Trial reportHuman genetics2015
Mutations of the SLIT2-ROBO2 pathway genes SLIT2 and SRGAP1 confer risk for congenital anomalies of the kidney and urinary tract.
Trial report in Human genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
40 citing papers in PubMed, 67 citations in OpenAlex.
- SLIT2 as a key regulator and therapeutic target in liver injury.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Genomic spectrum of congenital heart disease combined with kidney and urinary tract anomalies uncovered by exome sequencing and array-CGH.Frontiers in cell and developmental biology · 2026Article
- Genetic and Clinical Factors Influencing Congenital Anomalies of the Kidney and Urinary Tract in Children: Insights from Prenatal and Postnatal Assessments.Biomedicines · 2024Article
- Role of biophysics and mechanobiology in podocyte physiology.Nature reviews. Nephrology · 2024Review
- Whole-genome resequencing provides insights into the diversity and adaptation to desert environment in Xinjiang Mongolian cattle.BMC genomics · 2024Article
- The genetics and pathogenesis of CAKUT.Nature reviews. Nephrology · 2023Review
- Clinically diverse and perinatally lethal syndromes with urorectal septum malformation sequence.American journal of medical genetics. Part A · 2023Review
- Genome-wide evaluation of the effect of short tandem repeat variation on local DNA methylation.Genome research · 2023Article
- Role of the SLIT-ROBO signaling pathway in renal pathophysiology and various renal diseases.Frontiers in physiology · 2023Review
- Disease mechanisms of monogenic congenital anomalies of the kidney and urinary tract American Journal of Medical Genetics Part C.American journal of medical genetics. Part C, Seminars in medical genetics · 2022Review
- Novel dominant and recessive variants in human ROBO1 cause distinct neurodevelopmental defects through different mechanisms.Human molecular genetics · 2022Article
- Biallelic pathogenic variants in roundabout guidance receptor 1 associate with syndromic congenital anomalies of the kidney and urinary tract.Kidney international · 2022Article
- Reverse phenotyping facilitates disease allele calling in exome sequencing of patients with CAKUT.Genetics in medicine : official journal of the American College of Medical Genetics · 2022Article
- Genetic testing in the diagnosis of chronic kidney disease: recommendations for clinical practice.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2022Article
- Deciphering the mutation spectrum in south Indian children with congenital anomalies of the kidney and urinary tract.BMC nephrology · 2022Article
- The glomerular filtration barrier: a structural target for novel kidney therapies.Nature reviews. Drug discovery · 2021Review
- Slit2-Robo Signaling Promotes Glomerular Vascularization and Nephron Development.Journal of the American Society of Nephrology : JASN · 2021Article
- Single cell regulatory landscape of the mouse kidney highlights cellular differentiation programs and disease targets.Nature communications · 2021Article
- Molecular causes of congenital anomalies of the kidney and urinary tract (CAKUT).Molecular and cellular pediatrics · 2021Review
- Targeted broad-based genetic testing by next-generation sequencing informs diagnosis and facilitates management in patients with kidney diseases.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2021Article
Corrections and comments
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Authors and funding
25 authors at 15 institutions in 7 countries.
Funding
Abstract
Congenital anomalies of the kidney and urinary tract (CAKUT) account for 40-50% of chronic kidney disease that manifests in the first two decades of life. Thus far, 31 monogenic causes of isolated CAKUT have been described, explaining ~12% of cases. To identify additional CAKUT-causing genes, we performed whole-exome sequencing followed by a genetic burden analysis in 26 genetically unsolved families with CAKUT. We identified two heterozygous mutations in SRGAP1 in 2 unrelated families. SRGAP1 is a small GTPase-activating protein in the SLIT2-ROBO2 signaling pathway, which is essential for development of the metanephric kidney. We then examined the pathway-derived candidate gene SLIT2 for mutations in cohort of 749 individuals with CAKUT and we identified 3 unrelated individuals with heterozygous mutations. The clinical phenotypes of individuals with mutations in SLIT2 or SRGAP1 were cystic dysplastic kidneys, unilateral renal agenesis, and duplicated collecting system. We show that SRGAP1 is expressed in early mouse nephrogenic mesenchyme and that it is coexpressed with ROBO2 in SIX2-positive nephron progenitor cells of the cap mesenchyme in developing rat kidney. We demonstrate that the newly identified mutations in SRGAP1 lead to an augmented inhibition of RAC1 in cultured human embryonic kidney cells and that the SLIT2 mutations compromise the ability of the SLIT2 ligand to inhibit cell migration. Thus, we report on two novel candidate genes for causing monogenic isolated CAKUT in humans.
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