Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-61161
Am J Hum Genet 2024 Dec 27; doi: 10.1016/j.ajhg.2024.12.006.
Show Gene links Show Anatomy links

CIROZ is dispensable in ancestral vertebrates but essential for left-right patterning in humans.

Szenker-Ravi E , Ott T , Yusof A , Chopra M , Khatoo M , Pak B , Xuan Goh W , Beckers A , Brady AF , Ewans LJ , Djaziri N , Almontashiri NAM , Alghamdi MA , Alharby E , Dasouki M , Romo L , Tan WH , Maddirevula S , Alkuraya FS , Giordano JL , Alkelai A , Wapner RJ , Stals K , Alfadhel M , Alswaid AF , Bogusch S , Schafer-Kosulya A , Vogel S , Vick P , Schweickert A , Wakeling M , Moreau de Bellaing A , Alshamsi AM , Sanlaville D , Mbarek H , Saad C , Ellard S , Eisenhaber F , Tripolszki K , Beetz C , Bauer P , Gossler A , Eisenhaber B , Blum M , Bouvagnet P , Bertoli-Avella A , Amiel J , Gordon CT , Reversade B .


???displayArticle.abstract???
Four genes-DAND5, PKD1L1, MMP21, and CIROP-form a genetic module that has specifically evolved in vertebrate species that harbor motile cilia in their left-right organizer (LRO). We find here that CIROZ (previously known as C1orf127) is also specifically expressed in the LRO of mice, frogs, and fish, where it encodes a protein with a signal peptide followed by 3 zona pellucida N domains, consistent with extracellular localization. We report 16 individuals from 10 families with bi-allelic CIROZ inactivation variants, which cause heterotaxy with congenital heart defects. While the knockout of Ciroz in mice also leads to situs anomalies, we unexpectedly find that its targeted inactivation in zebrafish and Xenopus does not lead to observable LR anomalies. Moreover, CIROZ is absent or obsolete in select animals with motile cilia at their LRO, including Carnivora, Atherinomorpha fish, or jawless vertebrates. In summary, this evo-devo study identifies CIROZ as an essential gene for breaking bilateral embryonic symmetry in humans and mice, whereas we witness its contemporary pseudogenization in discrete vertebrate species.

???displayArticle.pubmedLink??? 39753129
???displayArticle.link??? Am J Hum Genet