OMIA:002757-9615 : Ataxia, cerebellar, RALGAPA1-related in Canis lupus familiaris (dog)

Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 608884 (gene) , 618797 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2023

Molecular basis: Christen et al. (2023) identified a likely causal variant in Belgian shepherd dogs: "Combined linkage and homozygosity mapping delineated a 5.5 Mb critical interval. The comparison of whole-genome sequence data of one affected dog to 929 control genomes revealed a private homozygous ~4.8 kb deletion in the critical interval, Chr8:14,468,376_14,473,136del4761. The deletion comprises exon 35 of the RALGAPA1 gene, XM_038544497.1:c.6080-2893_6944+1003del. It is predicted to introduce a premature stop codon into the transcript, truncating ~23% of the wild-type open reading frame of the encoded Ral GTPase-activating protein catalytic subunit α 1, XP_038400425.1:(p.Val2027Glnfs*7)."

Clinical features: Christen et al. (2023) "investigated a [Belgian shepherd] litter in which two puppies developed cerebellar ataxia. The clinical signs stabilized at around six weeks of age, but remained visible into adulthood. ... Genotyping additional ataxic Belgian shepherd dogs revealed three additional homozygous mutant dogs from a single litter, which had been euthanized at five weeks of age due to their severe clinical phenotype."

Pathology: Christen et al. (2023): "Histopathology revealed cytoplasmic accumulation of granular material within cerebellar Purkinje cells [in affected Belgian shepherds]."

Prevalence: Christen et al. (2023): "Genotyping a cohort of almost 900 Belgian shepherd dogs [for the ~4.8 kb deletion] showed ... a carrier frequency of 5% in the population."

Breed: Belgian Shepherd Dog (Dog) (VBO_0200144).
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
RALGAPA1 Ral GTPase activating protein, alpha subunit 1 (catalytic) Canis lupus familiaris 8 NC_051812.1 (14570610..14327816) RALGAPA1 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 Year Published PubMed ID(s) Acknowledgements
1613 Belgian Shepherd Dog (Dog) Ataxia, cerebellar, RALGAPA1-related RALGAPA1 deletion, gross (>20) Naturally occurring variant UU_Cfam_GSD_1.0 8 g.14468376_14473136del c.6080-2893_6944+1003del p.(V2027Qfs*7) XM_038544497.1; XP_038400425.1; published as g.14,468,376_14,473,136del4761 2023 37628572

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:002757-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset].


2023 Christen, M., Zdora, I., Leschnik, M., Jagannathan, V., Puff, C., Hünerfauth, E., Volk, H.A., Baumgärtner, W., Koch, T.C., Schäfer, W., Kleiter, M., Leeb, T. :
RALGAPA1 deletion in Belgian shepherd dogs with cerebellar ataxia. Genes (Basel) 14:1520, 2023. Pubmed reference: 37628572. DOI: 10.3390/genes14081520.

Edit History

  • Created by Imke Tammen2 on 27 Aug 2023
  • Changed by Tosso Leeb on 30 Aug 2023