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Abstract: SA-PO811

GEN1 Is a Likely Candidate Gene for Human Congenital Anomalies of the Kidney and Urinary Tract

Session Information

Category: Genetic Diseases of the Kidneys

  • 1202 Genetic Diseases of the Kidneys: Non-Cystic


  • Shen, Qian, Children's Hospital of Fudan University, Shanghai, China
  • Xu, Hong, Children's Hospital of Fudan University, Shanghai, China
  • Du, Xuanjin, Children's Hospital of Fudan University, Shanghai, China

Congenital anomalies of the kidneys and urinary tract (CAKUT) are among the most prevalent birth defects. Although many pathogenic genes of CAKUT have been discovered, they are far from enough to reveal the causes of all CAKUT patients. Previous studies suggest that Gen1 is a mouse CAKUT gene.


There are three main parts, population data collection, in vitro function verification, and point mutation mouse construction and phenotypic observation (Fig1).


DNA from 910 individuals with CAKUT were collected, among which 26 GEN1 variants were identified, and two GEN1 (missense) variants in a non-CAKUT group were found. In vitro,10 variants (eight in the CAKUT group and two in the non-CAKUT group) were selected to verify mutant protein stability and protein stability changed in six variants in the CAKUT group. Using an electrophoretic mobility shift assay
on eight variants (six in the CAKUT group and two in the non-CAKUT group) the enzymatic hydrolysis and DNA-binding abilities of mutant proteins were found to be impaired to varying degrees in CAKUT group, among which the most serious functional damage was observed in the Gen1 variant that produced a truncated protein. Moreover, a mini-gene splicing assay showed that the c.1071+3 A>G variant in CAKUT group significantly affected splicing function. Three point mutant mouse strains were constructed and CAKUT phenotypes were replicated


Our findings promoted that GEN1 is likely a human CAKUT candidate gene.


  • Government Support – Non-U.S.