Variant Synonymizer: Platform to identify mutations defined in different ways is available now!
Over 2,000 gene–disease validation summaries are now available—no login required!
The association between CHRM5 and congenital anomalies of the kidney and urinary tract is currently supported by limited genetic evidence. A homozygous missense variant c.551A>G (p.Gln184Arg) was identified by exome sequencing in a single proband (PMID:37213061), without any additional data on segregation in affected relatives. Although CHRM5 is expressed in both human and murine bladder tissues and shares similarities with CHRNA3—a gene implicated in bladder dysfunction—this genetic finding is based solely on one case report and remains preliminary.
In functional assessments, CHRM5 has been shown to be active in the bladder wall, and animal models of Chrm5 knockout exhibit bladder overactivity. However, in vitro experiments conducted to evaluate the impact of the identified variant did not produce conclusive functional evidence to reinforce its pathogenic role. Thus, while the biochemical and expression data offer a biological rationale, the overall evidence does not yet warrant a definitive causal interpretation. Further studies, including the identification of additional probands and comprehensive segregation analyses, are needed to clarify the clinical utility of CHRM5 in congenital anomalies of the kidney and urinary tract.
Gene–Disease AssociationLimitedThe association is based on a single proband with a homozygous missense variant and lacks supportive segregation data (PMID:37213061). Genetic EvidenceLimitedThe detection of the homozygous variant c.551A>G (p.Gln184Arg) in one affected individual provides preliminary support, but further familial and case-controlled data are required (PMID:37213061). Functional EvidenceLimitedAlthough CHRM5 is expressed in neurologically relevant tissues and animal models suggest a biological role, the in vitro functional assessments did not yield conclusive supportive evidence (PMID:37213061). |