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

MCID: NNN033 MIFTS: 40	Noonan Syndrome and Noonan-Related Syndrome Categories: Cardiovascular diseases, Fetal diseases, Rare diseases	Data Licensing For inquiries, contact: [email protected]
Genes Variations Tissues Related diseases Publications 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 ⁵

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 spitz nevus and cutaneous-skeletal hypophosphatemia syndrome. 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 Disease and ERK Signaling. Affiliated tissues include cortex and heart, and related phenotypes are Decreased viability 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 top 50) (show all 171)

#	Related Disease	Score	Top Affiliating Genes
1	spitz nevus	10.3	HRAS BRAF
2	cutaneous-skeletal hypophosphatemia syndrome	10.3	LRRC56 HRAS
3	melphalan allergy	10.3	NRAS BRAF
4	syringocystadenoma papilliferum	10.3	HRAS BRAF
5	childhood leptomeningeal melanoma	10.3	NRAS HRAS
6	malignant anus melanoma	10.3	NRAS HRAS
7	noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia	10.3	PTPN11 CBL
8	meningeal melanomatosis	10.3	NRAS HRAS
9	conjunctival nevus	10.3	NRAS HRAS
10	central nervous system melanocytic neoplasm	10.3	NRAS HRAS
11	testicular spermatocytic seminoma	10.2	PTPN11 HRAS
12	malignant struma ovarii	10.2	NRAS HRAS
13	cervix melanoma	10.2	NRAS HRAS
14	acute megakaryoblastic leukemia in down syndrome	10.2	PTPN11 NRAS
15	nuchal bleb, familial	10.2	SOS1 LZTR1
16	lip and oral cavity cancer	10.2	LRRC56 HRAS BRAF
17	acral lentiginous melanoma	10.2	NRAS HRAS BRAF
18	nodular malignant melanoma	10.2	NRAS HRAS BRAF
19	histiocytosis	10.2	NRAS MAP2K1 BRAF
20	melanocytic nevus syndrome, congenital	10.2	NRAS LRRC56 HRAS
21	thyroid gland follicular carcinoma	10.2	NRAS HRAS BRAF
22	villonodular synovitis	10.2	SOS1 PTPN11
23	spitzoid melanoma	10.2	NRAS HRAS
24	large congenital melanocytic nevus	10.2	NRAS LRRC56 HRAS
25	erdheim-chester disease	10.1	NRAS MAP2K1 BRAF
26	trachea carcinoma in situ	10.1	KRAS HRAS
27	common bile duct neoplasm	10.1	KRAS HRAS
28	lentigines	10.1	RAF1 PTPN11 BRAF
29	ampulla of vater benign neoplasm	10.1	KRAS HRAS
30	bladder urachal carcinoma	10.1	KRAS HRAS
31	hepatic flexure cancer	10.1	KRAS HRAS
32	vaginal carcinosarcoma	10.1	KRAS HRAS
33	optic nerve neoplasm	10.1	SPRED1 LZTR1
34	urachus cancer	10.1	KRAS HRAS
35	adenosquamous lung carcinoma	10.1	KRAS HRAS
36	descending colon cancer	10.1	KRAS HRAS
37	mucinous intrahepatic cholangiocarcinoma	10.1	KRAS HRAS
38	sigmoid neoplasm	10.1	KRAS HRAS
39	appendiceal neoplasm	10.1	KRAS HRAS
40	adenofibroma	10.1	KRAS BRAF
41	pancreatic mucinous cystadenoma	10.1	KRAS HRAS
42	transverse colon cancer	10.1	KRAS HRAS
43	legius syndrome	10.1	SPRED1 HRAS
44	liver angiosarcoma	10.1	KRAS HRAS
45	ascending colon cancer	10.1	KRAS HRAS
46	mucinous lung adenocarcinoma	10.1	KRAS HRAS
47	cystadenofibroma	10.1	KRAS HRAS
48	pigmented villonodular synovitis	10.1	SOS1 PTPN11
49	endosalpingiosis	10.1	KRAS HRAS
50	ovarian mucinous neoplasm	10.1	KRAS HRAS

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:

²⁵ (show all 35)

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Decreased viability	GR00055-A-1	10.41	CBL HRAS BRAF KRAS
2	Decreased viability	GR00055-A-2	10.41	CBL HRAS BRAF KRAS
3	Decreased viability	GR00055-A-3	10.41	KRAS
4	Decreased viability	GR00106-A-0	10.41	KRAS
5	Decreased viability	GR00107-A-1	10.41	MAP2K1
6	Decreased viability	GR00221-A-1	10.41	HRAS NRAS KRAS
7	Decreased viability	GR00221-A-2	10.41	CBL HRAS KRAS
8	Decreased viability	GR00221-A-3	10.41	CBL HRAS MAP2K1 NRAS
9	Decreased viability	GR00221-A-4	10.41	BRAF
10	Decreased viability	GR00249-S	10.41	BRAF
11	Decreased viability	GR00301-A	10.41	BRAF KRAS
12	Decreased viability	GR00381-A-1	10.41	BRAF KRAS
13	Increased shRNA abundance (Z-score > 2)	GR00366-A-116	10.05	RAF1
14	Increased shRNA abundance (Z-score > 2)	GR00366-A-126	10.05	SOS1
15	Increased shRNA abundance (Z-score > 2)	GR00366-A-130	10.05	CBL SOS1
16	Increased shRNA abundance (Z-score > 2)	GR00366-A-148	10.05	SOS1
17	Increased shRNA abundance (Z-score > 2)	GR00366-A-149	10.05	BRAF CBL
18	Increased shRNA abundance (Z-score > 2)	GR00366-A-150	10.05	RAF1
19	Increased shRNA abundance (Z-score > 2)	GR00366-A-151	10.05	CBL RAF1
20	Increased shRNA abundance (Z-score > 2)	GR00366-A-153	10.05	CBL
21	Increased shRNA abundance (Z-score > 2)	GR00366-A-165	10.05	SOS1
22	Increased shRNA abundance (Z-score > 2)	GR00366-A-178	10.05	PTPN11
23	Increased shRNA abundance (Z-score > 2)	GR00366-A-186	10.05	CBL
24	Increased shRNA abundance (Z-score > 2)	GR00366-A-201	10.05	CBL
25	Increased shRNA abundance (Z-score > 2)	GR00366-A-204	10.05	CBL
26	Increased shRNA abundance (Z-score > 2)	GR00366-A-210	10.05	CBL
27	Increased shRNA abundance (Z-score > 2)	GR00366-A-47	10.05	BRAF
28	Increased shRNA abundance (Z-score > 2)	GR00366-A-52	10.05	RAF1
29	Increased shRNA abundance (Z-score > 2)	GR00366-A-68	10.05	SOS1
30	Increased shRNA abundance (Z-score > 2)	GR00366-A-7	10.05	PTPN11
31	Increased shRNA abundance (Z-score > 2)	GR00366-A-72	10.05	RAF1
32	Increased shRNA abundance (Z-score > 2)	GR00366-A-78	10.05	PTPN11
33	Increased shRNA abundance (Z-score > 2)	GR00366-A-81	10.05	CBL
34	Increased shRNA abundance (Z-score > 2)	GR00366-A-91	10.05	SOS1
35	Reduced mammosphere formation	GR00396-S	9.17	BRAF HRAS KRAS NRAS PTPN11 SHOC2

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

⁴⁵ (show all 22)

#	Description	MGI Source Accession	Score	Top Affiliating Genes
1	growth/size/body region	MP:0005378	10.42	BRAF CBL HRAS KRAS LRRC56 LZTR1
2	homeostasis/metabolism	MP:0005376	10.41	BRAF CBL HRAS KRAS LRRC56 MAP2K1
3	cardiovascular system	MP:0005385	10.33	BRAF CBL HRAS KRAS LRRC56 LZTR1
4	craniofacial	MP:0005382	10.31	BRAF CBL HRAS KRAS LZTR1 MAP2K1
5	endocrine/exocrine gland	MP:0005379	10.28	BRAF CBL HRAS KRAS MAP2K1 MAP2K2
6	normal	MP:0002873	10.24	BRAF HRAS KRAS MAP2K1 MAP2K2 NRAS
7	cellular	MP:0005384	10.22	BRAF CBL KRAS LZTR1 MAP2K1 MAP2K2
8	neoplasm	MP:0002006	10.2	BRAF HRAS KRAS MAP2K1 MAP2K2 NRAS
9	muscle	MP:0005369	10.19	BRAF CBL HRAS KRAS LZTR1 PTPN11
10	hearing/vestibular/ear	MP:0005377	10.16	BRAF CBL KRAS MAP2K1 MAP2K2 PTPN11
11	digestive/alimentary	MP:0005381	10.16	BRAF HRAS KRAS MAP2K1 MAP2K2 NRAS
12	embryo	MP:0005380	10.13	BRAF KRAS MAP2K1 NRAS PTPN11 RAF1
13	immune system	MP:0005387	10.13	BRAF CBL KRAS LRRC56 NRAS PTPN11
14	skeleton	MP:0005390	10.1	BRAF CBL HRAS KRAS LZTR1 MAP2K1
15	respiratory system	MP:0005388	10.06	BRAF CBL HRAS KRAS LRRC56 PTPN11
16	limbs/digits/tail	MP:0005371	10.05	BRAF CBL KRAS NRAS PTPN11 SPRED1
17	reproductive system	MP:0005389	10.02	BRAF CBL KRAS LRRC56 MAP2K1 MAP2K2
18	pigmentation	MP:0001186	10	BRAF CBL KRAS NRAS PTPN11
19	vision/eye	MP:0005391	9.96	BRAF KRAS MAP2K1 MAP2K2 NRAS PTPN11
20	hematopoietic system	MP:0005397	9.85	BRAF CBL KRAS LZTR1 NRAS PTPN11
21	mortality/aging	MP:0010768	9.8	BRAF CBL HRAS KRAS LRRC56 LZTR1
22	integument	MP:0010771	9.44	BRAF CBL HRAS KRAS LRRC56 MAP2K1

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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

Organs/tissues related to Noonan Syndrome and Noonan-Related Syndrome:

MalaCards : Cortex, Heart

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Publications for Noonan Syndrome and Noonan-Related Syndrome

Articles related to Noonan Syndrome and Noonan-Related Syndrome:

(show all 26)

#	Title	Authors	PMID	Year
1	Synergy from gene expression and network mining (SynGeNet) method predicts synergistic drug combinations for diverse melanoma genomic subtypes. ⁵	Regan-Fendt KE...Li F	30820351	2019
2	NGS testing for cardiomyopathy: Utility of adding RASopathy-associated genes. ⁵	Ceyhan-Birsoy O...Mason-Suares H	29696744	2018
3	Oncogenic Signaling Pathways in The Cancer Genome Atlas. ⁵	Sanchez-Vega F...Schultz N	29625050	2018
4	Integrating Functional Analysis in the Next-Generation Sequencing Diagnostic Pipeline of RASopathies. ⁵	Leung GKC...Chung BHY	29402968	2018
5	Engineering and Functional Characterization of Fusion Genes Identifies Novel Oncogenic Drivers of Cancer. ⁵	Lu H...Scott KL	28512244	2017
6	Visual perception skills: a comparison between patients with Noonan syndrome and 22q11.2 deletion syndrome. ⁵	Piccini G...Alfieri P	28378436	2017
7	Inherited Disease Genetics Improves the Identification of Cancer-Associated Genes. ⁵	Zhao B...Pritchard JR	27304678	2016
8	Mutation Spectrum and Phenotypic Features in Noonan Syndrome with PTPN11 Mutations: Definition of Two Novel Mutations. ⁵	Atik T...Ozkinay F	26817465	2016
9	Chronic pain in Noonan Syndrome: A previously unreported but common symptom. ⁵	Vegunta S...Grebe TA	26297936	2015
10	External ear anomalies and hearing impairment in Noonan Syndrome. ⁵	van Trier DC...Admiraal RJC	25862627	2015
11	Impaired motor cortex plasticity in patients with Noonan syndrome. ⁵	Mainberger F...Mall V	23763990	2013
12	Noonan syndrome: comparing mutation-positive with mutation-negative dutch patients. ⁵	Croonen EA...Yntema HG	23885229	2013
13	Autoimmune disease and multiple autoantibodies in 42 patients with RASopathies. ⁵	Quaio CR...Bertola DR	22488759	2012
14	Alterations in RAS-MAPK genes in 200 Spanish patients with Noonan and other neuro-cardio-facio-cutaneous syndromes. Genotype and cardiopathy. ⁵	Ezquieta B...Galbis L	22465605	2012
15	Spectrum of mutations in Noonan syndrome and their correlation with phenotypes. ⁵	Lee BH...Yoo HW	21784453	2011
16	RASopathies: Clinical Diagnosis in the First Year of Life. ⁵	Digilio MC...Dallapiccola B	22190897	2011
17	SOS1 mutations in Noonan syndrome: molecular spectrum, structural insights on pathogenic effects, and genotype-phenotype correlations. ⁵	Lepri F...Tartaglia M	21387466	2011
18	Two cases of Noonan syndrome with severe respiratory and gastroenteral involvement and the SOS1 mutation F623I. ⁵	Fabretto A...Zenker M	20673819	2010
19	SOS1 and PTPN11 mutations in five cases of Noonan syndrome with multiple giant cell lesions. ⁵	Beneteau C...Leheup B	19352411	2009
20	Dominant-negative ALK2 allele associates with congenital heart defects. ⁵	Smith KA...Bakkers J	19506109	2009
21	Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum. ⁵	Sarkozy A...Tartaglia M	19206169	2009
22	Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome. ⁵	Neumann TE...Kalscheuer V	18854871	2009
23	Pigmented villonodular synovitis in a patient with Noonan syndrome and SOS1 gene mutation. ⁵	Mascheroni E...Ugazio AG	18925667	2008
24	PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype-phenotype correlation in Korean patients with Noonan syndrome. ⁵	Ko JM...Yoo HW	19020799	2008
25	SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome. ⁵	Zenker M...Kutsche K	17586837	2007
26	Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. ⁵	Tartaglia M...Gelb BD	17143282	2007

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Genes for Noonan Syndrome and Noonan-Related Syndrome

Genes related to Noonan Syndrome and Noonan-Related Syndrome (14 elite genes):

(show all 15)

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubMed IDs
1	BRAF	B-Raf Proto-Oncogene, Serine/Threonine Kinase	Protein Coding	425	Pathogenic ⁵ Likely pathogenic ⁵	19206169 22190897 23763990 (more) 28512244 30820351
2	CBL	Cbl Proto-Oncogene	Protein Coding	425	Pathogenic ⁵ Likely pathogenic ⁵
3	HRAS	HRas Proto-Oncogene, GTPase	Protein Coding	425	Pathogenic ⁵ Likely pathogenic ⁵
4	LRRC56	Leucine Rich Repeat Containing 56	Protein Coding	425	Pathogenic ⁵ Likely pathogenic ⁵
5	LZTR1	Leucine Zipper Like Transcription Regulator 1	Protein Coding	425	Pathogenic ⁵ Likely pathogenic ⁵
6	MAP2K1	Mitogen-Activated Protein Kinase Kinase 1	Protein Coding	425	Pathogenic ⁵ Likely pathogenic ⁵
7	NRAS	NRAS Proto-Oncogene, GTPase	Protein Coding	425	Pathogenic ⁵ Likely pathogenic ⁵
8	PTPN11	Protein Tyrosine Phosphatase Non-Receptor Type 11	Protein Coding	425	Pathogenic ⁵ Likely pathogenic ⁵	26817465 19506109
9	RAF1	Raf-1 Proto-Oncogene, Serine/Threonine Kinase	Protein Coding	425	Pathogenic ⁵ Likely pathogenic ⁵
10	RIT1	Ras Like Without CAAX 1	Protein Coding	425	Pathogenic ⁵ Likely pathogenic ⁵
11	SOS1	SOS Ras/Rac Guanine Nucleotide Exchange Factor 1	Protein Coding	425	Pathogenic ⁵ Likely pathogenic ⁵	17143282 17586837 18854871 (more) 18925667 19020799 19352411 21387466 21784453 22190897 22465605 22488759 23885229 25862627 26297936 27304678 28378436 29625050 29696744 20673819 29402968
12	SPRED1	Sprouty Related EVH1 Domain Containing 1	Protein Coding	425	Pathogenic ⁵ Likely pathogenic ⁵
13	KRAS	KRAS Proto-Oncogene, GTPase	Protein Coding	400	Pathogenic ⁵
14	SHOC2	SHOC2 Leucine Rich Repeat Scaffold Protein	Protein Coding	400	Pathogenic ⁵
15	MAP2K2	Mitogen-Activated Protein Kinase Kinase 2	Protein Coding	25	Likely pathogenic ⁵

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Variations for Noonan Syndrome and Noonan-Related Syndrome

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

⁵ (show top 50) (show all 558)

#	Gene	Name	Type	Significance	ClinVarId	dbSNP ID	Position
1	PTPN11	NM_002834.5(PTPN11):c.166A>G (p.Ile56Val)	SNV	Pathogenic	40485	rs397507504	GRCh37: 12:112888150-112888150 GRCh38: 12:112450346-112450346
2	BRAF	NM_004333.6(BRAF):c.741T>G (p.Phe247Leu)	SNV	Pathogenic	55793	rs397509343	GRCh37: 7:140501331-140501331 GRCh38: 7:140801531-140801531
3	BRAF	NM_004333.6(BRAF):c.739T>C (p.Phe247Leu)	SNV	Pathogenic	180784	rs397516903	GRCh37: 7:140501333-140501333 GRCh38: 7:140801533-140801533
4	BRAF	NM_004333.6(BRAF):c.735A>C (p.Leu245Phe)	SNV	Pathogenic	40347	rs397507466	GRCh37: 7:140501337-140501337 GRCh38: 7:140801537-140801537
5	BRAF	NM_004333.6(BRAF):c.1405G>A (p.Gly469Arg)	SNV	Pathogenic	177775	rs121913357	GRCh37: 7:140481403-140481403 GRCh38: 7:140781603-140781603
6	NRAS	NM_002524.5(NRAS):c.34G>A (p.Gly12Ser)	SNV	Pathogenic	177778	rs121913250	GRCh37: 1:115258748-115258748 GRCh38: 1:114716127-114716127
7	PTPN11	NM_002834.5(PTPN11):c.226G>C (p.Glu76Gln)	SNV	Pathogenic	181496	rs121918464	GRCh37: 12:112888210-112888210 GRCh38: 12:112450406-112450406
8	RIT1	NM_006912.6(RIT1):c.244T>C (p.Phe82Leu)	SNV	Pathogenic	183407	rs869025194	GRCh37: 1:155874287-155874287 GRCh38: 1:155904496-155904496
9	RIT1	NM_006912.6(RIT1):c.265T>C (p.Tyr89His)	SNV	Pathogenic	183411	rs869025197	GRCh37: 1:155874266-155874266 GRCh38: 1:155904475-155904475
10	NRAS	NM_002524.5(NRAS):c.35G>C (p.Gly12Ala)	SNV	Pathogenic	219097	rs121913237	GRCh37: 1:115258747-115258747 GRCh38: 1:114716126-114716126
11	SPRED1	NM_152594.3(SPRED1):c.796_797del (p.Met266fs)	DEL	Pathogenic	220172	rs864622410	GRCh37: 15:38643326-38643327 GRCh38: 15:38351125-38351126
12	PTPN11	NM_002834.5(PTPN11):c.179G>T (p.Gly60Val)	SNV	Pathogenic	55797	rs397507509	GRCh37: 12:112888163-112888163 GRCh38: 12:112450359-112450359
13	SOS1	NM_005633.4(SOS1):c.925G>T (p.Asp309Tyr)	SNV	Pathogenic	45379	rs397517180	GRCh37: 2:39262581-39262581 GRCh38: 2:39035440-39035440
14	SOS1	NM_005633.4(SOS1):c.1297G>A (p.Glu433Lys)	SNV	Pathogenic	40669	rs397517147	GRCh37: 2:39250272-39250272 GRCh38: 2:39023131-39023131
15	SOS1	NM_005633.4(SOS1):c.322G>A (p.Glu108Lys)	SNV	Pathogenic	40649	rs397517164	GRCh37: 2:39285837-39285837 GRCh38: 2:39058696-39058696
16	RAF1	NM_002880.4(RAF1):c.1279A>G (p.Ser427Gly)	SNV	Pathogenic	40616	rs730881002	GRCh37: 3:12632388-12632388 GRCh38: 3:12590889-12590889
17	RAF1	NM_002880.4(RAF1):c.776C>T (p.Ser259Phe)	SNV	Pathogenic	40603	rs397516827	GRCh37: 3:12645693-12645693 GRCh38: 3:12604194-12604194
18	PTPN11	NM_002834.5(PTPN11):c.328G>A (p.Glu110Lys)	SNV	Pathogenic	40507	rs397507518	GRCh37: 12:112888312-112888312 GRCh38: 12:112450508-112450508
19	PTPN11	NM_002834.5(PTPN11):c.228G>T (p.Glu76Asp)	SNV	Pathogenic	40502	rs397507514	GRCh37: 12:112888212-112888212 GRCh38: 12:112450408-112450408
20	PTPN11	NM_002834.5(PTPN11):c.174C>A (p.Asn58Lys)	SNV	Pathogenic	40488	rs397507506	GRCh37: 12:112888158-112888158 GRCh38: 12:112450354-112450354
21	PTPN11	NM_002834.5(PTPN11):c.1493G>T (p.Arg498Leu)	SNV	Pathogenic	40554	rs397507542	GRCh37: 12:112926873-112926873 GRCh38: 12:112489069-112489069
22	BRAF	NM_004333.6(BRAF):c.1695T>G (p.Asp565Glu)	SNV	Pathogenic	40383	rs397507480	GRCh37: 7:140454033-140454033 GRCh38: 7:140754233-140754233
23	HRAS, LRRC56	NM_005343.4(HRAS):c.37G>C (p.Gly13Arg)	SNV	Pathogenic	35554	rs104894228	GRCh37: 11:534286-534286 GRCh38: 11:534286-534286
24	BRAF	NM_004333.6(BRAF):c.1495A>G (p.Lys499Glu)	SNV	Pathogenic	13976	rs180177037	GRCh37: 7:140477813-140477813 GRCh38: 7:140778013-140778013
25	BRAF	NM_004333.6(BRAF):c.1789C>G (p.Leu597Val)	SNV	Pathogenic	13969	rs121913369	GRCh37: 7:140453146-140453146 GRCh38: 7:140753346-140753346
26	CBL	NM_005188.4(CBL):c.1100A>C (p.Gln367Pro)	SNV	Pathogenic	13807	rs267606704	GRCh37: 11:119148880-119148880 GRCh38: 11:119278170-119278170
27	PTPN11	NM_002834.5(PTPN11):c.227A>T (p.Glu76Val)	SNV	Pathogenic	13337	rs121918465	GRCh37: 12:112888211-112888211 GRCh38: 12:112450407-112450407
28	BRAF	NM_004333.6(BRAF):c.735A>T (p.Leu245Phe)	SNV	Pathogenic	40348	rs397507466	GRCh37: 7:140501337-140501337 GRCh38: 7:140801537-140801537
29	BRAF	NM_001374258.1(BRAF):c.1523T>C (p.Phe508Ser)	SNV	Pathogenic	40366	rs397507473	GRCh37: 7:140481405-140481405 GRCh38: 7:140781605-140781605
30	HRAS, LRRC56	NM_005343.4(HRAS):c.38G>A (p.Gly13Asp)	SNV	Pathogenic	12604	rs104894226	GRCh37: 11:534285-534285 GRCh38: 11:534285-534285
31	LZTR1	NM_006767.4(LZTR1):c.1234C>T (p.Arg412Cys)	SNV	Pathogenic	373089	rs747430075	GRCh37: 22:21347167-21347167 GRCh38: 22:20992878-20992878
32	SPRED1	NM_152594.3(SPRED1):c.304dup (p.Thr102fs)	DUP	Pathogenic	536688	rs1555391053	GRCh37: 15:38614537-38614538 GRCh38: 15:38322336-38322337
33	SPRED1	NM_152594.3(SPRED1):c.52C>T (p.Arg18Ter)	SNV	Pathogenic	536693	rs750777752	GRCh37: 15:38591593-38591593 GRCh38: 15:38299392-38299392
34	RIT1	NM_006912.6(RIT1):c.268A>G (p.Met90Val)	SNV	Pathogenic	561681		GRCh37: 1:155874263-155874263 GRCh38: 1:155904472-155904472
35	SPRED1	NM_152594.3(SPRED1):c.1044_1045del (p.Arg349fs)	DEL	Pathogenic	1334196		GRCh37: 15:38643574-38643575 GRCh38: 15:38351373-38351374
36	SPRED1	NM_152594.3(SPRED1):c.229A>T (p.Lys77Ter)	SNV	Pathogenic	1334310	rs727504170	GRCh37: 15:38614463-38614463 GRCh38: 15:38322262-38322262
37	KRAS	NM_004985.5(KRAS):c.40G>A (p.Val14Ile)	SNV	Pathogenic	12589	rs104894365	GRCh37: 12:25398279-25398279 GRCh38: 12:25245345-25245345
38	HRAS, LRRC56	NM_005343.4(HRAS):c.34G>A (p.Gly12Ser)	SNV	Pathogenic	12602	rs104894229	GRCh37: 11:534289-534289 GRCh38: 11:534289-534289
39	PTPN11	NM_002834.5(PTPN11):c.214G>T (p.Ala72Ser)	SNV	Pathogenic	13324	rs121918453	GRCh37: 12:112888198-112888198 GRCh38: 12:112450394-112450394
40	PTPN11	NM_002834.5(PTPN11):c.215C>G (p.Ala72Gly)	SNV	Pathogenic	13325	rs121918454	GRCh37: 12:112888199-112888199 GRCh38: 12:112450395-112450395
41	PTPN11	NM_002834.5(PTPN11):c.922A>G (p.Asn308Asp)	SNV	Pathogenic	13326	rs28933386	GRCh37: 12:112915523-112915523 GRCh38: 12:112477719-112477719
42	PTPN11	NM_002834.5(PTPN11):c.923A>G (p.Asn308Ser)	SNV	Pathogenic	13327	rs121918455	GRCh37: 12:112915524-112915524 GRCh38: 12:112477720-112477720
43	PTPN11	NM_002834.5(PTPN11):c.836A>G (p.Tyr279Cys)	SNV	Pathogenic	13328	rs121918456	GRCh37: 12:112910827-112910827 GRCh38: 12:112473023-112473023
44	PTPN11	NM_002834.5(PTPN11):c.184T>G (p.Tyr62Asp)	SNV	Pathogenic	13329	rs121918460	GRCh37: 12:112888168-112888168 GRCh38: 12:112450364-112450364
45	PTPN11	NM_002834.5(PTPN11):c.182A>G (p.Asp61Gly)	SNV	Pathogenic	13330	rs121918461	GRCh37: 12:112888166-112888166 GRCh38: 12:112450362-112450362
46	PTPN11	NM_002834.5(PTPN11):c.1403C>T (p.Thr468Met)	SNV	Pathogenic	13331	rs121918457	GRCh37: 12:112926270-112926270 GRCh38: 12:112488466-112488466
47	PTPN11	NM_002834.5(PTPN11):c.188A>G (p.Tyr63Cys)	SNV	Pathogenic	13333	rs121918459	GRCh37: 12:112888172-112888172 GRCh38: 12:112450368-112450368
48	PTPN11	NM_002834.5(PTPN11):c.218C>T (p.Thr73Ile)	SNV	Pathogenic	13334	rs121918462	GRCh37: 12:112888202-112888202 GRCh38: 12:112450398-112450398
49	PTPN11	NM_002834.5(PTPN11):c.854T>C (p.Phe285Ser)	SNV	Pathogenic	13335	rs121918463	GRCh37: 12:112915455-112915455 GRCh38: 12:112477651-112477651
50	PTPN11	NM_002834.5(PTPN11):c.236A>G (p.Gln79Arg)	SNV	Pathogenic	13340	rs121918466	GRCh37: 12:112888220-112888220 GRCh38: 12:112450416-112450416

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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 213)

#	Super pathways	Score	Top Affiliating Genes
1	Disease ⁶⁶ Show member pathways Infectious disease ⁶⁶	13.97	BRAF CBL HRAS KRAS MAP2K1 MAP2K2
2	ERK Signaling ⁶⁴ Show member pathways ILK Signaling ⁶⁴ MAPK Signaling ⁶⁴ Molecular Mechanisms of Cancer ⁶⁴ Rho Family GTPases ⁶⁴	13.94	SOS1 RAF1 NRAS MAP2K2 MAP2K1 KRAS
3	Apoptotic Pathways in Synovial Fibroblasts ⁶⁴ Show member pathways Actin-Based Motility by Rho Family GTPases ⁶⁴ Cellular Apoptosis Pathway ⁶⁴ DHA Signaling ⁶⁴ eIF2 Pathway ⁶⁴ ERK5 Signaling ⁶⁴ Glioma Invasiveness ⁶⁴ Mitochondrial Apoptosis ⁶⁴ Nuclear Receptor Activation by Vitamin-A ⁶⁴ p53 Mediated Apoptosis ⁶⁴ PPAR Pathway ⁶⁴ Rac1 Pathway ⁶⁴ Rap1 Pathway ⁶⁴ Telomerase Components in Cell Signaling ⁶⁴	13.92	BRAF HRAS KRAS MAP2K1 MAP2K2 NRAS
4	Signal Transduction ⁶⁶	13.92	SPRED1 SOS1 SHOC2 RIT1 RAF1 PTPN11
5	GPCR Pathway ⁶⁴ Show member pathways Breast Cancer Regulation by Stathmin1 ⁶⁴ Estrogen Pathway ⁶⁴ NFAT in Immune Response ⁶⁴ P2Y Receptor Signaling ⁶⁴ Pancreatic Adenocarcinoma ⁶⁴ Paxillin Interactions ⁶⁴ Ras Pathway ⁶⁴	13.81	SOS1 RAF1 NRAS MAP2K2 MAP2K1 KRAS
6	MIF Mediated Glucocorticoid Regulation ⁶⁴ Show member pathways all-trans-Retinoic Acid Signaling in Brain ⁶⁴ Endothelin-1 Signaling Pathway ⁶⁴ Glucocorticoid Receptor Signaling ⁶⁴ IL-6 Pathway ⁶⁴ MIF Regulation of Innate Immune Cells ⁶⁴ NFAT Signaling and Lymphocyte Interactions ⁶⁴ Overview of proinflammatory and profibrotic mediators ⁷⁴ PEDF Induced Signaling ⁶⁴ PGC1Alpha Pathway ⁶⁴ RAR-Gamma-RXR-Alpha Degradation ⁶⁴ STAT3 Pathway ⁶⁴	13.74	BRAF HRAS KRAS MAP2K1 MAP2K2 NRAS
7	TGF-Beta Pathway ⁶⁴ Show member pathways JAK-STAT Pathway ⁶⁴ JNK Pathway ⁶⁴ MAPK Family Pathway ⁶⁴ Regulation of eIF4 and p70S6K ⁶⁴ SOCS Pathway ⁶⁴	13.71	SOS1 RAF1 PTPN11 NRAS MAP2K2 MAP2K1
8	Activation of cAMP-Dependent PKA ⁶⁴ Show member pathways Activation of PKA through GPCR ⁶⁴ cAMP Pathway ⁶⁴ PKA Signaling ⁶⁴	13.68	BRAF HRAS KRAS MAP2K1 MAP2K2 NRAS
9	Prolactin Signaling ⁶⁴ Show member pathways Development Prolactin receptor signaling ²² EGFR Inhibitor Pathway, Pharmacodynamics ⁶⁰ EGFR tyrosine kinase inhibitor resistance ⁷⁴ ErbB Family Pathway ⁶⁴ ErbB signaling pathway ⁷⁴ ErbB2-ErbB3 Heterodimers ⁶⁴ ErbB4 Pathway ⁶⁴ Estrogen-stimulated signaling through PRKCZ ⁶⁶ Glioblastoma Multiforme ⁶⁴ Glioblastoma signaling pathways ⁷⁴ Growth Hormone Signaling ⁶⁴ HMGB1 Pathway ⁶⁴ IL-2 Pathway ⁶⁴ LPS Stimulated MAPK Signaling ⁶⁴ PACAP Signaling ⁶⁴ PI3K Signaling in B-Lymphocyte ⁶⁴ TCA cycle nutrient use and invasiveness of ovarian cancer ⁷⁴ Thrombopoietin Pathway ⁶⁴ TREM1 Pathway ⁶⁴ UVA-Induced MAPK Signaling ⁶⁴ UVB-Induced MAPK Signaling ⁶⁴ UVC-Induced MAPK Signaling ⁶⁴	13.65	SOS1 RAF1 PTPN11 NRAS MAP2K2 MAP2K1
10	Integrin Pathway ⁶⁴ Show member pathways FAK1 Signaling ⁶⁴ GnRH Signaling ⁶⁴ Inhibition of Angiogenesis by TSP1 ⁶⁴ Transendothelial Migration of Leukocytes ⁶⁴ UPA-UPAR Pathway ⁶⁴	13.55	BRAF HRAS KRAS MAP2K1 MAP2K2 NRAS
11	RAF/MAP kinase cascade ⁶⁶ Show member pathways Diseases of signal transduction by growth factor receptors and second messengers ⁶⁶ MAPK family signaling cascades ⁶⁶ MAPK1/MAPK3 signaling ⁶⁶	13.54	BRAF CBL HRAS KRAS MAP2K1 MAP2K2
12	Nanog in Mammalian ESC Pluripotency ⁶⁴ Show member pathways 14-3-3 Induced Intracellular Signaling ⁶⁴ eNOS Signaling ⁶⁴ GSK3 Signaling ⁶⁴	13.47	SOS1 RAF1 NRAS MAP2K2 MAP2K1 KRAS
13	CREB Pathway ⁶⁴ Show member pathways Activation of PKC through GPCR ⁶⁴ Intracellular Calcium Signaling ⁶⁴ IP3 Pathway ⁶⁴	13.45	SOS1 RAF1 NRAS MAP2K2 MAP2K1 KRAS
14	Cytokine Signaling in Immune system ⁶⁶ Show member pathways Signaling by Interleukins ⁶⁶	13.45	SOS1 PTPN11 NRAS MAP2K1 KRAS HRAS
15	ADORA2B mediated anti-inflammatory cytokines production ⁶⁶ Show member pathways Alpha-Adrenergic Signaling ⁶⁴ Androgen receptor signaling pathway ⁷⁴ Anti-inflammatory response favouring Leishmania parasite infection ⁶⁶ Beta-agonist/Beta-blocker Pathway, Pharmacodynamics ⁶⁰ CD163 mediating an anti-inflammatory response ⁶⁶ Cytoskeleton remodeling Role of PKA in cytoskeleton reorganisation ²² G alpha (z) signalling events ⁶⁶ G protein signaling pathways ⁷⁴ Glucagon signaling in metabolic regulation ⁶⁶ GPER1 signaling ⁶⁶ Hedgehog Signaling in Mammals ⁶⁴ Leishmania infection ⁶⁶ Leishmania parasite growth and survival ⁶⁶ LTC4-CYSLTR mediated IL4 production ⁶⁶ Relaxin Pathway ⁶⁴ Signal transduction cAMP signaling ²²	13.4	RAF1 NRAS MAP2K2 MAP2K1 KRAS HRAS
16	Response to elevated platelet cytosolic Ca2+ ⁶⁶ Show member pathways Disinhibition of SNARE formation ⁶⁶ Hemostasis ⁶⁶ Platelet activation, signaling and aggregation ⁶⁶ Platelet degranulation ⁶⁶	13.38	SOS1 RAF1 PTPN11 NRAS KRAS HRAS
17	Phospholipase-C Pathway ⁶⁴ Show member pathways PTEN Pathway ⁶⁴	13.27	SOS1 RAF1 NRAS MAP2K2 MAP2K1 KRAS
18	p70S6K Signaling ⁶⁴ Show member pathways mTOR Pathway ⁶⁴ Renin-Angiotensin Pathway ⁶⁴	13.23	SOS1 RAF1 NRAS MAP2K2 MAP2K1 KRAS
19	PI3K-Akt signaling pathway ⁷⁴ Show member pathways Focal adhesion: PI3K-Akt-mTOR-signaling pathway ⁷⁴	13.14	HRAS KRAS MAP2K1 MAP2K2 NRAS RAF1
20	Sertoli-Sertoli Cell Junction Dynamics ⁶⁴ Show member pathways Epithelial Tight Junctions ⁶⁴ Germ Cell-Sertoli Cell Junction Dynamics ⁶⁴	13.12	RAF1 NRAS MAP2K2 MAP2K1 KRAS HRAS
21	TCR Signaling (Qiagen) ⁶⁴ Show member pathways Fc-EpsilonRI Pathway ⁶⁴ ITK and TCR Signaling ⁶⁴ PDGF Pathway ⁶⁴ PKC-Theta Pathway ⁶⁴	13.11	SOS1 RAF1 NRAS MAP2K2 MAP2K1 KRAS
22	Beta-Adrenergic Signaling ⁶⁴ Show member pathways CDK5 Pathway ⁶⁴ Erythropoietin Pathway ⁶⁴ Insulin Pathway ⁷⁰ Insulin Receptor Pathway ⁶⁴	13.11	BRAF CBL HRAS KRAS MAP2K1 MAP2K2
23	NFAT and Cardiac Hypertrophy ⁶⁴ Show member pathways IGF1R Signaling ⁶⁴ Signaling Involved in Cardiac Hypertrophy ⁶⁴	13.09	SOS1 RAF1 NRAS MAP2K2 MAP2K1 KRAS
24	Toll-like receptor signaling pathway ⁷⁴ Show member pathways Hepatitis B infection ⁷⁴ Measles virus infection ⁷⁴ Regulation of toll-like receptor signaling pathway ⁷⁴	13.08	SOS1 RAF1 NRAS MAP2K2 MAP2K1 KRAS
25	TNFR1 Pathway ⁶⁴ Show member pathways Apoptosis ⁷⁴ Apoptosis and survival TNFR1 signaling pathway ²² Apoptosis modulation by HSP70 ⁷⁴ Apoptosis through Death Receptors ⁶⁴ Apoptotic Pathways Triggered By HIV1 ⁶⁴ Ceramide signaling pathway ⁶¹ DR3 Signaling ⁶⁴ GITR Pathway ⁶⁴ HIV-1 Nef: Negative effector of Fas and TNF-alpha ⁶¹ Stimulation of the cell death response by PAK-2p34 ⁶⁶ TNF Signaling ⁶⁴ TNF-related weak inducer of apoptosis (TWEAK) signaling pathway ⁷⁴ TRAIL Pathway ⁶⁴ TWEAK Pathway ⁶⁴	13.06	CBL HRAS MAP2K1 MAP2K2 RAF1 SOS1
26	CCR5 Pathway in Macrophages ⁶⁴ Show member pathways Androgen Signaling ⁶⁴ Chemokine Signaling ⁶⁴ Chemokine signaling pathway ⁷⁴	13.06	SOS1 RAF1 NRAS MAP2K1 KRAS HRAS
27	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	13.06	SOS1 RAF1 NRAS MAP2K2 MAP2K1 KRAS
28	Alzheimer's disease and miRNA effects ⁷⁴ Show member pathways Alzheimer's disease ⁷⁴	13.04	RAF1 NRAS MAP2K2 MAP2K1 KRAS HRAS
29	IL-9 Signaling Pathways ⁶⁵ Show member pathways Adipocytokines and Insulin Signaling ⁶⁵ Common Cytokine Receptor Gamma-Chain Family 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 Pathway ⁶⁴ IL-4 Signaling Pathways ⁶⁵ IL-7 Signaling Pathways ⁶⁵ IL-9 Pathway ⁶⁴ Immune response IL-9 signaling pathway ²² Interleukin-9 signaling ⁶⁶	13.04	SOS1 RAF1 PTPN11 NRAS MAP2K2 MAP2K1
30	Downstream signaling of activated FGFR2 ⁶⁶ Show member pathways Activated NTRK2 signals through CDK5 ⁶⁶ Activated NTRK2 signals through FRS2 and FRS3 ⁶⁶ Activated NTRK2 signals through FYN ⁶⁶ Activated NTRK2 signals through PI3K ⁶⁶ Activated NTRK2 signals through PLCG1 ⁶⁶ Activated NTRK2 signals through RAS ⁶⁶ Activated point mutants of FGFR2 ⁶⁶ BDNF activates NTRK2 (TRKB) signaling ⁶⁶ betaKlotho-mediated ligand binding ⁶⁶ Downstream signaling of activated FGFR1 ⁶⁶ Downstream signaling of activated FGFR3 ⁶⁶ Downstream signaling of activated FGFR4 ⁶⁶ FGFR2c ligand binding and activation ⁶⁶ FGFR4 ligand binding and activation ⁶⁶ FGFR4 mutant receptor activation ⁶⁶ FRS-mediated FGFR1 signaling ⁶⁶ FRS-mediated FGFR2 signaling ⁶⁶ FRS-mediated FGFR3 signaling ⁶⁶ FRS-mediated FGFR4 signaling ⁶⁶ Inhibition of Ribosome Biogenesis by p19(ARF) ⁶⁴ NTF3 activates NTRK2 (TRKB) signaling ⁶⁶ NTF4 activates NTRK2 (TRKB) signaling ⁶⁶ NTRK2 activates RAC1 ⁶⁶ Phospholipase C-mediated cascade: FGFR1 ⁶⁶ Phospholipase C-mediated cascade; FGFR2 ⁶⁶ Phospholipase C-mediated cascade; FGFR3 ⁶⁶ Phospholipase C-mediated cascade; FGFR4 ⁶⁶ PI-3K cascade:FGFR1 ⁶⁶ PI-3K cascade:FGFR2 ⁶⁶ PI-3K cascade:FGFR3 ⁶⁶ PI-3K cascade:FGFR4 ⁶⁶ SHC-mediated cascade:FGFR1 ⁶⁶ SHC-mediated cascade:FGFR2 ⁶⁶ SHC-mediated cascade:FGFR3 ⁶⁶ SHC-mediated cascade:FGFR4 ⁶⁶ Signaling by FGFR3 in disease ⁶⁶ Signaling by FGFR4 in disease ⁶⁶ Signaling by NTRK2 (TRKB) ⁶⁶	13.01	SOS1 PTPN11 NRAS KRAS HRAS
31	fMLP Pathway ⁶⁴ Show member pathways CXCR4 Pathway ⁶⁴ Huntington's Disease Pathway ⁶⁴ Internalin Pathway ⁶⁴ Signal transduction Activation of PKC via G-Protein coupled receptor ²²	13.01	SOS1 RAF1 NRAS MAP2K2 MAP2K1 KRAS
32	MAPK-Erk Pathway ⁶⁷ Show member pathways Actin Dynamics Signaling Pathway ⁶⁷ G Protein-coupled Receptors Signaling ⁶⁷	12.98	SPRED1 RAF1 NRAS MAP2K2 MAP2K1 KRAS
33	Translation Insulin regulation of translation ²² Show member pathways Butyrate-induced histone acetylation ⁷⁴ Cell adhesion PLAU signaling ²² Development CNTF receptor signaling ²² Development Growth hormone signaling via PI3K/AKT and MAPK cascades ²² Overview of perturbations to host-cell autophagy, induced by distinct proteins of SARS-CoV-2 ⁷⁴ Regulation of lipid metabolism Insulin signaling-generic cascades ²² Transcription Receptor-mediated HIF regulation ²² Translation Regulation of EIF2 activity ²² Translation Regulation of EIF4F activity ²² Translation inhibitors in chronically activated PDGFRA cells ⁷⁴	12.96	CBL HRAS MAP2K1 MAP2K2 PTPN11 RAF1
34	G-AlphaQ Signaling ⁶⁴ Show member pathways G-AlphaI Signaling ⁶⁴ PAR4-mediated thrombin signaling events ⁶¹ Thrombin Signaling ⁶⁴	12.94	BRAF HRAS KRAS MAP2K1 MAP2K2 NRAS
35	Endometrial cancer ⁷⁴ Show member pathways Chromosomal and microsatellite instability in colorectal cancer ⁷⁴ Melanoma ⁷⁴ Non-small cell lung cancer ⁷⁴ Pancreatic adenocarcinoma pathway ⁷⁴ Signal transduction PTEN pathway ²²	12.93	BRAF CBL HRAS KRAS MAP2K1 MAP2K2
36	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 Signaling in Gap Junctions ⁶⁴	12.92	SOS1 RAF1 NRAS MAP2K2 MAP2K1 KRAS
37	4-1BB Pathway ⁶⁴ Show member pathways CD27 Pathway ⁶⁴ CD40 Signaling ⁶⁴ CMV and MAPK Pathways ⁶⁴ NF-KappaB Activation by EBV ⁶⁴ NF-kappaB Activation by Viruses ⁶⁴ PKR Pathway ⁶⁴ SUMO Pathway ⁶⁴ TNFR2 Pathway ⁶⁴	12.9	RAF1 NRAS MAP2K2 MAP2K1 KRAS HRAS
38	Signaling downstream of RAS mutants ⁶⁶ Show member pathways MAP2K and MAPK activation ⁶⁶ Negative regulation of MAPK pathway ⁶⁶ Paradoxical activation of RAF signaling by kinase inactive BRAF ⁶⁶ RAF activation ⁶⁶ Signaling by high-kinase activity BRAF mutants ⁶⁶ Signaling by moderate kinase activity BRAF mutants ⁶⁶ Signaling by RAF1 mutants ⁶⁶ Signaling by RAS mutants ⁶⁶	12.9	BRAF HRAS KRAS MAP2K1 MAP2K2 NRAS
39	G-Beta Gamma Signaling ⁶⁴ Show member pathways CRHR Pathway ⁶⁴ GHRH Signaling ⁶⁴	12.9	SOS1 RAF1 NRAS MAP2K2 MAP2K1 KRAS
40	Signaling by Receptor Tyrosine Kinases ⁶⁶	12.89	BRAF CBL HRAS KRAS MAP2K1 MAP2K2
41	Neuropathic Pain-Signaling in Dorsal Horn Neurons ⁶⁴ Show member pathways Aldosterone Signaling in Epithelial Cells ⁶⁴ Cholera Infection ⁶⁴	12.86	BRAF KRAS MAP2K1 MAP2K2 RAF1 SOS1
42	IL-1 Family Signaling Pathways ⁶⁵ Show member pathways IL1 signaling pathway ⁶⁷ Immune response IL-1 signaling pathway ²² Interleukin-1 (IL-1) structural pathway ⁷⁴ Interleukin-33 signaling ⁶⁶ Interleukin-36 pathway ⁶⁶ Mucin expression in CF via TLRs, EGFR signaling pathways ²² Pathogen or Damage-activated C-Type Lectin Receptor Signaling Pathways ⁶⁵	12.86	SOS1 RAF1 PTPN11 MAP2K2 MAP2K1 KRAS
43	Insulin receptor signalling cascade ⁶⁶ Show member pathways Glucose homeostasis ⁷⁴ IGF1R signaling cascade ⁶⁶ IRS activation ⁶⁶ IRS-mediated signalling ⁶⁶ IRS-related events triggered by IGF1R ⁶⁶ PI3K Cascade ⁶⁶ SHC-related events triggered by IGF1R ⁶⁶ Signal attenuation ⁶⁶ Signaling by Insulin receptor ⁶⁶ Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) ⁶⁶ SOS-mediated signalling ⁶⁶	12.85	SOS1 PTPN11 NRAS KRAS HRAS
44	Malignant pleural mesothelioma ⁷⁴	12.84	SOS1 RAF1 MAP2K2 MAP2K1 HRAS
45	Overview of interferons-mediated signaling pathway ⁷⁴ Show member pathways all-trans-Retinoic Acid Mediated Apoptosis ⁶⁴ Cytokine Network ⁶⁴ Immune response IFN alpha/beta signaling pathway ²² Interferon alpha/beta signaling ⁶⁶ Jak/STAT Signaling Pathway ⁶⁵ Regulation of IFNA/IFNB signaling ⁶⁶ Type III interferon signaling ⁷⁴	12.84	RAF1 PTPN11 NRAS MAP2K2 MAP2K1 KRAS
46	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	12.83	SPRED1 SOS1 PTPN11 NRAS KRAS HRAS
47	CNTF Signaling ⁶⁴ Show member pathways Activation of the AP-1 family of transcription factors ⁶⁶ FLT3 Signaling ⁶⁴ G-protein signaling Ras family GTPases in kinase cascades (scheme) ²² Host-pathogen interaction of human coronaviruses - MAPK signaling ⁷⁴ IL-3 Pathway ⁶⁴ Immune response Oncostatin M signaling via MAPK in human cells ²² Inhibition of exosome biogenesis and secretion by Manumycin A in CRPC cells ⁷⁴ MAPK cascade ⁷⁴ Nur77-Induced AICD in Macrophage ⁶⁴ OSM Pathway ⁶⁴	12.82	SOS1 RAF1 PTPN11 NRAS MAP2K2 MAP2K1
48	TNF Superfamily - Human Ligand-Receptor Interactions and their Associated Functions ⁶⁵ Show member pathways 14-3-3 Induced Apoptosis ⁶⁴ TNF Superfamily Pathway ⁶⁴ TNFs bind their physiological receptors ⁶⁶ TRAF Pathway ⁶⁴	12.77	SOS1 RAF1 MAP2K2 MAP2K1 HRAS
49	Angiopoietin-like protein 8 regulatory pathway ⁷⁴ Show member pathways Insulin signaling ⁷⁴ Liver X receptor pathway ⁷⁴	12.77	SOS1 RAF1 PTPN11 MAP2K2 MAP2K1 HRAS
50	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	12.76	SOS1 RAF1 MAP2K2 MAP2K1 HRAS

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	GTPase complex	GO:1905360	8.92	SOS1 HRAS

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

(show all 26)

#	Name	GO ID	Score	Top Affiliating Genes
1	signal transduction	GO:0007165	10.36	BRAF CBL HRAS KRAS MAP2K1 NRAS
2	positive regulation of ERK1 and ERK2 cascade	GO:0070374	10.23	PTPN11 MAP2K1 HRAS BRAF
3	positive regulation of MAPK cascade	GO:0043410	10.1	RAF1 MAP2K2 MAP2K1 HRAS
4	positive regulation of protein phosphorylation	GO:0001934	10.09	RAF1 KRAS HRAS BRAF
5	epidermal growth factor receptor signaling pathway	GO:0007173	10.08	BRAF CBL PTPN11 SOS1
6	fibroblast growth factor receptor signaling pathway	GO:0008543	10.07	SOS1 SHOC2 PTPN11
7	thymus development	GO:0048538	10.06	BRAF MAP2K1 MAP2K2 RAF1
8	ERK1 and ERK2 cascade	GO:0070371	10.05	BRAF MAP2K1 MAP2K2
9	positive regulation of axonogenesis	GO:0050772	10	BRAF MAP2K1 MAP2K2
10	neurotrophin TRK receptor signaling pathway	GO:0048011	9.97	SOS1 RAF1 PTPN11
11	thyroid gland development	GO:0030878	9.97	RAF1 MAP2K2 MAP2K1 BRAF
12	Bergmann glial cell differentiation	GO:0060020	9.92	PTPN11 MAP2K1
13	regulation of stress-activated MAPK cascade	GO:0032872	9.91	MAP2K2 MAP2K1
14	regulation of early endosome to late endosome transport	GO:2000641	9.9	MAP2K2 MAP2K1
15	trachea formation	GO:0060440	9.88	MAP2K1 MAP2K2
16	face development	GO:0060324	9.86	RAF1 MAP2K2 MAP2K1 BRAF
17	regulation of Golgi inheritance	GO:0090170	9.85	MAP2K2 MAP2K1
18	epithelial cell proliferation involved in lung morphogenesis	GO:0060502	9.84	MAP2K2 MAP2K1
19	regulation of axon regeneration	GO:0048679	9.83	MAP2K2 MAP2K1 BRAF
20	cerebellar cortex formation	GO:0021697	9.81	PTPN11 MAP2K1
21	insulin receptor signaling pathway	GO:0008286	9.78	SOS1 RAF1 HRAS
22	Ras protein signal transduction	GO:0007265	9.73	HRAS KRAS NRAS RIT1 SHOC2 SOS1
23	positive regulation of protein serine/threonine kinase activity	GO:0071902	9.7	SOS1 RAF1 MAP2K2 MAP2K1 KRAS
24	insulin-like growth factor receptor signaling pathway	GO:0048009	9.62	MAP2K1 MAP2K2 RAF1 SOS1
25	positive regulation of miRNA maturation	GO:1903800	9.57	MAP2K2 MAP2K1
26	MAPK cascade	GO:0000165	9.47	RAF1 NRAS MAP2K2 MAP2K1 KRAS HRAS

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

#	Name	GO ID	Score	Top Affiliating Genes
1	nucleotide binding	GO:0000166	9.92	RIT1 RAF1 NRAS MAP2K2 MAP2K1 KRAS
2	scaffold protein binding	GO:0097110	9.85	MAP2K2 MAP2K1 BRAF
3	GDP binding	GO:0019003	9.76	HRAS KRAS NRAS RIT1
4	MAP kinase kinase activity	GO:0004708	9.73	MAP2K2 MAP2K1 BRAF
5	MAP-kinase scaffold activity	GO:0005078	9.71	MAP2K2 MAP2K1
6	G protein activity	GO:0003925	9.56	RIT1 NRAS KRAS HRAS
7	protein serine/threonine kinase activator activity	GO:0043539	9.23	SOS1 RAF1 MAP2K2 MAP2K1 KRAS HRAS