OMIA:001688-9796 : Auditory-pigmentary syndrome, PAX3-related in Equus caballus (horse)

In other species: domestic cat

Categories: Pigmentation phene , Hearing / vestibular / ear phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 193500 (trait) , 148820 (trait) , 606597 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal incomplete dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2012

Cross-species summary: The name of this phene was changed from "Coat colour, white spotting, PAX3-related" to "Auditory-pigmentary syndrome, PAX3-related" on 01-Mar-2024.
The phene includes altered pigmentation of the eyes and/or skin together with a predisposition for unilateral or bilateral sensineural deafness. Affected animals often have blue eyes or eyes with different colors (heterochromia iridis). Skin pigmentation may include variable degrees of white spotting ranging from tiny white spots up to completely white animals. The absence of pigment is caused by the absence of melanocytes ("leucism"), not by a failure in the biochemical reactions required for pigment synthesis. The increased risk for deafness is the consequence of lacking melanocytes in the stria vascularis of the inner ear.

Species-specific name: splashed white

Species-specific description: Currently (in 2016), the horse is among domesticated animals the species with the highest number of known genetic variants that lead to white spotting phenotypes. Related coat colour phenotypes are caused by variants in the EDNRB, KIT, MITF, PAX3 and TRPM1 genes. Combinations of multiple variants in these gene can lead to more pronounced coat colour phenotypes. The splashed white phenotype may be caused by variants in the PAX3 gene as outlined below. However, by far the most common causative varaint for the splashed white phenotype is a non-coding regulatory promoter variant in the MITF gene.

History: Hauswirth et al. (2012) reported the first functional variant in the equine PAX3 gene.

Inheritance: The mode of inheritance depends on the specific variant and there are interactions with other genes. Animals with the typical splashed white phenotype normally have only one copy of the mutant allele(s). Homozygosity for the mutant alleles results in either embryonic lethality or more pronounced depigmentation phenotypes. There is incomplete penetrance for the auditory phenotype. The risk for deafness further increases in horses that carry combinations of mutant PAX3 alleles with additional white-spotting alleles at other genes.

Molecular basis: Hauswirth et al. (2012) reported three independent variants causing the splashed white phenotype, two of them in the MITF gene and one in the PAX3 gene: A missense variant in the PAX3 gene [OMIAvariantID:791] (c.209G>A; p.C70Y; "SW2") was identified in Quarter Horses and American Paint Horses. Druml et al. (2018) demonstrated that the PAX3^C70Y allele also segregates in Noriker and Lippizan horses.
Hauswirth et al. (2013) reported a second missense variant in the PAX3 gene [OMIAvariantID:978] in an Appaloosa family segregating for a splashed white phenotype (c.95C>G; p:Pro32Arg). Table S1 of Dürig et al. (2017) provides details of all PAX3 alleles (plus alleles at EDNRB, KIT, MITF) known in July 2016. McFadden et al. (2023) "report two novel mutations, a stop-gain mutation in PAX3 [OMIAvariantID:1605] (XM_005610643.3:c.927C>T, ECA6:11,196,181, EquCab3.0) and a missense mutation in a binding domain of MITF [OMIAvariantID:1606] (NM_001163874.1:c.993A>T, ECA16:21,559,940, EquCab3.0), each with a strong association with increased depigmentation in Pura Raza Española horses ... ."

Clinical features: Magdesian et al. 2009 demonstrated an increased risk for deafness in horses with the splashed white and/or frame overo spotting phenotype. Hauswirth et al. 2012 reported that "Some, but not all, splashed white horses are deaf."

Prevalence: Druml et al. (2018) reported that "besides Quarter Horses, the PAX3^C70Y [SW2] allele is also present in Noriker (seven out of 189) and Lipizzan (three out of 329) horses" and that of "10 heterozygous PAX3^C70Y-carrier horses, two had nearly a splashed white phenotype".

Breeds: American Paint (Horse) (VBO_0000897), Appaloosa (Horse) (VBO_0000904), Lipizzan horse (Horse) (VBO_0001014), Noric (Horse) (VBO_0001030), Purebred Spanish (Horse) (VBO_0001056), Quarter Horse (Horse) (VBO_0001057).
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:

Symbol Description Species Chr Location OMIA gene details page Other Links
PAX3 paired box 3 Equus caballus 6 NC_009149.3 (11200892..11108461) PAX3 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 Year Published PubMed ID(s) Acknowledgements
1605 Purebred Spanish (Horse) Splashed white PAX3 SW10 nonsense (stop-gain) Naturally occurring variant EquCab3.0 6 NC_009149.3:g.11196181G>A XM_005610643.3:c.583C>T XP_005610700.1:p.(R195*) XM_005610643.3; XP_005610700.1; association with increased depigmentation, published as c.927C>T 2023 37406837
791 Lipizzan horse (Horse) Noric (Horse) Quarter Horse (Horse) Splashed white PAX3 SW2 missense Naturally occurring variant EquCab3.0 6 NC_009149.3:g.11199026C>T XM_001495160.4:c.209G>A XP_001495210.1:p.(C70Y) rs5334475189 2012 22511888 Variant coordinates gleaned from or confirmed by Table S1 of Durig et al. (2017) Anim Genet 48:123-124
978 Appaloosa (Horse) Splashed white PAX3 SW4 missense Naturally occurring variant EquCab3.0 6 NC_009149.3:g.11199140G>C XM_001495160.4:c.95C>G XP_001495210.1:p.(P32R) rs5334475206 2013 23659293

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:001688-9796: 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.

2024 Durward-Akhurst, S.A., Marlowe, J.L., Schaefer, R.J., Springer, K., Grantham, B., Carey, W.K., Bellone, R.R., Mickelson, J.R., McCue, M.E. :
Predicted genetic burden and frequency of phenotype-associated variants in the horse. Sci Rep 14:8396, 2024. Pubmed reference: 38600096. DOI: 10.1038/s41598-024-57872-8.
McFadden, A., Vierra, M., Martin, K., Brooks, S.A., Everts, R.E., Lafayette, C. :
Spotting the pattern: A review on white coat color in the domestic horse. Animals (Basel) 14:451, 2024. Pubmed reference: 38338094. DOI: 10.3390/ani14030451.
2023 Gossett, C.L., Guyer, D., Hein, J., Brooks, S.A. :
Digital phenotyping reveals phenotype diversity and epistasis among white spotting alleles in the American Paint horse. Genes (Basel) 14:2011, 2023. Pubmed reference: 38002953. DOI: 10.3390/genes14112011.
McFadden, A., Martin, K., Foster, G., Vierra, M., Lundquist, E.W., Everts, R.E., Martin, E., Volz, E., McLoone, K., Brooks, S.A., Lafayette, C. :
Two novel variants in MITF and PAX3 associated with splashed white phenotypes in horses. J Equine Vet Sci 128:104875, 2023. Pubmed reference: 37406837. DOI: 10.1016/j.jevs.2023.104875.
2019 Hauswirth, R., Haase, B., Blatter, M., Brooks, S.A., Burger, D., Drögemüller, C., Gerber, V., Henke, D., Janda, J., Jude, R., Magdesian, K.G., Matthews, J.M., Poncet, P.A., Svansson, V., Tozaki, T., Wilkinson-White, L., Penedo, M.C.T., Rieder, S., Leeb, T. :
Correction: Mutations in MITF and PAX3 cause "Splashed White" and other white spotting phenotypes in horses. PLoS Genet 15:e1008321, 2019. Pubmed reference: 31374075. DOI: 10.1371/journal.pgen.1008321.
2018 Druml, T., Grilz-Seger, G., Neuditschko, M., Horna, M., Ricard, A., Pausch, H., Brem, G. :
Novel insights into Sabino1 and splashed white coat color patterns in horses. Anim Genet 49:249-253, 2018. Pubmed reference: 29635692. DOI: 10.1111/age.12657.
2017 Dürig, N., Jude, R., Jagannathan, V., Leeb, T. :
A novel MITF variant in a white American Standardbred foal. Anim Genet 48:123-124, 2017. Pubmed reference: 27592871. DOI: 10.1111/age.12484.
Negro, S., Imsland, F., Valera, M., Molina, A., Solé, M., Andersson, L. :
Association analysis of KIT, MITF, and PAX3 variants with white markings in Spanish horses. Anim Genet 48:349-352, 2017. Pubmed reference: 28084638. DOI: 10.1111/age.12528.
2013 Hauswirth, R., Jude, R., Haase, B., Bellone, R.R., Archer, S., Holl, H., Brooks, S.A., Tozaki, T., Penedo, M.C., Rieder, S., Leeb, T. :
Novel variants in the KIT and PAX3 genes in horses with white-spotted coat colour phenotypes. Anim Genet 44:763-5, 2013. Pubmed reference: 23659293. DOI: 10.1111/age.12057.
2012 Hauswirth, R., Haase, B., Blatter, M., Brooks, S.A., Burger, D., Drögemüller, C., Gerber, V., Henke, D., Janda, J., Jude, R., Magdesian, K.G., Matthews, J.M., Poncet, P.A., Svansson, V., Tozaki, T., Wilkinson-White, L., Penedo, M.C., Rieder, S., Leeb, T. :
Mutations in MITF and PAX3 cause "splashed white" and other white spotting phenotypes in horses. PLoS Genet 8(4):e1002653, 2012. Pubmed reference: 22511888. DOI: 10.1371/journal.pgen.1002653.
2009 Magdesian, KG., Williams, DC., Aleman, M., LeCouteur, RA., Madigan, JE. :
Evaluation of deafness in American Paint Horses by phenotype, brainstem auditory-evoked responses, and endothelin receptor B genotype. J Am Vet Med Assoc 235:1204-11, 2009. Pubmed reference: 19912043. DOI: 10.2460/javma.235.10.1204.

Edit History

  • Created by Frank Nicholas on 19 Apr 2012
  • Changed by Frank Nicholas on 03 Jun 2013
  • Changed by Tosso Leeb on 02 Nov 2016
  • Changed by Tosso Leeb on 03 Nov 2016
  • Changed by Frank Nicholas on 02 Mar 2017
  • Changed by Frank Nicholas on 19 Apr 2018
  • Changed by Frank Nicholas on 15 May 2020
  • Changed by Imke Tammen2 on 23 Nov 2022
  • Changed by Imke Tammen2 on 18 Aug 2023
  • Changed by Imke Tammen2 on 27 Feb 2024
  • Changed by Tosso Leeb on 01 Mar 2024