OMIA:001271-9796 : Dwarfism, ACAN-related in Equus caballus (horse)

In other species: taurine cattle , indicine cattle (zebu)

Categories: Skeleton phene (incl. short stature & teeth) , Growth / size / body region phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 612813 (trait) , 165800 (trait) , 608361 (trait) , 155760 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2017

Mapping: By conducting a GWAS on 20 dwarf and 26 control Miniature horses, each of which had been genotyped with the Illumina Equine SNP50 chip (yielding 40,368 informative SNPs), Eberth (2013) mapped this disorder to a region on chromosome ECA1.

Molecular basis: Noting that the relevant region of chromosome ECA1 contains the ACAN gene that has been implicated in similar types of dwarfism in cattle (see OMIA 001271-9913) and humans (see MIM entry above), Eberth (2013) sequenced this comparative positional candidate gene in affected and normal Miniature horses, revealing four variants strongly associated with dwarfism: c.245del, p.K82fx in exon 2 (Acan-D1); c.1270G>A, p.V424M in exon 6 (Acan-D2); c.6700delC, p.P1875fx in exon 11 (Acan-D3); c.7299-7319del, p.F2433-O2440del in exon 15 (Acan-D4). Bailey (2014) mentioned Eberth's discovery, but made no mention of any specific likely causal variant. Metzger et al. (2017) reported a missense mutation (g.94370258G>C; p.A505P) as a likely causal variant in a "Miniature Shetland". Eberth's 2013 thesis results were published by Eberth et al. (2018), who reported four likely causal variants, namely "g.95291270del (rs1095048841), g.95284530C>T (ERP107353), g.95282140C>G (rs1095048823) and g.95257480_95257500del (rs1095048839)", all with respect to Ecab 3.0 (GCF_002863925.1), naming them D1, D2, D3*, and D4, respectively. As these authors noted, D3* is the same variant reported by Metzger et al. (2017). As explained by Eberth et al. (2018), D3* is given an asterisk to differentiate it from the original D3 allele described by Eberth (2013), a deletion in exon 11, which turned out to be a technical artifact. Ebert et al. (2018) reported that "Homozygotes for those variants and compound heterozygotes for any combination of those variants always expressed a dwarfism phenotype. However, eight additional horses with dwarfism were found, seven of which were heterozygotes for D2, D3* or D4 [and the other dwarf did not possess any of these variants], suggesting the existence of additional ACAN alleles causing dwarfism." Andrade et al. (2020; PMID 32943661) reported a fifth variant, namely a "missense SNP in coding exon 11 (g.95271115A > T, c.6465A > T-RefSeq XM_005602799.2), which resulted in the amino acid substitution p.Leu2155Phe (RefSeq XP_005602856.2)" that could be "a marker of disequilibrium or complex interactions in the Miniature horse genome could contribute to the associated dwarfism".

Clinical features: "Chondrodysplastic dwarfism in horses was identified based on severely shortened stature relative to horses of that age plus any of the following characteristics: shortened limbs relative to overall body size, bowed forelegs, shortened neck, disproportionately large cranium, compressed faces with large bulging eye sockets with prominent eyes, low nasal bridge, severe underbite, retruded muzzle, cleft palate and protruding tongue, a large abdominal hernia or embryonic loss with a dwarf phenotype of the fetus." (Eberth et al., 2018). Andrade et al. (2020; PMID 31906815) reported the first documented cases of homozygosity for the D4 variant: "2 Miniature horses with the genotype D4/D4 in the ACAN gene. Clinically, the 2 dwarfs had a domed head that was large compared to the rest of the body, mandibular prognathism, and short and bowed limbs, mainly in the proximal region of the metatarsal bones. Radiographic examination revealed contour irregularities of the subchondral bone in the long bones and confirmed mandibular prognathism; histopathology revealed irregular chondrocyte organization."

Prevalence: Eberth et al. (2018) reported the frequencies in Minatures of each variant were 0.03 for D1, 0.09 for D2, 0.02 for D3* and 0.03 for D4.

Breeds: Miniature Horse (Horse) (VBO_0016848), Shetland Pony (Horse) (VBO_0001066).
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
ACAN aggrecan Equus caballus 1 NC_009144.3 (95320479..95255524) ACAN 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
1001 Miniature Horse (Horse) Dwarfism, ACAN-related ACAN D4 deletion, gross (>20) Naturally occurring variant EquCab3.0 1 NC_009144.3:g.952574879_95257499del XM_005602799.2:c.7633_7653del XP_005602856.2:p.(F2545_C2551del) Genomic positions were previosuly incorreclty listed in OMIA as g.95257458_95257500del (until 10/01/2022) and g.95257480_95257500del (until 13/06/2024). Coordinates presented now reflect  the published rs1095048839.

rs1095048839 2018 30058072
788 Miniature Horse (Horse) Shetland Pony (Horse) Dwarfism, ACAN-related ACAN D3* missense Naturally occurring variant EquCab3.0 1 NC_009144.3:g.95282140C>G XM_023650286.1:c.1513G>C XP_023506054.1:p.(A505P) ENSECAT00000040213.1:c.1513G>C ENSECAP00000032890.1:p.Ala505Pro This variant was named D3* by Eberth et al. (2018) rs1095048823 2017 27942904 Variant coordinates obtained from Eberth et al. (2018) and EVA_ID link
1000 Miniature Horse (Horse) Quarter Horse (Horse) Warmblood (Horse) Dwarfism, ACAN-related ACAN D2 missense Naturally occurring variant EquCab3.0 1 NC_009144.3:g.95284530C>T XP_023506054.1:c.1270C>T XP_023506054.1:p.(V424M) rs3091781465 2018 30058072 Breed information updated based on PMID: 38600096
999 Miniature Horse (Horse) Dwarfism, ACAN-related ACAN D1 deletion, small (<=20) Naturally occurring variant EquCab3.0 1 NC_009144.3:g.95291271del XM_023650281.1:c.245del XP_023506054.1:p.(K82Rfs*54) 220110: changed g.95291270del to g.95291271del based on HGVS 3'rule. ENSECAT00000040213.1:c.245del ENSECAP00000032890.1:p.Lys82ArgfsTer54 rs1095048841 2018 30058072

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2021). OMIA:001271-9796: 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.
2020 Andrade, D.G.A., Basso, R.M., Castiglioni, M.C.R., Silva, J.P., Machado, V.M.V., Laufer-Amorim, R., Borges, A.S., Oliveira-Filho, J.P. :
Description of the D4/D4 genotype in Miniature horses with dwarfism. J Vet Diagn Invest 32:99-102, 2020. Pubmed reference: 31906815. DOI: 10.1177/1040638719898164.
Andrade, D.G.A., Basso, R.M., Magro, A.J., Laufer-Amorim, R., Borges, A.S., de Oliveira-Filho, J.P. :
Evaluation of a new variant in the aggrecan gene potentially associated with chondrodysplastic dwarfism in Miniature horses. Sci Rep 10:15238, 2020. Pubmed reference: 32943661. DOI: 10.1038/s41598-020-72192-3.
Graves, K.T., Eberth, J.E., Bailey, E. :
Heterozygotes for ACAN dwarfism alleles in horses have reduced stature. Anim Genet 51:420-422, 2020. Pubmed reference: 32065671. DOI: 10.1111/age.12921.
2018 Eberth, J.E., Graves, K.T., MacLeod, J.N., Bailey, E. :
Multiple alleles of ACAN associated with chondrodysplastic dwarfism in Miniature horses. Anim Genet , 2018. Pubmed reference: 30058072. DOI: 10.1111/age.12682.
2017 Metzger, J., Gast, A.C., Schrimpf, R., Rau, J., Eikelberg, D., Beineke, A., Hellige, M., Distl, O. :
Whole-genome sequencing reveals a potential causal mutation for dwarfism in the Miniature Shetland pony. Mamm Genome 28:143-151, 2017. Pubmed reference: 27942904. DOI: 10.1007/s00335-016-9673-4.
2014 Bailey, E. :
Five things equine veterinarians should know about genomics. Equine Vet J 46:404-7, 2014. Pubmed reference: 24909654. DOI: 10.1111/evj.12271.
2013 Eberth, J.E. :
Chondrodysplasia-Like Dwarfism in the Miniature Horse. Theses and Dissertations--Veterinary Science. Paper 11. Entire thesis is available at, 2013.
2009 Eberth, J., Swerczak, T. , Bailey, E. :
Investigation of dwarfism Among Miniature Horses using the Illumina Horse SNP50 Bead Chip. Journal of Equine Veterinary Science 29:315 only, 2009.

Edit History

  • Created by Frank Nicholas on 27 Jun 2014
  • Changed by Frank Nicholas on 27 Jun 2014
  • Changed by Frank Nicholas on 16 Oct 2014
  • Changed by Frank Nicholas on 11 Aug 2017
  • Changed by Frank Nicholas on 03 Aug 2018
  • Changed by Frank Nicholas on 05 Mar 2019
  • Changed by Frank Nicholas on 05 Aug 2020
  • Changed by Frank Nicholas on 26 Oct 2020
  • Changed by Imke Tammen2 on 30 Aug 2021