OMIA:000991-9796 : Androgen insensitivity syndrome (AIS) in Equus caballus (horse)

In other species: Burton's mouthbrooder , dog , domestic cat , pig , taurine cattle

Categories: Reproductive system phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 300068 (trait) , 313700 (gene)

Links to MONDO diseases:

Mendelian trait/disorder: yes

Mode of inheritance: X-linked recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2012

Cross-species summary: This is a type of XY difference of sexual development (XY DSD) due to variants in the AR gene. Previously known as Testicular Feminisation Syndrome. This is an abnormality of sexual development in which affected individuals have an XY chromosomal constitution, undescended testes and female secondary sexual characteristics (including female external genitalia). Also, instead of normally developed Mullerian duct derivatives (Fallopian tubes, uterus, cervix, and upper protion of the vagina), they have under-developed Wolffian duct derivatives (epididymis, vas deferens, and seminal vesicle). In all species so far investigated, the inheritance is X-linked recessive. In several species, this disorder is known to be due to a deficiency of an androgen receptor encoded by a gene on the X chromosome. The presence of a Y chromosome induces the undifferentiated embryonic gonads to develop as testes, but, in the absence of androgen receptor, the androgens produced by the testes cannot exert any effect. The result is that the embryo follows the "default" path of development, which is female.

Species-specific symbol: AIS

Markers: Figure 2 of Villagomez et al. (2020) provides a very clear summary of the five likely causal variants known to date.

Molecular basis: Révay et al. (2012) reported that this disorder in a family of American Quarter Horses is due to "a transition in the first nucleotide of the [androgen receptor] AR start codon (c.1A>G)", with the result that "a reduced amount of the functional AR is expressed during androgen-critical periods of development in the XY genetic male embryo, which alters its gonadal development and results in the observed phenotype". This is the first report of a mutation in the AR gene in domestic animals. In a "Warmblood horse pedigree segregating AIS", Welsford et al. (2017) "provided evidences that a 25-bp deletion of the DNA-binding domain [of the AR gene] is causative" in this breed. Villagomez et al. (2020) reported "two novel genetic variants for the AR-gene identified in a Tennessee Walking Horse and a Thoroughbred horse mare; each in individual clinical cases of horse AIS syndrome . . . c.183delT in Case #1 and c.2132C>T in Case #2".

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Breeds: Quarter Horse (Horse) (VBO_0001057), Tennessee Walking Horse (Horse) (VBO_0001081), Thoroughbred (Horse) (VBO_0001083).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
AR androgen receptor Equus caballus X NC_009175.3 (52728703..52884282) AR Homologene, Ensembl , NCBI gene


By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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
436 Quarter Horse (Horse) Androgen insensitivity syndrome (AIS) AR regulatory Naturally occurring variant EquCab3.0 X NC_009175.3:g.52728703A>G NM_001163891.1:c.1A>G  mutation in start codon for  NP_001157363.1; 2012 22095250 The genomic position in EquCab3.0 was provided by Ceara Mulvey, working under the guidance of Professor Ernie Bailey in April 2022
1143 Tennessee Walking Horse (Horse) Androgen insensitivity syndrome (AIS) AR deletion, small (<=20) Naturally occurring variant EquCab3.0 X NC_009175.3:g.52728885del NM_001163891.1:c.183del NP_001157363.1:p.(R63Gfs) published as c.183delT and p.(Ser61fs); c. and p. information in the table has been updated to HGVS nomenclature 2020 31936796 The genomic position in EquCab3.0 was provided by Ceara Mulvey, working under the guidance of Professor Ernie Bailey in April 2022
783 Androgen insensitivity syndrome AR deletion, gross (>20) Naturally occurring variant EquCab3.0 X NC_009175.3:g.52808634_52808658del NM_001163891.1:c.1630_1654del the deletion is predicted to create a frameshift: "resulting in altered amino acid composition from p.543Lys and a premature stop codon 44 amino acid residues downstream in exon 3 2017 28192783
786 Thoroughbred (Horse) Androgen insensitivity syndrome AR missense Naturally occurring variant EquCab3.0 X NC_009175.3:g.52872393G>C NM_001163891.1:c.2042G>C NP_001157363.1:p.(W681S) 2016 27073903 The genomic position in EquCab3.0 was provided by Ceara Mulvey, working under the guidance of Professor Ernie Bailey in April 2022; p. coordinates obtained from Villagomez et al. (2019)
1144 Thoroughbred (Horse) Androgen insensitivity syndrome (AIS) AR missense Naturally occurring variant EquCab3.0 X NC_009175.3:g.52878093C>T NM_001163891.1:c.2132C>T NP_001157363.1:p.(A711V) 2020 31936796

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2022). OMIA:000991-9796: Online Mendelian Inheritance in Animals (OMIA) [dataset].


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.

2020 Villagomez, D.A.F., Welsford, E.G., King, W.A., Revay, T. :
Androgen receptor gene variants in new vases of equine androgen insensitivity syndrome. Genes (Basel) 11:78, 2020. Pubmed reference: 31936796. DOI: 10.3390/genes11010078.
2017 Welsford, G.E., Munk, R., Villagómez, D.A., Hyttel, P., King, W.A., Revay, T. :
Androgen insensitivity syndrome in a family of Warmblood horses caused by a 25-bp deletion of the DNA-binding domain of the androgen receptor gene. Sex Dev 11:40-45, 2017. Pubmed reference: 28192783. DOI: 10.1159/000455114.
2016 Bolzon, C., Joonè, C.J., Schulman, M.L., Harper, C.K., Villagómez, D.A., King, W.A., Révay, T. :
Missense mutation in the ligand-binding domain of the horse androgen receptor gene in a thoroughbred family with inherited 64,XY (SRY+) disorder of sex development. Sex Dev 10:37-44, 2016. Pubmed reference: 27073903. DOI: 10.1159/000444991.
2012 Révay, T., Villagómez, D.A., Brewer, D., Chenier, T., King, W.A. :
GTG mutation in the start codon of the androgen receptor gene in a family of horses with 64,XY disorder of sex development. Sex Dev 6:108-16, 2012. Pubmed reference: 22095250. DOI: 10.1159/000334049.
2011 Villagómez, D.A., Lear, T.L., Chenier, T., Lee, S., McGee, R.B., Cahill, J., Foster, R.A., Reyes, E., St John, E., King, W.A. :
Equine disorders of sexual development in 17 mares including XX, SRY-negative, XY, SRY-negative and XY, SRY-positive genotypes. Sex Dev 5:16-25, 2011. Pubmed reference: 21196712. DOI: 10.1159/000322811.
2005 Switonski, M., Chmurzynska, A., Szczerbal, I., Lipczynski, A., Yang, F., Nowicka-Posluszna, A. :
Sex reversal syndrome (64,XY; SRY-positive) in a mare demonstrating masculine behaviour. J Anim Breed Genet 122 Suppl 1:60-3, 2005. Pubmed reference: 16130458.
2004 Howden, K.J. :
Androgen insensitivity syndrome in a thoroughbred mare (64, XY--testicular feminization). Can Vet J 45:501-3, 2004. Pubmed reference: 15283519.
1992 Crabbe, B.G., Freeman, D.A., Grant, B.D., Kennedy, P., Whitlatch, L., Macrae, K. :
Testicular feminization syndrome in a mare. Journal of the American Veterinary Medical Association 200:1689-1691, 1992. Pubmed reference: 1624347.
1986 Enbergs, H., Schulte-Beckhausen, W. :
[Sex chromosome anomalies in mares and cytogenetic investigations on mares with severe fertility disturbances] Zuchthygiene 21:105-114, 1986.
1976 Kieffer, N.M. :
Male pseudohermaphroditism of the testicular feminizing type in a horse. Equine Vet J 8:38-41, 1976. Pubmed reference: 943286.

Edit History

  • Created by Frank Nicholas on 06 Sep 2005
  • Changed by Frank Nicholas on 04 Jul 2012
  • Changed by Frank Nicholas on 06 Aug 2017
  • Changed by Frank Nicholas on 27 Jan 2020
  • Changed by Frank Nicholas on 03 Feb 2020
  • Changed by Imke Tammen2 on 30 Apr 2022