MRAS

Chr 3AD

muscle RAS oncogene homolog

Also known as: M-RAs, NS11, R-RAS3, RRAS3

NCBI Gene: 22808ENSG00000158186UniProt: O14807

This gene encodes a member of the Ras family of small GTPases. These membrane-associated proteins function as signal transducers in multiple processes including cell growth and differentiation, and dysregulation of Ras signaling has been associated with many types of cancer. The encoded protein may play a role in the tumor necrosis factor-alpha and MAP kinase signaling pathways. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

Primary Disease Associations & Inheritance

Noonan syndrome 11MIM #618499
AD
290
ClinVar variants
25
Pathogenic / LP
0.92
pLI score· haploinsufficient
2
Active trials
Clinical Summary— MRAS
🧬
Gene-Disease Validity (ClinGen)
Noonan syndrome · ADModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
25 Pathogenic / Likely Pathogenic· 129 VUS of 290 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.37LOEUF
pLI 0.921
Z-score 2.64
OE 0.00 (0.00–0.37)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.33Z-score
OE missense 0.43 (0.34–0.53)
56 obs / 130.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.37)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.43 (0.34–0.53)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.89
0≤1.21.6
LoF obs/exp: 0 / 8.1Missense obs/exp: 56 / 130.9Syn Z: 0.59

ClinVar Variant Classifications

290 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic6
VUS129
Likely Benign121
Benign11
Conflicting4
19
Pathogenic
6
Likely Pathogenic
129
VUS
121
Likely Benign
11
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
5
1
0
6
VUS
6
102
21
0
129
Likely Benign
0
0
43
78
121
Benign
1
0
8
2
11
Conflicting
—4
Total71079280290

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MRAS · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

MRAS-related Noonan syndrome

definitive
ADGain Of FunctionAltered Gene Product Structure
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Noonan syndrome 11

MIM #618499

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — MRAS
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Primary Aldosteronism: An Endocrine Society Clinical Practice Guideline.
Adler GK et al.·J Clin Endocrinol Metab
2025Guideline
Cardiovascular disease in chronic kidney disease.
Marx-Schütt K et al.·Eur Heart J
2025Review
Diverse alterations associated with resistance to KRAS(G12C) inhibition.
Zhao Y et al.·Nature
2021
Finerenone in patients with heart failure with mildly reduced or preserved ejection fraction: Rationale and design of the FINEARTS-HF trial.
Vaduganathan M et al.·Eur J Heart Fail
2024Clinical trial
Novel non-steroidal mineralocorticoid receptor antagonists in cardiorenal disease.
Kintscher U et al.·Br J Pharmacol
2022Review
Heart Failure Drug Treatment-Inertia, Titration, and Discontinuation: A Multinational Observational Study (EVOLUTION HF).
Savarese G et al.·JACC Heart Fail
2023
Mineralocorticoid receptor antagonists and kidney diseases: pathophysiological basis.
Barrera-Chimal J et al.·Kidney Int
2019Review
Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and Their Combination in Patients with Chronic Kidney Disease: A Randomized Crossover Clinical Trial.
Provenzano M et al.·J Am Soc Nephrol
2022Cohort
Cardiovascular-renal protective effect and molecular mechanism of finerenone in type 2 diabetic mellitus.
Lv R et al.·Front Endocrinol (Lausanne)
2023Review
Mineralocorticoid receptor antagonists in diabetic kidney disease - mechanistic and therapeutic effects.
Barrera-Chimal J et al.·Nat Rev Nephrol
2022Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Evolving Mineralocorticoid Receptor Antagonism: a Narrative Review on Differences between Steroidal MRAs, Non-Steroidal MRAs and Aldosterone Synthase Inhibitors in Cardiorenal Disease.
Erzeel J et al.·Curr Heart Fail Rep
2026Review
Novel characterization of MRAS mutation-associated Noonan syndrome: Mild adult-onset hypertrophic cardiomyopathy combined with infective endocarditis: A case report.
Mou X et al.·Medicine (Baltimore)
2026🔓 Open AccessCase report
Finerenone: Extending MRAs Prognostic Benefit to the Recently Hospitalized and More Symptomatic Patient with HFpEF.
Tinti MD et al.·J Clin Med
2025🔓 Open Access
Evidence-based validation of cardiovascular benefits from novel MRAs in type 2 diabetes: A meta-analysis of over 30,000 patients.
Fan Q et al.·J Diabetes Complications
2026Cohort
Sensorless Direct Field-Oriented Control of Induction Motor Drive Using Artificial Neural Network-Based Reactive Power MRAS.
Kubatko M et al.·Sensors (Basel)
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
RASopathy

Study of the Thyroid Function and Echostructural Morphology in Patients Affected With Rasopathies (ECORAS2023)

RECRUITING
NCT06489067University of Bari Aldo MoroStarted 2024-01-15
Diabetic NephropathiesKidney DiseasesRenal Insufficiency, Chronic

Transformative Research in Diabetic Nephropathy 2.0

RECRUITING
NCT07444203University of PennsylvaniaStarted 2025-11-12
Sodium-glucose cotransporter 2 inhibitors (SGLT2i)Renin-angiotensin-aldosterone system blockadeGlucagon-like peptide-1 receptor agonists (GLP 1 RA)

External Resources

Links to major genomics databases and tools