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In severe cases, neurogenic bladder can lead to vesicoureteral reflux, hydroureter, and chronic kidney disease. These complications overlap with manifestations of congenital anomalies of the kidney and urinary tract (CAKUT). To identify novel monogenic causes of neurogenic bladder, we applied exome sequencing (ES) to our cohort of families with CAKUT. By ES, we have identified a homozygous missense variant (p.Gln184Arg) in <jats:italic>CHRM5<\/jats:italic> (<jats:italic>cholinergic receptor<\/jats:italic>, <jats:italic>muscarinic<\/jats:italic>, <jats:italic>5<\/jats:italic>) in a patient with neurogenic bladder and secondary complications of CAKUT. <jats:italic>CHRM5<\/jats:italic> codes for a seven transmembrane\u2010spanning G\u2010protein\u2010coupled muscarinic acetylcholine receptor. <jats:italic>CHRM5<\/jats:italic> is shown to be expressed in murine and human bladder walls and is reported to cause bladder overactivity in <jats:italic>Chrm5<\/jats:italic> knockout mice. We investigated <jats:italic>CHRM5<\/jats:italic> as a potential novel candidate gene for neurogenic bladder with secondary complications of CAKUT. <jats:italic>CHRM5<\/jats:italic> is similar to the cholinergic bladder neuron receptor <jats:italic>CHRNA3<\/jats:italic>, which Mann et al. published as the first monogenic cause of neurogenic bladder. However, functional in vitro studies did not reveal evidence to strengthen the status as a candidate gene. Discovering additional families with <jats:italic>CHRM5<\/jats:italic> variants could help to further assess the genes' candidate status.<\/jats:p>","DOI":"10.1002\/ajmg.a.63241","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T14:56:45Z","timestamp":1684767405000},"page":"2083-2091","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Recessive <scp><i>CHRM5<\/i><\/scp> variant as a potential cause of neurogenic bladder"],"prefix":"10.1002","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4872-0093","authenticated-orcid":false,"given":"Sophia","family":"Schneider","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Boston Children's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Schierbaum","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Boston Children's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wessel A. 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