ArticleHuman mutation2014
A Novel SHOC2 Variant in Rasopathy.
Article in Human mutation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 34 citations in OpenAlex.
- Effects of neighborhood level health and environment quality on academic and executive abilities in youth with Noonan syndrome spectrum disorder.Journal of the International Neuropsychological Society : JINS · 2026Article
- Severe Thrombocytopenia and Facial Asymmetry in a Mexican Patient with Noonan Syndrome-Like Disorder with Loose Anagen Hair: Clinical Observations and Diagnostic Considerations.Molecular syndromology · 2026Article
- Article
- The expression of congenital Shoc2 variants induces AKT-dependent crosstalk activation of the ERK1/2 pathway.Human molecular genetics · 2024Article
- RAS and SHOC2 Roles in RAF Activation and Therapeutic Considerations.Annual review of cancer biology · 2024Article
- Structural insights into the role of SHOC2-MRAS-PP1C complex in RAF activation.The FEBS journal · 2023Review
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- Structure of the SHOC2-MRAS-PP1C complex provides insights into RAF activation and Noonan syndrome.Nature structural & molecular biology · 2022Article
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- Article
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- Expanding the molecular spectrum of pathogenic SHOC2 variants underlying Mazzanti syndrome.Human molecular genetics · 2022Article
- Case report: AFrontiers in genetics · 2022Article
- The role of USP7 in the Shoc2-ERK1/2 signaling axis and Noonan-like syndrome with loose anagen hair.Journal of cell science · 2021Article
- Review
- A Leucine-Rich Repeat Protein Provides a SHOC2 the RAS Circuit: a Structure-Function Perspective.Molecular and cellular biology · 2021Review
- The leucine-rich repeat signaling scaffolds Shoc2 and Erbin: cellular mechanism and role in disease.The FEBS journal · 2021Review
- Single-domain antibodies for functional targeting of the signaling scaffold Shoc2.Molecular immunology · 2020Article
- VCP/p97 controls signals of the ERK1/2 pathway transmitted via the Shoc2 scaffolding complex: novel insights into IBMPFD pathology.Molecular biology of the cell · 2019Article
- M-Ras/Shoc2 signaling modulates E-cadherin turnover and cell-cell adhesion during collective cell migration.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Rasopathies are a group of genetic disorders caused by germline mutations in multiple genes of the Extracellular signal-Regulated Kinases 1 and 2 (ERK1/2) pathway. The only previously identified missense mutation in SHOC2, a scaffold protein of the ERK1/2 pathway, led to Noonan-like syndrome with loose anagen hair. Here, we report a novel mutation in SHOC2(c.519G>A; p.M173I) that leads to a Rasopathy with clinical features partially overlapping those occurring in Noonan and cardiofaciocutaneous syndromes. Studies to clarify the significance of this SHOC2 variant revealed that the mutant protein has impaired capacity to interact with protein phosphatase 1c (PP1c), leading to insufficient activation of RAF-1 kinase. This SHOC2 variant thus is unable to fully rescue ERK1/2 activity in cells depleted of endogenous SHOC2. We conclude that SHOC2 mutations can cause a spectrum of Rasopathy phenotypes in heterozygous individuals. Importantly, our work suggests that individuals with mild Rasopathy symptoms may be underdiagnosed.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.