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

MCID: NNN033 MIFTS: 27	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 ⁵⁸ ⁶

Classifications:

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

See all MalaCards categories (disease lists)

Orphanet: ⁵⁸

Rare cardiac malformations

Developmental anomalies during embryogenesis

External Ids:

Orphanet ⁵⁸ 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 pulmonic stenosis and keratosis pilaris atrophicans faciei. An important gene associated with Noonan Syndrome and Noonan-Related Syndrome is SOS1 (SOS Ras/Rac Guanine Nucleotide Exchange Factor 1), and among its related pathways/superpathways are Innate Immune System and HIV Life Cycle. Related phenotypes are Decreased shRNA abundance (Z-score < -2) and Decreased shRNA abundance (Z-score < -2)

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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 38)

#	Related Disease	Score	Top Affiliating Genes
1	pulmonic stenosis	10.0	SOS1 BRAF
2	keratosis pilaris atrophicans faciei	9.9	SOS1 PTPN11
3	villonodular synovitis	9.9	SOS1 PTPN11
4	noonan syndrome-like disorder with loose anagen hair 2	9.9	SOS1 PTPN11
5	noonan syndrome-like disorder with loose anagen hair	9.9	SOS1 PTPN11
6	leopard syndrome 2	9.9	RAF1 PTPN11
7	melanoma in congenital melanocytic nevus	9.9	RAF1 BRAF
8	pilomyxoid astrocytoma	9.9	RAF1 BRAF
9	juvenile xanthogranuloma	9.9	PTPN11 BRAF
10	thyroid carcinoma, familial medullary	9.9	RAF1 BRAF
11	embryonal rhabdomyosarcoma	9.8	SOS1 PTPN11
12	heart septal defect	9.8	SOS1 PTPN11
13	adenocarcinoma	9.8	SOS1 RAF1 BRAF
14	patent ductus arteriosus 1	9.7	SOS1 PTPN11
15	lentigines	9.7	RAF1 PTPN11 BRAF
16	noonan syndrome 3	9.7	SOS1 RAF1 PTPN11
17	leopard syndrome 1	9.6	RAF1 PTPN11 BRAF
18	hypertelorism	9.6	RAF1 PTPN11 BRAF
19	leukemia, chronic myeloid	9.6	RAF1 PTPN11 BRAF
20	skin granular cell tumor	9.5	SOS1 PTPN11 MAP2K2
21	pulmonary valve disease	9.5	SOS1 PTPN11 MAP2K2
22	neurofibromatosis-noonan syndrome	9.5	SOS1 PTPN11 MAP2K2
23	pancreatic adenocarcinoma	9.5	RAF1 MAP2K2 BRAF
24	skin melanoma	9.5	RAF1 MAP2K2 BRAF
25	pilocytic astrocytoma	9.4	SOS1 RAF1 PTPN11 BRAF
26	juvenile myelomonocytic leukemia	9.4	SOS1 RAF1 PTPN11 BRAF
27	lung cancer susceptibility 3	9.4	SOS1 RAF1 PTPN11 BRAF
28	pulmonary valve stenosis	9.3	SOS1 PTPN11 MAP2K2 BRAF
29	costello syndrome	9.3	SOS1 PTPN11 MAP2K2 BRAF
30	gastric adenocarcinoma	9.2	RAF1 PTPN11 MAP2K2 BRAF
31	skin carcinoma	9.2	RAF1 MAP2K2 BRAF
32	noonan syndrome with multiple lentigines	9.0	SOS1 RAF1 PTPN11 MAP2K2 BRAF
33	cardiofaciocutaneous syndrome 1	9.0	SOS1 RAF1 PTPN11 MAP2K2 BRAF
34	neurofibromatosis, type i	9.0	SOS1 RAF1 PTPN11 MAP2K2 BRAF
35	rasopathy	9.0	SOS1 RAF1 PTPN11 MAP2K2 BRAF
36	pseudo-turner syndrome	9.0	SOS1 RAF1 PTPN11 MAP2K2 BRAF
37	noonan syndrome 1	9.0	SOS1 RAF1 PTPN11 MAP2K2 BRAF
38	hypertrophic cardiomyopathy	9.0	SOS1 RAF1 PTPN11 MAP2K2 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 (show all 25)

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Decreased shRNA abundance (Z-score < -2)	GR00366-A-100	10.02	SOS1
2	Decreased shRNA abundance (Z-score < -2)	GR00366-A-110	10.02	BRAF
3	Decreased shRNA abundance (Z-score < -2)	GR00366-A-118	10.02	PTPN11
4	Decreased shRNA abundance (Z-score < -2)	GR00366-A-120	10.02	SOS1
5	Decreased shRNA abundance (Z-score < -2)	GR00366-A-121	10.02	PTPN11
6	Decreased shRNA abundance (Z-score < -2)	GR00366-A-138	10.02	PTPN11
7	Decreased shRNA abundance (Z-score < -2)	GR00366-A-149	10.02	PTPN11 RAF1 SOS1
8	Decreased shRNA abundance (Z-score < -2)	GR00366-A-161	10.02	RAF1
9	Decreased shRNA abundance (Z-score < -2)	GR00366-A-166	10.02	BRAF
10	Decreased shRNA abundance (Z-score < -2)	GR00366-A-177	10.02	BRAF
11	Decreased shRNA abundance (Z-score < -2)	GR00366-A-190	10.02	PTPN11
12	Decreased shRNA abundance (Z-score < -2)	GR00366-A-194	10.02	BRAF
13	Decreased shRNA abundance (Z-score < -2)	GR00366-A-203	10.02	SOS1
14	Decreased shRNA abundance (Z-score < -2)	GR00366-A-204	10.02	RAF1
15	Decreased shRNA abundance (Z-score < -2)	GR00366-A-29	10.02	BRAF
16	Decreased shRNA abundance (Z-score < -2)	GR00366-A-31	10.02	BRAF
17	Decreased shRNA abundance (Z-score < -2)	GR00366-A-32	10.02	BRAF
18	Decreased shRNA abundance (Z-score < -2)	GR00366-A-37	10.02	PTPN11
19	Decreased shRNA abundance (Z-score < -2)	GR00366-A-47	10.02	PTPN11
20	Decreased shRNA abundance (Z-score < -2)	GR00366-A-65	10.02	SOS1
21	Decreased shRNA abundance (Z-score < -2)	GR00366-A-72	10.02	BRAF
22	Decreased cell migration	GR00055-A-1	9.43	MAP2K2 SOS1
23	Decreased cell migration	GR00055-A-3	9.43	BRAF
24	Decreased human cytomegalovirus (HCMV) strain AD169 replication	GR00248-A	9.33	BRAF MAP2K2 RAF1
25	Upregulation of Wnt/beta-catenin pathway after WNT3A stimulation	GR00016-A	8.8	BRAF MAP2K2 PTPN11

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

⁴⁶ (show all 11)

#	Description	MGI Source Accession	Score	Top Affiliating Genes
1	cardiovascular system	MP:0005385	9.89	BRAF MAP2K2 PTPN11 RAF1 SOS1
2	cellular	MP:0005384	9.88	BRAF MAP2K2 PTPN11 RAF1 SOS1
3	craniofacial	MP:0005382	9.85	BRAF MAP2K2 PTPN11 RAF1 SOS1
4	endocrine/exocrine gland	MP:0005379	9.8	BRAF MAP2K2 PTPN11 RAF1 SOS1
5	digestive/alimentary	MP:0005381	9.73	BRAF MAP2K2 PTPN11 SOS1
6	integument	MP:0010771	9.72	BRAF MAP2K2 PTPN11 RAF1 SOS1
7	hearing/vestibular/ear	MP:0005377	9.67	BRAF MAP2K2 PTPN11 RAF1
8	muscle	MP:0005369	9.56	BRAF PTPN11 RAF1 SOS1
9	neoplasm	MP:0002006	9.46	BRAF MAP2K2 PTPN11 RAF1
10	skeleton	MP:0005390	9.35	BRAF MAP2K2 PTPN11 RAF1 SOS1
11	vision/eye	MP:0005391	9.02	BRAF MAP2K2 PTPN11 RAF1 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	SOS1	SOS Ras/Rac Guanine Nucleotide Exchange Factor 1	Protein Coding	433.7	Pathogenic ⁶ Likely pathogenic ⁶ GeneCards inferred via : Variants (show sections)
2	BRAF	B-Raf Proto-Oncogene, Serine/Threonine Kinase	Protein Coding	433.49	Pathogenic ⁶ Likely pathogenic ⁶ GeneCards inferred via : Variants (show sections)
3	PTPN11	Protein Tyrosine Phosphatase Non-Receptor Type 11	Protein Coding	432.94	Pathogenic ⁶ Likely pathogenic ⁶ GeneCards inferred via : Variants (show sections)
4	MAP2K2	Mitogen-Activated Protein Kinase Kinase 2	Protein Coding	7.94	GeneCards inferred via : Variants (show sections)
5	RAF1	Raf-1 Proto-Oncogene, Serine/Threonine Kinase	Protein Coding	7.6	GeneCards inferred via : Variants (show sections)

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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	Name	Type	Significance	ClinVarId	dbSNP ID	GRCh37 Pos	GRCh38 Pos
1	SOS1	NM_005633.3(SOS1):c.1656G>T (p.Arg552Ser)	SNV	Pathogenic	40684	rs267607079	2:39249913-39249913	2:39022772-39022772
2	SOS1	NM_005633.3(SOS1):c.1656G>C (p.Arg552Ser)	SNV	Pathogenic	12872	rs267607079	2:39249913-39249913	2:39022772-39022772
3	PTPN11	NM_002834.5(PTPN11):c.166A>G (p.Ile56Val)	SNV	Pathogenic	40485	rs397507504	12:112888150-112888150	12:112450346-112450346
4	BRAF	NM_004333.6(BRAF):c.741T>G (p.Phe247Leu)	SNV	Pathogenic	55793	rs397509343	7:140501331-140501331	7:140801531-140801531
5	BRAF	NM_004333.6(BRAF):c.739T>C (p.Phe247Leu)	SNV	Pathogenic	180784	rs397516903	7:140501333-140501333	7:140801533-140801533
6	BRAF	NM_001374258.1(BRAF):c.735A>T (p.Leu245Phe)	SNV	Pathogenic	40348	rs397507466	7:140501337-140501337	7:140801537-140801537
7	BRAF	NM_001374258.1(BRAF):c.735A>C (p.Leu245Phe)	SNV	Pathogenic	40347	rs397507466	7:140501337-140501337	7:140801537-140801537
8	SOS1	NM_005633.3(SOS1):c.1655G>T (p.Arg552Met)	SNV	Likely pathogenic	40681	rs397517154	2:39249914-39249914	2:39022773-39022773
9	BRAF	NM_004333.6(BRAF):c.740T>C (p.Phe247Ser)	SNV	Likely pathogenic	40349	rs397507467	7:140501332-140501332	7:140801532-140801532
10	PTPN11	NM_002834.4(PTPN11):c.167T>C (p.Ile56Thr)	SNV	Likely pathogenic	477669	rs1052382672	12:112888151-112888151	12:112450347-112450347
11	BRAF	NM_001374258.1(BRAF):c.739T>G (p.Phe247Val)	SNV	Likely pathogenic	44830	rs397516903	7:140501333-140501333	7:140801533-140801533
12	SOS1	NM_005633.3(SOS1):c.1654A>T (p.Arg552Trp)	SNV	Likely pathogenic	372656	rs137852814	2:39249915-39249915	2:39022774-39022774
13	SOS1	NM_005633.3(SOS1):c.1867T>A (p.Phe623Ile)	SNV	Likely pathogenic	636262	rs727505093	2:39241979-39241979	2:39014838-39014838
14	SOS1	NM_005633.3(SOS1):c.512T>C (p.Val171Ala)	SNV	Likely pathogenic	45373	rs397517174	2:39281963-39281963	2:39054822-39054822
15	MAP2K2	NM_030662.3(MAP2K2):c.692G>T (p.Arg231Leu)	SNV	Uncertain significance	40818	rs730880511	19:4101030-4101030	19:4101032-4101032
16	MAP2K2	NM_030662.3(MAP2K2):c.692G>A (p.Arg231His)	SNV	Uncertain significance	543999	rs730880511	19:4101030-4101030	19:4101032-4101032
17	SOS1	NM_005633.3(SOS1):c.1867_1869delinsGAA (p.Phe623Glu)	Indel	Uncertain significance	636263	rs1572823606	2:39241977-39241979	2:39014836-39014838
18	SOS1	NM_005633.3(SOS1):c.3600C>G (p.Asp1200Glu)	SNV	Likely benign	40733	rs141594736	2:39213367-39213367	2:38986226-38986226
19	SOS1	NM_005633.3(SOS1):c.1018C>T (p.Pro340Ser)	SNV	Benign	40664	rs190222208	2:39262409-39262409	2:39035268-39035268
20	RAF1	NM_001354689.3(RAF1):c.94A>G (p.Ile32Val)	SNV	Benign	40584	rs372738063	3:12660127-12660127	3:12618628-12618628

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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 159)

#	Super pathways	Score	Top Affiliating Genes
1	Innate Immune System ⁶⁵ Show member pathways Immune System ⁶⁵ Neutrophil degranulation ⁶⁵	13.81	SOS1 RAF1 PTPN11 MAP2K2 BRAF
2	HIV Life Cycle ⁶⁵ Show member pathways 2-LTR circle formation ⁶⁵ APOBEC3G mediated resistance to HIV-1 infection ⁶⁵ Assembly Of The HIV Virion ⁶⁵ Binding and entry of HIV virion ⁶⁵ Disease ⁶⁵ Diseases of signal transduction ⁶⁵ Early Phase of HIV Life Cycle ⁶⁵ HIV Infection ⁶⁵ Host Interactions of HIV factors ⁶⁵ Infectious disease ⁶⁵ Integration of provirus ⁶⁵ Late Phase of HIV Life Cycle ⁶⁵	13.55	SOS1 RAF1 PTPN11 MAP2K2 BRAF
3	TGF-Beta Pathway ⁶³ Show member pathways JAK-STAT Pathway ⁶³ JNK Pathway ⁶³ MAPK Family Pathway ⁶³ Regulation of eIF4 and p70S6K ⁶³ SOCS Pathway ⁶³	13.4	SOS1 RAF1 PTPN11 MAP2K2 BRAF
4	Activation of cAMP-Dependent PKA ⁶³ Show member pathways Activation of PKA through GPCR ⁶³ cAMP Pathway ⁶³ PKA Signaling ⁶³	13.37	SOS1 RAF1 MAP2K2 BRAF
5	Developmental Biology ⁶⁵ Show member pathways Axon guidance ⁶⁵	13.36	SOS1 RAF1 PTPN11 MAP2K2 BRAF
6	Integrin Pathway ⁶³ Show member pathways FAK1 Signaling ⁶³ GnRH Signaling ⁶³ Inhibition of Angiogenesis by TSP1 ⁶³ Transendothelial Migration of Leukocytes ⁶³ UPA-UPAR Pathway ⁶³	13.25	SOS1 RAF1 MAP2K2 BRAF
7	Cytokine Signaling in Immune system ⁶⁵ Show member pathways Signaling by Interleukins ⁶⁵	13.24	SOS1 RAF1 PTPN11 MAP2K2 BRAF
8	Nanog in Mammalian ESC Pluripotency ⁶³ Show member pathways 14-3-3 Induced Intracellular Signaling ⁶³ eNOS Signaling ⁶³ GSK3 Signaling ⁶³	13.14	SOS1 RAF1 MAP2K2 BRAF
9	IL-2 Pathway ⁶³ Show member pathways ErbB Family Pathway ⁶³ ErbB2-ErbB3 Heterodimers ⁶³ ErbB4 Pathway ⁶³ Growth Hormone Signaling ⁶³ HMGB1 Pathway ⁶³ IL-4 Pathway ⁶³ LPS Stimulated MAPK Signaling ⁶³ PACAP Signaling ⁶³ PI3K Signaling in B-Lymphocyte ⁶³ Prolactin Signaling ⁶³ Thrombopoietin Pathway ⁶³ TREM1 Pathway ⁶³ UVC-Induced MAPK Signaling ⁶³	13.08	SOS1 RAF1 MAP2K2 BRAF
10	Phospholipase-C Pathway ⁶³ Show member pathways PTEN Pathway ⁶³	12.97	SOS1 RAF1 MAP2K2 BRAF
11	Toll-like Receptor Signaling Pathway ³⁶ ¹ Show member pathways Chagas disease ³⁶ Hepatitis B ³⁶ Hepatitis C ³⁶ Regulation of toll-like receptor signaling pathway ¹	12.96	SOS1 RAF1 MAP2K2 BRAF
12	G-Beta Gamma Signaling ⁶³ Show member pathways CRHR Pathway ⁶³ GHRH Signaling ⁶³ Hedgehog Signaling in Mammals ⁶³ Relaxin Pathway ⁶³ Signaling in Gap Junctions ⁶³	12.94	SOS1 RAF1 MAP2K2 BRAF
13	fMLP Pathway ⁶³ Show member pathways Alpha-Adrenergic Signaling ⁶³ CCR3 Pathway in Eosinophils ⁶³ CXCR4 Pathway ⁶³ Huntington's Disease Pathway ⁶³ Internalin Pathway ⁶³ Signal transduction Activation of PKC via G-Protein coupled receptor ²³ VEGF and S-1P Signaling ⁶³	12.91	SOS1 RAF1 MAP2K2 BRAF
14	Focal Adhesion ³⁶ ¹ Show member pathways HGF Pathway ⁶³ Integrin-mediated Cell Adhesion ¹	12.83	SOS1 RAF1 MAP2K2 BRAF
15	Regulation of lipid metabolism Insulin signaling-generic cascades ²³ Show member pathways acetyl-CoA biosynthesis from citrate ¹ Butyrate-induced histone acetylation ¹ Cell adhesion PLAU signaling ²³ Class IB PI3K non-lipid kinase events ¹ Development CNTF receptor signaling ²³ Development Growth hormone signaling via PI3K/AKT and MAPK cascades ²³ ErbB2/ErbB3 signaling events ¹ Glucose Homeostasis ¹ Insulin signaling pathway ³⁶ IRS activation ⁶⁵ Signal attenuation ⁶⁵ Transcription Receptor-mediated HIF regulation ²³ Translation Regulation of EIF2 activity ²³ Translation Regulation of EIF4F activity ²³ Translation Insulin regulation of translation ²³	12.81	SOS1 RAF1 PTPN11 MAP2K2 BRAF
16	Human cytomegalovirus infection ³⁶ Show member pathways Human immunodeficiency virus 1 infection ³⁶ Kaposi sarcoma-associated herpesvirus infection ³⁶	12.8	SOS1 RAF1 MAP2K2
17	NFAT and Cardiac Hypertrophy ⁶³ Show member pathways IGF1R Signaling ⁶³ Signaling Involved in Cardiac Hypertrophy ⁶³	12.8	SOS1 RAF1 MAP2K2 BRAF
18	Development Angiotensin activation of ERK ²³ Show member pathways Cell adhesion Integrin inside-out signaling ²³ Development ACM2 and ACM4 activation of ERK ²³ Development Angiotensin signaling via PYK2 ²³ Development EDNRB signaling ²³ Development EPO-induced MAPK pathway ²³ Development G-Proteins mediated regulation MARK-ERK signaling ²³ Signal transduction IP3 signaling ²³	12.79	SOS1 RAF1 MAP2K2 BRAF
19	Sertoli-Sertoli Cell Junction Dynamics ⁶³ Show member pathways Epithelial Tight Junctions ⁶³ Germ Cell-Sertoli Cell Junction Dynamics ⁶³	12.78	RAF1 MAP2K2 BRAF
20	Pathways in cancer ³⁶	12.78	SOS1 RAF1 MAP2K2 BRAF
21	Endometrial cancer ³⁶ Show member pathways Acute myeloid leukemia ³⁶ Binding of TCF/LEF-CTNNB1 to target gene promoters ⁶⁵ Chronic myeloid leukemia ³⁶ Colorectal cancer ³⁶ Pancreatic cancer ³⁶ Prostate cancer ³⁶ Signal transduction PTEN pathway ²³ Thyroid cancer ³⁶	12.77	SOS1 RAF1 PTPN11 MAP2K2 BRAF
22	Aldosterone synthesis and secretion ³⁶ Show member pathways Ca2+ activated K+ channels ⁶⁵ Cortisol synthesis and secretion ³⁶ Cushing syndrome ³⁶ Insulin secretion ³⁶ Melanogenesis ³⁶ Thyroid hormone synthesis ³⁶	12.76	RAF1 MAP2K2 BRAF
23	CCR5 Pathway in Macrophages ⁶³ Show member pathways Androgen Signaling ⁶³ Chemokine Signaling ⁶³ Chemokine signaling pathway ³⁶	12.75	SOS1 RAF1 BRAF
24	Beta-Adrenergic Signaling ⁶³ Show member pathways CDK5 Pathway ⁶³ Erythropoietin Pathway ⁶³ Insulin Receptor Pathway ⁶³	12.75	SOS1 RAF1 MAP2K2 BRAF
25	MAPK signaling pathway ³⁶ ¹	12.71	SOS1 RAF1 MAP2K2 BRAF
26	Gastric cancer ³⁶ Show member pathways Breast cancer ³⁶ Hepatocellular carcinoma ³⁶	12.71	SOS1 RAF1 MAP2K2 BRAF
27	Common Cytokine Receptor Gamma-Chain Family Signaling Pathways ⁶⁴ Show member pathways Adipokines and Insulin Signaling Pathways ⁶⁴ Development Thrombopoietin-regulated cell processes ²³ IL-15 Signaling Pathways ⁶⁴ IL-2 Signaling Pathways ⁶⁴ IL-21 Signaling Pathways ⁶⁴ IL-4 Signaling Pathways ⁶⁴ IL-7 Signaling Pathways ⁶⁴ IL-9 Pathway ⁶³ IL-9 Signaling Pathways ⁶⁴ Immune response IL-9 signaling pathway ²³	12.68	SOS1 RAF1 PTPN11 MAP2K2 BRAF
28	Salmonella infection (KEGG) ³⁶ Show member pathways Salmonella infection ³⁶	12.64	RAF1 PTPN11 MAP2K2
29	Glioma ³⁶ Show member pathways Endocrine resistance ³⁶ Melanoma ³⁶ Non-small cell lung cancer ³⁶ Signaling Pathways in Glioblastoma ¹	12.64	SOS1 RAF1 MAP2K2 BRAF
30	G-AlphaQ Signaling ⁶³ Show member pathways G-AlphaI Signaling ⁶³ Thrombin Signaling ⁶³	12.63	SOS1 RAF1 MAP2K2 BRAF
31	Ras signaling pathway ³⁶ Show member pathways Rap1 signaling pathway ³⁶	12.63	SOS1 RAF1 PTPN11 MAP2K2 BRAF
32	Toll-Like receptor Signaling Pathways ⁶⁴ Show member pathways IL-1 Family Signaling Pathways ⁶⁴ Immune response IL-1 signaling pathway ²³ Immune response TLR3 and TLR4 induce TICAM1-specific signaling pathway ²³ Inflammasome Activation Pathways ⁶⁴ Mucin expression in CF via TLRs, EGFR signaling pathways ²³ NOD-like Receptor Signaling Pathways ⁶⁴	12.62	SOS1 RAF1 MAP2K2
33	Neuropathic Pain-Signaling in Dorsal Horn Neurons ⁶³ Show member pathways Aldosterone Signaling in Epithelial Cells ⁶³ Cholera Infection ⁶³	12.62	SOS1 RAF1 MAP2K2 BRAF
34	Development HGF signaling pathway ²³ Show member pathways Apoptosis and survival Anti-apoptotic action of membrane-bound ESR1 ²³ Apoptosis and survival NGF signaling pathway ²³ Apoptosis and survival Role of CDK5 in neuronal death and survival ²³ Development Neurotrophin family signaling ²³ MET activates PTPN11 ⁶⁵ MET activates STAT3 ⁶⁵ Neurotrophin signaling pathway ³⁶ Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met) ¹ Signaling of Hepatocyte Growth Factor Receptor ¹	12.6	SOS1 RAF1 PTPN11 MAP2K2 BRAF
35	Regulation of actin cytoskeleton ³⁶ ¹	12.59	SOS1 RAF1 MAP2K2 BRAF
36	Relaxin signaling pathway ³⁶ Show member pathways Estrogen signaling pathway ³⁶ Growth hormone synthesis, secretion and action ³⁶ Relaxin receptors ⁶⁵	12.58	SOS1 RAF1 MAP2K2
37	4-1BB Pathway ⁶³ Show member pathways CD27 Pathway ⁶³ CD40 Signaling ⁶³ CMV and MAPK Pathways ⁶³ NF-KappaB Activation by EBV ⁶³ NF-kappaB Activation by Viruses ⁶³ PKR Pathway ⁶³ SUMO Pathway ⁶³ TNFR2 Pathway ⁶³	12.57	RAF1 MAP2K2 BRAF
38	Development Endothelin-1/EDNRA signaling ²³ Show member pathways Cytoskeleton remodeling FAK signaling ²³ Development Endothelin-1/EDNRA transactivation of EGFR ²³ GnRH signaling pathway ³⁶ Inflammatory mediator regulation of TRP channels ³⁶	12.56	SOS1 RAF1 MAP2K2
39	T cell receptor signaling pathway ³⁶ Show member pathways PD-L1 expression and PD-1 checkpoint pathway in cancer ³⁶ T-Cell antigen Receptor (TCR) Signaling Pathway ¹ T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection ¹	12.56	SOS1 RAF1 PTPN11 MAP2K2
40	Immune response Fc epsilon RI pathway ²³ Show member pathways Fc epsilon RI signaling pathway ³⁶ Fc-epsilon receptor I signaling in mast cells ¹ Immune response BCR pathway ²³ VEGF signaling pathway ³⁶	12.55	SOS1 RAF1 PTPN11 MAP2K2
41	Immune response NFAT in immune response ²³ Show member pathways Immune response CD28 signaling ²³ Immune response ICOS pathway in T-helper cell ²³ Immune response T cell receptor signaling pathway ²³	12.54	SOS1 RAF1 MAP2K2
42	Development Dopamine D2 receptor transactivation of EGFR ²³ Show member pathways Apoptosis and survival BAD phosphorylation ²³ BAD Phosphorylation ⁶³ Chemotaxis CXCR4 signaling pathway ²³ Development Alpha-2 adrenergic receptor activation of ERK ²³	12.53	SOS1 RAF1 PTPN11 MAP2K2
43	Cytoskeleton remodeling Regulation of actin cytoskeleton by Rho GTPases ²³ Show member pathways Cell adhesion Integrin-mediated cell adhesion and migration ²³ Cell adhesion Tight junctions ²³ Cytoskeleton remodeling Integrin outside-in signaling ²³ Development MAG-dependent inhibition of neurite outgrowth ²³	12.52	SOS1 RAF1 MAP2K2
44	TRAF Pathway ⁶³ Show member pathways 14-3-3 Induced Apoptosis ⁶³ TNF Superfamily Pathway ⁶³ Toll-Like Receptors Pathway ⁶³	12.51	SOS1 RAF1 MAP2K2
45	Negative regulation of FGFR1 signaling ⁶⁵ Show member pathways FGFR1 ligand binding and activation ⁶⁵ FGFR1b ligand binding and activation ⁶⁵ FGFR1c and Klotho ligand binding and activation ⁶⁵ FGFR1c ligand binding and activation ⁶⁵ FGFRL1 modulation of FGFR1 signaling ⁶⁵ Negative regulation of FGFR2 signaling ⁶⁵ Negative regulation of FGFR3 signaling ⁶⁵ Negative regulation of FGFR4 signaling ⁶⁵ Signaling by activated point mutants of FGFR1 ⁶⁵ Signaling by FGFR1 ⁶⁵ Signaling by FGFR1 amplification mutants ⁶⁵ Signaling by FGFR3 ⁶⁵ Signaling by FGFR4 ⁶⁵ Spry regulation of FGF signaling ⁶⁵	12.5	SOS1 PTPN11 BRAF
46	ErbB signaling pathway ³⁶ ¹ Show member pathways EGFR Inhibitor Pathway, Pharmacodynamics ⁶⁰ EGFR tyrosine kinase inhibitor resistance ³⁶ Renal cell carcinoma ³⁶ TCA Cycle Nutrient Utilization and Invasiveness of Ovarian Cancer ¹	12.49	SOS1 RAF1 PTPN11 MAP2K2 BRAF
47	Angiopoietin Like Protein 8 Regulatory Pathway ¹ Show member pathways Insulin Signaling ¹ Liver X Receptor Pathway ¹	12.48	SOS1 RAF1 PTPN11 MAP2K2
48	MicroRNAs in cancer ³⁶	12.46	SOS1 RAF1 MAP2K2
49	mTOR signaling pathway (KEGG) ³⁶ Show member pathways mTOR Signaling Pathway ⁶⁴	12.46	SOS1 RAF1 MAP2K2 BRAF
50	Prolactin Signaling Pathway ¹ ³⁶ Show member pathways Development Prolactin receptor signaling ²³ Leptin signaling pathway ¹	12.45	SOS1 RAF1 PTPN11 MAP2K2

Sources

GO Terms for Noonan Syndrome and Noonan-Related Syndrome

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

#	Name	GO ID	Score	Top Affiliating Genes
1	mitochondrion	GO:0005739	8.92	RAF1 PTPN11 MAP2K2 BRAF

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

(show all 11)

#	Name	GO ID	Score	Top Affiliating Genes
1	protein phosphorylation	GO:0006468	9.67	RAF1 MAP2K2 BRAF
2	positive regulation of peptidyl-serine phosphorylation	GO:0033138	9.48	RAF1 BRAF
3	multicellular organism growth	GO:0035264	9.46	SOS1 PTPN11
4	MAPK cascade	GO:0000165	9.46	SOS1 RAF1 MAP2K2 BRAF
5	somatic stem cell population maintenance	GO:0035019	9.43	RAF1 BRAF
6	thymus development	GO:0048538	9.4	RAF1 BRAF
7	activation of MAPKK activity	GO:0000186	9.37	RAF1 BRAF
8	thyroid gland development	GO:0030878	9.32	RAF1 BRAF
9	face development	GO:0060324	9.26	RAF1 BRAF
10	epidermal growth factor receptor signaling pathway	GO:0007173	9.13	SOS1 PTPN11 BRAF
11	neurotrophin TRK receptor signaling pathway	GO:0048011	8.8	SOS1 RAF1 PTPN11

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

#	Name	GO ID	Score	Top Affiliating Genes
1	protein kinase activity	GO:0004672	9.5	RAF1 MAP2K2 BRAF
2	protein serine/threonine kinase activity	GO:0004674	9.33	RAF1 MAP2K2 BRAF
3	scaffold protein binding	GO:0097110	9.26	MAP2K2 BRAF
4	MAP kinase kinase kinase activity	GO:0004709	8.96	RAF1 BRAF
5	mitogen-activated protein kinase kinase binding	GO:0031434	8.62	RAF1 BRAF

Sources

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 GARD

²¹ GeneAnalytics

²² GeneCards

²³ GeneGo (Thomson Reuters)

²⁴ GeneHancer via GeneCards

²⁵ GeneReviews

²⁶ GenomeRNAi

²⁷ GEO DataSets

²⁸ GO

²⁹ GTR

³⁰ HMDB

³¹ HPO

³² ICD10

³³ ICD10 via Orphanet

³⁴ ICD9CM

³⁵ IUPHAR

³⁶ KEGG

³⁷ LifeMap

³⁸ LncRNADisease

³⁹ LOVD

⁴⁰ MalaCards

⁴¹ MedGen

⁴² MedlinePlus

⁴³ MedlinePlus Genetics

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 NINDS

⁵⁴ Novoseek

⁵⁵ Novus Biologicals

⁵⁶ OMIM via Orphanet

⁵⁷ OMIM® (Updated 05-Mar-2021)

⁵⁸ Orphanet

⁵⁹ PathCards

⁶⁰ PharmGKB

⁶¹ PubMed

⁶² PubMed Health

⁶³ QIAGEN

⁶⁴ R&D Systems

⁶⁵ Reactome

⁶⁶ Sino Biological

⁶⁷ SNOMED-CT

⁶⁸ SNOMED-CT via HPO

⁶⁹ TGDB

⁷⁰ Tocris

⁷¹ UMLS

⁷² UMLS via Orphanet

⁷³ UniProtKB/Swiss-Prot

⁷⁴ Wikipedia