OMIA:002219-9685 : Hypogonadotropic hypogonadism, TAC3-related in Felis catus (domestic cat)
Categories: Reproductive system phene
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2019
Species-specific name: Testicular Hypoplasia and Persistent Primary Dentition
Molecular basis: Whole-genome sequencing of a Domestic Shorthair cat with delayed puberty, and subsequent searching for private variants in 40 comparative candidate genes for the homologous trait (hypogonadotropic hypogonadism) in humans enabled Hug et al. (2019) to identify a potentially causal variant as "TAC3:c.220G>A or p.(Val74Met)". The authors noted that TAC3 encodes "tachykinin 3, a precursor protein of the signaling molecule neurokinin B, which is known to play a role in sexual development". The authors stressed the need for caution with this result: "Given that this is a single case investigation and that we have no functional confirmation of neurokinin B deficiency, this result must be considered preliminary and should be interpreted with caution."
Have human generated variants been created, e.g. through genetic engineering and gene editing
Clinical features: Hug et al. (2019): "A 3-year-old male domestic shorthair cat was presented with persistent primary dentition consisting of one primary maxillary canine . . . . Upon examination there was one small right testicle located in the scrotum. The left testicle could not be located. It was neither scrotal, nor palpable in the inguinal area. The external genitalia, including the urethral orifice, were in the normal position, although with a juvenile appearance because of their small size. The hair coat had an unkempt appearance. The cat had small body size but proportional growth. It had reportedly displayed mounting behavior toward another female cat in the household and showed an increasingly dominant–aggressive behavior toward other cats outside. The cat was presented for a follow-up examination at 4 years of age. No changes in behavior or the stage of adolescence were noticed."
Prevalence: Hug et al. (2019): "The affected cat was homozygous for the mutant allele. In a cohort of 171 randomly sampled cats, 169 were homozygous for the wildtype allele and 2 were heterozygous."
Control: Interestingly, Hug et al. (2019) noted that "In felines, efforts are underway to develop a method to permanently sterilize cats by RNAi-mediated silencing of KISS1 and TAC3 [KISS1 is another gene which, when mutated, gives rise to Hypogonadotropic hypogonadism in humans]. This method is predicted to lead to a reduction in the stray animal population and therefore decrease animal suffering and vectors for human disease".
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|TAC3||tachykinin 3||Felis catus||B4||NC_058374.1 (83383919..83376824)||TAC3||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1132||Domestic Shorthair||Hypogonadotropic hypogonadism, TAC3-related||TAC3||missense||Naturally occurring variant||Felis_catus_9.0||B4||g.85517451C>T||c.220G>A||p.(V74M)||Hug et al. (2019): XM_003988924.5:c.220G>A; XP_003988973.1:p.(Val74Met)||2019||31615056|
Cite this entry
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2021||Rodney, A.R., Buckley, R.M., Fulton, R.S., Fronick, C., Richmond, T., Helps, C.R., Pantke, P., Trent, D.J., Vernau, K.M., Munday, J.S., Lewin, A.C., Middleton, R., Lyons, L.A., Warren, W.C. :|
|A domestic cat whole exome sequencing resource for trait discovery. Sci Rep 11:7159, 2021. Pubmed reference: 33785770. DOI: 10.1038/s41598-021-86200-7.|
|2020||Szczerbal, I., Switonski, M. :|
|Genetic disorders of sex development in cats: An update. Anim Reprod Sci 216:106353, 2020. Pubmed reference: 32414464. DOI: 10.1016/j.anireprosci.2020.106353.|
|2019||Hug, P., Kern, P., Jagannathan, V., Leeb, T. :|
|A TAC3 missense variant in a domestic shorthair cat with testicular hypoplasia and persistent primary dentition. Genes (Basel) 10, 2019. Pubmed reference: 31615056. DOI: 10.3390/genes10100806.|
- Created by Frank Nicholas on 23 Oct 2019
- Changed by Frank Nicholas on 23 Oct 2019
- Changed by Tosso Leeb on 24 Oct 2019
- Changed by Imke Tammen2 on 17 Sep 2021