Noonan Syndrome with Multiple Lentigines disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

NSML MCID: NNN026 MIFTS: 49	Noonan Syndrome with Multiple Lentigines (NSML) Categories: Cardiovascular diseases, Ear diseases, Fetal diseases, Genetic diseases, Rare diseases, Skin diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Expand all tables

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Aliases & Classifications for Noonan Syndrome with Multiple Lentigines

MalaCards integrated aliases for Noonan Syndrome with Multiple Lentigines:

Name: Noonan Syndrome with Multiple Lentigines ²⁵ ²⁶ ⁶⁰ ³⁰ ⁶

Leopard Syndrome ²⁵ ²⁶ ⁶⁰ ⁷⁴

Multiple Lentigines Syndrome ²⁵ ²⁶

Cardiomyopathic Lentiginosis ²⁶ ⁶⁰

Cardio-Cutaneous Syndrome ²⁶ ⁶

Lentiginosis Profusa ²⁶ ⁷⁴

Alopecia Epilepsy Oligophrenia Syndrome of Moynahan ⁷⁴

Progressive Cardiomyopathic Lentiginosis ²⁶

Familial Multiple Lentigines Syndrome ⁶⁰

Diffuse Lentiginosis ²⁶

Moynahan Syndrome ²⁶

Nsml ²⁶

Characteristics:

Orphanet epidemiological data:

⁶⁰

noonan syndrome with multiple lentigines
Inheritance: Autosomal dominant; Age of onset: Childhood;

GeneReviews:

²⁵

Penetrance Penetrance of nsml is difficult to determine because of ascertainment bias and variable expressivity, frequently with subtlety of phenotypic features. affected adults may be diagnosed only after the birth of a more obviously affected infant...

Classifications:

MalaCards categories:
Global: Fetal diseases Rare diseases Genetic diseases
Anatomical: Cardiovascular diseases Ear diseases Skin diseases

See all MalaCards categories (disease lists)

ICD10: ³⁵

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

Orphanet: ⁶⁰

Rare cardiac malformations

Rare otorhinolaryngological diseases

Rare skin diseases

Developmental anomalies during embryogenesis

External Ids:

MESH via Orphanet ⁴⁶ C537116 D044542

ICD10 via Orphanet ³⁵ Q87.1

UMLS via Orphanet ⁷⁵ C0175704 C2931424

Orphanet ⁶⁰ ORPHA500

SNOMED-CT via HPO ⁷⁰ 102594003 109995007 111266001 more

UMLS ⁷⁴ C0175704 C0265328 C3492944

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Summaries for Noonan Syndrome with Multiple Lentigines

Genetics Home Reference : ²⁶ Noonan syndrome with multiple lentigines (formerly called LEOPARD syndrome) is a condition that affects many areas of the body. As the condition name suggests, Noonan syndrome with multiple lentigines is very similar to a condition called Noonan syndrome, and it can be difficult to tell the two disorders apart in early childhood. However, the features of these two conditions differ later in life. The characteristic features of Noonan syndrome with multiple lentigines include brown skin spots called lentigines that are similar to freckles, heart defects, widely spaced eyes (ocular hypertelorism), a sunken chest (pectus excavatum) or protruding chest (pectus carinatum), and short stature. These features vary, however, even among affected individuals in the same family. Not all individuals with Noonan syndrome with multiple lentigines have all the characteristic features of this condition.

MalaCards based summary : Noonan Syndrome with Multiple Lentigines, also known as leopard syndrome, is related to leopard syndrome and lentigines, and has symptoms including seizures and hyposmia. An important gene associated with Noonan Syndrome with Multiple Lentigines is PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11), and among its related pathways/superpathways are Common Cytokine Receptor Gamma-Chain Family Signaling Pathways and Ras signaling pathway. Affiliated tissues include skin, heart and eye, and related phenotypes are hypertelorism and hypertrophic cardiomyopathy

Wikipedia : ⁷⁷ Noonan syndrome with multiple lentigines (NSML) which is part of a group called Ras/MAPK pathway... more...

GeneReviews: NBK1383

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Related Diseases for Noonan Syndrome with Multiple Lentigines

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

(show top 50) (show all 63)

#	Related Disease	Score	Top Affiliating Genes
1	leopard syndrome	32.0	BRAF PTPN11 RAF1
2	lentigines	30.9	BRAF PTPN11 RAF1
3	noonan syndrome 1	30.3	BRAF PTPN11 RAF1 RPL6
4	hypertrophic cardiomyopathy	30.1	BRAF PTPN11 RAF1
5	leopard syndrome 2	12.5
6	leopard syndrome 3	12.5
7	lentiginosis, inherited patterned	11.9
8	legius syndrome	11.1
9	leopard syndrome 1	10.7
10	pseudo-turner syndrome	10.7
11	orthostatic intolerance	10.3
12	myoblastoma	10.3
13	neuropathy	10.3
14	craniosynostosis	10.1
15	keratosis	10.1
16	granular cell tumor	10.1
17	melanoma	10.0
18	pilomyxoid astrocytoma	10.0	BRAF RAF1
19	metachondromatosis	10.0	PTPN11 RPL6
20	cardiofaciocutaneous syndrome 1	10.0	BRAF PTPN11
21	ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus	9.9
22	leukemia	9.9
23	heart disease	9.9
24	leukemia, chronic lymphocytic 2	9.9	BRAF PTPN11
25	neurofibromatosis, type i	9.9
26	neurofibromatosis, type iv, of riccardi	9.9
27	teeth, supernumerary	9.9
28	renal hypodysplasia/aplasia 1	9.9
29	renal hypodysplasia/aplasia 3	9.9
30	dermatitis	9.9
31	rhabdomyosarcoma	9.9
32	aorto-right ventricular tunnel	9.9
33	pulmonic stenosis	9.9	BRAF PTPN11 RAF1
34	hypertelorism	9.9	BRAF PTPN11 RAF1
35	juvenile myelomonocytic leukemia	9.8	BRAF PTPN11 RAF1
36	noonan syndrome 3	9.8	PTPN11 RAF1
37	cardiac conduction defect	9.8
38	marfan syndrome	9.8
39	steatocystoma multiplex	9.8
40	wolff-parkinson-white syndrome	9.8
41	alopecia-epilepsy-oligophrenia syndrome of moynahan	9.8
42	autism	9.8
43	schizencephaly	9.8
44	neurofibromatosis-noonan syndrome	9.8
45	patent ductus arteriosus 1	9.8
46	leukemia, acute lymphoblastic	9.8
47	corpus callosum, agenesis of, with facial anomalies and cerebellar ataxia	9.8
48	pulmonary hypertension	9.8
49	infective endocarditis	9.8
50	autism spectrum disorder	9.8

Graphical network of the top 20 diseases related to Noonan Syndrome with Multiple Lentigines:

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Symptoms & Phenotypes for Noonan Syndrome with Multiple Lentigines

Human phenotypes related to Noonan Syndrome with Multiple Lentigines:

⁶⁰ ³³ (show top 50) (show all 53)

#	Description	HPO Frequency	Orphanet Frequency	HPO Source Accession
1	hypertelorism ⁶⁰ ³³	hallmark (90%)	Very frequent (99-80%)	HP:0000316
2	hypertrophic cardiomyopathy ⁶⁰ ³³	hallmark (90%)	Very frequent (99-80%)	HP:0001639
3	arrhythmia ⁶⁰ ³³	hallmark (90%)	Very frequent (99-80%)	HP:0011675
4	intrauterine growth retardation ⁶⁰ ³³	hallmark (90%)	Very frequent (99-80%)	HP:0001511
5	melanocytic nevus ⁶⁰ ³³	hallmark (90%)	Very frequent (99-80%)	HP:0000995
6	bundle branch block ⁶⁰ ³³	hallmark (90%)	Very frequent (99-80%)	HP:0011710
7	pulmonic stenosis ⁶⁰ ³³	hallmark (90%)	Very frequent (99-80%)	HP:0001642
8	abnormality of the pulmonary artery ⁶⁰ ³³	hallmark (90%)	Very frequent (99-80%)	HP:0004414
9	hyperextensible skin ⁶⁰ ³³	hallmark (90%)	Very frequent (99-80%)	HP:0000974
10	multiple lentigines ⁶⁰ ³³	hallmark (90%)	Very frequent (99-80%)	HP:0001003
11	severe sensorineural hearing impairment ⁶⁰ ³³	hallmark (90%)	Very frequent (99-80%)	HP:0008625
12	freckling ⁶⁰ ³³	hallmark (90%)	Very frequent (99-80%)	HP:0001480
13	abnormal pulmonary valve morphology ³³	hallmark (90%)		HP:0001641
14	pectus excavatum ⁶⁰ ³³	frequent (33%)	Frequent (79-30%)	HP:0000767
15	ptosis ⁶⁰ ³³	frequent (33%)	Frequent (79-30%)	HP:0000508
16	wide nasal bridge ⁶⁰ ³³	frequent (33%)	Frequent (79-30%)	HP:0000431
17	pectus carinatum ⁶⁰ ³³	frequent (33%)	Frequent (79-30%)	HP:0000768
18	short stature ⁶⁰ ³³	frequent (33%)	Frequent (79-30%)	HP:0004322
19	cryptorchidism ⁶⁰ ³³	frequent (33%)	Frequent (79-30%)	HP:0000028
20	webbed neck ⁶⁰ ³³	frequent (33%)	Frequent (79-30%)	HP:0000465
21	sprengel anomaly ⁶⁰ ³³	frequent (33%)	Frequent (79-30%)	HP:0000912
22	scapular winging ⁶⁰ ³³	frequent (33%)	Frequent (79-30%)	HP:0003691
23	mitral valve prolapse ⁶⁰ ³³	frequent (33%)	Frequent (79-30%)	HP:0001634
24	low-set, posteriorly rotated ears ⁶⁰ ³³	frequent (33%)	Frequent (79-30%)	HP:0000368
25	decreased fertility ⁶⁰ ³³	frequent (33%)	Frequent (79-30%)	HP:0000144
26	atrioventricular canal defect ⁶⁰ ³³	frequent (33%)	Frequent (79-30%)	HP:0006695
27	scoliosis ⁶⁰ ³³	occasional (7.5%)	Occasional (29-5%)	HP:0002650
28	global developmental delay ⁶⁰ ³³	occasional (7.5%)	Occasional (29-5%)	HP:0001263
29	intellectual disability, mild ⁶⁰ ³³	occasional (7.5%)	Occasional (29-5%)	HP:0001256
30	subcutaneous nodule ⁶⁰ ³³	occasional (7.5%)	Occasional (29-5%)	HP:0001482
31	brachycephaly ⁶⁰ ³³	occasional (7.5%)	Occasional (29-5%)	HP:0000248
32	myocardial infarction ⁶⁰ ³³	occasional (7.5%)	Occasional (29-5%)	HP:0001658
33	myelodysplasia ⁶⁰ ³³	occasional (7.5%)	Occasional (29-5%)	HP:0002863
34	aplasia/hypoplasia of the abdominal wall musculature ⁶⁰ ³³	occasional (7.5%)	Occasional (29-5%)	HP:0010318
35	melanoma ⁶⁰ ³³	occasional (7.5%)	Occasional (29-5%)	HP:0002861
36	hypospadias ⁶⁰ ³³	occasional (7.5%)	Occasional (29-5%)	HP:0000047
37	abnormality of the voice ⁶⁰ ³³	occasional (7.5%)	Occasional (29-5%)	HP:0001608
38	spina bifida occulta ⁶⁰ ³³	occasional (7.5%)	Occasional (29-5%)	HP:0003298
39	triangular face ⁶⁰ ³³	occasional (7.5%)	Occasional (29-5%)	HP:0000325
40	abnormal localization of kidney ⁶⁰ ³³	occasional (7.5%)	Occasional (29-5%)	HP:0100542
41	neuroblastoma ⁶⁰ ³³	occasional (7.5%)	Occasional (29-5%)	HP:0003006
42	excessive wrinkled skin ⁶⁰ ³³	occasional (7.5%)	Occasional (29-5%)	HP:0007392
43	dilatation ³³	occasional (7.5%)		HP:0002617
44	abnormal endocardium morphology ³³	occasional (7.5%)		HP:0004306
45	sensorineural hearing impairment ⁶⁰		Very frequent (99-80%)
46	malformation of the heart and great vessels ⁶⁰		Frequent (79-30%)
47	growth delay ⁶⁰		Very frequent (99-80%)
48	abnormality of the endocardium ⁶⁰		Occasional (29-5%)
49	abnormality of the face ⁶⁰		Frequent (79-30%)
50	abnormality of the pulmonary valve ⁶⁰		Very frequent (99-80%)

UMLS symptoms related to Noonan Syndrome with Multiple Lentigines:

seizures, hyposmia

GenomeRNAi Phenotypes related to Noonan Syndrome with Multiple Lentigines according to GeneCards Suite gene sharing:

²⁷ (show all 21)

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Increased shRNA abundance (Z-score > 2)	GR00366-A-110	9.7	BRAF
2	Increased shRNA abundance (Z-score > 2)	GR00366-A-116	9.7	RAF1
3	Increased shRNA abundance (Z-score > 2)	GR00366-A-118	9.7	PTPN11
4	Increased shRNA abundance (Z-score > 2)	GR00366-A-121	9.7	PTPN11
5	Increased shRNA abundance (Z-score > 2)	GR00366-A-138	9.7	PTPN11
6	Increased shRNA abundance (Z-score > 2)	GR00366-A-149	9.7	BRAF PTPN11 RAF1
7	Increased shRNA abundance (Z-score > 2)	GR00366-A-151	9.7	RAF1
8	Increased shRNA abundance (Z-score > 2)	GR00366-A-161	9.7	RAF1
9	Increased shRNA abundance (Z-score > 2)	GR00366-A-166	9.7	BRAF
10	Increased shRNA abundance (Z-score > 2)	GR00366-A-177	9.7	BRAF
11	Increased shRNA abundance (Z-score > 2)	GR00366-A-178	9.7	PTPN11
12	Increased shRNA abundance (Z-score > 2)	GR00366-A-190	9.7	PTPN11
13	Increased shRNA abundance (Z-score > 2)	GR00366-A-194	9.7	BRAF
14	Increased shRNA abundance (Z-score > 2)	GR00366-A-29	9.7	BRAF
15	Increased shRNA abundance (Z-score > 2)	GR00366-A-31	9.7	BRAF
16	Increased shRNA abundance (Z-score > 2)	GR00366-A-32	9.7	BRAF
17	Increased shRNA abundance (Z-score > 2)	GR00366-A-37	9.7	PTPN11
18	Increased shRNA abundance (Z-score > 2)	GR00366-A-47	9.7	BRAF PTPN11
19	Increased shRNA abundance (Z-score > 2)	GR00366-A-52	9.7	RAF1
20	Increased shRNA abundance (Z-score > 2)	GR00366-A-7	9.7	PTPN11
21	Increased shRNA abundance (Z-score > 2)	GR00366-A-78	9.7	PTPN11

MGI Mouse Phenotypes related to Noonan Syndrome with Multiple Lentigines:

⁴⁷

#	Description	MGI Source Accession	Score	Top Affiliating Genes
1	endocrine/exocrine gland	MP:0005379	9.02	BRAF MKRN2 PPP1R13L PTPN11 RAF1

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Drugs & Therapeutics for Noonan Syndrome with Multiple Lentigines

Interventional clinical trials:

#	Name	Status	NCT ID	Phase	Drugs
1	Hormonal Sensitivity in Patients With Noonan and LEOPARD Syndromes	Unknown status	NCT02486731

Search NIH Clinical Center for Noonan Syndrome with Multiple Lentigines

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Genetic Tests for Noonan Syndrome with Multiple Lentigines

Genetic tests related to Noonan Syndrome with Multiple Lentigines:

#	Genetic test	Affiliating Genes
1	Noonan Syndrome with Multiple Lentigines ³⁰

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Anatomical Context for Noonan Syndrome with Multiple Lentigines

MalaCards organs/tissues related to Noonan Syndrome with Multiple Lentigines:

⁴²

Skin, Heart, Eye, Kidney

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Publications for Noonan Syndrome with Multiple Lentigines

Articles related to Noonan Syndrome with Multiple Lentigines:

(show all 17)

#	Title	Authors	Year
1	Noonan syndrome with multiple lentigines and associated craniosynostosis. ( 29356064 )	McDonald B.S....Batta K.	2018
2	Widespread keratosis pilaris in a patient with Noonan syndrome with multiple lentigines. ( 30152106 )	Purnak S...Yal??n B	2018
3	Generation of an induced pluripotent stem cell line (TRNDi003-A) from a Noonan syndrome with multiple lentigines (NSML) patient carrying a p.Q510P mutation in the PTPN11 gene. ( 30640061 )	Li R...Zheng W	2018
4	In vivo efficacy of the AKT inhibitor ARQ 092 in Noonan Syndrome with multiple lentigines-associated hypertrophic cardiomyopathy. ( 28582432 )	Wang J....Kontaridis M.I.	2017
5	Heterozygous deletion of AKT1 rescues cardiac contractility, but not hypertrophy, in a mouse model of Noonan Syndrome with Multiple Lentigines. ( 28911943 )	Roy R....Krenz M.	2017
6	Noonan syndrome with multiple lentigines with PTPN11 (T468M) gene mutation accompanied with solitary granular cell tumor. ( 28681392 )	Park S.H....Lee S.H.	2017
7	Cochlear implantation and clinical features in patients with Noonan syndrome and Noonan syndrome with multiple lentigines caused by a mutation in PTPN11. ( 28483241 )	van Nierop J.W.I....Kunst H.P.M.	2017
8	Multiple giant cell lesions in a patient with Noonan syndrome with multiple lentigines. ( 27238887 )	van den Berg H....de Lange J.	2016
9	Developmental SHP2 dysfunction underlies cardiac hypertrophy in Noonan syndrome with multiple lentigines. ( 27348588 )	Lauriol J....Kontaridis M.I.	2016
10	Hypertrophic neuropathy in Noonan syndrome with multiple lentigines. ( 26952712 )	Maridet C....Taieb A.	2016
11	Elevated calcium transients and increased myofibrillar power generation cause cardiac hypercontractility in a model of Noonan Syndrome with Multiple Lentigines. ( 25724491 )	Clay S.A....Krenz M.	2015
12	Paraspinal neurofibromas and hypertrophic neuropathy in Noonan syndrome with multiple lentigines. ( 26337637 )	Conboy E....Babovic-Vuksanovic D.	2015
13	Rapidly progressive hypertrophic cardiomyopathy in an infant with Noonan syndrome with multiple lentigines: Palliative treatment with a rapamycin analog. ( 25708222 )	Hahn A....Schranz D.	2015
14	A novel heterozygous MAP2K1 mutation in a patient with Noonan syndrome with multiple lentigines. ( 25423878 )	Nishi E....Kosho T.	2015
15	The case of 17-year-old male with LEOPARD syndrome. ( 30533116 )	Dzemeshkevich S...Rizun L	2013
16	A Novel A461S Mutation of PTPN11 in a Female with LEOPARD Syndrome. ( 24790373 )	Yoshida R...Ogata T	2008
17	Gerstmann tetrad in leopard syndrome. ( 2604805 )	Garty BZ...Weitz R	1989

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Genes for Noonan Syndrome with Multiple Lentigines

Genes related to Noonan Syndrome with Multiple Lentigines (4 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubmedIds
1	PTPN11	Protein Tyrosine Phosphatase Non-Receptor Type 11	Protein Coding	779.62	Pathogenic ⁶ Causative germline mutation ⁶⁰ GeneCards inferred via : Publications Variants (show sections)	20301557 25173338
2	RAF1	Raf-1 Proto-Oncogene, Serine/Threonine Kinase	Protein Coding	769.57	Pathogenic ⁶ Causative germline mutation (gain of function) ⁶⁰ GeneCards inferred via : Variants (show sections)	20301557 25173338
3	BRAF	B-Raf Proto-Oncogene, Serine/Threonine Kinase	Protein Coding	769.35	Pathogenic/Likely pathogenic ⁶ Causative germline mutation ⁶⁰ GeneCards inferred via : Variants (show sections)	20301557 25173338
4	PPP1R13L	Protein Phosphatase 1 Regulatory Subunit 13 Like	Protein Coding	400	Pathogenic ⁶
5	MKRN2	Makorin Ring Finger Protein 2	Protein Coding	18.7	GeneCards inferred via : Variants (show sections)
6	RPL6	Ribosomal Protein L6	Protein Coding	8.62	GeneCards inferred via : Variants (show sections)
7	LOC105375536	Uncharacterized LOC105375536	RNA Gene	8.42	GeneCards inferred via : Variants (show sections)

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Variations for Noonan Syndrome with Multiple Lentigines

ClinVar genetic disease variations for Noonan Syndrome with Multiple Lentigines:

⁶ (show top 50) (show all 256)

#	Gene	Variation	Type	Significance	SNP ID	Assembly	Location
1	RAF1	NM_002880.3(RAF1): c.321-14T> A	single nucleotide variant	Benign/Likely benign	rs3730270	GRCh37	Chromosome 3, 12650848: 12650848
2	RAF1	NM_002880.3(RAF1): c.321-14T> A	single nucleotide variant	Benign/Likely benign	rs3730270	GRCh38	Chromosome 3, 12609349: 12609349
3	RAF1	NM_002880.3(RAF1): c.-416C> G	single nucleotide variant	Benign/Likely benign	rs61730434	GRCh37	Chromosome 3, 12705701: 12705701
4	RAF1	NM_002880.3(RAF1): c.-416C> G	single nucleotide variant	Benign/Likely benign	rs61730434	GRCh38	Chromosome 3, 12664202: 12664202
5	RAF1	NM_002880.3(RAF1): c.1721A> G (p.Tyr574Cys)	single nucleotide variant	Uncertain significance	rs370242565	GRCh37	Chromosome 3, 12626428: 12626428
6	RAF1	NM_002880.3(RAF1): c.1721A> G (p.Tyr574Cys)	single nucleotide variant	Uncertain significance	rs370242565	GRCh38	Chromosome 3, 12584929: 12584929
7	BRAF	NM_004333.4(BRAF): c.*7T> C	single nucleotide variant	Conflicting interpretations of pathogenicity	rs727502903	GRCh37	Chromosome 7, 140434390: 140434390
8	BRAF	NM_004333.4(BRAF): c.*7T> C	single nucleotide variant	Conflicting interpretations of pathogenicity	rs727502903	GRCh38	Chromosome 7, 140734590: 140734590
9	PTPN11	NM_002834.4(PTPN11): c.1403C> T (p.Thr468Met)	single nucleotide variant	Pathogenic	rs121918457	GRCh37	Chromosome 12, 112926270: 112926270
10	PTPN11	NM_002834.4(PTPN11): c.1403C> T (p.Thr468Met)	single nucleotide variant	Pathogenic	rs121918457	GRCh38	Chromosome 12, 112488466: 112488466
11	PTPN11	NM_002834.4(PTPN11): c.1381G> A (p.Ala461Thr)	single nucleotide variant	Pathogenic	rs121918468	GRCh37	Chromosome 12, 112926248: 112926248
12	PTPN11	NM_002834.4(PTPN11): c.1381G> A (p.Ala461Thr)	single nucleotide variant	Pathogenic	rs121918468	GRCh38	Chromosome 12, 112488444: 112488444
13	PTPN11	NM_002834.4(PTPN11): c.1529A> C (p.Gln510Pro)	single nucleotide variant	Pathogenic	rs121918470	GRCh37	Chromosome 12, 112926909: 112926909
14	PTPN11	NM_002834.4(PTPN11): c.1529A> C (p.Gln510Pro)	single nucleotide variant	Pathogenic	rs121918470	GRCh38	Chromosome 12, 112489105: 112489105
15	RAF1	NM_002880.3(RAF1): c.770C> T (p.Ser257Leu)	single nucleotide variant	Pathogenic	rs80338796	GRCh37	Chromosome 3, 12645699: 12645699
16	RAF1	NM_002880.3(RAF1): c.770C> T (p.Ser257Leu)	single nucleotide variant	Pathogenic	rs80338796	GRCh38	Chromosome 3, 12604200: 12604200
17	RAF1	NM_002880.3(RAF1): c.1837C> G (p.Leu613Val)	single nucleotide variant	Pathogenic	rs80338797	GRCh37	Chromosome 3, 12626123: 12626123
18	RAF1	NM_002880.3(RAF1): c.1837C> G (p.Leu613Val)	single nucleotide variant	Pathogenic	rs80338797	GRCh38	Chromosome 3, 12584624: 12584624
19	RAF1	NM_002880.3(RAF1): c.1456G> A (p.Asp486Asn)	single nucleotide variant	Pathogenic	rs80338798	GRCh37	Chromosome 3, 12627260: 12627260
20	RAF1	NM_002880.3(RAF1): c.1456G> A (p.Asp486Asn)	single nucleotide variant	Pathogenic	rs80338798	GRCh38	Chromosome 3, 12585761: 12585761
21	RAF1	NM_002880.3(RAF1): c.1472C> T (p.Thr491Ile)	single nucleotide variant	Pathogenic	rs80338799	GRCh37	Chromosome 3, 12627244: 12627244
22	RAF1	NM_002880.3(RAF1): c.1472C> T (p.Thr491Ile)	single nucleotide variant	Pathogenic	rs80338799	GRCh38	Chromosome 3, 12585745: 12585745
23	BRAF	NM_004333.4(BRAF): c.721A> C (p.Thr241Pro)	single nucleotide variant	Pathogenic/Likely pathogenic	rs387906661	GRCh37	Chromosome 7, 140501351: 140501351
24	BRAF	NM_004333.4(BRAF): c.721A> C (p.Thr241Pro)	single nucleotide variant	Pathogenic/Likely pathogenic	rs387906661	GRCh38	Chromosome 7, 140801551: 140801551
25	PTPN11	NM_002834.4(PTPN11): c.255C> T (p.His85=)	single nucleotide variant	Benign	rs61736914	GRCh37	Chromosome 12, 112888239: 112888239
26	PTPN11	NM_002834.4(PTPN11): c.255C> T (p.His85=)	single nucleotide variant	Benign	rs61736914	GRCh38	Chromosome 12, 112450435: 112450435
27	BRAF	NM_004333.5(BRAF): c.36G> A (p.Ala12=)	single nucleotide variant	Benign	rs397507454	GRCh37	Chromosome 7, 140624468: 140624468
28	BRAF	NM_004333.5(BRAF): c.36G> A (p.Ala12=)	single nucleotide variant	Benign	rs397507454	GRCh38	Chromosome 7, 140924668: 140924668
29	BRAF	NM_004333.5(BRAF): c.78G> T (p.Glu26Asp)	single nucleotide variant	Benign/Likely benign	rs371877084	GRCh37	Chromosome 7, 140624426: 140624426
30	BRAF	NM_004333.5(BRAF): c.78G> T (p.Glu26Asp)	single nucleotide variant	Benign/Likely benign	rs371877084	GRCh38	Chromosome 7, 140924626: 140924626
31	BRAF	NM_004333.4(BRAF): c.735A> T (p.Leu245Phe)	single nucleotide variant	Conflicting interpretations of pathogenicity	rs397507466	GRCh37	Chromosome 7, 140501337: 140501337
32	BRAF	NM_004333.4(BRAF): c.735A> T (p.Leu245Phe)	single nucleotide variant	Conflicting interpretations of pathogenicity	rs397507466	GRCh38	Chromosome 7, 140801537: 140801537
33	BRAF	NM_004333.5(BRAF): c.1227A> G (p.Ser409=)	single nucleotide variant	Benign	rs145035762	GRCh37	Chromosome 7, 140482908: 140482908
34	BRAF	NM_004333.5(BRAF): c.1227A> G (p.Ser409=)	single nucleotide variant	Benign	rs145035762	GRCh38	Chromosome 7, 140783108: 140783108
35	BRAF	NM_004333.5(BRAF): c.1332G> A (p.Arg444=)	single nucleotide variant	Benign	rs56101602	GRCh37	Chromosome 7, 140481476: 140481476
36	BRAF	NM_004333.5(BRAF): c.1332G> A (p.Arg444=)	single nucleotide variant	Benign	rs56101602	GRCh38	Chromosome 7, 140781676: 140781676
37	BRAF	NM_004333.5(BRAF): c.1383A> G (p.Gln461=)	single nucleotide variant	Benign	rs56216404	GRCh37	Chromosome 7, 140481425: 140481425
38	BRAF	NM_004333.5(BRAF): c.1383A> G (p.Gln461=)	single nucleotide variant	Benign	rs56216404	GRCh38	Chromosome 7, 140781625: 140781625
39	BRAF	NM_004333.5(BRAF): c.1929A> G (p.Gly643=)	single nucleotide variant	Benign	rs9648696	GRCh37	Chromosome 7, 140449150: 140449150
40	BRAF	NM_004333.5(BRAF): c.1929A> G (p.Gly643=)	single nucleotide variant	Benign	rs9648696	GRCh38	Chromosome 7, 140749350: 140749350
41	BRAF	NM_004333.5(BRAF): c.2235A> G (p.Leu745=)	single nucleotide variant	Benign	rs56046546	GRCh37	Chromosome 7, 140434463: 140434463
42	BRAF	NM_004333.5(BRAF): c.2235A> G (p.Leu745=)	single nucleotide variant	Benign	rs56046546	GRCh38	Chromosome 7, 140734663: 140734663
43	PTPN11	NM_002834.4(PTPN11): c.1093-9C> A	single nucleotide variant	Benign/Likely benign	rs12301915	GRCh37	Chromosome 12, 112919869: 112919869
44	PTPN11	NM_002834.4(PTPN11): c.1093-9C> A	single nucleotide variant	Benign/Likely benign	rs12301915	GRCh38	Chromosome 12, 112482065: 112482065
45	PTPN11	NM_002834.4(PTPN11): c.1381G> T (p.Ala461Ser)	single nucleotide variant	Pathogenic	rs121918468	GRCh37	Chromosome 12, 112926248: 112926248
46	PTPN11	NM_002834.4(PTPN11): c.1381G> T (p.Ala461Ser)	single nucleotide variant	Pathogenic	rs121918468	GRCh38	Chromosome 12, 112488444: 112488444
47	PTPN11	NM_002834.4(PTPN11): c.1517A> C (p.Gln506Pro)	single nucleotide variant	Pathogenic	rs397507548	GRCh37	Chromosome 12, 112926897: 112926897
48	PTPN11	NM_002834.4(PTPN11): c.1517A> C (p.Gln506Pro)	single nucleotide variant	Pathogenic	rs397507548	GRCh38	Chromosome 12, 112489093: 112489093
49	RAF1	NM_002880.3(RAF1): c.-337_-336delAG	deletion	Conflicting interpretations of pathogenicity	rs527774250	GRCh37	Chromosome 3, 12705621: 12705622
50	RAF1	NM_002880.3(RAF1): c.-337_-336delAG	deletion	Conflicting interpretations of pathogenicity	rs527774250	GRCh38	Chromosome 3, 12664122: 12664123

Sources

Expression for Noonan Syndrome with Multiple Lentigines

Search GEO for disease gene expression data for Noonan Syndrome with Multiple Lentigines.

Sources

Pathways for Noonan Syndrome with Multiple Lentigines

Pathways related to Noonan Syndrome with Multiple Lentigines according to GeneCards Suite gene sharing:

(show all 29)

#	Super pathways	Score	Top Affiliating Genes
1	Common Cytokine Receptor Gamma-Chain Family Signaling Pathways ⁶⁶ Show member pathways Adipokines and Insulin Signaling Pathways ⁶⁶ Development Thrombopoietin-regulated cell processes ²³ IL-15 Signaling Pathways ⁶⁶ IL-2 Signaling Pathways ⁶⁶ IL-21 Signaling Pathways ⁶⁶ IL-4 Signaling Pathways ⁶⁶ IL-7 Signaling Pathways ⁶⁶ IL-9 Pathway ⁶⁵ IL-9 Signaling Pathways ⁶⁶ Immune response IL-9 signaling pathway ²³	12.49	BRAF PTPN11 RAF1
2	Ras signaling pathway ³⁸ Show member pathways Rap1 signaling pathway ³⁸	12.45	BRAF PTPN11 RAF1
3	Development HGF signaling pathway ²³ Show member pathways Apoptosis and survival Anti-apoptotic action of membrane-bound ESR1 ²³ Apoptosis and survival NGF signaling pathway ²³ Apoptosis and survival Role of CDK5 in neuronal death and survival ²³ Development Neurotrophin family signaling ²³ MET activates PTPN11 ⁶⁷ MET activates STAT3 ⁶⁷ Neurotrophin signaling pathway ³⁸ Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met) ¹ Signaling of Hepatocyte Growth Factor Receptor ¹	12.43	BRAF PTPN11 RAF1
4	ErbB signaling pathway ¹ ³⁸ Show member pathways EGFR Inhibitor Pathway, Pharmacodynamics ⁶² EGFR tyrosine kinase inhibitor resistance ³⁸ Renal cell carcinoma ³⁸ TCA Cycle Nutrient Utilization and Invasiveness of Ovarian Cancer ¹	12.24	BRAF PTPN11 RAF1
5	Immune response Role of DAP12 receptors in NK cells ²³ Show member pathways Immune response CD16 signaling in NK cells ²³ Natural killer cell mediated cytotoxicity ³⁸	12.18	BRAF PTPN11 RAF1
6	Development VEGF signaling via VEGFR2 - generic cascades ²³ Show member pathways Development VEGF signaling and activation ²³ VEGF - VEGF R2 Signaling Pathways ⁶⁶	12.02	BRAF PTPN11 RAF1
7	B cell receptor signaling pathway (KEGG) ³⁸ Show member pathways B Cell Receptor Signaling Pathway ¹ BCR signaling pathway ¹	11.95	BRAF PTPN11 RAF1
8	G-protein signaling Ras family GTPases in kinase cascades (scheme) ²³ Show member pathways Activation of the AP-1 family of transcription factors ⁶⁷ Immune response Oncostatin M signaling via MAPK in human cells ²³ MAPK Cascade ¹ Oncostatin M Signaling Pathway ¹	11.69	BRAF PTPN11 RAF1
9	Proteoglycans in cancer ³⁸	11.64	BRAF PTPN11 RAF1
10	VEGF Pathway (Tocris) ⁷³ Show member pathways Sorafenib Pharmacodynamics ⁶²	11.56	BRAF RAF1
11	Bladder cancer ³⁸ ¹	11.5	BRAF RAF1
12	Human Thyroid Stimulating Hormone (TSH) signaling pathway ¹	11.45	BRAF RAF1
13	Negative regulation of MAPK pathway ⁶⁷ Show member pathways RAF activation ⁶⁷	11.42	BRAF RAF1
14	Downstream signaling in naive CD8+ T cells ¹ Show member pathways Ras signaling in the CD4+ TCR pathway ¹	11.38	BRAF RAF1
15	mTOR signaling pathway (Pathway Interaction Database) ¹	11.38	BRAF RAF1
16	Long-term depression ³⁸	11.36	BRAF RAF1
17	EGF/EGFR Signaling Pathway ¹	11.35	BRAF PTPN11 RAF1
18	Signaling events mediated by focal adhesion kinase ¹	11.31	BRAF RAF1
19	G-protein signaling_Rap1A regulation pathway ²³	11.27	BRAF RAF1
20	Semaphorin Signaling ⁶⁵	11.26	BRAF RAF1
21	Immune response_Role of integrins in NK cells cytotoxicity ²³	11.2	PTPN11 RAF1
22	Interleukin-11 Signaling Pathway ¹	11.19	PTPN11 RAF1
23	Vemurafenib Pathway, Pharmacodynamics ⁶²	11.17	BRAF RAF1
24	Immune response_IL-6 signaling pathway ²³	11.01	PTPN11 RAF1
25	Trk receptor signaling mediated by the MAPK pathway ¹ Show member pathways Signalling to ERK5 ⁶⁷	10.97	BRAF RAF1
26	Development_Leptin signaling via JAK/STAT and MAPK cascades ²³ Show member pathways phospho-PLA2 pathway ⁶⁷	10.91	PTPN11 RAF1
27	MAP Kinase Signaling ⁴	10.85	BRAF PTPN11 RAF1
28	IGF1 pathway ¹	10.82	PTPN11 RAF1
29	G-protein signaling_K-RAS regulation pathway ²³	10.75	BRAF RAF1

Sources

GO Terms for Noonan Syndrome with Multiple Lentigines

Biological processes related to Noonan Syndrome with Multiple Lentigines according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	somatic stem cell population maintenance	GO:0035019	9.37	BRAF RAF1
2	activation of MAPKK activity	GO:0000186	9.32	BRAF RAF1
3	thymus development	GO:0048538	9.26	BRAF RAF1
4	thyroid gland development	GO:0030878	9.16	BRAF RAF1
5	neurotrophin TRK receptor signaling pathway	GO:0048011	8.96	PTPN11 RAF1
6	face development	GO:0060324	8.62	BRAF RAF1

Molecular functions related to Noonan Syndrome with Multiple Lentigines according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	MAP kinase kinase kinase activity	GO:0004709	9.16	BRAF RAF1
2	small GTPase binding	GO:0031267	8.96	BRAF RAF1
3	mitogen-activated protein kinase kinase binding	GO:0031434	8.62	BRAF RAF1

Sources

Sources for Noonan Syndrome with Multiple Lentigines

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⁷¹ SNOMED-CT via Orphanet

⁷² TGDB

⁷³ Tocris

⁷⁴ UMLS

⁷⁵ UMLS via Orphanet

⁷⁶ UniProtKB/Swiss-Prot

⁷⁷ Wikipedia

Noonan Syndrome with Multiple Lentigines (NSML)

Aliases & Classifications for Noonan Syndrome with Multiple Lentigines

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Summaries for Noonan Syndrome with Multiple Lentigines

Related Diseases for Noonan Syndrome with Multiple Lentigines

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Graphical network of the top 20 diseases related to Noonan Syndrome with Multiple Lentigines:

Symptoms & Phenotypes for Noonan Syndrome with Multiple Lentigines

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Expression for Noonan Syndrome with Multiple Lentigines

Pathways for Noonan Syndrome with Multiple Lentigines

Pathways related to Noonan Syndrome with Multiple Lentigines according to GeneCards Suite gene sharing:

GO Terms for Noonan Syndrome with Multiple Lentigines

Biological processes related to Noonan Syndrome with Multiple Lentigines according to GeneCards Suite gene sharing:

Molecular functions related to Noonan Syndrome with Multiple Lentigines according to GeneCards Suite gene sharing:

Sources for Noonan Syndrome with Multiple Lentigines