OMIA:002254-9615 : Glucocorticoid resistance in Canis lupus familiaris
Categories: Homeostasis / metabolism phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 615962 (trait) , 138040 (gene)
Links to MONDO diseases:
Mendelian trait/disorder: yes
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2019
Molecular basis: 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  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."
Breed: Mixed breed (dog).
|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|
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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||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1171||Mixed breed (dog)||Glucocorticoid resistance||NR3C1||splicing||Naturally occurring variant||2||c.2032_2033insN||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|
|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.|
- Changed by Frank Nicholas on 18 Mar 2020
- Created by Frank Nicholas on 18 Mar 2020
- Changed by Frank Nicholas on 15 May 2020
- Changed by Imke Tammen2 on 25 Jan 2023