Table 2.
Genes Associated with Hydronephrosis and Hydroureter due to Lower Urinary Tract Defects
| Gene | Chr | Exp | Type of protein | Signaling | Human disease (OMIM) |
Urinary tract defects in animal models |
Ref |
|---|---|---|---|---|---|---|---|
| L1cam | Xq28 | ue | Adhesion molecule | Ectopic UB, duplex ureters, megaureter, hydronephrosis | 297 | ||
| Agtr2 | Xq22-q23 | um | G-protein coupled angiotensin II receptor | RAS | X-linked mental retardation-88 (OMIM 300852) | Ectopic UB, duplex ureters, hydroureter, hydronephrosis | 82 |
| Ptprf | 1p34 | Receptor Tyrosine Phosphatase | Hydroureter, hydronephrosis, and ureterocele | 178 | |||
| Nfia | 1p31.3-p31.2 | ue, um | Nuclear Factor 1 transcription factor | Chromosome 1p32-p31 deletion syndrome (OMIM 613735): VUR | duplex ureters, VUR, UPJ defects, hydroureter, hydronephrosis, megaureter | 284 | |
| Agt | 1q42.2 | k | Secreted angiotensinogen | RAS | Peristalsis defect, hydronephrosis | 298 | |
| Id2 | 2p25 | ue, um | bHLH DNA binding factor | ID | UPJ defect, hydronephrosis | 299 | |
| Ppp3r1 | 2p15 | um | Protein phosphatase | Peristalsis defect, hydronephrosis | 193 | ||
| Hoxd13 | 2q31.1 | Transcription factor | Wnt | Hydroureter and hydronephrosis | 300 | ||
| Robo2 | 3p12.3 | mm | Slit receptor, Ig superfamily | Robo/Slit | Vesicoureteral reflux 2 (OMIM 610878) | Ectopic UB, multiple ureters, hydroureter, hydronephrosis | 10, 119 |
| Ctnnb1 | 3p21 | β-catenin | Wnt | Hydroureter and hydronephrosis | 301 | ||
| Rarb2 | 3p24.2 | ue | Retinoic acid receptor | Retinoic acid signaling | Ectopia of distal ureter ends, hydroureter, megaureter, hydronephrosis | 43 | |
| Gata2 | 3q21.3 | ue, um | Zinc Finger transcription factor | Wnt | Megaureter, hydroureter, hydronephrosis, hypoplastic kidneys | 302 | |
| Agtr1a/b | 3q24 | um | Angiotensin 2 receptor | RAS | Peristalsis defect, hydroureter, hydronephrosis, pelvis agenesis | 199 | |
| Dlg1 | 3q29 | ue, um | Membrane-associated guanylate kinase scaffolding protein | p38 | Congenital hydronephrosis, smooth muscle orientation defect, peristalsis defect | 190 | |
| Slit2 | 4p15.2 | ue | Secreted protein -Robo ligand | Robo/Slit | Ectopic UB, multiple ureters, hydroureter, hydronephrosis | 119 | |
| Wfs1 | 4p16.1 | transmembrane protein | Wolfram syndrome (OMIM 222300): hydronephrosis, dilated ureters, distended bladder without VUR | 303 | |||
| Scarb2 | 4q21.1 | glycoprotein | Kidney and ureter duplication, UPJ obstruction, hydroureter, and hydronephrosis | 304 | |||
| Spry1 | 4q28.1 | wd, mm | Receptor Tyrosine Kinase antagonist | GDNF/RET | Ectopic UB, multiple ureters, hydroureter, hydronephrosis | 120 | |
| Bmp5 | 6p12.1 | um | Secreted molecule | TGF-beta | Hydroureter, hydronephrosis | 305 | |
| Foxc1 | 6p25 | um | Forkhead transcription factor | Foxc | Axenfeld-Rieger syndrome type 3 (OMIM 602482) | Ectopic UB, duplex ureters, hydroureter, hydronephrosis | 121, 174 |
| Unknown gene | 6p | Multicystic renal dysplasia, bilateral; MCRD (OMIM 143400): UPJ obstruction, hydronephrosis | 306 | ||||
| Tbx18 | 6q14-q15 | um | T-box transcription factor | Bmp, wnt, hedgehog | Lack of smooth muscles in the ureter, short ureter, hydronephrosis | 29 | |
| Gli3 | 7p13 | zinc finger | hedgehog | Pallister-Hall syndrome (OMIM 146510) | peristalsis defect, hydroureter, and hydronephrosis | 76, 288 | |
| Smo | 7q32.3 | G protein-coupled receptor | Hedgehog | Ureter dyskinesia, functional obstruction, hydroureter and hydronephrosis | 76 | ||
| Shh | 7q36 | ue | Secreted Sonic Hedgehog | Hedgehog | Smooth muscle defects, short hydroureter, hydronephrosis | 32 | |
| Ret | 10q11.21 | Receptor | RTK | Hydronephrosis, megaureters, renal dysplasia | Abnormal distal ureter maturation | 43, 141 | |
| Upk2 | 11q23 | uro | Transmembrane glycocalyx component | VUR, hydroureter, hydronephrosis | 28 | ||
| Aqp2 | 12q12-q13 | Water channel protein | Hydronephrosis | 187 | |||
| Bmp4 | 14q22-q23 | um | Secreted molecule-TGF-beta family | TGF-beta | Renal hypoplasia | Ectopic UB, duplex ureters, ectopic UVJ, hydroureter | 77 |
| Aldh1a2 | 15q21.3 | Retinaldehyde dehydrogenase | Urogenital sinus abnormalities hydronephrosis and megaureter | 44 | |||
| Stra6 | 15q24.1 | A receptor for retinol/retinol binding protein complexes | Retinoic acid signaling | Hydronephrosis | 307 | ||
| Foxc2 | 16q24.1 | um | Forkhead transcription factor | Foxc | Ectopic UB, duplex ureters, hydroureter, ureter agenesis | 121 | |
| Rara | 17q21.2 | Retinoic acid receptor | Retinoic acid signaling | Ectopia of distal ureter ends, hydroureter, megaureter | 43, 44 | ||
| Smad4 | 18q21.1 | ue, um | TGF-β | Hydroureter, hydronephrosis | 79 | ||
| Tshz3 | 19q12 | Transcription factor | Hedgehog | Smooth muscle differentiation, congenital hydronephrosis | 31 | ||
| Adamts1 | 21q21.2 | um | Secreted protease | enlarged renal calices; ureteropelvic junction obstruction | 308 | ||
| Upk3a | 22q13.31 | uro | Trans-membrane glycocalyx component | VUR, hydroureter, hydronephrosis | 27 | ||
| Unknown gene | Hardihar syndrome (OMIM 612726): hydroureter, hydronephrosis | 309 | |||||
| Unknown gene | Fryns syndrome (OMIM 229850): Cryptorchidism, megaureter, hydroureter, cystic ureter, ectopic or blind urethral opening | 310 |
Abbreviations: Chr: chromosomal location; Exp: expression in the urinary tract; Signaling: signaling pathway; Ref: References; k: kidney; ue: ureteric epithelium; um: ureteric mesenchyme; uro: urothelium; TGF-β: transforming growth factor-β; UPJ: ureteropelvic junction; VUR: vesicoureteric reflux; RAS: Renin-angiotensin system.