Noonan Syndrome 3 disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

NS3 MCID: NNN010 MIFTS: 49	Noonan Syndrome 3 (NS3) Categories: Cardiovascular diseases, Ear diseases, Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Reproductive diseases, Skin diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Expand all tables

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Aliases & Classifications for Noonan Syndrome 3

MalaCards integrated aliases for Noonan Syndrome 3:

Name: Noonan Syndrome 3 ⁵⁶ ¹² ⁵² ⁷³ ²⁹ ¹³ ⁶ ¹⁵ ⁷¹

Ns3 ⁵⁶ ¹² ⁵² ⁷³

Kras Gene Related Noonan Syndrome ⁵²

Noonan Syndrome, Type 3 ³⁹

Characteristics:

OMIM:

⁵⁶

Inheritance:
autosomal dominant

Miscellaneous:
variable features present

HPO:

³¹

noonan syndrome 3:
Inheritance autosomal dominant inheritance

Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Fetal diseases
Anatomical: Ear diseases Neuronal diseases Eye diseases Cardiovascular diseases Nephrological diseases Reproductive diseases Skin diseases Endocrine diseases

See all MalaCards categories (disease lists)

ICD10: ³²

Congenital malformations, deformations and chromosomal abnormalities

Other congenital malformations

Other specified congenital malformation syndromes affecting multiple systems

Congenital malformation syndromes predominantly associated with short stature

External Ids:

Disease Ontology ¹² DOID:0060581

OMIM ⁵⁶ 609942

OMIM Phenotypic Series ⁵⁶ PS163950

MeSH ⁴³ D009634

ICD10 ³² Q87.1

MedGen ⁴¹ C1860991

UMLS ⁷¹ C1860991

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Summaries for Noonan Syndrome 3

UniProtKB/Swiss-Prot : ⁷³ Noonan syndrome 3: A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells.

MalaCards based summary : Noonan Syndrome 3, also known as ns3, is related to hepatitis c virus and hepatitis c. An important gene associated with Noonan Syndrome 3 is KRAS (KRAS Proto-Oncogene, GTPase), and among its related pathways/superpathways are Regulation of lipid metabolism Insulin signaling-generic cascades and Endometrial cancer. Affiliated tissues include heart, skin and bone, and related phenotypes are cryptorchidism and cystic hygroma

Disease Ontology : ¹² A Noonan syndrome that has material basis in heterozygous mutation in the KRAS gene.

OMIM : ⁵⁶ Noonan syndrome is an autosomal dominant dysmorphic syndrome characterized primarily by dysmorphic facial features, cardiac abnormalities, and short stature, among other features (summary by Shah et al., 1999). For a phenotypic description and a discussion of genetic heterogeneity of Noonan syndrome, see NS1 (163950), which is caused by mutations in the PTPN11 gene (176876). Approximately 50% of cases of Noonan syndrome are caused by mutations in PTPN11. (609942)

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Related Diseases for Noonan Syndrome 3

Diseases in the Noonan Syndrome 1 family:

Noonan Syndrome 2	Noonan Syndrome 3
Noonan Syndrome 4	Noonan Syndrome 5
Noonan Syndrome 6	Noonan Syndrome 7
Noonan Syndrome 8	Noonan Syndrome 9
Noonan Syndrome 10	Noonan Syndrome 11
Noonan Syndrome 12

Diseases related to Noonan Syndrome 3 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 120)

#	Related Disease	Score	Top Affiliating Genes
1	hepatitis c virus	11.3
2	hepatitis c	11.2
3	dengue virus	11.0
4	encephalitis	10.8
5	west nile virus	10.7
6	japanese encephalitis	10.7
7	diarrhea	10.7
8	vaccinia	10.7
9	signet ring basal cell carcinoma	10.7	KRAS HRAS
10	trachea carcinoma in situ	10.7	KRAS HRAS
11	yellow fever	10.7
12	cobblestone retinal degeneration	10.7	KRAS HRAS
13	nasal cavity adenocarcinoma	10.7	KRAS HRAS
14	breast squamous cell carcinoma	10.6	LRRC56 HRAS
15	ampulla of vater neoplasm	10.6	KRAS HRAS
16	liver cirrhosis	10.6
17	descending colon cancer	10.6	KRAS HRAS
18	periampullary adenoma	10.6	KRAS HRAS
19	adenosquamous lung carcinoma	10.6	KRAS HRAS
20	spitz nevus	10.6	LRRC56 HRAS
21	acneiform dermatitis	10.6	KRAS HRAS
22	transverse colon cancer	10.6	KRAS HRAS
23	appendiceal neoplasm	10.6	KRAS HRAS
24	gallbladder benign neoplasm	10.6	KRAS HRAS
25	neurofibromatosis	10.6	PTPN11 KRAS HRAS
26	myh-associated polyposis	10.6	KRAS HRAS
27	appendix adenocarcinoma	10.6	KRAS HRAS
28	leopard syndrome 2	10.6	RAF1 PTPN11
29	mucinous lung adenocarcinoma	10.6	KRAS HRAS
30	large intestine adenocarcinoma	10.6	LRRC56 KRAS HRAS
31	noonan syndrome and noonan-related syndrome	10.6	SOS1 RAF1 PTPN11
32	skin granular cell tumor	10.6	SOS1 SHOC2 PTPN11
33	testicular spermatocytic seminoma	10.6	PTPN11 HRAS
34	pulmonary valve disease	10.6	SOS1 SHOC2 PTPN11
35	respiratory system benign neoplasm	10.6	RAF1 KRAS HRAS
36	pulmonary valve stenosis	10.6	SOS1 SHOC2 PTPN11
37	wolffian duct adenocarcinoma	10.6	KRAS HRAS
38	lung adenoma	10.6	RAF1 KRAS HRAS
39	heart septal defect	10.6	SOS1 SHOC2 PTPN11
40	embryonal rhabdomyosarcoma	10.6	PTPN11 KRAS HRAS
41	dengue disease	10.6
42	villonodular synovitis	10.6	SOS1 PTPN11
43	ascending colon cancer	10.6	KRAS HRAS
44	biliary tract benign neoplasm	10.6	KRAS HRAS
45	serous cystadenocarcinoma	10.6	LRRC56 KRAS HRAS
46	tumor of exocrine pancreas	10.6	KRAS HRAS
47	patent ductus arteriosus 1	10.6	SOS1 SHOC2 PTPN11
48	pancreatic acinar cell adenocarcinoma	10.5	KRAS HRAS
49	endosalpingiosis	10.5	KRAS HRAS
50	neurofibromatosis-noonan syndrome	10.5	SOS1 SHOC2 PTPN11 HRAS

Graphical network of the top 20 diseases related to Noonan Syndrome 3:

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Symptoms & Phenotypes for Noonan Syndrome 3

Human phenotypes related to Noonan Syndrome 3:

³¹ (show all 29)

#	Description	HPO Frequency	HPO Source Accession
1	cryptorchidism ³¹	very rare (1%)	HP:0000028
2	cystic hygroma ³¹	very rare (1%)	HP:0000476
3	global developmental delay ³¹		HP:0001263
4	delayed skeletal maturation ³¹		HP:0002750
5	hypertelorism ³¹		HP:0000316
6	macrocephaly ³¹		HP:0000256
7	short nose ³¹		HP:0003196
8	anteverted nares ³¹		HP:0000463
9	short stature ³¹		HP:0004322
10	hypertrophic cardiomyopathy ³¹		HP:0001639
11	frontal bossing ³¹		HP:0002007
12	high palate ³¹		HP:0000218
13	low-set ears ³¹		HP:0000369
14	webbed neck ³¹		HP:0000465
15	epicanthus ³¹		HP:0000286
16	pectus excavatum ³¹		HP:0000767
17	atrial septal defect ³¹		HP:0001631
18	mitral valve prolapse ³¹		HP:0001634
19	downslanted palpebral fissures ³¹		HP:0000494
20	polyhydramnios ³¹		HP:0001561
21	patent ductus arteriosus ³¹		HP:0001643
22	ventricular septal defect ³¹		HP:0001629
23	pulmonic stenosis ³¹		HP:0001642
24	posteriorly rotated ears ³¹		HP:0000358
25	hypoplastic nasal bridge ³¹		HP:0005281
26	sagittal craniosynostosis ³¹		HP:0004442
27	scaphocephaly ³¹		HP:0030799
28	atrial septal dilatation ³¹		HP:0011995
29	juvenile myelomonocytic leukemia ³¹		HP:0012209

Symptoms via clinical synopsis from OMIM:

⁵⁶

Head And Neck Head:
macrocephaly
dolichocephaly
scaphocephaly

Growth Height:
short stature

Head And Neck Face:
frontal bossing

Head And Neck Ears:
low-set ears
posteriorly rotated ears

Genitourinary Internal Genitalia Male:
cryptorchidism (in some patients)

Skeletal:
delayed bone age

Head And Neck Neck:
webbed neck (in some patients)
cystic hygroma (in some patients)

Chest External Features:
broad thorax
thorax deformities

Head And Neck Nose:
short nose
anteverted nares
hypoplastic nasal bridge

Cardiovascular Heart:
hypertrophic cardiomyopathy
atrial septal defect
mitral valve prolapse
patent ductus arteriosus
ventricular septal defect
more

Head And Neck Mouth:
high palate

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Head And Neck Eyes:
downslanting palpebral fissures
epicanthal folds

Skeletal Skull:
craniosynostosis (in some patients)

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum, mild

Neurologic Central Nervous System:
developmental delay, mild to severe (in some patients)

Clinical features from OMIM:

609942

MGI Mouse Phenotypes related to Noonan Syndrome 3:

⁴⁵

#	Description	MGI Source Accession	Score	Top Affiliating Genes
1	endocrine/exocrine gland	MP:0005379	9.61	AFF4 DBH HRAS KRAS PTPN11 RAF1
2	respiratory system	MP:0005388	9.17	AFF4 GNL3 HRAS KRAS PTPN11 RAF1

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Drugs & Therapeutics for Noonan Syndrome 3

Search Clinical Trials , NIH Clinical Center for Noonan Syndrome 3

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Genetic Tests for Noonan Syndrome 3

Genetic tests related to Noonan Syndrome 3:

#	Genetic test	Affiliating Genes
1	Noonan Syndrome 3 ²⁹	KRAS

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Anatomical Context for Noonan Syndrome 3

MalaCards organs/tissues related to Noonan Syndrome 3:

⁴⁰

Heart, Skin, Bone

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Publications for Noonan Syndrome 3

Articles related to Noonan Syndrome 3:

(show all 13)

#	Title	Authors	PMID	Year
1	Craniosynostosis in patients with Noonan syndrome caused by germline KRAS mutations. ⁶ ⁵⁶	Kratz CP...Zenker M	19396835	2009
2	Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome. ⁶ ⁵⁶	Niihori T...Matsubara Y	16474404	2006
3	Germline KRAS mutations cause Noonan syndrome. ⁵⁶ ⁶	Schubbert S...Kratz CP	16474405	2006
4	2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). ⁶	Authors/Task Force members...Watkins H	25173338	2014
5	Multiple, diffuse schwannomas in a RASopathy phenotype patient with germline KRAS mutation: a causal relationship? ⁶	Bertola DR...Messiaen LM	22211815	2012
6	Noonan syndrome: clinical features, diagnosis, and management guidelines. ⁶	Romano AA...Noonan JA	20876176	2010
7	Leopard syndrome. ⁶	Sarkozy A...Dallapiccola B	18505544	2008
8	The diagnosis of Costello syndrome: nomenclature in Ras/MAPK pathway disorders. ⁶	Kerr B...Rauen KA	18386799	2008
9	Further evidence of genetic heterogeneity in Costello syndrome: involvement of the KRAS gene. ⁶	Bertola DR...Krieger JE	17468812	2007
10	Germline missense mutations affecting KRAS Isoform B are associated with a severe Noonan syndrome phenotype. ⁶	Carta C...Tartaglia M	16773572	2006
11	Noonan Syndrome ⁶	Allanson JE...Roberts AE	20301303	2001
12	Feeding difficulties and foregut dysmotility in Noonan's syndrome. ⁵⁶	Shah N...Milla PJ	10373129	1999
13	Ocular pathology in congenital heart disease. ⁶¹	Mansour AM...Salti HI	15184955	2005

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Genes for Noonan Syndrome 3

Genes related to Noonan Syndrome 3 (6 elite genes):

(show all 42)

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubmedIds
1	KRAS	KRAS Proto-Oncogene, GTPase	Protein Coding	1318.01	Molecular basis known ⁵⁶ Pathogenic ⁶ Causative variation ⁷³ Genetic Tests ²⁹ GeneCards inferred via : Disorders Variants (show sections)	17468812 20301303 22211815 (more) 16773572 25173338 18386799 19396835 16474404 16474405 20876176
2	PTPN11	Protein Tyrosine Phosphatase Non-Receptor Type 11	Protein Coding	408.5	Pathogenic/Likely pathogenic ⁶ GeneCards inferred via : Variants (show sections)	18505544 20301303 25173338 (more) 20876176
3	HRAS	HRas Proto-Oncogene, GTPase	Protein Coding	407.43	Pathogenic/Likely pathogenic ⁶ GeneCards inferred via : Variants (show sections)	25173338 20301303 20876176
4	SOS1	SOS Ras/Rac Guanine Nucleotide Exchange Factor 1	Protein Coding	407.43	Pathogenic ⁶ GeneCards inferred via : Variants (show sections)	25173338 20301303 20876176
5	RAF1	Raf-1 Proto-Oncogene, Serine/Threonine Kinase	Protein Coding	407.09	Pathogenic/Likely pathogenic ⁶ GeneCards inferred via : Variants (show sections)	25173338 20301303 20876176
6	SHOC2	SHOC2 Leucine Rich Repeat Scaffold Protein	Protein Coding	407.09	Pathogenic ⁶ GeneCards inferred via : Variants (show sections)	25173338 20301303 20876176
7	LRRC56	Leucine Rich Repeat Containing 56	Protein Coding	7.43	GeneCards inferred via : Variants (show sections)
8	LSG1	Large 60S Subunit Nuclear Export GTPase 1	Protein Coding	7.11	DISEASES inferred ¹⁵
9	RAB39B	RAB39B, Member RAS Oncogene Family	Protein Coding	6.58	DISEASES inferred ¹⁵
10	DBH	Dopamine Beta-Hydroxylase	Protein Coding	6.5	DISEASES inferred ¹⁵
11	GNL3	G Protein Nucleolar 3	Protein Coding	5.8	DISEASES inferred ¹⁵
12	LNP1	Leukemia NUP98 Fusion Partner 1	Protein Coding	5.7	DISEASES inferred ¹⁵
13	MOSPD3	Motile Sperm Domain Containing 3	Protein Coding	5.56	DISEASES inferred ¹⁵
14	SH2D3C	SH2 Domain Containing 3C	Protein Coding	5.45	DISEASES inferred ¹⁵
15	SPATA6	Spermatogenesis Associated 6	Protein Coding	5.43	DISEASES inferred ¹⁵
16	PRSS57	Serine Protease 57	Protein Coding	5.22	DISEASES inferred ¹⁵
17	AFF4	AF4/FMR2 Family Member 4	Protein Coding	5.21	DISEASES inferred ¹⁵
18	SNORD82	Small Nucleolar RNA, C/D Box 82	RNA Gene	5.2	DISEASES inferred ¹⁵
19	SNORD81	Small Nucleolar RNA, C/D Box 81	RNA Gene	5.17	DISEASES inferred ¹⁵
20	SNORD80	Small Nucleolar RNA, C/D Box 80	RNA Gene	5.11	DISEASES inferred ¹⁵
21	G3BP2	G3BP Stress Granule Assembly Factor 2	Protein Coding	5.09	DISEASES inferred ¹⁵
22	XRN2	5'-3' Exoribonuclease 2	Protein Coding	5.06	DISEASES inferred ¹⁵
23	SNORD74	Small Nucleolar RNA, C/D Box 74	RNA Gene	5.03	DISEASES inferred ¹⁵
24	TNPO3	Transportin 3	Protein Coding	4.97	DISEASES inferred ¹⁵
25	SNORD79	Small Nucleolar RNA, C/D Box 79	RNA Gene	4.97	DISEASES inferred ¹⁵
26	MAL	Mal, T Cell Differentiation Protein	Protein Coding	4.88	DISEASES inferred ¹⁵
27	NANS	N-Acetylneuraminate Synthase	Protein Coding	4.88	DISEASES inferred ¹⁵
28	PRC1	Protein Regulator Of Cytokinesis 1	Protein Coding	4.86	DISEASES inferred ¹⁵
29	SENP8	SUMO Peptidase Family Member, NEDD8 Specific	Protein Coding	4.84	DISEASES inferred ¹⁵
30	EEF1B2	Eukaryotic Translation Elongation Factor 1 Beta 2	Protein Coding	4.84	DISEASES inferred ¹⁵
31	DCP1A	Decapping MRNA 1A	Protein Coding	4.81	DISEASES inferred ¹⁵
32	SH2D3A	SH2 Domain Containing 3A	Protein Coding	4.79	DISEASES inferred ¹⁵
33	DUSP26	Dual Specificity Phosphatase 26	Protein Coding	4.78	DISEASES inferred ¹⁵
34	DDX6	DEAD-Box Helicase 6	Protein Coding	4.74	DISEASES inferred ¹⁵
35	MIR4505	MicroRNA 4505	RNA Gene	4.72	DISEASES inferred ¹⁵
36	ITPA	Inosine Triphosphatase	Protein Coding	4.71	DISEASES inferred ¹⁵
37	CD82	CD82 Molecule	Protein Coding	4.69	DISEASES inferred ¹⁵
38	EDC4	Enhancer Of MRNA Decapping 4	Protein Coding	4.69	DISEASES inferred ¹⁵
39	DDX3X	DEAD-Box Helicase 3 X-Linked	Protein Coding	4.68	DISEASES inferred ¹⁵
40	MFAP4	Microfibril Associated Protein 4	Protein Coding	4.68	DISEASES inferred ¹⁵
41	XRN1	5'-3' Exoribonuclease 1	Protein Coding	4.67	DISEASES inferred ¹⁵
42	SLC31A2	Solute Carrier Family 31 Member 2	Protein Coding	4.65	DISEASES inferred ¹⁵

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Variations for Noonan Syndrome 3

ClinVar genetic disease variations for Noonan Syndrome 3:

⁶ (show all 40) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎

#	Gene	Name	Type	Significance	ClinVarId	dbSNP ID	GRCh37 Pos	GRCh38 Pos
1	KRAS	NM_033360.4(KRAS):c.440A>G (p.Lys147Arg)	SNV	Pathogenic	431103	rs1135401776	12:25378558-25378558	12:25225624-25225624
2	SHOC2	NM_007373.4(SHOC2):c.4A>G (p.Ser2Gly)	SNV	Pathogenic	6821	rs267607048	10:112724120-112724120	10:110964362-110964362
3	KRAS	NM_033360.4(KRAS):c.*12A>T	SNV	Pathogenic	12587	rs104894360	12:25362838-25362838	12:25209904-25209904
4	KRAS	NM_033360.4(KRAS):c.173C>T (p.Thr58Ile)	SNV	Pathogenic	12588	rs104894364	12:25380285-25380285	12:25227351-25227351
5	KRAS	NM_033360.4(KRAS):c.40G>A (p.Val14Ile)	SNV	Pathogenic	12589	rs104894365	12:25398279-25398279	12:25245345-25245345
6	PTPN11	NM_002834.5(PTPN11):c.923A>G (p.Asn308Ser)	SNV	Pathogenic	13327	rs121918455	12:112915524-112915524	12:112477720-112477720
7	PTPN11	NM_002834.5(PTPN11):c.188A>G (p.Tyr63Cys)	SNV	Pathogenic	13333	rs121918459	12:112888172-112888172	12:112450368-112450368
8	PTPN11	NM_002834.5(PTPN11):c.236A>G (p.Gln79Arg)	SNV	Pathogenic	13340	rs121918466	12:112888220-112888220	12:112450416-112450416
9	PTPN11	NM_002834.5(PTPN11):c.1381G>A (p.Ala461Thr)	SNV	Pathogenic	13342	rs121918468	12:112926248-112926248	12:112488444-112488444
10	PTPN11	NM_002834.5(PTPN11):c.1529A>C (p.Gln510Pro)	SNV	Pathogenic	13344	rs121918470	12:112926909-112926909	12:112489105-112489105
11	KRAS	NM_033360.4(KRAS):c.65A>G (p.Gln22Arg)	SNV	Pathogenic	40452	rs727503110	12:25398254-25398254	12:25245320-25245320
12	KRAS	NM_033360.4(KRAS):c.*9T>G	SNV	Pathogenic	12591	rs104894367	12:25362841-25362841	12:25209907-25209907
13	PTPN11	NM_002834.5(PTPN11):c.174C>A (p.Asn58Lys)	SNV	Pathogenic	40488	rs397507506	12:112888158-112888158	12:112450354-112450354
14	PTPN11	NM_002834.4(PTPN11):c.181G>C (p.Asp61His)	SNV	Pathogenic	40494	rs397507510	12:112888165-112888165	12:112450361-112450361
15	PTPN11	NM_002834.5(PTPN11):c.181G>A (p.Asp61Asn)	SNV	Pathogenic	40495	rs397507510	12:112888165-112888165	12:112450361-112450361
16	KRAS	NM_033360.4(KRAS):c.178G>A (p.Gly60Ser)	SNV	Pathogenic	12597	rs104894359	12:25380280-25380280	12:25227346-25227346
17	PTPN11	NM_002834.5(PTPN11):c.417G>C (p.Glu139Asp)	SNV	Pathogenic	40513	rs397507520	12:112891083-112891083	12:112453279-112453279
18	PTPN11	NM_002834.5(PTPN11):c.1528C>G (p.Gln510Glu)	SNV	Pathogenic	40566	rs397507549	12:112926908-112926908	12:112489104-112489104
19	SOS1	NM_005633.3(SOS1):c.1655G>A (p.Arg552Lys)	SNV	Pathogenic	40683	rs397517154	2:39249914-39249914	2:39022773-39022773
20	PTPN11	NM_002834.5(PTPN11):c.855T>G (p.Phe285Leu)	SNV	Pathogenic	44615	rs397516810	12:112915456-112915456	12:112477652-112477652
21	SOS1	NM_005633.3(SOS1):c.2197A>T (p.Ile733Phe)	SNV	Pathogenic/Likely pathogenic	40701	rs574088829	2:39239460-39239460	2:39012319-39012319
22	PTPN11	NM_002834.5(PTPN11):c.853T>C (p.Phe285Leu)	SNV	Pathogenic/Likely pathogenic	40528	rs397507531	12:112910844-112910844	12:112473040-112473040
23	HRAS	NM_005343.4(HRAS):c.181C>A (p.Gln61Lys)	SNV	Pathogenic/Likely pathogenic	12601	rs28933406	11:533875-533875	11:533875-533875
24	PTPN11	NM_002834.5(PTPN11):c.215C>G (p.Ala72Gly)	SNV	Pathogenic/Likely pathogenic	13325	rs121918454	12:112888199-112888199	12:112450395-112450395
25	PTPN11	NM_002834.5(PTPN11):c.211T>C (p.Phe71Leu)	SNV	Pathogenic/Likely pathogenic	40499	rs397507512	12:112888195-112888195	12:112450391-112450391
26	PTPN11	NM_002834.5(PTPN11):c.214G>C (p.Ala72Pro)	SNV	Pathogenic/Likely pathogenic	40500	rs121918453	12:112888198-112888198	12:112450394-112450394
27	PTPN11	NM_002834.5(PTPN11):c.328G>A (p.Glu110Lys)	SNV	Pathogenic/Likely pathogenic	40507	rs397507518	12:112888312-112888312	12:112450508-112450508
28	KRAS	NM_033360.4(KRAS):c.101C>G (p.Pro34Arg)	SNV	Pathogenic/Likely pathogenic	12590	rs104894366	12:25398218-25398218	12:25245284-25245284
29	RAF1	NM_001354689.3(RAF1):c.788T>A (p.Val263Asp)	SNV	Pathogenic/Likely pathogenic	496189	rs397516830	3:12645681-12645681	3:12604182-12604182
30	KRAS	NM_033360.4(KRAS):c.355G>A (p.Asp119Asn)	SNV	Likely pathogenic	40460	rs730880471	12:25378643-25378643	12:25225709-25225709
31	KRAS	NM_033360.4(KRAS):c.13A>G (p.Lys5Glu)	SNV	Likely pathogenic	12596	rs193929331	12:25398306-25398306	12:25245372-25245372
32	KRAS	NM_033360.4(KRAS):c.458A>T (p.Glu153Val)	SNV	Likely pathogenic	637030		12:25368487-25368487	12:25215553-25215553
33	PTPN11	NM_002834.5(PTPN11):c.206A>T (p.Glu69Val)	SNV	Likely pathogenic	164997	rs727503380	12:112888190-112888190	12:112450386-112450386
34	HRAS	NM_005343.4(HRAS):c.183G>T (p.Gln61His)	SNV	Likely pathogenic	376318	rs121913496	11:533873-533873	11:533873-533873
35	KRAS	NM_033360.4(KRAS):c.112-5C>T	SNV	Conflicting interpretations of pathogenicity	626130	rs376520586	12:25380351-25380351	12:25227417-25227417
36	KRAS	NM_033360.4(KRAS):c.111+8T>G	SNV	Uncertain significance	883635		12:25398200-25398200	12:25245266-25245266
37	KRAS	NM_033360.4(KRAS):c.194G>T (p.Ser65Ile)	SNV	Uncertain significance	438796	rs1555194026	12:25380264-25380264	12:25227330-25227330
38	KRAS	NM_033360.4(KRAS):c.*44C>T	SNV	Likely benign	547512	rs1555192443	12:25362806-25362806	12:25209872-25209872
39	KRAS	NM_033360.4(KRAS):c.*5-9G>A	SNV	Benign/Likely benign	40464	rs12313763	12:25362854-25362854	12:25209920-25209920
40	KRAS	NM_033360.4(KRAS):c.483= (p.Arg161=)	SNV	Benign	46538	rs4362222	12:25368462-25368462	12:25215528-25215528

UniProtKB/Swiss-Prot genetic disease variations for Noonan Syndrome 3:

⁷³

#	Symbol	AA change	Variation ID	SNP ID
1	KRAS	p.Val14Ile	VAR_026109	rs104894365
2	KRAS	p.Thr58Ile	VAR_026111	rs104894364
3	KRAS	p.Gln22Arg	VAR_064851	rs727503110
4	KRAS	p.Pro34Leu	VAR_064852	rs104894366
5	KRAS	p.Pro34Gln	VAR_064853
6	KRAS	p.Ile36Met	VAR_064854	rs727503109
7	KRAS	p.Lys5Glu	VAR_065144	rs193929331
8	KRAS	p.Gly60Ser	VAR_065146	rs104894359

Sources

Expression for Noonan Syndrome 3

Search GEO for disease gene expression data for Noonan Syndrome 3.

Sources

Pathways for Noonan Syndrome 3

Pathways related to Noonan Syndrome 3 according to GeneCards Suite gene sharing:

(show top 50) (show all 83)

#	Super pathways	Score	Top Affiliating Genes
1	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	12.92	SOS1 RAF1 PTPN11 KRAS HRAS
2	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	12.89	SOS1 RAF1 PTPN11 KRAS HRAS
3	Common Cytokine Receptor Gamma-Chain Family Signaling Pathways ⁶⁴ Show member pathways Adipocytokines and Insulin Signaling 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	12.81	SOS1 RAF1 PTPN11 KRAS HRAS
4	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	12.74	SOS1 RAF1 PTPN11 KRAS HRAS
5	Ras signaling pathway ³⁶ Show member pathways Rap1 signaling pathway ³⁶	12.7	SOS1 SHOC2 RAF1 PTPN11 KRAS HRAS
6	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	12.65	SOS1 RAF1 PTPN11 KRAS HRAS
7	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	12.63	SOS1 RAF1 PTPN11 KRAS HRAS
8	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	12.6	SOS1 RAF1 PTPN11 KRAS HRAS
9	MicroRNAs in cancer ³⁶	12.55	SOS1 RAF1 KRAS HRAS
10	Angiopoietin Like Protein 8 Regulatory Pathway ¹ Show member pathways Insulin Signaling ¹ Liver X Receptor Pathway ¹	12.54	SOS1 RAF1 PTPN11 HRAS
11	mTOR signaling pathway (KEGG) ³⁶ Show member pathways mTOR Signaling ⁶⁴	12.52	SOS1 RAF1 KRAS HRAS
12	VEGF Signaling ⁶⁶ Show member pathways EGFR Signaling Pathway ⁶⁶ TGF-beta Signaling Pathway ⁶⁶ VEGF Signaling Pathway ⁶⁰	12.52	SOS1 RAF1 KRAS HRAS
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 ³⁶	12.52	SOS1 RAF1 PTPN11 KRAS HRAS
14	MET promotes cell motility ⁶⁵ Show member pathways Alpha 6 Beta 4 signaling pathway ¹ Laminin interactions ⁶⁵ MET activates PTK2 signaling ⁶⁵ MET activates RAP1 and RAC1 ⁶⁵ MET activates RAS signaling ⁶⁵ MET interacts with TNS proteins ⁶⁵ MET Receptor Activation ⁶⁵ MET receptor recycling ⁶⁵ Non-integrin membrane-ECM interactions ⁶⁵ Signaling by MET ⁶⁵ Syndecan interactions ⁶⁵	12.51	SOS1 PTPN11 KRAS HRAS
15	Prolactin Signaling Pathway ³⁶ ¹ Show member pathways Development Prolactin receptor signaling ²² Leptin signaling pathway ¹	12.49	SOS1 RAF1 PTPN11 KRAS HRAS
16	JAK-STAT signaling pathway ³⁶ Show member pathways B-Cell Development ⁶³ IL-7 Signaling and its Primary Biological Effects in Different Immune Cell Types ⁶⁴ Interleukin-19, 20, 22, 24 ⁶⁵ Jak/STAT Signaling Pathway ⁶⁴ Type III interferon signaling ¹	12.47	SOS1 RAF1 PTPN11 KRAS HRAS
17	B Cell Receptor Signaling Pathway (sino) ⁶⁶ Show member pathways B Cell Receptor Signaling Pathway ⁶⁶	12.45	SOS1 RAF1 PTPN11 KRAS HRAS
18	VEGF Pathway (Qiagen) ⁶³ Show member pathways CCKBR-Gastrin Stimulated Signaling ⁶³ Development VEGF-family signaling ²² Neurophilin interactions with VEGF and VEGFR ⁶⁵ VEGF Pathway ⁶³	12.43	SOS1 RAF1 KRAS HRAS
19	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	12.42	SOS1 RAF1 PTPN11 HRAS
20	B cell receptor signaling pathway (KEGG) ³⁶ Show member pathways B Cell Receptor Signaling Pathway ¹ BCR signaling pathway ¹	12.4	SOS1 RAF1 PTPN11 KRAS HRAS
21	Phospholipase D signaling pathway ³⁶ Show member pathways Choline metabolism in cancer ³⁶	12.39	SOS1 RAF1 PTPN11 KRAS HRAS
22	Development VEGF signaling via VEGFR2 - generic cascades ²² Show member pathways Development VEGF signaling and activation ²² VEGF - VEGF R2 Signaling Pathways ⁶⁴	12.38	SOS1 RAF1 PTPN11 KRAS HRAS
23	CNTF Signaling ⁶³ Show member pathways FLT3 Signaling ⁶³ IL-3 Pathway ⁶³ Nur77-Induced AICD in Macrophage ⁶³ OSM Pathway ⁶³	12.36	SOS1 RAF1 KRAS HRAS
24	Development EGFR signaling pathway ²² Show member pathways Development ERBB-family signaling ²² EGF Pathway ⁶³ ErbB receptor signaling network ¹	12.34	SOS1 RAF1 KRAS HRAS
25	Toll Comparative Pathway ⁶³ Show member pathways IL-1 Pathway ⁶³ Immune response MIF in innate immunity response ²² iNOS Signaling ⁶³ TLR-TRIF Pathway ⁶³	12.33	SOS1 RAF1 PTPN11 HRAS
26	Development FGFR signaling pathway ²² Show member pathways Development FGF-family signaling ²² Development Flt3 signaling ²² FGF Pathway ⁶³	12.32	SOS1 RAF1 PTPN11 KRAS HRAS
27	Signaling by FGFR2 ⁶⁵ Show member pathways FGFR2 ligand binding and activation ⁶⁵ FGFR2b ligand binding and activation ⁶⁵ Signaling by FGFR ⁶⁵	12.3	SOS1 PTPN11 KRAS HRAS
28	Axon guidance ³⁶	12.27	RAF1 PTPN11 KRAS HRAS
29	Cell surface interactions at the vascular wall ⁶⁵ Show member pathways Fibronectin matrix formation ⁶⁵ PECAM1 interactions ⁶⁵ Tie2 Signaling ⁶⁵	12.26	SOS1 PTPN11 KRAS HRAS
30	C-type lectin receptor signaling pathway ³⁶ Show member pathways Pathogen or Damage-activated C-Type Lectin Receptor Signaling Pathways ⁶⁴	12.24	RAF1 PTPN11 KRAS HRAS
31	GDNF-Family Ligands and Receptor Interactions ⁶³ Show member pathways BDNF Pathway ⁶³ Development GDNF family signaling ²²	12.23	SOS1 RAF1 KRAS HRAS
32	Proteoglycans in cancer ³⁶	12.23	SOS1 RAF1 PTPN11 KRAS HRAS
33	G-protein signaling Ras family GTPases in kinase cascades (scheme) ²² Show member pathways Activation of the AP-1 family of transcription factors ⁶⁵ Immune response Oncostatin M signaling via MAPK in human cells ²² MAPK Cascade ¹ Nanoparticle-mediated activation of receptor signaling ¹ Oncostatin M Signaling Pathway ¹	12.21	SOS1 RAF1 PTPN11 KRAS HRAS
34	Kit receptor signaling pathway ¹ Show member pathways IL-3 Signaling Pathway ¹ Signaling events mediated by Stem cell factor receptor (c-Kit) ¹	12.2	SOS1 RAF1 PTPN11 HRAS
35	NGF Pathway ⁶³ Show member pathways TRKA Signaling ⁶³	12.16	SOS1 RAF1 KRAS HRAS
36	Jak Stat Signaling Pathway ⁶⁶ Show member pathways Commom Cytokine Receptor G Chain Siganaling Pathway ⁶⁶	12.13	RAF1 KRAS HRAS
37	FoxO signaling pathway ³⁶ Show member pathways PLK2 and PLK4 events ¹ Polo-like kinase signaling events in the cell cycle ¹	12.09	SOS1 RAF1 KRAS HRAS
38	Autophagy - animal ³⁶	12.09	RAF1 RAB39B KRAS HRAS
39	EGF/EGFR Signaling Pathway ¹	12.09	SOS1 RAF1 PTPN11 KRAS HRAS
40	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	12.03	SOS1 RAF1 PTPN11 KRAS HRAS
41	Long-term potentiation ³⁶ Show member pathways Common Pathways Underlying Drug Addiction ¹	11.97	RAF1 KRAS HRAS
42	Glioblastoma Multiforme ⁶³	11.97	SOS1 RAF1 KRAS HRAS
43	Signaling by ERBB4 ⁶⁵ Show member pathways Downregulation of ERBB4 signaling ⁶⁵ ErbB4 signaling events ¹ Nuclear signaling by ERBB4 ⁶⁵	11.96	SOS1 KRAS HRAS
44	IL-2 Signaling Pathway ¹ Show member pathways IL2-mediated signaling events ¹ IL-5 Signaling Pathway ¹	11.96	SOS1 RAF1 PTPN11 KRAS HRAS
45	TGF-beta Signaling Pathways ⁶⁴	11.9	SOS1 RAF1 KRAS
46	Signaling events mediated by VEGFR1 and VEGFR2 ¹ Show member pathways VEGFR1 specific signals ¹	11.88	SOS1 PTPN11 HRAS
47	Signaling by Ligand-Responsive EGFR Variants in Cancer ⁶⁵ Show member pathways Constitutive Signaling by EGFRvIII ⁶⁵ Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants ⁶⁵ Signaling by EGFR in Cancer ⁶⁵ Signaling by EGFRvIII in Cancer ⁶⁵	11.88	SOS1 KRAS HRAS
48	FGFR1 mutant receptor activation ⁶⁵ Show member pathways Signaling by cytosolic FGFR1 fusion mutants ⁶⁵ Signaling by FGFR1 in disease ⁶⁵ Signaling by plasma membrane FGFR1 fusions ⁶⁵	11.87	SOS1 KRAS HRAS
49	Development EPO-induced Jak-STAT pathway ²² Show member pathways EPO Receptor Signaling ¹ EPO signaling pathway ¹	11.87	SOS1 RAF1 PTPN11 HRAS
50	VEGF Pathway (Tocris) ⁶⁰ Show member pathways VEGF Pathway ⁷⁰	11.83	RAF1 KRAS HRAS

Sources

GO Terms for Noonan Syndrome 3

Biological processes related to Noonan Syndrome 3 according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	MAPK cascade	GO:0000165	9.56	SOS1 RAF1 KRAS HRAS
2	stimulatory C-type lectin receptor signaling pathway	GO:0002223	9.5	RAF1 KRAS HRAS
3	response to isolation stress	GO:0035900	9.16	KRAS HRAS
4	neurotrophin TRK receptor signaling pathway	GO:0048011	9.13	SOS1 RAF1 PTPN11
5	Ras protein signal transduction	GO:0007265	8.92	SOS1 SHOC2 KRAS HRAS

Molecular functions related to Noonan Syndrome 3 according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	GTP binding	GO:0005525	9.02	RAB39B LSG1 KRAS HRAS GNL3

Sources

Sources for Noonan Syndrome 3

¹ BioSystems

² BitterDB

³ CDC

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¹⁰ dbSNP

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²⁰ GeneAnalytics

²¹ GeneCards

²² GeneGo (Thomson Reuters)

²³ GeneHancer via GeneCards

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²⁷ GEO DataSets

²⁸ GO

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³² ICD10

³³ ICD10 via Orphanet

³⁴ ICD9CM

³⁵ IUPHAR

³⁶ KEGG

³⁷ LifeMap

³⁸ LncRNADisease

³⁹ LOVD

⁴⁰ MalaCards

⁴¹ MedGen

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⁴³ MeSH

⁴⁴ MESH via Orphanet

⁴⁵ MGI

⁴⁶ miR2Disease

⁴⁷ NCBI Bookshelf

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⁵¹ NIH Clinical Center

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⁵³ NINDS

⁵⁴ Novoseek

⁵⁵ Novus Biologicals

⁵⁶ OMIM

⁵⁷ OMIM via Orphanet

⁵⁸ Orphanet

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⁶¹ PubMed

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⁶⁷ SNOMED-CT

⁶⁸ SNOMED-CT via HPO

⁶⁹ TGDB

⁷⁰ Tocris

⁷¹ UMLS

⁷² UMLS via Orphanet

⁷³ UniProtKB/Swiss-Prot

⁷⁴ Wikipedia

Noonan Syndrome 3 (NS3)

Aliases & Classifications for Noonan Syndrome 3

MalaCards integrated aliases for Noonan Syndrome 3:

Characteristics:

OMIM:

HPO:

Classifications:

External Ids:

Summaries for Noonan Syndrome 3

Related Diseases for Noonan Syndrome 3

Diseases in the Noonan Syndrome 1 family:

Diseases related to Noonan Syndrome 3 via text searches within MalaCards or GeneCards Suite gene sharing:

Graphical network of the top 20 diseases related to Noonan Syndrome 3:

Symptoms & Phenotypes for Noonan Syndrome 3

Human phenotypes related to Noonan Syndrome 3:

Symptoms via clinical synopsis from OMIM:

Clinical features from OMIM:

MGI Mouse Phenotypes related to Noonan Syndrome 3:

Drugs & Therapeutics for Noonan Syndrome 3

Genetic Tests for Noonan Syndrome 3

Genetic tests related to Noonan Syndrome 3:

Anatomical Context for Noonan Syndrome 3

MalaCards organs/tissues related to Noonan Syndrome 3:

Publications for Noonan Syndrome 3

Articles related to Noonan Syndrome 3:

Genes for Noonan Syndrome 3

Genes related to Noonan Syndrome 3 (6 elite genes):

Variations for Noonan Syndrome 3

ClinVar genetic disease variations for Noonan Syndrome 3:

UniProtKB/Swiss-Prot genetic disease variations for Noonan Syndrome 3:

Expression for Noonan Syndrome 3

Pathways for Noonan Syndrome 3

Pathways related to Noonan Syndrome 3 according to GeneCards Suite gene sharing:

GO Terms for Noonan Syndrome 3

Biological processes related to Noonan Syndrome 3 according to GeneCards Suite gene sharing:

Molecular functions related to Noonan Syndrome 3 according to GeneCards Suite gene sharing:

Sources for Noonan Syndrome 3