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

MCID: NNN033 MIFTS: 29	Noonan Syndrome and Noonan-Related Syndrome Categories: Cardiovascular diseases, Fetal diseases, Rare diseases
Genes Variations Tissues 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 villonodular synovitis and pontocerebellar hypoplasia, type 8. 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. Affiliated tissues include skin, heart and thyroid, and related phenotypes are Increased shRNA abundance (Z-score > 2) and Increased 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 29)

#	Related Disease	Score	Top Affiliating Genes
1	villonodular synovitis	9.9	SOS1 PTPN11
2	pontocerebellar hypoplasia, type 8	9.9	RAF1 BRAF
3	pilomyxoid astrocytoma	9.9	RAF1 BRAF
4	cystic lymphangioma	9.9	SOS1 PTPN11
5	embryonal rhabdomyosarcoma	9.8	SOS1 PTPN11
6	heart septal defect	9.8	SOS1 PTPN11
7	thyroid carcinoma, familial medullary	9.8	RAF1 BRAF
8	patent ductus arteriosus 1	9.7	SOS1 PTPN11
9	skin squamous cell carcinoma	9.6	RAF1 BRAF
10	neurofibromatosis-noonan syndrome	9.6	PTPN11 MAP2K2
11	noonan syndrome 3	9.5	SOS1 RAF1 PTPN11
12	adenocarcinoma	9.5	SOS1 RAF1 BRAF
13	lentigines	9.5	RAF1 PTPN11 BRAF
14	hypertelorism	9.5	RAF1 PTPN11 BRAF
15	skin granular cell tumor	9.3	SOS1 PTPN11 MAP2K2
16	pulmonary valve disease	9.3	SOS1 PTPN11 MAP2K2
17	melanoma, cutaneous malignant 1	9.3	RAF1 MAP2K2 BRAF
18	pulmonary valve stenosis	9.3	SOS1 PTPN11 MAP2K2
19	juvenile myelomonocytic leukemia	9.1	SOS1 RAF1 PTPN11 BRAF
20	leukemia	9.1	SOS1 RAF1 PTPN11 BRAF
21	pancreatic adenocarcinoma	9.1	RAF1 MAP2K2 BRAF
22	costello syndrome	8.9	SOS1 PTPN11 MAP2K2 BRAF
23	gastric adenocarcinoma	8.8	RAF1 MAP2K2 BRAF
24	pulmonic stenosis	8.5	SOS1 RAF1 PTPN11 MAP2K2 BRAF
25	rasopathy	8.5	SOS1 RAF1 PTPN11 MAP2K2 BRAF
26	cardiofaciocutaneous syndrome 1	8.5	SOS1 RAF1 PTPN11 MAP2K2 BRAF
27	leopard syndrome	8.5	SOS1 RAF1 PTPN11 MAP2K2 BRAF
28	hypertrophic cardiomyopathy	8.5	SOS1 RAF1 PTPN11 MAP2K2 BRAF
29	noonan syndrome 1	8.5	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 26)

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Increased shRNA abundance (Z-score > 2)	GR00366-A-100	10.09	SOS1
2	Increased shRNA abundance (Z-score > 2)	GR00366-A-110	10.09	BRAF
3	Increased shRNA abundance (Z-score > 2)	GR00366-A-118	10.09	PTPN11
4	Increased shRNA abundance (Z-score > 2)	GR00366-A-120	10.09	SOS1
5	Increased shRNA abundance (Z-score > 2)	GR00366-A-121	10.09	PTPN11
6	Increased shRNA abundance (Z-score > 2)	GR00366-A-126	10.09	SOS1
7	Increased shRNA abundance (Z-score > 2)	GR00366-A-138	10.09	PTPN11
8	Increased shRNA abundance (Z-score > 2)	GR00366-A-149	10.09	BRAF PTPN11 RAF1 SOS1
9	Increased shRNA abundance (Z-score > 2)	GR00366-A-151	10.09	RAF1
10	Increased shRNA abundance (Z-score > 2)	GR00366-A-161	10.09	RAF1
11	Increased shRNA abundance (Z-score > 2)	GR00366-A-166	10.09	BRAF
12	Increased shRNA abundance (Z-score > 2)	GR00366-A-177	10.09	BRAF
13	Increased shRNA abundance (Z-score > 2)	GR00366-A-178	10.09	PTPN11
14	Increased shRNA abundance (Z-score > 2)	GR00366-A-190	10.09	PTPN11
15	Increased shRNA abundance (Z-score > 2)	GR00366-A-194	10.09	BRAF
16	Increased shRNA abundance (Z-score > 2)	GR00366-A-29	10.09	BRAF
17	Increased shRNA abundance (Z-score > 2)	GR00366-A-31	10.09	BRAF
18	Increased shRNA abundance (Z-score > 2)	GR00366-A-32	10.09	BRAF
19	Increased shRNA abundance (Z-score > 2)	GR00366-A-37	10.09	PTPN11
20	Increased shRNA abundance (Z-score > 2)	GR00366-A-47	10.09	BRAF PTPN11
21	Increased shRNA abundance (Z-score > 2)	GR00366-A-52	10.09	RAF1
22	Increased shRNA abundance (Z-score > 2)	GR00366-A-7	10.09	PTPN11
23	Increased shRNA abundance (Z-score > 2)	GR00366-A-78	10.09	PTPN11
24	Decreased cell migration	GR00055-A-1	9.43	BRAF MAP2K2 SOS1
25	Increased human cytomegalovirus (HCMV) strain AD169 replication	GR00248-A	9.33	BRAF MAP2K2 RAF1
26	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:

⁴⁵ (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

MalaCards organs/tissues related to Noonan Syndrome and Noonan-Related Syndrome:

⁴⁰

Skin, Heart, Thyroid

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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	408.81	Pathogenic ⁶ GeneCards inferred via : Variants (show sections)
2	BRAF	B-Raf Proto-Oncogene, Serine/Threonine Kinase	Protein Coding	408.61	Pathogenic ⁶ GeneCards inferred via : Variants (show sections)
3	PTPN11	Protein Tyrosine Phosphatase Non-Receptor Type 11	Protein Coding	408.06	Pathogenic ⁶ GeneCards inferred via : Variants (show sections)
4	MAP2K2	Mitogen-Activated Protein Kinase Kinase 2	Protein Coding	8.06	GeneCards inferred via : Variants (show sections)
5	RAF1	Raf-1 Proto-Oncogene, Serine/Threonine Kinase	Protein Coding	7.71	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	BRAF	NM_004333.6(BRAF):c.739T>C (p.Phe247Leu)	SNV	Pathogenic	180784	rs397516903	7:140501333-140501333	7:140801533-140801533
2	SOS1	NM_005633.3(SOS1):c.1656G>C (p.Arg552Ser)	SNV	Pathogenic	12872	rs267607079	2:39249913-39249913	2:39022772-39022772
3	BRAF	NM_004333.6(BRAF):c.735A>C (p.Leu245Phe)	SNV	Pathogenic	40347	rs397507466	7:140501337-140501337	7:140801537-140801537
4	BRAF	NM_004333.6(BRAF):c.735A>T (p.Leu245Phe)	SNV	Pathogenic	40348	rs397507466	7:140501337-140501337	7:140801537-140801537
5	PTPN11	NM_002834.4(PTPN11):c.166A>G (p.Ile56Val)	SNV	Pathogenic	40485	rs397507504	12:112888150-112888150	12:112450346-112450346
6	SOS1	NM_005633.3(SOS1):c.1656G>T (p.Arg552Ser)	SNV	Pathogenic	40684	rs267607079	2:39249913-39249913	2:39022772-39022772
7	BRAF	NM_004333.6(BRAF):c.741T>G (p.Phe247Leu)	SNV	Pathogenic	55793	rs397509343	7:140501331-140501331	7:140801531-140801531
8	SOS1	NM_005633.3(SOS1):c.1654A>T (p.Arg552Trp)	SNV	Likely pathogenic	372656	rs137852814	2:39249915-39249915	2:39022774-39022774
9	PTPN11	NM_002834.4(PTPN11):c.167T>C (p.Ile56Thr)	SNV	Likely pathogenic	477669	rs1052382672	12:112888151-112888151	12:112450347-112450347
10	SOS1	NM_005633.3(SOS1):c.1655G>T (p.Arg552Met)	SNV	Likely pathogenic	40681	rs397517154	2:39249914-39249914	2:39022773-39022773
11	BRAF	NM_004333.6(BRAF):c.739T>G (p.Phe247Val)	SNV	Likely pathogenic	44830	rs397516903	7:140501333-140501333	7:140801533-140801533
12	SOS1	NM_005633.3(SOS1):c.512T>C (p.Val171Ala)	SNV	Likely pathogenic	45373	rs397517174	2:39281963-39281963	2:39054822-39054822
13	BRAF	NM_004333.6(BRAF):c.740T>C (p.Phe247Ser)	SNV	Likely pathogenic	40349		7:140501332-140501332	7:140801532-140801532
14	SOS1	NM_005633.3(SOS1):c.1867T>A (p.Phe623Ile)	SNV	Likely pathogenic	636262		2:39241979-39241979	2:39014838-39014838
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		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	RAF1	NM_002880.3(RAF1):c.94A>G (p.Ile32Val)	SNV	Benign	40584	rs372738063	3:12660127-12660127	3:12618628-12618628
20	SOS1	NM_005633.3(SOS1):c.1018C>T (p.Pro340Ser)	SNV	Benign	40664	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 155)

#	Super pathways	Score	Top Affiliating Genes
1	Innate Immune System ⁶⁵ Show member pathways Immune System ⁶⁵ Neutrophil degranulation ⁶⁵	13.8	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	13.39	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	13.15	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	Toll-like Receptor Signaling Pathway ¹ ³⁶ Show member pathways Chagas disease (American trypanosomiasis) ³⁶ Hepatitis B ³⁶ Hepatitis C ³⁶ NOD-like Receptor Signaling Pathways ⁶⁴ Regulation of toll-like receptor signaling pathway ¹	13.02	SOS1 RAF1 MAP2K2 BRAF
11	Phospholipase-C Pathway ⁶³ Show member pathways PTEN Pathway ⁶³	12.97	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 ²² VEGF and S-1P Signaling ⁶³	12.91	SOS1 RAF1 MAP2K2 BRAF
14	Focal Adhesion ¹ ³⁶ Show member pathways HGF Pathway ⁶³ Integrin-mediated Cell Adhesion ¹	12.82	SOS1 RAF1 MAP2K2 BRAF
15	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 ³⁶ IRS activation ⁶⁵ Signal attenuation ⁶⁵ Transcription Receptor-mediated HIF regulation ²² Translation Regulation of EIF2 activity ²² Translation Regulation of EIF4F activity ²² Translation Insulin regulation of translation ²²	12.8	SOS1 RAF1 PTPN11 MAP2K2 BRAF
16	NFAT and Cardiac Hypertrophy ⁶³ Show member pathways IGF1R Signaling ⁶³ Signaling Involved in Cardiac Hypertrophy ⁶³	12.79	SOS1 RAF1 MAP2K2 BRAF
17	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
18	Development Angiotensin activation of ERK ²² Show member pathways Cell adhesion Integrin inside-out signaling ²² Development ACM2 and ACM4 activation of ERK ²² Development Angiotensin signaling via PYK2 ²² Development EDNRB signaling ²² Development EPO-induced MAPK pathway ²² Development G-Proteins mediated regulation MARK-ERK signaling ²² Signal transduction IP3 signaling ²²	12.78	SOS1 RAF1 MAP2K2 BRAF
19	Pathways in cancer ³⁶	12.77	SOS1 RAF1 MAP2K2 BRAF
20	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
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 ²² Thyroid cancer ³⁶	12.76	SOS1 RAF1 PTPN11 MAP2K2 BRAF
22	CCR5 Pathway in Macrophages ⁶³ Show member pathways Androgen Signaling ⁶³ Chemokine Signaling ⁶³ Chemokine signaling pathway ³⁶	12.75	SOS1 RAF1 BRAF
23	Beta-Adrenergic Signaling ⁶³ Show member pathways CDK5 Pathway ⁶³ Erythropoietin Pathway ⁶³ Insulin Receptor Pathway ⁶³	12.74	SOS1 RAF1 MAP2K2 BRAF
24	MAPK-Erk Pathway ⁶⁶ Show member pathways Actin Dynamics Signaling Pathway ⁶⁶ G Protein-coupled Receptors Signaling ⁶⁶	12.71	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	12.7	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 ²² 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 ²²	12.67	SOS1 RAF1 PTPN11 MAP2K2 BRAF
28	Ras signaling pathway ³⁶ Show member pathways Rap1 signaling pathway ³⁶	12.63	SOS1 RAF1 PTPN11 MAP2K2 BRAF
29	Glioma ³⁶ Show member pathways Endocrine resistance ³⁶ Melanoma ³⁶ Non-small cell lung cancer ³⁶ Signaling Pathways in Glioblastoma ¹	12.62	SOS1 RAF1 MAP2K2 BRAF
30	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
31	G-AlphaQ Signaling ⁶³ Show member pathways G-AlphaI Signaling ⁶³ Thrombin Signaling ⁶³	12.62	SOS1 RAF1 MAP2K2 BRAF
32	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 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
33	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
34	Regulation of actin cytoskeleton ³⁶ ¹	12.58	SOS1 RAF1 MAP2K2 BRAF
35	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
36	Development Endothelin-1/EDNRA signaling ²² Show member pathways Cytoskeleton remodeling FAK signaling ²² Development Endothelin-1/EDNRA transactivation of EGFR ²² GnRH signaling pathway ³⁶ Inflammatory mediator regulation of TRP channels ³⁶	12.56	SOS1 RAF1 MAP2K2
37	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
38	Immune response NFAT in immune response ²² Show member pathways Immune response CD28 signaling ²² Immune response ICOS pathway in T-helper cell ²² Immune response T cell receptor signaling pathway ²²	12.54	SOS1 RAF1 MAP2K2
39	Immune response Fc epsilon RI pathway ²² Show member pathways Fc epsilon RI signaling pathway ³⁶ Fc-epsilon receptor I signaling in mast cells ¹ Immune response BCR pathway ²² VEGF signaling pathway ³⁶	12.54	SOS1 RAF1 PTPN11 MAP2K2
40	Development Dopamine D2 receptor transactivation of EGFR ²² Show member pathways Apoptosis and survival BAD phosphorylation ²² BAD Phosphorylation ⁶³ Chemotaxis CXCR4 signaling pathway ²² Development Alpha-2 adrenergic receptor activation of ERK ²²	12.53	SOS1 RAF1 PTPN11 MAP2K2
41	Cytoskeleton remodeling Regulation of actin cytoskeleton by Rho GTPases ²² Show member pathways Cell adhesion Integrin-mediated cell adhesion and migration ²² Cell adhesion Tight junctions ²² Cytoskeleton remodeling Integrin outside-in signaling ²² Development MAG-dependent inhibition of neurite outgrowth ²²	12.52	SOS1 RAF1 MAP2K2
42	TRAF Pathway ⁶³ Show member pathways 14-3-3 Induced Apoptosis ⁶³ TNF Superfamily Pathway ⁶³ Toll-Like Receptors Pathway ⁶³	12.5	SOS1 RAF1 MAP2K2
43	Negative regulation of FGFR3 signaling ⁶⁵ Show member pathways FGFR1 ligand binding and activation ⁶⁵ FGFR1c ligand binding and activation ⁶⁵ FGFRL1 modulation of FGFR1 signaling ⁶⁵ Negative regulation of FGFR1 signaling ⁶⁵ Negative regulation of FGFR2 signaling ⁶⁵ Negative regulation of FGFR4 signaling ⁶⁵ Signaling by activated point mutants of FGFR1 ⁶⁵ Signaling by FGFR1 ⁶⁵ Signaling by FGFR3 ⁶⁵ Signaling by FGFR4 ⁶⁵ Spry regulation of FGF signaling ⁶⁵	12.49	SOS1 PTPN11 BRAF
44	Angiopoietin Like Protein 8 Regulatory Pathway ¹ Show member pathways Insulin Signaling ¹ Liver X Receptor Pathway ¹	12.48	SOS1 RAF1 PTPN11 MAP2K2
45	Development ERBB-family signaling ²² Show member pathways Development EGFR signaling pathway ²² EGF Pathway ⁶³ EGFR Signaling Pathway ⁶⁶ ErbB receptor signaling network ¹ GRB7 events in ERBB2 signaling ⁶⁵ PLCG1 events in ERBB2 signaling ⁶⁵	12.48	SOS1 RAF1 MAP2K2 BRAF
46	ErbB signaling pathway ¹ ³⁶ 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	12.48	SOS1 RAF1 PTPN11 MAP2K2 BRAF
47	MicroRNAs in cancer ³⁶	12.46	SOS1 RAF1 MAP2K2
48	mTOR signaling pathway (KEGG) ⁶⁴ Show member pathways mTOR signaling pathway ³⁶	12.46	SOS1 RAF1 MAP2K2 BRAF
49	Prolactin Signaling Pathway ¹ ³⁶ Show member pathways Development Prolactin receptor signaling ²² Leptin signaling pathway ¹	12.44	SOS1 RAF1 PTPN11 MAP2K2
50	Oxytocin signaling pathway ³⁶ Show member pathways Vascular smooth muscle contraction ³⁶	12.42	RAF1 MAP2K2 BRAF

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 14)

#	Name	GO ID	Score	Top Affiliating Genes
1	heart development	GO:0007507	9.58	RAF1 PTPN11 MAP2K2
2	MAPK cascade	GO:0000165	9.56	SOS1 RAF1 MAP2K2 BRAF
3	multicellular organism growth	GO:0035264	9.54	SOS1 PTPN11
4	regulation of Rho protein signal transduction	GO:0035023	9.52	SOS1 RAF1
5	positive regulation of peptidyl-serine phosphorylation	GO:0033138	9.51	RAF1 BRAF
6	thymus development	GO:0048538	9.5	RAF1 MAP2K2 BRAF
7	somatic stem cell population maintenance	GO:0035019	9.49	RAF1 BRAF
8	epidermal growth factor receptor signaling pathway	GO:0007173	9.48	SOS1 PTPN11
9	activation of MAPKK activity	GO:0000186	9.46	RAF1 BRAF
10	positive regulation of axonogenesis	GO:0050772	9.43	MAP2K2 BRAF
11	regulation of axon regeneration	GO:0048679	9.37	MAP2K2 BRAF
12	thyroid gland development	GO:0030878	9.33	RAF1 MAP2K2 BRAF
13	neurotrophin TRK receptor signaling pathway	GO:0048011	9.13	SOS1 RAF1 PTPN11
14	face development	GO:0060324	8.8	RAF1 MAP2K2 BRAF

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	9.61	RAF1 MAP2K2 BRAF
2	protein heterodimerization activity	GO:0046982	9.58	SOS1 RAF1 BRAF
3	protein serine/threonine kinase activity	GO:0004674	9.54	RAF1 MAP2K2 BRAF
4	nucleotide binding	GO:0000166	9.5	RAF1 MAP2K2 BRAF
5	small GTPase binding	GO:0031267	9.26	RAF1 BRAF
6	MAP kinase kinase kinase activity	GO:0004709	9.16	RAF1 BRAF
7	Ras GTPase binding	GO:0017016	8.96	RAF1 BRAF
8	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 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 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 MeSH

⁴⁴ MESH via Orphanet

⁴⁵ MGI

⁴⁶ miR2Disease

⁴⁷ NCBI Bookshelf

⁴⁸ NCI

⁴⁹ NCIt

⁵⁰ NDF-RT

⁵¹ NIH Clinical Center

⁵² NIH Rare Diseases

⁵³ NINDS

⁵⁴ Novoseek

⁵⁵ Novus Biologicals

⁵⁶ OMIM

⁵⁷ OMIM via Orphanet

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