Biology:Cadherin related family member 3
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Cadherin related family member 3 (CDHR3), also known as CDH28 or its abbreviation CDHR3, is a protein that in humans is encoded by the CDHR3 gene. [1] The protein is predominately expressed in respiratory epithelium[2] and the first notion of its clinical implications was from the discovery that genetic variation of CDHR3 is strongly associated to early severe asthma exacerbations in children.[3] Subsequent studies have suggested that CDHR3 is a receptor for a subtype of rhinovirus.[4][5]
Function and cellular location
The exact physiological role of CDHR3 is not known, but as the CDHR3 protein is expressed in epithelial tissues and has six extracellular cadherin domains plus a short transmembrane segment, it is believed to be related to the function of similar cadherins which function in cell adhesion and cell-to-cell signaling.[3] Two single-cell RNA expression studies furthermore found CDHR3 to be highly selectively expressed in ciliated epithelial cells, compared to other cell types in the respiratory epithelium, and thereby to be a marker for ciliated cells in respiratory airway tissue.[6][7]
Clinical significance
A nonsynonymous mutation in CDHR3 at rs6967330 (C529Y) was at first found to be associated with severe asthma exacerbations in early childhood, with genome-wide significance. Functional experiments further indicated that this gene polymorphism leads to increased surface expression of the CDHR3 protein.[3] A subsequent study found that CDHR3 is a probable receptor for rhinovirus type C, a common form of rhinovirus.[4]
Recent studies furthermore found that CDHR3 gene variation is not associated with childhood bronchiolitis from respiratory syncytial virus (RSV) infection,[5] which resemble early asthma exacerbations as a phenotype. However, childhood bronchiolitis not caused by RSV infection, of which rhinovirus is often implicated, was associated with the CDHR3 gene variation. This is line with the results from a study on chronic rhinosinusitis, which often is associated rhinovirus infection, where CDHR3 gene variation also was found to be a strong risk factor.[8] Therefore, CDHR3 seems to causally linked to increased propensity for rhinovirus C infection.
References
- ↑ "Entrez Gene: Cadherin related family member 3". https://www.ncbi.nlm.nih.gov/gene/222256.
- ↑ "Tissue expression of CDHR3 - Summary - The Human Protein Atlas". http://www.proteinatlas.org/ENSG00000128536-CDHR3/tissue.
- ↑ 3.0 3.1 3.2 "A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations". Nature Genetics 46 (1): 51–5. January 2014. doi:10.1038/ng.2830. PMID 24241537.
- ↑ 4.0 4.1 "Cadherin-related family member 3, a childhood asthma susceptibility gene product, mediates rhinovirus C binding and replication". Proceedings of the National Academy of Sciences of the United States of America 112 (17): 5485–90. April 2015. doi:10.1073/pnas.1421178112. PMID 25848009. Bibcode: 2015PNAS..112.5485B.
- ↑ 5.0 5.1 "CDHR3 gene variation and childhood bronchiolitis". The Journal of Allergy and Clinical Immunology 140 (5): 1469–1471.e7. November 2017. doi:10.1016/j.jaci.2017.06.044. PMID 28782631.
- ↑ "A revised airway epithelial hierarchy includes CFTR-expressing ionocytes". Nature 560 (7718): 319–324. August 2018. doi:10.1038/s41586-018-0393-7. PMID 30069044. Bibcode: 2018Natur.560..319M.
- ↑ "Allergic inflammatory memory in human respiratory epithelial progenitor cells". Nature 560 (7720): 649–654. August 2018. doi:10.1038/s41586-018-0449-8. PMID 30135581.
- ↑ "Association between the CDHR3 rs6967330 risk allele and chronic rhinosinusitis". The Journal of Allergy and Clinical Immunology 139 (6): 1990–1992.e2. June 2017. doi:10.1016/j.jaci.2016.10.027. PMID 27923563.
Further reading
- "A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations". Nature Genetics 46 (1): 51–5. January 2014. doi:10.1038/ng.2830. PMID 24241537.
- "Cadherin-related family member 3, a childhood asthma susceptibility gene product, mediates rhinovirus C binding and replication". Proceedings of the National Academy of Sciences of the United States of America 112 (17): 5485–90. April 2015. doi:10.1073/pnas.1421178112. PMID 25848009. Bibcode: 2015PNAS..112.5485B.
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