and capacitation. Here, we report on three heterozygous SLC26A8 missense mutations identified in a cohort of 146 men presenting with asthenozoospermia: c.260G>A (p.Arg87Gln), c.2434G>A (p.Glu812Lys), and c.2860C>T (p.Arg954Cys). These mutations were not present in 121 controls matched for ethnicity, and statistical analysis on a control population of 8,600 individuals (from dbSNP and 1000 Genomes) showed them to be associated with asthenozoospermia with a power > 95%. By cotransfecting Chinese hamster ovary (CHO)-K1 cells with SLC26A8 variants and CFTR, we showed that the physical interaction between the two proteins was partly conserved but that the capacity to activate CFTR-dependent anion transport was completely abolished for all mutants. Biochemical studies revealed the presence of much smaller amounts of protein for all variants, but these amounts were restored to wild-type levels upon treatment with the proteasome inhibitor MG132. Immunocytochemistry also showed the amounts of SLC26A8 in sperm to be abnormally small in individuals carrying the mutations. These mutations might therefore impair formation of the SLC26A8-CFTR complex, principally by affecting SLC26A8 stability, consistent with an impairment of CFTR-dependent sperm-activation events in affected individuals.
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