Noonan syndrome 13

Summary

Noonan syndrome 13 (MONDO:0033669) is a disease caused by MAPK1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: MAPK1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Noonan syndrome 13
Mondo ID	MONDO:0033669
OMIM	619087
DOID	DOID:0112161
NCIT	C177121
UMLS	C5436773
MedGen	1761918
GARD	0016419
Is cancer (heuristic)	no

Also known as: NS13

Data availability: 14 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Noonan syndrome › Noonan syndrome 13

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 11, noonan syndrome 12

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

14 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 4 pathogenic, 2 likely pathogenic, 2 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
917742	NM_002745.5(MAPK1):c.221T>A (p.Ile74Asn)	MAPK1	Pathogenic	criteria provided, single submitter
917743	NM_002745.5(MAPK1):c.238C>T (p.His80Tyr)	MAPK1	Pathogenic	criteria provided, multiple submitters, no conflicts
917744	NM_002745.5(MAPK1):c.521C>T (p.Ala174Val)	MAPK1	Pathogenic	criteria provided, multiple submitters, no conflicts
917745	NM_002745.5(MAPK1):c.952G>A (p.Asp318Asn)	MAPK1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
917746	NM_002745.5(MAPK1):c.953A>G (p.Asp318Gly)	MAPK1	Pathogenic	criteria provided, multiple submitters, no conflicts
917748	NM_002745.5(MAPK1):c.964G>C (p.Glu322Gln)	MAPK1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1804005	NM_002745.5(MAPK1):c.946T>C (p.Tyr316His)	MAPK1	Likely pathogenic	criteria provided, single submitter
3587857	NM_002745.5(MAPK1):c.244A>G (p.Asn82Asp)	MAPK1	Likely pathogenic	criteria provided, single submitter
1299571	NM_002745.5(MAPK1):c.763A>G (p.Ile255Val)	MAPK1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1699351	NM_002745.5(MAPK1):c.155C>A (p.Ala52Asp)	MAPK1	Uncertain significance	criteria provided, single submitter
3359118	NM_002745.5(MAPK1):c.320T>C (p.Leu107Pro)	MAPK1	Uncertain significance	criteria provided, single submitter
4056597	NM_002745.5(MAPK1):c.966+3A>G	MAPK1	Uncertain significance	criteria provided, single submitter
4280603	NM_002745.5(MAPK1):c.128A>T (p.Tyr43Phe)	MAPK1	Uncertain significance	criteria provided, single submitter
4814088	NM_002745.5(MAPK1):c.43C>G (p.Arg15Gly)	MAPK1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
MAPK1	Strong	Autosomal dominant	Noonan syndrome 13	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MAPK1	Orphanet:261330	Distal 22q11.2 microdeletion 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
MAPK1	HGNC:6871	ENSG00000100030	P28482	Mitogen-activated protein kinase 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MAPK1	Mitogen-activated protein kinase 1	Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MAPK1	Kinase	yes	2.7.11.24	Prot_kinase_dom, MAP_kinase_CS, Ser/Thr_kinase_AS

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
Brodmann (1909) area 23	1
middle temporal gyrus	1
postcentral gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MAPK1	299	ubiquitous	marker	middle temporal gyrus, postcentral gyrus, Brodmann (1909) area 23

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAPK1	8,003

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MAPK1	P28482	160

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 172. 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
phospho-PLA2 pathway	1	5710.0×	0.007	MAPK1
Signaling by MAP2K mutants	1	2855.0×	0.007	MAPK1
Negative feedback regulation of MAPK pathway	1	1903.3×	0.007	MAPK1
Estrogen-stimulated signaling through PRKCZ	1	1631.4×	0.007	MAPK1
Suppression of apoptosis	1	1631.4×	0.007	MAPK1
Signaling by MAPK mutants	1	1631.4×	0.007	MAPK1
Signaling by LTK in cancer	1	1631.4×	0.007	MAPK1
Formation of apoptosome	1	1427.5×	0.007	MAPK1
Prolonged ERK activation events	1	1427.5×	0.007	MAPK1
RSK activation	1	1427.5×	0.007	MAPK1
Response of Mtb to phagocytosis	1	1427.5×	0.007	MAPK1
IFNG signaling activates MAPKs	1	1427.5×	0.007	MAPK1
Cytochrome c-mediated apoptotic response	1	1268.9×	0.007	MAPK1
MAPK1 (ERK2) activation	1	1142.0×	0.007	MAPK1
Activation of the AP-1 family of transcription factors	1	1142.0×	0.007	MAPK1
Signaling by FGFR3	1	1142.0×	0.007	MAPK1
Infection with Mycobacterium tuberculosis	1	1142.0×	0.007	MAPK1
Signaling by FGFR4	1	1038.2×	0.007	MAPK1
Signal attenuation	1	1038.2×	0.007	MAPK1
Regulation of the apoptosome activity	1	1038.2×	0.007	MAPK1
Frs2-mediated activation	1	951.7×	0.007	MAPK1
Apoptotic factor-mediated response	1	878.5×	0.007	MAPK1
ERKs are inactivated	1	878.5×	0.007	MAPK1
CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling	1	878.5×	0.007	MAPK1
Signaling by Insulin receptor	1	878.5×	0.007	MAPK1
Gastrin-CREB signalling pathway via PKC and MAPK	1	878.5×	0.007	MAPK1
Golgi Cisternae Pericentriolar Stack Reorganization	1	815.7×	0.007	MAPK1
Signaling by FGFR1	1	815.7×	0.007	MAPK1
RUNX2 regulates bone development	1	815.7×	0.007	MAPK1
Signaling by Activin	1	761.3×	0.008	MAPK1

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
cytosine metabolic process	1	8426.0×	0.002	MAPK1
cardiac neural crest cell development involved in heart development	1	5617.3×	0.002	MAPK1
interleukin-34-mediated signaling pathway	1	5617.3×	0.002	MAPK1
regulation of Golgi inheritance	1	4213.0×	0.002	MAPK1
obsolete regulation of cellular pH	1	3370.4×	0.002	MAPK1
ERBB signaling pathway	1	3370.4×	0.002	MAPK1
response to epidermal growth factor	1	3370.4×	0.002	MAPK1
caveolin-mediated endocytosis	1	3370.4×	0.002	MAPK1
positive regulation of macrophage proliferation	1	3370.4×	0.002	MAPK1
trachea formation	1	2407.4×	0.002	MAPK1
regulation of early endosome to late endosome transport	1	2106.5×	0.002	MAPK1
positive regulation of peptidyl-threonine phosphorylation	1	1872.4×	0.002	MAPK1
regulation of stress-activated MAPK cascade	1	1872.4×	0.002	MAPK1
ERBB2-ERBB3 signaling pathway	1	1685.2×	0.002	MAPK1
mammary gland epithelial cell proliferation	1	1532.0×	0.002	MAPK1
outer ear morphogenesis	1	1532.0×	0.002	MAPK1
Bergmann glial cell differentiation	1	1532.0×	0.002	MAPK1
regulation of ossification	1	1203.7×	0.002	MAPK1
positive regulation of neuroinflammatory response	1	1203.7×	0.002	MAPK1
positive regulation of cholesterol biosynthetic process	1	1123.5×	0.002	MAPK1
Schwann cell development	1	1053.2×	0.002	MAPK1
lung morphogenesis	1	1053.2×	0.002	MAPK1
positive regulation of macrophage chemotaxis	1	802.5×	0.003	MAPK1
face development	1	802.5×	0.003	MAPK1
labyrinthine layer blood vessel development	1	802.5×	0.003	MAPK1
stress-activated MAPK cascade	1	702.2×	0.003	MAPK1
regulation of cytoskeleton organization	1	648.1×	0.003	MAPK1
thyroid gland development	1	543.6×	0.003	MAPK1
lipopolysaccharide-mediated signaling pathway	1	526.6×	0.003	MAPK1
response to exogenous dsRNA	1	526.6×	0.003	MAPK1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
MAPK1	PHENYLBUTAZONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MAPK1	324	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PHENYLBUTAZONE	4	MAPK1
CANDESARTAN CILEXETIL	4	MAPK1
TELMISARTAN	4	MAPK1
PROGESTERONE	4	MAPK1
CLOTRIMAZOLE	4	MAPK1
LATANOPROST	4	MAPK1
OXAPROZIN	4	MAPK1
CARBAMAZEPINE	4	MAPK1
SALMETEROL XINAFOATE	4	MAPK1
BRETYLIUM TOSYLATE	4	MAPK1
CHLORMADINONE ACETATE	4	MAPK1
DROPERIDOL	4	MAPK1
PYRIDOSTIGMINE	4	MAPK1
IDARUBICIN	4	MAPK1
IODIPAMIDE	4	MAPK1
TETRABENAZINE	4	MAPK1
PRAMOXINE	4	MAPK1
ESCITALOPRAM OXALATE	4	MAPK1
NICARDIPINE HYDROCHLORIDE	4	MAPK1
MORICIZINE HYDROCHLORIDE	4	MAPK1
SULCONAZOLE NITRATE	4	MAPK1
DOBUTAMINE HYDROCHLORIDE	4	MAPK1
TRIPELENNAMINE HYDROCHLORIDE	4	MAPK1
PYRITHIONE ZINC	4	MAPK1
DICYCLOMINE HYDROCHLORIDE	4	MAPK1
AVOBENZONE	4	MAPK1
OXYMETHOLONE	4	MAPK1
PROMETHAZINE HYDROCHLORIDE	4	MAPK1
CHLOROTRIANISENE	4	MAPK1
CITALOPRAM HYDROBROMIDE	4	MAPK1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
MAPK1	1,369	Binding:1348, Functional:16, ADMET:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MAPK1	2.7.11.24	mitogen-activated protein kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
MAPK1	1,369

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

30 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.

Compound	Max phase	Cohort target (bioactivity)
PHENYLBUTAZONE	4	MAPK1
CANDESARTAN CILEXETIL	4	MAPK1
TELMISARTAN	4	MAPK1
PROGESTERONE	4	MAPK1
CLOTRIMAZOLE	4	MAPK1
LATANOPROST	4	MAPK1
OXAPROZIN	4	MAPK1
CARBAMAZEPINE	4	MAPK1
SALMETEROL XINAFOATE	4	MAPK1
BRETYLIUM TOSYLATE	4	MAPK1
CHLORMADINONE ACETATE	4	MAPK1
DROPERIDOL	4	MAPK1
PYRIDOSTIGMINE	4	MAPK1
IDARUBICIN	4	MAPK1
IODIPAMIDE	4	MAPK1
TETRABENAZINE	4	MAPK1
PRAMOXINE	4	MAPK1
ESCITALOPRAM OXALATE	4	MAPK1
NICARDIPINE HYDROCHLORIDE	4	MAPK1
MORICIZINE HYDROCHLORIDE	4	MAPK1
SULCONAZOLE NITRATE	4	MAPK1
DOBUTAMINE HYDROCHLORIDE	4	MAPK1
TRIPELENNAMINE HYDROCHLORIDE	4	MAPK1
PYRITHIONE ZINC	4	MAPK1
DICYCLOMINE HYDROCHLORIDE	4	MAPK1
AVOBENZONE	4	MAPK1
OXYMETHOLONE	4	MAPK1
PROMETHAZINE HYDROCHLORIDE	4	MAPK1
CHLOROTRIANISENE	4	MAPK1
CITALOPRAM HYDROBROMIDE	4	MAPK1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MAPK1
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.