Categories: Reproductive system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 615358 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Probably autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2021

Species-specific description: O’Callaghan et al. (2023) "present a detailed phenotypic and molecular characterization of an intronic variant in cattle that activates cryptic splicing of the adenylate kinase 9 (AK9) gene resulting in extreme subfertility associated with impaired sperm hyperactivation, failure of oocyte binding/penetration, and low frequency of embryo development culminating in severely compromised field fertility."

Molecular basis: Abdollahi-Arpanahi et al. (2021) "identified a set of high-impact mutations in low-fertility bulls, including nonsense, missense, and frameshift variants. Some of these mutations may be considered as strong candidate causal variants for bull subfertility.... Genes affected by these candidate causal variants include AK9, TTLL9, TCHP, and FOXN4." The AK9 variant is listed as chr9:40620329A>G (ARS-UCD1.2; rs457222030). O’Callaghan et al. (2023): "Whole- genome sequencing from semen and RNA sequencing of testis tissue revealed a critical mutation [Chr9:40620329A>G] in adenylate kinase 9 (AK9) that impaired splicing, leading to a premature termination codon and a severely truncated protein. Mice deficient in AK9 were generated to further investigate the function of the gene; knockout males were phenotypically indistinguishable from their wild-type littermates but produced immotile sperm that were incapable of normal fertilization."

Breed: Holstein Friesian (Cattle) (VBO_0000239).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: