OMIA:002254-9615 : Glucocorticoid resistance in Canis lupus familiaris (dog)

Categories: Homeostasis / metabolism phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 615962 (trait) , 138040 (gene)

Links to relevant human diseases in MONDO:

Mendelian trait/disorder: yes

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2019

Cross-species summary: also called Chrousos syndrome

Molecular basis: Costa et al. (2015) sequenced the coding regions of the NR3C1 gene in 97 dogs from different breeds to identify variants that may explain individual variation in response to corticosteroid therapy. "A total of six single nucleotide polymorphisms (SNPs) were identified including four synonymous SNPs and two nonsynonymous SNPs (c.811A>T and c.2111T>C)." Both missense variants were predicted to be to be ‘probably damaging’. Yamanaka et al. (2019) "discovered a mutant GR [glucocorticoid receptor, now named NR3C1] in a dog suspected to have iatrogenic Cushing syndrome. The mutant GR had [69] extra nucleotides between exons 6 and 7, resulting in a truncated form of GR that was 98 amino acids shorter than the wild-type dog GR. The truncated GR exhibited very low reactivity to prednisolone, irrespective of concentration." The authors showed that the "truncated form showed the very less sensitivity to glucocorticoid in vitro, unfortunately, we could not elucidate its clinical significance."

Clinical features: Yamanaka et al. (2019) reported a single affected '6-year-old spayed, mixed-breed dog ... . The dog was tentatively diagnosed with pemphigus foliaceus at a private hospital 9 months previously. The dog had been treated with prednisolone ... for approximately 3 months. After the dog was started on the medication, polyuria, polydipsia, and abdominal distension were observed. The pemphigus foliaceus was neither ameliorated nor aggravated. After prednisolone withdrawal, calcinosis cutis was observed on the dorsal skin. Two months later ... the adverse reaction due to glucocorticoid therapy had already disappeared, except for extremely severe calcinosis cutis over the entire dorsal skin ... ." The authors diagnosed glucocorticoid resistance in this dog with iatrogenic Cushing syndrome.

Breed: Mixed Breed (Dog) (VBO_0200902).
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
NR3C1 nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor) Canis lupus familiaris 2 NC_051806.1 (38692463..38573084) NR3C1 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
1171 Mixed Breed (Dog) Glucocorticoid resistance NR3C1 splicing Naturally occurring variant 2 c.2032_2033insN[69] An insertion of "69 nucleotides between nucleotides 2032 and 2033 compared with dog wild type GR [i.e. NR3C1]. These extra 69 nucleotides matched a part of the nucleotide sequence of dog genomic DNA corresponding to intron 6 . . . . Insertion of these extra 69 nucleotides between exons 6 and 7 introduced a frameshift and a premature termination codon (TGA) 15 bp downstream of the insertion. This insertion is thus predicted to result in a truncated protein of 682 amino acids, compared to the normal (wild type) 780 amino acids" (Yamanaka et al., 2019) The cause of this splice variant could not be determined in genomic DNA. 2019 31651346

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:002254-9615: 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.

2019 Yamanaka, K., Okuda, M., Mizuno, T. :
Functional characterization of canine wild type glucocorticoid receptor and an insertional mutation in a dog. BMC Vet Res 15:363, 2019. Pubmed reference: 31651346. DOI: 10.1186/s12917-019-2129-9.
2016 Costa, A., Sellon, R.K., Court, M., Burke, N.S., Mealey, K.L. :
Polymorphisms in the canine glucocorticoid receptor alpha gene (NR3C1α). J Vet Pharmacol Ther 39:16-21, 2016. Pubmed reference: 25989385. DOI: 10.1111/jvp.12241.

Edit History

  • Created by Frank Nicholas on 18 Mar 2020
  • Changed by Frank Nicholas on 18 Mar 2020
  • Changed by Frank Nicholas on 15 May 2020
  • Changed by Imke Tammen2 on 25 Jan 2023
  • Changed by Imke Tammen2 on 19 May 2023