Noonan syndrome 11

Summary

Noonan syndrome 11 (MONDO:0032786) is a disease caused by MRAS (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: MRAS (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Noonan syndrome 11
Mondo ID	MONDO:0032786
OMIM	618499
DOID	DOID:0112169
NCIT	C177119
UMLS	C5193130
MedGen	1681177
GARD	0016357
Is cancer (heuristic)	no

Also known as: NS11

Data availability: 8 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Noonan syndrome › Noonan syndrome 11

Related subtypes (13): Noonan syndrome 1, Noonan syndrome 2, Noonan syndrome 3, Noonan syndrome 4, Noonan syndrome 5, Noonan syndrome 6, Noonan syndrome 7, Noonan syndrome 8, Noonan syndrome 9, Noonan syndrome 10, Noonan syndrome 14, noonan syndrome 12, Noonan syndrome 13

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

8 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 3 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
635781	NM_001085049.3(MRAS):c.68G>T (p.Gly23Val)	MRAS	Likely pathogenic	reviewed by expert panel
635782	NM_001085049.3(MRAS):c.203C>T (p.Thr68Ile)	MRAS	Likely pathogenic	reviewed by expert panel
635783	NM_001085049.3(MRAS):c.212A>G (p.Gln71Arg)	MRAS	Likely pathogenic	reviewed by expert panel
1353763	NM_001085049.3(MRAS):c.347+6_347+22del	MRAS	Uncertain significance	criteria provided, multiple submitters, no conflicts
1367684	NM_001085049.3(MRAS):c.13G>A (p.Ala5Thr)	MRAS	Uncertain significance	criteria provided, multiple submitters, no conflicts
2662976	NM_001085049.3(MRAS):c.196C>G (p.Leu66Val)	MRAS	Uncertain significance	criteria provided, multiple submitters, no conflicts
2992622	NM_001085049.3(MRAS):c.251C>T (p.Thr84Met)	MRAS	Uncertain significance	criteria provided, multiple submitters, no conflicts
3392563	NM_001085049.3(MRAS):c.136A>T (p.Ile46Phe)	MRAS	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
MRAS	Definitive	Autosomal dominant	Noonan syndrome 11	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MRAS	Orphanet:648	Noonan syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MRAS	HGNC:7227	ENSG00000158186	O14807	Ras-related protein M-Ras	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MRAS	Ras-related protein M-Ras	Signal transducer in the Ras-MAPK signaling pathway that regulates cell proliferation and survival.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MRAS	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lateral globus pallidus	1
medial globus pallidus	1
nucleus accumbens	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MRAS	263	ubiquitous	marker	lateral globus pallidus, medial globus pallidus, nucleus accumbens

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MRAS	2,391

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MRAS	O14807	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
SHOC2 M1731 mutant abolishes MRAS complex function	1	1427.5×	0.001	MRAS
Gain-of-function MRAS complexes activate RAF signaling	1	1427.5×	0.001	MRAS
RAF activation	1	335.9×	0.003	MRAS

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
Ras protein signal transduction	1	205.5×	0.009	MRAS
cellular response to leukemia inhibitory factor	1	159.0×	0.009	MRAS
actin cytoskeleton organization	1	79.1×	0.013	MRAS

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MRAS	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MRAS

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
MRAS	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.