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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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MRAS
muscle RAS oncogene homolog
Chromosome 3 · 3q22.3
NCBI Gene: 22808Ensembl: ENSG00000158186.14HGNC: HGNC:7227UniProt: O14807
55PubMed Papers
21Diseases
0Drugs
5Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
Ras protein signal transductionprotein phosphatase type 1 complexprotein bindingcytoplasmNoonan syndrome 11Noonan syndromecoronary artery diseasehypertension
✦AI Summary

MRAS (muscle RAS oncogene homolog) is a signal transducer in the Ras-MAPK signaling pathway that regulates cell proliferation and survival 1. It functions as a core component of the SHOC2-MRAS-PP1c (SMP) holophosphatase complex, which regulates MAPK pathway activation 2. Formation of the SMP complex occurs exclusively when MRAS is in its GTP-bound state 3. The SMP complex specifically dephosphorylates inhibitory phosphorylation sites on RAF family kinases—Ser-259 of RAF1, Ser-365 of BRAF, and Ser-214 of ARAF—thereby stimulating their kinase activities and promoting downstream signaling 4. MRAS possesses low intrinsic GTPase activity and may require additional factors for proper activation 5. Disease relevance is established through association with Noonan syndrome 11, a RAS/MAPK pathway disorder. While the provided abstracts focus primarily on mineralocorticoid receptor antagonists and do not contain specific disease mechanisms or clinical applications directly relevant to MRAS dysfunction, the gene's central role in MAPK pathway regulation positions it as therapeutically significant in conditions characterized by pathway dysregulation.

Sources cited
1
MRAS is a signal transducer in the Ras-MAPK pathway regulating cell proliferation and survival; core component of SMP complex that dephosphorylates RAF kinases
PMID: 16630891
2
MRAS forms the SMP holophosphatase complex when GTP-bound and dephosphorylates inhibitory RAF kinase phosphorylation sites
PMID: 35768504
3
SMP complex formation requires MRAS in GTP-bound state; complex dephosphorylates RAF kinases
PMID: 35830882
4
MRAS-containing SMP complex regulates MAPK pathway by dephosphorylating RAF kinase inhibitory sites
PMID: 36175670
5
MRAS has low intrinsic GTPase activity and may require additional factors for activation; SMP formation requires GTP-bound MRAS
PMID: 39809765
6
MRAS:SHOC2:PP1C trimeric complex activation occurs in response to KRAS G12C inhibitors through Scribble and Hippo-dependent pathways
PMID: 38072173
Disease Associationsⓘ21
Noonan syndrome 11Open Targets
0.70Moderate
Noonan syndromeOpen Targets
0.66Moderate
coronary artery diseaseOpen Targets
0.51Moderate
hypertensionOpen Targets
0.51Moderate
type 2 diabetes mellitusOpen Targets
0.47Moderate
myocardial infarctionOpen Targets
0.46Moderate
coronary atherosclerosisOpen Targets
0.42Moderate
rasopathyOpen Targets
0.41Moderate
goutOpen Targets
0.40Moderate
Increased blood pressureOpen Targets
0.40Weak
essential hypertensionOpen Targets
0.38Weak
diabetes mellitusOpen Targets
0.38Weak
cardiovascular diseaseOpen Targets
0.38Weak
esophageal carcinomaOpen Targets
0.37Weak
Myocardial IschemiaOpen Targets
0.34Weak
angina pectorisOpen Targets
0.34Weak
coronary artery bypassOpen Targets
0.34Weak
heart diseaseOpen Targets
0.33Weak
gram-negative bacterial infectionsOpen Targets
0.32Weak
obesityOpen Targets
0.31Weak
Noonan syndrome 11UniProt
Pathogenic Variants5
NM_001085049.3(MRAS):c.212A>G (p.Gln71Arg)Likely pathogenic
Noonan syndrome 11|RASopathy
★★★☆2024→ Residue 71
NM_001085049.3(MRAS):c.67G>C (p.Gly23Arg)Likely pathogenic
RASopathy
★★★☆2024→ Residue 23
NM_001085049.3(MRAS):c.68G>T (p.Gly23Val)Likely pathogenic
Noonan syndrome 11|RASopathy|not provided
★★★☆2024→ Residue 23
NM_001085049.3(MRAS):c.203C>T (p.Thr68Ile)Likely pathogenic
Noonan syndrome 11|not provided|RASopathy
★★★☆2024→ Residue 68
NM_001085049.3(MRAS):c.359C>T (p.Pro120Leu)Likely pathogenic
Male infertility with azoospermia or oligozoospermia due to single gene mutation
★☆☆☆2023→ Residue 120
View on ClinVar ↗
Related Genes
PIK3R3Protein interaction100%PIK3R1Protein interaction100%SHOC2Protein interaction100%NF1Protein interaction100%TIAM1Protein interaction100%RALGDSProtein interaction99%
Tissue Expression6 tissues
Heart
100%
Brain
31%
Ovary
30%
Lung
11%
Bone Marrow
5%
Liver
3%
Gene Interaction Network
Click a node to explore
MRASPIK3R3PIK3R1SHOC2NF1TIAM1RALGDS
PROTEIN STRUCTURE
Preparing viewer…
PDB7TXH · 1.95 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.44Moderately Constrained
pLIⓘ
0.99Intolerant
Observed/Expected LoF0.19 [0.10–0.44]
RankingsWhere MRAS stands among ~20K protein-coding genes
  • #8,223of 20,598
    Most Researched55
  • #3,574of 5,498
    Most Pathogenic Variants5
  • #2,448of 17,882
    Most Constrained (LOEUF)0.44 · top quartile
Genes detectedMRAS
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Primary Aldosteronism: An Endocrine Society Clinical Practice Guideline.
PMID: 40658480
J Clin Endocrinol Metab · 2025
1.00
2
Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine.
PMID: 33099609
Eur Heart J · 2021
0.90
3
New strategies for the treatment of hyperkalemia.
PMID: 39489630
Eur J Intern Med · 2025
0.80
4
Mineralocorticoid receptor antagonists in heart failure: an individual patient level meta-analysis.
PMID: 39232490
Lancet · 2024
0.70
5
Novel non-steroidal mineralocorticoid receptor antagonists in cardiorenal disease.
PMID: 34811750
Br J Pharmacol · 2022
0.60