OMIA:002602-9615 : Cerebellar abiotrophy, VMP1-related in Canis lupus familiaris (dog)

Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 611753 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2022

Species-specific description: Cerebellar abiotropy has been first described in Australian kelpies by Thomas and Robertson in 1989. Wade et al. (2022) "identified two distinct clinical and pathological features of CA in Australian working kelpies. These were associated with two separate genomic regions ... An early-onset CA form is observable within a few weeks of birth and in some cases is seen within days of birth. This form affects dogs that are homozygous for a risk marker on CFA20 [see 'OMIA 000175-9615 : Cerebellar abiotrophy in Canis lupus familiaris']. A second region of association, identified on CFA9, is associated with a later-onset form of CA [described in this OMIA entry] that is not usually diagnosed until the dogs are 4–6 months or older."

Mapping: Wade et al. (2022): “Investigation of clinical and pathological features [in Australian working kelpie dogs] indicated two closely related diseases with differences in age of onset. … A genome-wide association study on 45 CA affected and 290 normal healthy Kelpies identified two significantly associated loci, one on CFA9 and a second on CFA20. [See 'OMIA 000175-9615 : Cerebellar abiotrophy in Canis lupus familiaris' for information on the early onset (clinical signs before ten weeks of age) disease associated with the the risk haplotype on CFA20] ... Genome-wide significant association identified a second significant region of association CFA9:32,419,297–35,242,435 (UU GSD1.0)."

Molecular basis: Wade et al. (2022): "one dog exhibiting symptoms of CA, its dam, and a sib without symptoms at the time of observation ... were subjected to whole-genome sequencing (WGS) on the Illumina HiSeq 2500 platform ... . A further five whole genome sequences from unrelated healthy AWK were obtained by collaboration ... . ... The most associated array marker: BICF2G630835610 CFA9:32,949,504G>A, (pgenome 5.13 × 10−8) segregated in perfect LD with a missense variant in the fifth exon of VMP1 NM_030938p.P160Q."

Clinical features: Clinical presentation in the two forms of CA in Australian Kelpies mainly differ in regard to onset of clinical signs. The form with later onset of disease at 4-6 month of age is associated with the VMP1 variant (Wade et al., 2022). Clinical signs include ataxia, wide-based stance, head tremors/intention tremor, dysmetria/incoordination, hypermetria/high-stepping gate, decreased limb proprioception (particularly hind limbs), and/or body tremors when excited. The condition is non-painful and does not affect the dog’s normal mentation or alertness. More severe forms can include fitting/grand mal seizures when overheated or excited. The condition may present mildly with only occasional periods of incoordination and no progression to more severe forms. Commonly, it will present with signs that become more obvious or progress as the animal ages (Thomas and Robertson, 1989; Shearman et al., 2008; Shearman et al., 2011; Pan et al., 2017; Wade et al., 2022). IT thanks DVM student Beatrice Humphries, who provided the basis of this contribution in May 2023.

Pathology: Wade et al. (2022) "Histopathology shows that affected animals regardless of age of onset exhibit granule cell loss, regional Purkinje cell loss and activated astrocytes. However, the histopathological features are distinct between animals affected with the early-onset disease associated with homozygosity at CFA20 and those affected with the later-onset disease that were homozygous at CFA9. The early-onset group (CFA20) demonstrate abnormality of foliar development in the cerebellar cortex, and a relatively reduced molecular layer (ML). Dogs that were homozygous for the CFA9 locus had normal foliar development, later disorder onset, and demonstrated axonal spheroids in their white matter tracts."

Breed: Working Kelpie (Dog) (VBO_0201434).
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
VMP1 vacuole membrane protein 1 Canis lupus familiaris 9 NC_006591.3 (34197093..34341502) VMP1 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
1512 Working Kelpie (Dog) Cerebellar abiotrophy VMP1 missense Naturally occurring variant UU_Cfam_GSD_1.0 9 g.34218228C>A p.(P160Q) 2022 36292596

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:002602-9615: 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.

2023 Stee, K., Van Poucke, M., Lowrie, M., Van Ham, L., Peelman, L., Olby, N., Bhatti, S.F.M. :
Phenotypic and genetic aspects of hereditary ataxia in dogs. J Vet Intern Med 37:1306-1322, 2023. Pubmed reference: 37341581. DOI: 10.1111/jvim.16742.
2022 Wade, C.M., Pan, A.Y.H., Taylor, R.M., Williamson, P. :
Cerebellar abiotrophy in Australian Working Kelpies is associated with two major risk loci. Genes (Basel) 13:1709, 2022. Pubmed reference: 36292596. DOI: 10.3390/genes13101709.
2017 Pan, A.Y.H., Wade, C.M., Taylor, R.M., Williamson, P. :
Exclusion of known gene loci for cerebellar abiotrophy in the Australian Working Kelpie. Anim Genet 48:730-732, 2017. Pubmed reference: 28850678. DOI: 10.1111/age.12594.
2011 Shearman, J.R., Cook, R.W., McCowan, C., Fletcher, J.L., Taylor, R.M., Wilton, A.N. :
Mapping cerebellar abiotrophy in Australian Kelpies. Anim Genet 42:675-678, 2011. Pubmed reference: 22035013. DOI: 10.1111/j.1365-2052.2011.02199.x.
2008 Shearman, JR., Lau, VM., Wilton, AN. :
Elimination of SETX, SYNE1 and ATCAY as the cause of cerebellar abiotrophy in Australian Kelpies. Anim Genet 39:573, 2008. Pubmed reference: 18557972. DOI: 10.1111/j.1365-2052.2008.01753.x.
1989 Thomas, JB., Robertson, D. :
Hereditary cerebellar abiotrophy in Australian kelpie dogs. Aust Vet J 66:301-2, 1989. Pubmed reference: 2818374.

Edit History

  • Created by Imke Tammen2 on 26 Nov 2022
  • Changed by Imke Tammen2 on 26 Nov 2022
  • Changed by Imke Tammen2 on 07 May 2023
  • Changed by Imke Tammen2 on 23 Jun 2023