Noonan Syndrome and Noonan-Related Syndrome disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

MCID: NNN033 MIFTS: 23	Noonan Syndrome and Noonan-Related Syndrome Categories: Cardiovascular diseases, Fetal diseases, Rare diseases
Genes Variations Related diseases Pathways Expand all tables

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Aliases & Classifications for Noonan Syndrome and Noonan-Related Syndrome

MalaCards integrated aliases for Noonan Syndrome and Noonan-Related Syndrome:

Name: Noonan Syndrome and Noonan-Related Syndrome ⁵⁹ ⁶

Classifications:

MalaCards categories:
Global: Fetal diseases Rare diseases
Anatomical: Cardiovascular diseases

See all MalaCards categories (disease lists)

Orphanet: ⁵⁹

Rare cardiac malformations

Developmental anomalies during embryogenesis

External Ids:

Orphanet ⁵⁹ ORPHA98733

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Summaries for Noonan Syndrome and Noonan-Related Syndrome

MalaCards based summary : Noonan Syndrome and Noonan-Related Syndrome is related to villonodular synovitis and pulmonary valve stenosis. An important gene associated with Noonan Syndrome and Noonan-Related Syndrome is BRAF (B-Raf Proto-Oncogene, Serine/Threonine Kinase), and among its related pathways/superpathways are Developmental Biology and Cytokine Signaling in Immune system. Related phenotypes are Reduced mammosphere formation and craniofacial

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Related Diseases for Noonan Syndrome and Noonan-Related Syndrome

Diseases related to Noonan Syndrome and Noonan-Related Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 17)

#	Related Disease	Score	Top Affiliating Genes
1	villonodular synovitis	9.7	SOS1 PTPN11
2	pulmonary valve stenosis	9.7	SOS1 PTPN11
3	pulmonary valve disease	9.7	SOS1 PTPN11
4	costello syndrome	9.6	SOS1 PTPN11
5	lentigines	9.6	PTPN11 BRAF
6	leopard syndrome	9.5	PTPN11 BRAF
7	leukemia, chronic lymphocytic 2	9.5	PTPN11 BRAF
8	noonan syndrome 3	9.5	SOS1 PTPN11
9	hypertelorism	9.4	PTPN11 BRAF
10	cryptorchidism, unilateral or bilateral	9.4	SOS1 PTPN11
11	myeloma, multiple	9.4	PTPN11 BRAF
12	pulmonic stenosis	9.2	SOS1 PTPN11 BRAF
13	cardiofaciocutaneous syndrome 1	9.2	SOS1 PTPN11 BRAF
14	juvenile myelomonocytic leukemia	9.2	SOS1 PTPN11 BRAF
15	hypertrophic cardiomyopathy	9.1	SOS1 PTPN11 BRAF
16	noonan syndrome 1	9.1	SOS1 PTPN11 BRAF
17	lung squamous cell carcinoma	9.1	PTPN11 BRAF

Graphical network of the top 20 diseases related to Noonan Syndrome and Noonan-Related Syndrome:

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Symptoms & Phenotypes for Noonan Syndrome and Noonan-Related Syndrome

GenomeRNAi Phenotypes related to Noonan Syndrome and Noonan-Related Syndrome according to GeneCards Suite gene sharing:

²⁶

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Reduced mammosphere formation	GR00396-S	8.8	BRAF PTPN11 SOS1

MGI Mouse Phenotypes related to Noonan Syndrome and Noonan-Related Syndrome:

⁴⁶

#	Description	MGI Source Accession	Score	Top Affiliating Genes
1	craniofacial	MP:0005382	9.33	BRAF PTPN11 SOS1
2	digestive/alimentary	MP:0005381	9.13	BRAF PTPN11 SOS1
3	muscle	MP:0005369	8.8	BRAF PTPN11 SOS1

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Drugs & Therapeutics for Noonan Syndrome and Noonan-Related Syndrome

Search Clinical Trials , NIH Clinical Center for Noonan Syndrome and Noonan-Related Syndrome

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Genetic Tests for Noonan Syndrome and Noonan-Related Syndrome

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Anatomical Context for Noonan Syndrome and Noonan-Related Syndrome

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Publications for Noonan Syndrome and Noonan-Related Syndrome

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Genes for Noonan Syndrome and Noonan-Related Syndrome

Genes related to Noonan Syndrome and Noonan-Related Syndrome (3 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence
1	BRAF	B-Raf Proto-Oncogene, Serine/Threonine Kinase	Protein Coding	400	Pathogenic ⁶
2	PTPN11	Protein Tyrosine Phosphatase Non-Receptor Type 11	Protein Coding	400	Pathogenic ⁶
3	SOS1	SOS Ras/Rac Guanine Nucleotide Exchange Factor 1	Protein Coding	400	Pathogenic ⁶

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Variations for Noonan Syndrome and Noonan-Related Syndrome

ClinVar genetic disease variations for Noonan Syndrome and Noonan-Related Syndrome:

⁶ (show all 20)

#	Gene	Variation	Type	Significance	SNP ID	GRCh37 Pos	GRCh38 Pos
1	SOS1	NM_005633.3(SOS1): c.1656G> C (p.Arg552Ser)	single nucleotide variant	Pathogenic	rs267607079	2:39249913-39249913	2:39022772-39022772
2	BRAF	NM_004333.6(BRAF): c.735A> C (p.Leu245Phe)	single nucleotide variant	Pathogenic	rs397507466	7:140501337-140501337	7:140801537-140801537
3	BRAF	NM_004333.6(BRAF): c.735A> T (p.Leu245Phe)	single nucleotide variant	Pathogenic	rs397507466	7:140501337-140501337	7:140801537-140801537
4	PTPN11	NM_002834.4(PTPN11): c.166A> G (p.Ile56Val)	single nucleotide variant	Pathogenic	rs397507504	12:112888150-112888150	12:112450346-112450346
5	SOS1	NM_005633.3(SOS1): c.1656G> T (p.Arg552Ser)	single nucleotide variant	Pathogenic	rs267607079	2:39249913-39249913	2:39022772-39022772
6	BRAF	NM_004333.6(BRAF): c.741T> G (p.Phe247Leu)	single nucleotide variant	Pathogenic	rs397509343	7:140501331-140501331	7:140801531-140801531
7	BRAF	NM_004333.6(BRAF): c.739T> C (p.Phe247Leu)	single nucleotide variant	Pathogenic	rs397516903	7:140501333-140501333	7:140801533-140801533
8	BRAF	NM_004333.6(BRAF): c.739T> G (p.Phe247Val)	single nucleotide variant	Likely pathogenic	rs397516903	7:140501333-140501333	7:140801533-140801533
9	SOS1	NM_005633.3(SOS1): c.512T> C (p.Val171Ala)	single nucleotide variant	Likely pathogenic	rs397517174	2:39281963-39281963	2:39054822-39054822
10	SOS1	NM_005633.3(SOS1): c.1655G> T (p.Arg552Met)	single nucleotide variant	Likely pathogenic	rs397517154	2:39249914-39249914	2:39022773-39022773
11	SOS1	NM_005633.3(SOS1): c.1654A> T (p.Arg552Trp)	single nucleotide variant	Likely pathogenic	rs137852814	2:39249915-39249915	2:39022774-39022774
12	PTPN11	NM_002834.4(PTPN11): c.167T> C (p.Ile56Thr)	single nucleotide variant	Likely pathogenic	rs1052382672	12:112888151-112888151	12:112450347-112450347
13	BRAF	NM_004333.6(BRAF): c.740T> C (p.Phe247Ser)	single nucleotide variant	Likely pathogenic	rs397507467	7:140501332-140501332	7:140801532-140801532
14	SOS1	NM_005633.3(SOS1): c.1867T> A (p.Phe623Ile)	single nucleotide variant	Likely pathogenic		2:39241979-39241979	2:39014838-39014838
15	MAP2K2	NM_030662.3(MAP2K2): c.692G> A (p.Arg231His)	single nucleotide variant	Uncertain significance	rs730880511	19:4101030-4101030	19:4101032-4101032
16	MAP2K2	NM_030662.3(MAP2K2): c.692G> T (p.Arg231Leu)	single nucleotide variant	Uncertain significance	rs730880511	19:4101030-4101030	19:4101032-4101032
17	SOS1	NM_005633.3(SOS1): c.1867_1869delinsGAA (p.Phe623Glu)	indel	Uncertain significance		2:39241977-39241979	2:39014836-39014838
18	SOS1	NM_005633.3(SOS1): c.3600C> G (p.Asp1200Glu)	single nucleotide variant	Likely benign	rs141594736	2:39213367-39213367	2:38986226-38986226
19	RAF1	NM_002880.3(RAF1): c.94A> G (p.Ile32Val)	single nucleotide variant	Benign	rs372738063	3:12660127-12660127	3:12618628-12618628
20	SOS1	NM_005633.3(SOS1): c.1018C> T (p.Pro340Ser)	single nucleotide variant	Benign	rs190222208	2:39262409-39262409	2:39035268-39035268

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Expression for Noonan Syndrome and Noonan-Related Syndrome

Search GEO for disease gene expression data for Noonan Syndrome and Noonan-Related Syndrome.

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Pathways for Noonan Syndrome and Noonan-Related Syndrome

Pathways related to Noonan Syndrome and Noonan-Related Syndrome according to GeneCards Suite gene sharing:

(show top 50) (show all 59)

#	Super pathways	Score	Top Affiliating Genes
1	Developmental Biology ⁶⁶ Show member pathways Axon guidance ⁶⁶	13.11	SOS1 PTPN11 BRAF
2	Cytokine Signaling in Immune system ⁶⁶ Show member pathways Signaling by Interleukins ⁶⁶	13	SOS1 PTPN11 BRAF
3	Regulation of lipid metabolism Insulin signaling-generic cascades ²² Show member pathways acetyl-CoA biosynthesis from citrate ¹ Butyrate-induced histone acetylation ¹ Cell adhesion PLAU signaling ²² Class IB PI3K non-lipid kinase events ¹ Development CNTF receptor signaling ²² Development Growth hormone signaling via PI3K/AKT and MAPK cascades ²² ErbB2/ErbB3 signaling events ¹ Glucose Homeostasis ¹ Insulin signaling pathway ³⁷ IRS activation ⁶⁶ Signal attenuation ⁶⁶ Transcription Receptor-mediated HIF regulation ²² Translation Regulation of EIF2 activity ²² Translation Regulation of EIF4F activity ²² Translation Insulin regulation of translation ²²	12.58	SOS1 PTPN11 BRAF
4	Endometrial cancer ³⁷ Show member pathways Acute myeloid leukemia ³⁷ Binding of TCF/LEF-CTNNB1 to target gene promoters ⁶⁶ Chronic myeloid leukemia ³⁷ Colorectal cancer ³⁷ Pancreatic cancer ³⁷ Prostate cancer ³⁷ Signal transduction PTEN pathway ²² Thyroid cancer ³⁷	12.54	SOS1 PTPN11 BRAF
5	Common Cytokine Receptor Gamma-Chain Family Signaling Pathways ⁶⁵ Show member pathways Adipokines and Insulin Signaling Pathways ⁶⁵ Development Thrombopoietin-regulated cell processes ²² IL-15 Signaling Pathways ⁶⁵ IL-2 Signaling Pathways ⁶⁵ IL-21 Signaling Pathways ⁶⁵ IL-4 Signaling Pathways ⁶⁵ IL-7 Signaling Pathways ⁶⁵ IL-9 Pathway ⁶⁴ IL-9 Signaling Pathways ⁶⁵ Immune response IL-9 signaling pathway ²²	12.44	SOS1 PTPN11 BRAF
6	Ras signaling pathway ³⁷ Show member pathways Rap1 signaling pathway ³⁷	12.38	SOS1 PTPN11 BRAF
7	Development HGF signaling pathway ²² Show member pathways Apoptosis and survival Anti-apoptotic action of membrane-bound ESR1 ²² Apoptosis and survival NGF signaling pathway ²² Apoptosis and survival Role of CDK5 in neuronal death and survival ²² Development Neurotrophin family signaling ²² MET activates PTPN11 ⁶⁶ MET activates STAT3 ⁶⁶ Neurotrophin signaling pathway ³⁷ Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met) ¹ Signaling of Hepatocyte Growth Factor Receptor ¹	12.35	SOS1 PTPN11 BRAF
8	MET promotes cell motility ⁶⁶ Show member pathways Alpha 6 Beta 4 signaling pathway ¹ Laminin interactions ⁶⁶ MET activates PTK2 signaling ⁶⁶ MET activates RAP1 and RAC1 ⁶⁶ MET activates RAS signaling ⁶⁶ MET interacts with TNS proteins ⁶⁶ MET Receptor Activation ⁶⁶ MET receptor recycling ⁶⁶ Non-integrin membrane-ECM interactions ⁶⁶ Signaling by MET ⁶⁶ Syndecan interactions ⁶⁶	12.18	SOS1 PTPN11
9	Negative regulation of FGFR1 signaling ⁶⁶ Show member pathways FGFR1 ligand binding and activation ⁶⁶ FGFR1b ligand binding and activation ⁶⁶ FGFR1c and Klotho ligand binding and activation ⁶⁶ FGFR1c ligand binding and activation ⁶⁶ FGFRL1 modulation of FGFR1 signaling ⁶⁶ Negative regulation of FGFR2 signaling ⁶⁶ Negative regulation of FGFR3 signaling ⁶⁶ Negative regulation of FGFR4 signaling ⁶⁶ Signaling by activated point mutants of FGFR1 ⁶⁶ Signaling by FGFR1 ⁶⁶ Signaling by FGFR1 amplification mutants ⁶⁶ Signaling by FGFR3 ⁶⁶ Signaling by FGFR4 ⁶⁶ Spry regulation of FGF signaling ⁶⁶	12.18	SOS1 PTPN11 BRAF
10	ErbB signaling pathway ³⁷ ¹ Show member pathways EGFR Inhibitor Pathway, Pharmacodynamics ⁶¹ EGFR tyrosine kinase inhibitor resistance ³⁷ Renal cell carcinoma ³⁷ TCA Cycle Nutrient Utilization and Invasiveness of Ovarian Cancer ¹	12.16	SOS1 PTPN11 BRAF
11	Phospholipase D signaling pathway ³⁷ Show member pathways Choline metabolism in cancer ³⁷	12.12	SOS1 PTPN11
12	Development IGF-1 receptor signaling ²² Show member pathways IL-4 Signaling Pathway ¹ Immune response IL-4 signaling pathway ²² Signal transduction AKT signaling ²²	12.11	SOS1 PTPN11
13	Immune response Role of DAP12 receptors in NK cells ²² Show member pathways Immune response CD16 signaling in NK cells ²² Natural killer cell mediated cytotoxicity ³⁷	12.11	SOS1 PTPN11 BRAF
14	G-protein signaling G-Protein alpha-i signaling cascades ²² Show member pathways Development Beta-adrenergic receptors regulation of ERK ²² G-protein signaling G-Protein alpha-s signaling cascades ²² G-protein signaling G-Protein beta/gamma signaling cascades ²²	12.09	SOS1 BRAF
15	CNTF Signaling ⁶⁴ Show member pathways FLT3 Signaling ⁶⁴ IL-3 Pathway ⁶⁴ Nur77-Induced AICD in Macrophage ⁶⁴ OSM Pathway ⁶⁴	12.05	SOS1 BRAF
16	Development VEGF signaling via VEGFR2 - generic cascades ²² Show member pathways Development VEGF signaling and activation ²² VEGF - VEGF R2 Signaling Pathways ⁶⁵	11.97	SOS1 PTPN11 BRAF
17	Cell surface interactions at the vascular wall ⁶⁶ Show member pathways Fibronectin matrix formation ⁶⁶ PECAM1 interactions ⁶⁶ Tie2 Signaling ⁶⁶	11.96	SOS1 PTPN11
18	B cell receptor signaling pathway (KEGG) ¹ Show member pathways B cell receptor signaling pathway ³⁷ BCR signaling pathway ¹	11.94	SOS1 PTPN11 BRAF
19	Colorectal Cancer Metastasis ⁶⁴	11.92	SOS1 BRAF
20	Kit receptor signaling pathway ¹ Show member pathways IL-3 Signaling Pathway ¹ Signaling events mediated by Stem cell factor receptor (c-Kit) ¹	11.91	SOS1 PTPN11
21	NGF Pathway ⁶⁴ Show member pathways TRKA Signaling ⁶⁴	11.88	SOS1 BRAF
22	Development EGFR signaling via small GTPases ²² Show member pathways Development EGFR signaling via PIP3 ²² Development PDGF signaling via MAPK cascades ²² PDGF Pathway ¹	11.88	SOS1 PTPN11
23	FoxO signaling pathway ³⁷ Show member pathways PLK2 and PLK4 events ¹ Polo-like kinase signaling events in the cell cycle ¹	11.83	SOS1 BRAF
24	IL-2 Signaling Pathway ¹ Show member pathways IL2-mediated signaling events ¹ IL-5 Signaling Pathway ¹	11.82	SOS1 PTPN11
25	Development A2B receptor- action via G-protein alpha s ²² Show member pathways Development A2A receptor signaling ²²	11.78	SOS1 BRAF
26	G-protein signaling Ras family GTPases in kinase cascades (scheme) ²² Show member pathways Activation of the AP-1 family of transcription factors ⁶⁶ Immune response Oncostatin M signaling via MAPK in human cells ²² MAPK Cascade ¹ Oncostatin M Signaling Pathway ¹	11.75	SOS1 PTPN11 BRAF
27	Proteoglycans in cancer ³⁷	11.74	SOS1 PTPN11 BRAF
28	Glioblastoma Multiforme ⁶⁴	11.73	SOS1 BRAF
29	Immune response IL-2 activation and signaling pathway ²² Show member pathways Immune response IL-3 activation and signaling pathway ²²	11.72	SOS1 PTPN11
30	TCR signaling in naive CD4+ T cells ¹ Show member pathways TCR signaling in naive CD8+ T cells ¹	11.72	SOS1 PTPN11
31	ErbB1 downstream signaling ¹	11.69	SOS1 BRAF
32	S-1P Stimulated Signaling ⁶⁴	11.68	SOS1 BRAF
33	G-protein signaling N-RAS regulation pathway ²² Show member pathways Immune response Antigen presentation by MHC class II ²²	11.67	SOS1 BRAF
34	Development EPO-induced Jak-STAT pathway ²² Show member pathways EPO Receptor Signaling ¹ EPO signaling pathway ¹	11.66	SOS1 PTPN11
35	TGF-beta Signaling Pathways ⁶⁵	11.65	SOS1 BRAF
36	Signaling events mediated by VEGFR1 and VEGFR2 ¹ Show member pathways VEGFR1 specific signals ¹	11.63	SOS1 PTPN11
37	Signaling by FGFR2 ⁶⁶ Show member pathways FGFR2 ligand binding and activation ⁶⁶ FGFR2b ligand binding and activation ⁶⁶ Signaling by FGFR ⁶⁶	11.62	SOS1 PTPN11 BRAF
38	IL-6 signaling pathway ¹ Show member pathways IL6-mediated signaling events ¹	11.59	SOS1 PTPN11
39	IL2 signaling events mediated by PI3K ¹ Show member pathways IL2 signaling events mediated by STAT5 ¹	11.48	SOS1 PTPN11
40	Neurotrophic factor-mediated Trk receptor signaling ¹ Show member pathways Signalling to STAT3 ⁶⁶ TRKA activation by NGF ⁶⁶	11.43	SOS1 PTPN11
41	G-protein signaling TC21 regulation pathway ²² Show member pathways G-protein signaling M-RAS regulation pathway ²² Negative feedback regulation of MAPK pathway ⁶⁶	11.41	SOS1 BRAF
42	Signaling events mediated by focal adhesion kinase ¹	11.37	SOS1 BRAF
43	PDGFR-beta signaling pathway ¹	11.37	SOS1 PTPN11
44	EGF/EGFR Signaling Pathway ¹	11.35	SOS1 PTPN11 BRAF
45	Hepatitis C and Hepatocellular Carcinoma ¹	11.34	SOS1 PTPN11
46	Semaphorin Signaling ⁶⁴	11.31	SOS1 BRAF
47	FGF signaling pathway ¹	11.29	SOS1 PTPN11
48	Immune response_Role of integrins in NK cells cytotoxicity ²²	11.25	SOS1 PTPN11
49	Insulin Pathway ¹	11.24	SOS1 PTPN11
50	Vemurafenib Pathway, Pharmacodynamics ⁶¹	11.23	SOS1 BRAF

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GO Terms for Noonan Syndrome and Noonan-Related Syndrome

Biological processes related to Noonan Syndrome and Noonan-Related Syndrome according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	MAPK cascade	GO:0000165	9.37	SOS1 BRAF
2	axon guidance	GO:0007411	9.32	SOS1 PTPN11
3	leukocyte migration	GO:0050900	9.26	SOS1 PTPN11
4	multicellular organism growth	GO:0035264	9.16	SOS1 PTPN11
5	epidermal growth factor receptor signaling pathway	GO:0007173	8.96	SOS1 PTPN11
6	neurotrophin TRK receptor signaling pathway	GO:0048011	8.62	SOS1 PTPN11

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Sources for Noonan Syndrome and Noonan-Related Syndrome

¹ BioSystems

² BitterDB

³ CDC

⁴ Cell Signaling Technology

⁵ ClinicalTrials

⁶ ClinVar

⁷ CNVD

⁸ Cochrane Library

⁹ Cosmic

¹⁰ dbSNP

¹¹ DGIdb

¹² Disease Ontology

¹³ diseasecard

¹⁴ DiseaseEnhancer

¹⁵ DISEASES

¹⁶ DrugBank

¹⁷ EFO

¹⁸ ExPASy

¹⁹ FMA

²⁰ GeneAnalytics

²¹ GeneCards

²² GeneGo (Thomson Reuters)

²³ GeneHancer via GeneCards

²⁴ GeneReviews

²⁵ Genetics Home Reference

²⁶ GenomeRNAi

²⁷ GEO DataSets

²⁸ GO

²⁹ GTR

³⁰ HGMD

³¹ HMDB

³² HPO

³³ ICD10

³⁴ ICD10 via Orphanet

³⁵ ICD9CM

³⁶ IUPHAR

³⁷ KEGG

³⁸ LifeMap

³⁹ LncRNADisease

⁴⁰ LOVD

⁴¹ MalaCards

⁴² MedGen

⁴³ MedlinePlus

⁴⁴ MeSH

⁴⁵ MESH via Orphanet

⁴⁶ MGI

⁴⁷ miR2Disease

⁴⁸ NCBI Bookshelf

⁴⁹ NCI

⁵⁰ NCIt

⁵¹ NDF-RT

⁵² NIH Clinical Center

⁵³ NIH Rare Diseases

⁵⁴ NINDS

⁵⁵ Novoseek

⁵⁶ Novus Biologicals

⁵⁷ OMIM

⁵⁸ OMIM via Orphanet

⁵⁹ Orphanet

⁶⁰ PathCards

⁶¹ PharmGKB

⁶² PubMed

⁶³ PubMed Health

⁶⁴ QIAGEN

⁶⁵ R&D Systems

⁶⁶ Reactome

⁶⁷ Sino Biological

⁶⁸ SNOMED-CT

⁶⁹ SNOMED-CT via HPO

⁷⁰ TGDB

⁷¹ Tocris

⁷² UMLS

⁷³ UMLS via Orphanet

⁷⁴ UniProtKB/Swiss-Prot

⁷⁵ Wikipedia