Cadherin related family member 3 (CDHR3), also known as CDH28 or its abbreviation CDHR3, is a protein that in humans is encoded by the CDHR3gene.
[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]
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.
↑Montoro DT, Haber AL, Biton M, Vinarsky V, Lin B, Birket SE, et al. (August 2018). "A revised airway epithelial hierarchy includes CFTR-expressing ionocytes". Nature. 560 (7718): 319–324. doi:10.1038/s41586-018-0393-7. PMID30069044.
