Incidental Mutation 'P0017:Il20ra'

• ID: 7718
• Institutional Source: Beutler Lab
• Gene Symbol: Il20ra
• Ensembl Gene: ENSMUSG00000020007
• Gene Name: interleukin 20 receptor, alpha
• MMRRC Submission: 038270-MU
• Accession Numbers:

  Ncbi RefSeq: NM_172786.2; MGI:3605069

• Essential gene?: Non essential (E-score: 0.000)
• Stock #: P0017 (G1)
• Status: Validated
• Chromosome: 10
• Chromosomal Location: 19712570-19760053 bp(+) (GRCm38)
• Type of Mutation: missense
• DNA Base Change (assembly): A to G at 19759406 bp (GRCm38)
• Zygosity: Heterozygous
• Amino Acid Change: Glutamic Acid to Glycine at position 465 (E465G)
• Ref Sequence: ENSEMBL: ENSMUSP00000020185
• Gene Model: predicted gene model for transcript(s): [ENSMUST00000020185] [ENSMUST00000217389]
• AlphaFold: Q6PHB0
• Predicted Effect: probably damaging; Transcript: ENSMUST00000020185; AA Change: E465G; PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
• SMART Domains: Protein: ENSMUSP00000020185; Gene: ENSMUSG00000020007; AA Change: E465G

Domain	Start	End	E-Value	Type
Pfam:Tissue_fac	16	126	1.8e-33	PFAM
Pfam:Interfer-bind	138	243	4.6e-23	PFAM
transmembrane domain	255	277	N/A	INTRINSIC

• Predicted Effect: probably benign; Transcript: ENSMUST00000217389
• Meta Mutation Damage Score: 0.0666
• Coding Region Coverage:
  • 1x: 82.5%
  • 3x: 74.9%
  • 10x: 52.3%
  • 20x: 31.8%
• Validation Efficiency: 59% (51/87)
• MGI Phenotype: Strain: 5302406; FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the type II cytokine receptor family. The encoded protein is a subunit of the receptor for interleukin 20, a cytokine that may be involved in epidermal function. The interleukin 20 receptor is a heterodimeric complex consisting of the encoded protein and interleukin 20 receptor beta. This gene and interleukin 20 receptor beta are highly expressed in skin, and are upregulated in psoriasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013] ; PHENOTYPE: Mice homozygous for a knock-out allele exhibit increased bone mineral density, impaired osteoclast differentiation, and resistance to ovariectomized-inducced bone loss. [provided by MGI curators]
• Allele List at MGI:

  All alleles(4) : Targeted(4)

• Posted On: 2012-10-29
• Science Writer: Anne Murray

Protein Function and Prediction

Il20ra is a alternative splicing production of the Il20r1 gene, which associates with Il20rb to form the Il20 receptor type I (IL-20-RI), a receptor that mediates the activities of IL-19 subfamily of cytokines  (1-3). Il20ra is a soluble protein that can directly associate with mesangial cells to facilitate the phosphorylation of AKT and C-Jun N-terminal kinase (JNK) (4).  It is proposed that IL-20ra stimulates the production of chemoattractants, renal fibrogenic factors and reactive oxygen species (ROS) by mesangial cells (4).  In a transgenic mouse line that expressed full-length mIl20ra with a His tag, Wei et al (2009) proposed that mIL-20R1a is involved in calcium deposits associated with the pathogenesis of renal stone formation (5).

Expression/Localization

The IL-20-RI receptor is expressed mainly in the skin, lung, various glands, and the reproductive organs (1-3).

Background

Il20ra^{tm1.1Misc/tm1.1Misc}; MGI:5302406

involves: C57BL/6

Mice homozygous for a knock-out allele exhibit increased bone mineral density, impaired osteoclast differentiation, and resistance to ovariectomized-induced bone loss (6).

References

  1. Blumberg, H., Conklin, D., Xu, W. F., Grossmann, A., Brender, T., Carollo, S., Eagan, M., Foster, D., Haldeman, B. A., Hammond, A., Haugen, H., Jelinek, L., Kelly, J. D., Madden, K., Maurer, M. F., Parrish-Novak, J., Prunkard, D., Sexson, S., Sprecher, C., Waggie, K., West, J., Whitmore, T. E., Yao, L., Kuechle, M. K., Dale, B. A., and Chandrasekher, Y. A. (2001) Interleukin 20: Discovery, Receptor Identification, and Role in Epidermal Function. Cell. 104, 9-19.

  2. Dumoutier, L., Leemans, C., Lejeune, D., Kotenko, S. V., and Renauld, J. C. (2001) Cutting Edge: STAT Activation by IL-19, IL-20 and Mda-7 through IL-20 Receptor Complexes of Two Types. J Immunol. 167, 3545-3549.

  3. Pletnev, S., Magracheva, E., Kozlov, S., Tobin, G., Kotenko, S. V., Wlodawer, A., and Zdanov, A. (2003) Characterization of the Recombinant Extracellular Domains of Human Interleukin-20 Receptors and their Complexes with Interleukin-19 and Interleukin-20. Biochemistry. 42, 12617-12624.

  4. Wei, C. C., and Chang, M. S. (2008) A Novel Transcript of Mouse Interleukin-20 Receptor Acts on Glomerular Mesangial Cells as an Aggravating Factor in Lupus Nephritis. Genes Immun. 9, 668-679.

  5. Wei, C. C., and Chang, M. S. (2009) Mouse Interleukin-20 Receptor 1a Targets Renal Epithelial Cells and is Associated with Renal Calcium Deposition. Genes Immun. 10, 237-247.

  6. Hsu, Y. H., Chen, W. Y., Chan, C. H., Wu, C. H., Sun, Z. J., and Chang, M. S. (2011) Anti-IL-20 Monoclonal Antibody Inhibits the Differentiation of Osteoclasts and Protects Against Osteoporotic Bone Loss. J Exp Med. 208, 1849-1861.