Proud to share the labs first preprint! Led by Yeon, whose hard work, dedication and drive have been instrumental in bringing the project to this point. Thank you to everyone involved, especially long-term collaborators Yvonne and Yuguang. #Wnt #WntUK #RASopathy #ERK
www.biorxiv.org/content/10.6...
www.biorxiv.org/content/10.6...
GPC6 Lipid Shielding Sustains WNT5A Gradients to Prevent a RASopathy-like Developmental State
Morphogen gradients require ligands to disperse across tissues from their sites of production, yet receptor engagement can consume ligand before it reaches distant cells. This poses a particular chall...
www.biorxiv.org
September 22, 2026 at 2:42 PM
Proud to share the labs first preprint! Led by Yeon, whose hard work, dedication and drive have been instrumental in bringing the project to this point. Thank you to everyone involved, especially long-term collaborators Yvonne and Yuguang. #Wnt #WntUK #RASopathy #ERK
www.biorxiv.org/content/10.6...
www.biorxiv.org/content/10.6...
Loss of GPC6 drives pathological ERK activation in developing bone — without any mutation in the RAS–MAPK pathway. pERK signal (green) is markedly elevated in GPC6 KO compared to wildtype. A RASopathy-like state from a WNT gradient defect 🤯 #RASopathy #ERK #WNT5A"
September 22, 2026 at 2:42 PM
Loss of GPC6 drives pathological ERK activation in developing bone — without any mutation in the RAS–MAPK pathway. pERK signal (green) is markedly elevated in GPC6 KO compared to wildtype. A RASopathy-like state from a WNT gradient defect 🤯 #RASopathy #ERK #WNT5A"
Hello! Newly diagnosed with a #RASopathy syndrome? (#Noonan, #Costello, #Cardiofaciocutaneous #CFCsyndrome, #Neurofibromatosis 1, #Legius, and others) ⬇️ Here's a helpful whiteboard video to explain more youtu.be/-ZbyIWLVTds?...
What are the RASopathies (updated)
YouTube video by RASopathies Network Videos
youtu.be
November 25, 2024 at 8:21 PM
Hello! Newly diagnosed with a #RASopathy syndrome? (#Noonan, #Costello, #Cardiofaciocutaneous #CFCsyndrome, #Neurofibromatosis 1, #Legius, and others) ⬇️ Here's a helpful whiteboard video to explain more youtu.be/-ZbyIWLVTds?...
More on RASopathies and hearts 🫀
16% of pediatric hypertrophic cardiomyopathy cases were due to RASopathy in this cohort. #cardiosky #pedsky 🧪
rdcu.be/eL36v
16% of pediatric hypertrophic cardiomyopathy cases were due to RASopathy in this cohort. #cardiosky #pedsky 🧪
rdcu.be/eL36v
October 21, 2025 at 9:01 PM
More on RASopathies and hearts 🫀
16% of pediatric hypertrophic cardiomyopathy cases were due to RASopathy in this cohort. #cardiosky #pedsky 🧪
rdcu.be/eL36v
16% of pediatric hypertrophic cardiomyopathy cases were due to RASopathy in this cohort. #cardiosky #pedsky 🧪
rdcu.be/eL36v
Describes use of #MEKi (MEK inhibitor) for arrhythmia in absence of cardiomyopathy in child with #Costellosyndrome #RASopathy More evidence for therapeutic benefit of MEKi
#pedsky #cardiosky 🫀🧪
pubmed.ncbi.nlm.nih.gov/39757526/
#pedsky #cardiosky 🫀🧪
pubmed.ncbi.nlm.nih.gov/39757526/
January 11, 2025 at 2:44 PM
Describes use of #MEKi (MEK inhibitor) for arrhythmia in absence of cardiomyopathy in child with #Costellosyndrome #RASopathy More evidence for therapeutic benefit of MEKi
#pedsky #cardiosky 🫀🧪
pubmed.ncbi.nlm.nih.gov/39757526/
#pedsky #cardiosky 🫀🧪
pubmed.ncbi.nlm.nih.gov/39757526/
🧪 #medsky Interesting report of clinical 'misdiagnosis', indeed several syndromes look like #noonansyndrome
🧬Non‐RASopathy Genetic Syndromes Identified as the Molecular Cause of Disease in Patients Previously Diagnosed With Noonan Syndrome - Kim - AJMGPart A onlinelibrary.wiley.com/doi/10.1002/...
🧬Non‐RASopathy Genetic Syndromes Identified as the Molecular Cause of Disease in Patients Previously Diagnosed With Noonan Syndrome - Kim - AJMGPart A onlinelibrary.wiley.com/doi/10.1002/...
Non‐RASopathy Genetic Syndromes Identified as the Molecular Cause of Disease in Patients Previously Diagnosed With Noonan Syndrome
Noonan Syndrome (NS) is a clinically and genetically heterogeneous condition characterized by typical facial dysmorphisms, short stature, congenital heart defects, and developmental delays. While var....
onlinelibrary.wiley.com
October 26, 2025 at 5:17 PM
🧪 #medsky Interesting report of clinical 'misdiagnosis', indeed several syndromes look like #noonansyndrome
🧬Non‐RASopathy Genetic Syndromes Identified as the Molecular Cause of Disease in Patients Previously Diagnosed With Noonan Syndrome - Kim - AJMGPart A onlinelibrary.wiley.com/doi/10.1002/...
🧬Non‐RASopathy Genetic Syndromes Identified as the Molecular Cause of Disease in Patients Previously Diagnosed With Noonan Syndrome - Kim - AJMGPart A onlinelibrary.wiley.com/doi/10.1002/...
Severe intellectual disability is associated with BRAF-associated RASopathy, but the neurobiological mechanisms were unclear.
Yong-Seok Lee & team now show a RASopathy-associated BRAF mutation increases reactive astrocytes and disrupts spatial learning in mouse models: buff.ly/jPOFfPt
Yong-Seok Lee & team now show a RASopathy-associated BRAF mutation increases reactive astrocytes and disrupts spatial learning in mouse models: buff.ly/jPOFfPt
April 24, 2025 at 1:20 PM
Severe intellectual disability is associated with BRAF-associated RASopathy, but the neurobiological mechanisms were unclear.
Yong-Seok Lee & team now show a RASopathy-associated BRAF mutation increases reactive astrocytes and disrupts spatial learning in mouse models: buff.ly/jPOFfPt
Yong-Seok Lee & team now show a RASopathy-associated BRAF mutation increases reactive astrocytes and disrupts spatial learning in mouse models: buff.ly/jPOFfPt
#NIH funding supports collaboration with our advocacy organization to accelerate therapies for our patient community. Natural history study and defining the risk and types of cancer in the #RASopathy syndromes
#oncosky #pedsky #medsky
Together we are accelerating research and advancing therapies.
#oncosky #pedsky #medsky
Together we are accelerating research and advancing therapies.
January 26, 2025 at 5:16 PM
#NIH funding supports collaboration with our advocacy organization to accelerate therapies for our patient community. Natural history study and defining the risk and types of cancer in the #RASopathy syndromes
#oncosky #pedsky #medsky
Together we are accelerating research and advancing therapies.
#oncosky #pedsky #medsky
Together we are accelerating research and advancing therapies.
Source-proximal WNT5A hyperactivation has a completely unexpected consequence — it engages a previously unrecognised WNT5A–RAC–PAK–MEK–ERK cascade, driving pathological ERK activation in developing bone without any mutation in the conventional RAS–MAPK pathway. #RASopathy #ERK #WNT5A
September 22, 2026 at 2:42 PM
Source-proximal WNT5A hyperactivation has a completely unexpected consequence — it engages a previously unrecognised WNT5A–RAC–PAK–MEK–ERK cascade, driving pathological ERK activation in developing bone without any mutation in the conventional RAS–MAPK pathway. #RASopathy #ERK #WNT5A
Rocking our zebra stripes for #RareDisease
highlighting the unmet needs of #RASopathy patients at the #RAS initiative conference
highlighting the unmet needs of #RASopathy patients at the #RAS initiative conference
February 28, 2025 at 7:09 PM
Rocking our zebra stripes for #RareDisease
highlighting the unmet needs of #RASopathy patients at the #RAS initiative conference
highlighting the unmet needs of #RASopathy patients at the #RAS initiative conference
Loss of GPC6 generates a molecular hybrid of 2 developmental diseases: WNT5A deficiency characteristic of Robinow syndrome and pathological ERK activation characteristic of the RASopathies. Omodysplasia caused by loss of GPC6 overlaps both disease classes. #omodysplasia #RASopathy #Robinow
September 22, 2026 at 2:42 PM
Loss of GPC6 generates a molecular hybrid of 2 developmental diseases: WNT5A deficiency characteristic of Robinow syndrome and pathological ERK activation characteristic of the RASopathies. Omodysplasia caused by loss of GPC6 overlaps both disease classes. #omodysplasia #RASopathy #Robinow
🧪JCI - Aberrant ERK signaling in astrocytes impairs learning and memory in RASopathy-associated BRAF mutant mouse models www.jci.org/articles/vie...
JCI -
Aberrant ERK signaling in astrocytes impairs learning and memory in RASopathy-associated BRAF mutant mouse models
www.jci.org
February 23, 2025 at 9:54 PM
🧪JCI - Aberrant ERK signaling in astrocytes impairs learning and memory in RASopathy-associated BRAF mutant mouse models www.jci.org/articles/vie...
Frequency of Thoracic Aortic Dilation in Noonan Syndrome #RASopathy
N=37
0.6~32 y/o
14 PTPN11 variant carriers (out of 16 known variants)
Aortic diameter Z > 2
10 Aortic annulus
8 Aortic Root
2 Ascending aorta
#AortaEd
#AmJCardiol 2014
www.sciencedirect.com/science/arti...
N=37
0.6~32 y/o
14 PTPN11 variant carriers (out of 16 known variants)
Aortic diameter Z > 2
10 Aortic annulus
8 Aortic Root
2 Ascending aorta
#AortaEd
#AmJCardiol 2014
www.sciencedirect.com/science/arti...
June 29, 2026 at 12:08 PM
Frequency of Thoracic Aortic Dilation in Noonan Syndrome #RASopathy
N=37
0.6~32 y/o
14 PTPN11 variant carriers (out of 16 known variants)
Aortic diameter Z > 2
10 Aortic annulus
8 Aortic Root
2 Ascending aorta
#AortaEd
#AmJCardiol 2014
www.sciencedirect.com/science/arti...
N=37
0.6~32 y/o
14 PTPN11 variant carriers (out of 16 known variants)
Aortic diameter Z > 2
10 Aortic annulus
8 Aortic Root
2 Ascending aorta
#AortaEd
#AmJCardiol 2014
www.sciencedirect.com/science/arti...
Interested in RASopathy and RAS-driven cancers? This month we feature SHOC-MRAS holophosphatase complexes.....CPX-25716, CPX-25719, CPX-25720. Visit the Complex Portal (www.ebi.ac.uk/complexporta...) to learn more!
March 4, 2025 at 9:45 AM
Interested in RASopathy and RAS-driven cancers? This month we feature SHOC-MRAS holophosphatase complexes.....CPX-25716, CPX-25719, CPX-25720. Visit the Complex Portal (www.ebi.ac.uk/complexporta...) to learn more!
GPC6 Lipid Shielding Sustains WNT5A Gradients to Prevent a RASopathy-like Developmental State https://www.biorxiv.org/content/10.64898/2026.09.20.752969v1
September 22, 2026 at 11:31 AM
GPC6 Lipid Shielding Sustains WNT5A Gradients to Prevent a RASopathy-like Developmental State https://www.biorxiv.org/content/10.64898/2026.09.20.752969v1
GPC6 Lipid Shielding Sustains WNT5A Gradients to Prevent a RASopathy-like Developmental State https://www.biorxiv.org/content/10.64898/2026.09.20.752969v1
September 22, 2026 at 11:31 AM
GPC6 Lipid Shielding Sustains WNT5A Gradients to Prevent a RASopathy-like Developmental State https://www.biorxiv.org/content/10.64898/2026.09.20.752969v1
Noonan Syndrome with Multiple Lentigines (NMSL/LEOPARD Syndrome): a rare genetic RASopathy causing skin spots, heart defects, short stature & hearing loss.
Learn more: https://dub.sh/NMSL
You may be rare, but you're not alone!
#rareDisease #rareDiseaseAwareness
Learn more: https://dub.sh/NMSL
You may be rare, but you're not alone!
#rareDisease #rareDiseaseAwareness
May 18, 2026 at 2:00 PM
Noonan Syndrome with Multiple Lentigines (NMSL/LEOPARD Syndrome): a rare genetic RASopathy causing skin spots, heart defects, short stature & hearing loss.
Learn more: https://dub.sh/NMSL
You may be rare, but you're not alone!
#rareDisease #rareDiseaseAwareness
Learn more: https://dub.sh/NMSL
You may be rare, but you're not alone!
#rareDisease #rareDiseaseAwareness
Childhood-onset RASopathy-associated hypertrophic cardiomyopathy, diastolic dysfunction, and arrhythmias url: academic.oup.com/eurheartj/ar...
Childhood-onset RASopathy-associated hypertrophic cardiomyopathy, diastolic dysfunction, and arrhythmias
The RASopathies account for ∼18%1 of childhood hypertrophic cardiomyopathy (HCM) cases and up to 42%2 of infantile (<1 year of age) presentations, makin
academic.oup.com
December 24, 2025 at 4:29 PM
Childhood-onset RASopathy-associated hypertrophic cardiomyopathy, diastolic dysfunction, and arrhythmias url: academic.oup.com/eurheartj/ar...
🧪🧬
BLOG: LZTR variants are linked to autosomal dominant & recessive forms of #Noonansyndrome #RASopathy
LZTR’s role in regulating RAS signaling via degradation points to disease mechanism & therapeutic possibilities.
#Medsky #oncosky #pedsky #RAS
frederick.cancer.gov/news/exploit...
BLOG: LZTR variants are linked to autosomal dominant & recessive forms of #Noonansyndrome #RASopathy
LZTR’s role in regulating RAS signaling via degradation points to disease mechanism & therapeutic possibilities.
#Medsky #oncosky #pedsky #RAS
frederick.cancer.gov/news/exploit...
Exploiting cellular degradation machinery as a potential treatment strategy for RAS-driven cancers | Frederick National Laboratory
Image
frederick.cancer.gov
December 18, 2025 at 2:36 PM
🧪🧬
BLOG: LZTR variants are linked to autosomal dominant & recessive forms of #Noonansyndrome #RASopathy
LZTR’s role in regulating RAS signaling via degradation points to disease mechanism & therapeutic possibilities.
#Medsky #oncosky #pedsky #RAS
frederick.cancer.gov/news/exploit...
BLOG: LZTR variants are linked to autosomal dominant & recessive forms of #Noonansyndrome #RASopathy
LZTR’s role in regulating RAS signaling via degradation points to disease mechanism & therapeutic possibilities.
#Medsky #oncosky #pedsky #RAS
frederick.cancer.gov/news/exploit...
Wow this could potentially be useful for the #RASopathy #NF1 community who experience not only hypertrophic neuropathy but Schwann cell dysfunction and cancer. Markers for resident and infiltrating cells. 🧪
Study reveals perineurial hyperplasia, lipid-associated nerve macrophages in 33 PNP patients vs. 4 controls using 365,708 nuclei for deeper PNP insights. PMID:40849297, Nat Commun 2025, @NatureComms https://doi.org/10.1038/s41467-025-62964-8 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪
Multi-omic identification of perineurial hyperplasia and lipid-associated nerve macrophages in human polyneuropathies | Nature Communications
Diseases affecting multiple peripheral nerves, termed polyneuropathies (PNPs), are common, mechanistically heterogeneous, and their causes are challenging to identify. Here, we integrated single-nucleus transcriptomics of peripheral nerves from 33 human PNP patients and four controls (365,708 nuclei) with subcellular spatial transcriptomics. We identified nerve cell type markers and uncovered unexpected heterogeneity of perineurial cells. PNPs shared a loss of myelinating and an increase in repair Schwann cells and endoneurial lipid-phagocytizing macrophages. Transcriptional changes affected multiple cells outside of the endoneurium across PNPs, suggesting PNPs as ‘pan-nerve diseases’. Spatially, PNPs—particularly those mediated by autoimmunity—exhibited focal perineurial hyperplasia and increased expression of CXCL14, identified as perineurial cell marker. Multi-omic characterization of human nerve biopsies thus identified novel mechanisms in PNPs with diagnostic potential. Polyneurop
doi.org
September 28, 2025 at 12:38 PM
Wow this could potentially be useful for the #RASopathy #NF1 community who experience not only hypertrophic neuropathy but Schwann cell dysfunction and cancer. Markers for resident and infiltrating cells. 🧪
Ras-MAPK pathway in patients with lupus nephritis lupus.bmj.com/content/12/1...
This pathway and mutations keep turning up when sequencing is done in various conditions 🧬🧪
This pathway and mutations keep turning up when sequencing is done in various conditions 🧬🧪
Ras-MAPK pathway in patients with lupus nephritis
Background Pathogenic mutations in genes encoding components of the Ras/mitogen-activated protein kinase (Ras-MAPK) pathway cause RASopathy. Here, we describe five unrelated patients with SLE carrying...
lupus.bmj.com
March 23, 2025 at 9:20 PM
Ras-MAPK pathway in patients with lupus nephritis lupus.bmj.com/content/12/1...
This pathway and mutations keep turning up when sequencing is done in various conditions 🧬🧪
This pathway and mutations keep turning up when sequencing is done in various conditions 🧬🧪
Thanks for highlighting NSML
#Noonansyndrome with multiple lentigines- a rare RASopathy caused by mutations in PTPN11 (SHP2). Distinct variants from the bulk of typical NS PTPN11 mutations. 🧪🧬
Interesting genotype -phenotype expression in human disease.
#pediatrics
#Noonansyndrome with multiple lentigines- a rare RASopathy caused by mutations in PTPN11 (SHP2). Distinct variants from the bulk of typical NS PTPN11 mutations. 🧪🧬
Interesting genotype -phenotype expression in human disease.
#pediatrics
Noonan Syndrome with Multiple Lentigines (NMSL/LEOPARD Syndrome): a rare genetic RASopathy causing skin spots, heart defects, short stature & hearing loss.
Learn more: https://dub.sh/NMSL
You may be rare, but you're not alone!
#rareDisease #rareDiseaseAwareness
Learn more: https://dub.sh/NMSL
You may be rare, but you're not alone!
#rareDisease #rareDiseaseAwareness
May 18, 2026 at 3:14 PM
Thanks for highlighting NSML
#Noonansyndrome with multiple lentigines- a rare RASopathy caused by mutations in PTPN11 (SHP2). Distinct variants from the bulk of typical NS PTPN11 mutations. 🧪🧬
Interesting genotype -phenotype expression in human disease.
#pediatrics
#Noonansyndrome with multiple lentigines- a rare RASopathy caused by mutations in PTPN11 (SHP2). Distinct variants from the bulk of typical NS PTPN11 mutations. 🧪🧬
Interesting genotype -phenotype expression in human disease.
#pediatrics
Genetic activation of ERK2 recapitulates core neurodevelopmental features of Rasopathy syndromes in mice
Genetic activation of ERK2 recapitulates core neurodevelopmental features of Rasopathy syndromes in mice
News update via NF Bot
pubmed.ncbi.nlm.nih.gov
April 30, 2026 at 10:39 AM
Genetic activation of ERK2 recapitulates core neurodevelopmental features of Rasopathy syndromes in mice
🧪The HRAS Variant c.175G>A (p.Ala59Thr) Causes a Predominantly Ectodermal Phenotype Lacking Classic Costello Syndrome Features - Rautiainen - American Journal of Medical Genetics Part A - Wiley Online Library onlinelibrary.wiley.com/doi/10.1002/...
The HRAS Variant c.175G>A (p.Ala59Thr) Causes a Predominantly Ectodermal Phenotype Lacking Classic Costello Syndrome Features
Costello syndrome (CS) is a rare dominant HRAS RASopathy characterized by curly hair, cardiac abnormalities, craniofacial anomalies, and developmental delay. HRAS codon 58, 59, and 60 variants are as....
onlinelibrary.wiley.com
October 26, 2025 at 4:58 PM
🧪The HRAS Variant c.175G>A (p.Ala59Thr) Causes a Predominantly Ectodermal Phenotype Lacking Classic Costello Syndrome Features - Rautiainen - American Journal of Medical Genetics Part A - Wiley Online Library onlinelibrary.wiley.com/doi/10.1002/...
🧪Nice structural work from @Castel @Simanshu groups to understand #RAS GTPase family degradation & consequences of human variants in LZTR-related #Noonansyndrome #RASopathy #raredisease
💠Structural basis for LZTR1 recognition of RAS GTPases for degradation | Science www.science.org/doi/10.1126/...
💠Structural basis for LZTR1 recognition of RAS GTPases for degradation | Science www.science.org/doi/10.1126/...
Structural basis for LZTR1 recognition of RAS GTPases for degradation
The RAS family of small guanosine triphosphatases (GTPases) are tightly regulated signaling molecules that are further modulated by ubiquitination and proteolysis. Leucine Zipper-like Transcription Re...
www.science.org
September 12, 2025 at 8:38 PM
🧪Nice structural work from @Castel @Simanshu groups to understand #RAS GTPase family degradation & consequences of human variants in LZTR-related #Noonansyndrome #RASopathy #raredisease
💠Structural basis for LZTR1 recognition of RAS GTPases for degradation | Science www.science.org/doi/10.1126/...
💠Structural basis for LZTR1 recognition of RAS GTPases for degradation | Science www.science.org/doi/10.1126/...