ArticleAmerican journal of human genetics2013
Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome.
Article in American journal of human genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers, 2 of them syntheses that pooled it.
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Who cites it
163 citing papers in PubMed, 2 syntheses or guidelines pooled it, 329 citations in OpenAlex.
- Update on the Clinical and Molecular Characterization of Noonan Syndrome and Other RASopathies: A Retrospective Study and Systematic Review.International journal of molecular sciences · 2025Pooled it
- ClinGen's RASopathy Expert Panel consensus methods for variant interpretation.Genetics in medicine : official journal of the American College of Medical Genetics · 2018Guideline
- Genetic Spectrum of Non-PTPN11 Variants in Noonan Syndrome and Related RASopathies: Findings From a Russian Cohort.Clinical genetics · 2026Article
- Clinical consensus guidelines for the management of Noonan syndrome in Japan.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2026Article
- Clinical and Molecular Characterization of a RASopathy Cohort From Türkiye and an AMMECR1-Related Noonan Syndrome-Mimicking Phenotype.Clinical genetics · 2026Article
- Clinical and Molecular Portraits of Pediatric RASopathies: A Study of 118 Genotype-Confirmed Cases.Clinical genetics · 2026Article
- Article
- Unveiling the Prevalence and Surgical Burden of Neurocristopathies: A Scoping Review and Statistical Analysis.Research square · 2026Article
- Impact of RASopathy subtype on the early disease course of RASopathy-associated hypertrophic cardiomyopathy: clinical outcomes and genetic insights.Pediatric research · 2026Article
- Clinical and Molecular characteristics of kidney and urinary tract congenital anomalies in a cohort of Egyptian patients using whole-exome sequencing.Molecular biology reports · 2026Article
- Molecular Diagnosis and Phenotypic Variability of Noonan Syndrome: Experience from a Romanian Multicenter Study.Diagnostics (Basel, Switzerland) · 2026Article
- Neonatal Noonan syndrome with acute kidney injury and systemic capillary leak syndrome caused by aFrontiers in pediatrics · 2026Article
- Noonan Syndrome, Cancer Risk, and Growth Hormone TreatmentJournal of clinical research in pediatric endocrinology · 2025Review
- Phenotypic Analysis of Embryos in a Noonan Syndrome Model Mouse With the Rit1 A57G Mutation.Molecular genetics & genomic medicine · 2025Article
- Mutant RIT1 cooperates with YAP to drive an EMT-like lung cancer state.Cell reports · 2025Article
- Structural basis for LZTR1 recognition of RAS GTPases for degradation.Science (New York, N.Y.) · 2025Article
- RIT1 Drives Oncogenic Transformation and Is an Actionable Target in Lung Adenocarcinoma.Cancer research · 2025Article
- Recurrent cellulitis associated with lymphoedema in Noonan syndrome: case reports with RIT1 variants and literature review.Human genome variation · 2025Article
- Article
- Oncogenic RIT1 mutations confer ferroptosis vulnerability in lung adenocarcinoma.Biology direct · 2025Article
103 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 17 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RAS GTPases mediate a wide variety of cellular functions, including cell proliferation, survival, and differentiation. Recent studies have revealed that germline mutations and mosaicism for classical RAS mutations, including those in HRAS, KRAS, and NRAS, cause a wide spectrum of genetic disorders. These include Noonan syndrome and related disorders (RAS/mitogen-activated protein kinase [RAS/MAPK] pathway syndromes, or RASopathies), nevus sebaceous, and Schimmelpenning syndrome. In the present study, we identified a total of nine missense, nonsynonymous mutations in RIT1, encoding a member of the RAS subfamily, in 17 of 180 individuals (9%) with Noonan syndrome or a related condition but with no detectable mutations in known Noonan-related genes. Clinical manifestations in the RIT1-mutation-positive individuals are consistent with those of Noonan syndrome, which is characterized by distinctive facial features, short stature, and congenital heart defects. Seventy percent of mutation-positive individuals presented with hypertrophic cardiomyopathy; this frequency is high relative to the overall 20% incidence in individuals with Noonan syndrome. Luciferase assays in NIH 3T3 cells showed that five RIT1 alterations identified in children with Noonan syndrome enhanced ELK1 transactivation. The introduction of mRNAs of mutant RIT1 into 1-cell-stage zebrafish embryos was found to result in a significant increase of embryos with craniofacial abnormalities, incomplete looping, a hypoplastic chamber in the heart, and an elongated yolk sac. These results demonstrate that gain-of-function mutations in RIT1 cause Noonan syndrome and show a similar biological effect to mutations in other RASopathy-related genes.
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