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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
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Aliases & Classifications for Noonan Syndrome with Multiple Lentigines

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MalaCards integrated aliases for Noonan Syndrome with Multiple Lentigines:

Name: Noonan Syndrome with Multiple Lentigines 24 25 59 29 6
Leopard Syndrome 24 25 59 73
Multiple Lentigines Syndrome 24 25
Cardiomyopathic Lentiginosis 25 59
Cardio-Cutaneous Syndrome 25 6
Lentiginosis Profusa 25 73
Alopecia Epilepsy Oligophrenia Syndrome of Moynahan 73
Progressive Cardiomyopathic Lentiginosis 25
Familial Multiple Lentigines Syndrome 59
Diffuse Lentiginosis 25
Moynahan Syndrome 25
Nsml 25

Characteristics:

Orphanet epidemiological data:

59
noonan syndrome with multiple lentigines
Inheritance: Autosomal dominant; Age of onset: Childhood;

GeneReviews:

24
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: 34
Orphanet: 59  
Rare cardiac malformations
Rare otorhinolaryngological diseases
Rare skin diseases
Developmental anomalies during embryogenesis


Sources

Summaries for Noonan Syndrome with Multiple Lentigines

About this section
Genetics Home Reference : 25 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 noonan syndrome 1 and leopard syndrome, 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 pectus excavatum

Wikipedia : 76 Noonan syndrome with multiple lentigines (NSML) which is part of a group called Ras/MAPK pathway... more...

GeneReviews: NBK1383
Sources

Related Diseases for Noonan Syndrome with Multiple Lentigines

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

(show top 50) (show all 62)
# Related Disease Score Top Affiliating Genes
1 noonan syndrome 1 32.1 BRAF PTPN11 RAF1 RPL6
2 leopard syndrome 32.0 BRAF PTPN11 RAF1
3 lentigines 30.9 BRAF PTPN11 RAF1
4 hypertrophic cardiomyopathy 30.2 BRAF PTPN11 RAF1
5 leopard syndrome 2 12.4
6 leopard syndrome 3 12.4
7 lentiginosis, inherited patterned 11.9
8 legius syndrome 11.0
9 leopard syndrome 1 10.6
10 pseudo-turner syndrome 10.6
11 orthostatic intolerance 10.3
12 myoblastoma 10.3
13 neuropathy 10.2
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 leukemia, chronic lymphocytic 2 9.9 BRAF PTPN11
22 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 9.9
23 leukemia 9.9
24 heart disease 9.9
25 pulmonic stenosis 9.9 BRAF PTPN11 RAF1
26 hypertelorism 9.9 BRAF PTPN11 RAF1
27 juvenile myelomonocytic leukemia 9.9 BRAF PTPN11 RAF1
28 noonan syndrome 3 9.9 PTPN11 RAF1
29 neurofibromatosis, type i 9.9
30 teeth, supernumerary 9.9
31 renal hypodysplasia/aplasia 1 9.9
32 renal hypodysplasia/aplasia 3 9.9
33 dermatitis 9.9
34 rhabdomyosarcoma 9.9
35 aorto-right ventricular tunnel 9.9
36 large intestine cancer 9.9 BRAF 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:



Diseases related to Noonan Syndrome with Multiple Lentigines
Sources

Symptoms & Phenotypes for Noonan Syndrome with Multiple Lentigines

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Human phenotypes related to Noonan Syndrome with Multiple Lentigines:

59 32 (show top 50) (show all 53)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertelorism 59 32 hallmark (90%) Very frequent (99-80%) HP:0000316
2 pectus excavatum 59 32 frequent (33%) Frequent (79-30%) HP:0000767
3 ptosis 59 32 frequent (33%) Frequent (79-30%) HP:0000508
4 scoliosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0002650
5 global developmental delay 59 32 occasional (7.5%) Occasional (29-5%) HP:0001263
6 wide nasal bridge 59 32 frequent (33%) Frequent (79-30%) HP:0000431
7 pectus carinatum 59 32 frequent (33%) Frequent (79-30%) HP:0000768
8 short stature 59 32 frequent (33%) Frequent (79-30%) HP:0004322
9 intellectual disability, mild 59 32 occasional (7.5%) Occasional (29-5%) HP:0001256
10 subcutaneous nodule 59 32 occasional (7.5%) Occasional (29-5%) HP:0001482
11 brachycephaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0000248
12 hypertrophic cardiomyopathy 59 32 hallmark (90%) Very frequent (99-80%) HP:0001639
13 arrhythmia 59 32 hallmark (90%) Very frequent (99-80%) HP:0011675
14 myocardial infarction 59 32 occasional (7.5%) Occasional (29-5%) HP:0001658
15 myelodysplasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002863
16 aplasia/hypoplasia of the abdominal wall musculature 59 32 occasional (7.5%) Occasional (29-5%) HP:0010318
17 cryptorchidism 59 32 frequent (33%) Frequent (79-30%) HP:0000028
18 intrauterine growth retardation 59 32 hallmark (90%) Very frequent (99-80%) HP:0001511
19 webbed neck 59 32 frequent (33%) Frequent (79-30%) HP:0000465
20 melanocytic nevus 59 32 hallmark (90%) Very frequent (99-80%) HP:0000995
21 melanoma 59 32 occasional (7.5%) Occasional (29-5%) HP:0002861
22 sprengel anomaly 59 32 frequent (33%) Frequent (79-30%) HP:0000912
23 scapular winging 59 32 frequent (33%) Frequent (79-30%) HP:0003691
24 hypospadias 59 32 occasional (7.5%) Occasional (29-5%) HP:0000047
25 bundle branch block 59 32 hallmark (90%) Very frequent (99-80%) HP:0011710
26 low-set, posteriorly rotated ears 59 32 frequent (33%) Frequent (79-30%) HP:0000368
27 mitral valve prolapse 59 32 frequent (33%) Frequent (79-30%) HP:0001634
28 abnormality of the voice 59 32 occasional (7.5%) Occasional (29-5%) HP:0001608
29 decreased fertility 59 32 frequent (33%) Frequent (79-30%) HP:0000144
30 pulmonic stenosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0001642
31 spina bifida occulta 59 32 occasional (7.5%) Occasional (29-5%) HP:0003298
32 triangular face 59 32 occasional (7.5%) Occasional (29-5%) HP:0000325
33 abnormality of the pulmonary artery 59 32 hallmark (90%) Very frequent (99-80%) HP:0004414
34 hyperextensible skin 59 32 hallmark (90%) Very frequent (99-80%) HP:0000974
35 multiple lentigines 59 32 hallmark (90%) Very frequent (99-80%) HP:0001003
36 abnormal localization of kidney 59 32 occasional (7.5%) Occasional (29-5%) HP:0100542
37 atrioventricular canal defect 59 32 frequent (33%) Frequent (79-30%) HP:0006695
38 neuroblastoma 59 32 occasional (7.5%) Occasional (29-5%) HP:0003006
39 severe sensorineural hearing impairment 59 32 hallmark (90%) Very frequent (99-80%) HP:0008625
40 freckling 59 32 hallmark (90%) Very frequent (99-80%) HP:0001480
41 excessive wrinkled skin 59 32 occasional (7.5%) Occasional (29-5%) HP:0007392
42 sensorineural hearing impairment 59 Very frequent (99-80%)
43 malformation of the heart and great vessels 59 Frequent (79-30%)
44 growth delay 59 Very frequent (99-80%)
45 abnormality of the endocardium 59 Occasional (29-5%)
46 abnormality of the face 59 Frequent (79-30%)
47 abnormality of the pulmonary valve 59 Very frequent (99-80%)
48 abnormality of the mitral valve 59 Frequent (79-30%)
49 abnormality of the genital system 59 Very frequent (99-80%)
50 aneurysm 59 Occasional (29-5%)

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:

26 (show all 20)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-110 9.68 BRAF
2 Increased shRNA abundance (Z-score > 2) GR00366-A-118 9.68 PTPN11
3 Increased shRNA abundance (Z-score > 2) GR00366-A-121 9.68 PTPN11
4 Increased shRNA abundance (Z-score > 2) GR00366-A-138 9.68 PTPN11
5 Increased shRNA abundance (Z-score > 2) GR00366-A-149 9.68 BRAF PTPN11 RAF1
6 Increased shRNA abundance (Z-score > 2) GR00366-A-151 9.68 RAF1
7 Increased shRNA abundance (Z-score > 2) GR00366-A-161 9.68 RAF1
8 Increased shRNA abundance (Z-score > 2) GR00366-A-166 9.68 BRAF
9 Increased shRNA abundance (Z-score > 2) GR00366-A-177 9.68 BRAF
10 Increased shRNA abundance (Z-score > 2) GR00366-A-178 9.68 PTPN11
11 Increased shRNA abundance (Z-score > 2) GR00366-A-190 9.68 PTPN11
12 Increased shRNA abundance (Z-score > 2) GR00366-A-194 9.68 BRAF
13 Increased shRNA abundance (Z-score > 2) GR00366-A-29 9.68 BRAF
14 Increased shRNA abundance (Z-score > 2) GR00366-A-31 9.68 BRAF
15 Increased shRNA abundance (Z-score > 2) GR00366-A-32 9.68 BRAF
16 Increased shRNA abundance (Z-score > 2) GR00366-A-37 9.68 PTPN11
17 Increased shRNA abundance (Z-score > 2) GR00366-A-47 9.68 BRAF PTPN11
18 Increased shRNA abundance (Z-score > 2) GR00366-A-52 9.68 RAF1
19 Increased shRNA abundance (Z-score > 2) GR00366-A-7 9.68 PTPN11
20 Increased shRNA abundance (Z-score > 2) GR00366-A-78 9.68 PTPN11

MGI Mouse Phenotypes related to Noonan Syndrome with Multiple Lentigines:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 9.02 BRAF MKRN2 PPP1R13L PTPN11 RAF1
Sources

Drugs & Therapeutics for Noonan Syndrome with Multiple Lentigines

About this section

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

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Genetic tests related to Noonan Syndrome with Multiple Lentigines:

# Genetic test Affiliating Genes
1 Noonan Syndrome with Multiple Lentigines 29
Sources

Anatomical Context for Noonan Syndrome with Multiple Lentigines

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

41
Skin, Heart, Eye, Kidney, Bone, Myeloid, Bone Marrow
Sources

Publications for Noonan Syndrome with Multiple Lentigines

About this section

Articles related to Noonan Syndrome with Multiple Lentigines:

(show all 22)
# Title Authors Year
1
Noonan syndrome with multiple lentigines and associated craniosynostosis. ( 29356064 )
2018
2
Importance of cardiovascular examination in patients with multiple lentigines: two cases of LEOPARD syndrome with hypertrophic cardiomyopathy. ( 29717636 )
2018
3
Widespread keratosis pilaris in a patient with Noonan syndrome with multiple lentigines. ( 30152106 )
2018
4
A Rare Case of Left Ventricular Noncompaction in LEOPARD Syndrome. ( 29629024 )
2018
5
Generalised lentiginosis and café noir spots leading to a diagnosis of LEOPARD syndrome. ( 29891643 )
2018
6
In vivo efficacy of the AKT inhibitor ARQ 092 in Noonan Syndrome with multiple lentigines-associated hypertrophic cardiomyopathy. ( 28582432 )
2017
7
Heterozygous deletion of AKT1 rescues cardiac contractility, but not hypertrophy, in a mouse model of Noonan Syndrome with Multiple Lentigines. ( 28911943 )
2017
8
Noonan syndrome with multiple lentigines with PTPN11 (T468M) gene mutation accompanied with solitary granular cell tumor. ( 28681392 )
2017
9
Cochlear implantation and clinical features in patients with Noonan syndrome and Noonan syndrome with multiple lentigines caused by a mutation in PTPN11. ( 28483241 )
2017
10
Multiple giant cell lesions in a patient with Noonan syndrome with multiple lentigines. ( 27238887 )
2016
11
Developmental SHP2 dysfunction underlies cardiac hypertrophy in Noonan syndrome with multiple lentigines. ( 27348588 )
2016
12
Hypertrophic neuropathy in Noonan syndrome with multiple lentigines. ( 26952712 )
2016
13
Elevated calcium transients and increased myofibrillar power generation cause cardiac hypercontractility in a model of Noonan Syndrome with Multiple Lentigines. ( 25724491 )
2015
14
Paraspinal neurofibromas and hypertrophic neuropathy in Noonan syndrome with multiple lentigines. ( 26337637 )
2015
15
Rapidly progressive hypertrophic cardiomyopathy in an infant with Noonan syndrome with multiple lentigines: Palliative treatment with a rapamycin analog. ( 25708222 )
2015
16
A novel heterozygous MAP2K1 mutation in a patient with Noonan syndrome with multiple lentigines. ( 25423878 )
2015
17
Leopard syndrome caused by heterozygous missense mutation of Tyr 279 Cys in the PTPN11 gene in a sporadic case of Chinese Han. ( 24820750 )
2014
18
The case of 17-year-old male with LEOPARD syndrome. ( 30533116 )
2013
19
Leopard syndrome and hypertrophic cardiomyopathy: an association related to sudden death. ( 19629299 )
2009
20
A Novel A461S Mutation of PTPN11 in a Female with LEOPARD Syndrome. ( 24790373 )
2008
21
LEOPARD syndrome and hypertrophic obstructive cardiomyopathy: a case report. ( 15641276 )
2004
22
Gerstmann tetrad in leopard syndrome. ( 2604805 )
1989
Sources

Variations for Noonan Syndrome with Multiple Lentigines

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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 PTPN11 NM_002834.4(PTPN11): c.1403C> T (p.Thr468Met) single nucleotide variant Pathogenic rs121918457 GRCh37 Chromosome 12, 112926270: 112926270
2 PTPN11 NM_002834.4(PTPN11): c.1403C> T (p.Thr468Met) single nucleotide variant Pathogenic rs121918457 GRCh38 Chromosome 12, 112488466: 112488466
3 PTPN11 NM_002834.4(PTPN11): c.1381G> A (p.Ala461Thr) single nucleotide variant Pathogenic rs121918468 GRCh37 Chromosome 12, 112926248: 112926248
4 PTPN11 NM_002834.4(PTPN11): c.1381G> A (p.Ala461Thr) single nucleotide variant Pathogenic rs121918468 GRCh38 Chromosome 12, 112488444: 112488444
5 PTPN11 NM_002834.4(PTPN11): c.1529A> C (p.Gln510Pro) single nucleotide variant Pathogenic rs121918470 GRCh37 Chromosome 12, 112926909: 112926909
6 PTPN11 NM_002834.4(PTPN11): c.1529A> C (p.Gln510Pro) single nucleotide variant Pathogenic rs121918470 GRCh38 Chromosome 12, 112489105: 112489105
7 RAF1 NM_002880.3(RAF1): c.770C> T (p.Ser257Leu) single nucleotide variant Pathogenic rs80338796 GRCh37 Chromosome 3, 12645699: 12645699
8 RAF1 NM_002880.3(RAF1): c.770C> T (p.Ser257Leu) single nucleotide variant Pathogenic rs80338796 GRCh38 Chromosome 3, 12604200: 12604200
9 RAF1 NM_002880.3(RAF1): c.1837C> G (p.Leu613Val) single nucleotide variant Pathogenic rs80338797 GRCh37 Chromosome 3, 12626123: 12626123
10 RAF1 NM_002880.3(RAF1): c.1837C> G (p.Leu613Val) single nucleotide variant Pathogenic rs80338797 GRCh38 Chromosome 3, 12584624: 12584624
11 RAF1 NM_002880.3(RAF1): c.1456G> A (p.Asp486Asn) single nucleotide variant Pathogenic rs80338798 GRCh37 Chromosome 3, 12627260: 12627260
12 RAF1 NM_002880.3(RAF1): c.1456G> A (p.Asp486Asn) single nucleotide variant Pathogenic rs80338798 GRCh38 Chromosome 3, 12585761: 12585761
13 RAF1 NM_002880.3(RAF1): c.1472C> T (p.Thr491Ile) single nucleotide variant Pathogenic rs80338799 GRCh37 Chromosome 3, 12627244: 12627244
14 RAF1 NM_002880.3(RAF1): c.1472C> T (p.Thr491Ile) single nucleotide variant Pathogenic rs80338799 GRCh38 Chromosome 3, 12585745: 12585745
15 BRAF NM_004333.4(BRAF): c.721A> C (p.Thr241Pro) single nucleotide variant Pathogenic/Likely pathogenic rs387906661 GRCh37 Chromosome 7, 140501351: 140501351
16 BRAF NM_004333.4(BRAF): c.721A> C (p.Thr241Pro) single nucleotide variant Pathogenic/Likely pathogenic rs387906661 GRCh38 Chromosome 7, 140801551: 140801551
17 PTPN11 NM_002834.4(PTPN11): c.255C> T (p.His85=) single nucleotide variant Benign rs61736914 GRCh37 Chromosome 12, 112888239: 112888239
18 PTPN11 NM_002834.4(PTPN11): c.255C> T (p.His85=) single nucleotide variant Benign rs61736914 GRCh38 Chromosome 12, 112450435: 112450435
19 BRAF NM_004333.4(BRAF): c.36G> A (p.Ala12=) single nucleotide variant Benign rs397507454 GRCh37 Chromosome 7, 140624468: 140624468
20 BRAF NM_004333.4(BRAF): c.36G> A (p.Ala12=) single nucleotide variant Benign rs397507454 GRCh38 Chromosome 7, 140924668: 140924668
21 BRAF NM_004333.4(BRAF): c.78G> T (p.Glu26Asp) single nucleotide variant Benign/Likely benign rs371877084 GRCh37 Chromosome 7, 140624426: 140624426
22 BRAF NM_004333.4(BRAF): c.78G> T (p.Glu26Asp) single nucleotide variant Benign/Likely benign rs371877084 GRCh38 Chromosome 7, 140924626: 140924626
23 BRAF NM_004333.4(BRAF): c.735A> T (p.Leu245Phe) single nucleotide variant Conflicting interpretations of pathogenicity rs397507466 GRCh37 Chromosome 7, 140501337: 140501337
24 BRAF NM_004333.4(BRAF): c.735A> T (p.Leu245Phe) single nucleotide variant Conflicting interpretations of pathogenicity rs397507466 GRCh38 Chromosome 7, 140801537: 140801537
25 BRAF NM_004333.4(BRAF): c.1227A> G (p.Ser409=) single nucleotide variant Benign rs145035762 GRCh37 Chromosome 7, 140482908: 140482908
26 BRAF NM_004333.4(BRAF): c.1227A> G (p.Ser409=) single nucleotide variant Benign rs145035762 GRCh38 Chromosome 7, 140783108: 140783108
27 BRAF NM_004333.4(BRAF): c.1332G> A (p.Arg444=) single nucleotide variant Benign rs56101602 GRCh37 Chromosome 7, 140481476: 140481476
28 BRAF NM_004333.4(BRAF): c.1332G> A (p.Arg444=) single nucleotide variant Benign rs56101602 GRCh38 Chromosome 7, 140781676: 140781676
29 BRAF NM_004333.4(BRAF): c.1383A> G (p.Gln461=) single nucleotide variant Benign rs56216404 GRCh37 Chromosome 7, 140481425: 140481425
30 BRAF NM_004333.4(BRAF): c.1383A> G (p.Gln461=) single nucleotide variant Benign rs56216404 GRCh38 Chromosome 7, 140781625: 140781625
31 BRAF NM_004333.4(BRAF): c.1929A> G (p.Gly643=) single nucleotide variant Benign rs9648696 GRCh37 Chromosome 7, 140449150: 140449150
32 BRAF NM_004333.4(BRAF): c.1929A> G (p.Gly643=) single nucleotide variant Benign rs9648696 GRCh38 Chromosome 7, 140749350: 140749350
33 BRAF NM_004333.4(BRAF): c.2235A> G (p.Leu745=) single nucleotide variant Benign rs56046546 GRCh37 Chromosome 7, 140434463: 140434463
34 BRAF NM_004333.4(BRAF): c.2235A> G (p.Leu745=) single nucleotide variant Benign rs56046546 GRCh38 Chromosome 7, 140734663: 140734663
35 PTPN11 NM_002834.4(PTPN11): c.1093-9C> A single nucleotide variant Benign/Likely benign rs12301915 GRCh37 Chromosome 12, 112919869: 112919869
36 PTPN11 NM_002834.4(PTPN11): c.1093-9C> A single nucleotide variant Benign/Likely benign rs12301915 GRCh38 Chromosome 12, 112482065: 112482065
37 PTPN11 NM_002834.4(PTPN11): c.1381G> T (p.Ala461Ser) single nucleotide variant Pathogenic rs121918468 GRCh37 Chromosome 12, 112926248: 112926248
38 PTPN11 NM_002834.4(PTPN11): c.1381G> T (p.Ala461Ser) single nucleotide variant Pathogenic rs121918468 GRCh38 Chromosome 12, 112488444: 112488444
39 PTPN11 NM_002834.4(PTPN11): c.1517A> C (p.Gln506Pro) single nucleotide variant Pathogenic rs397507548 GRCh37 Chromosome 12, 112926897: 112926897
40 PTPN11 NM_002834.4(PTPN11): c.1517A> C (p.Gln506Pro) single nucleotide variant Pathogenic rs397507548 GRCh38 Chromosome 12, 112489093: 112489093
41 RAF1 NM_002880.3(RAF1): c.-337_-336delAG deletion Conflicting interpretations of pathogenicity rs527774250 GRCh37 Chromosome 3, 12705621: 12705622
42 RAF1 NM_002880.3(RAF1): c.-337_-336delAG deletion Conflicting interpretations of pathogenicity rs527774250 GRCh38 Chromosome 3, 12664122: 12664123
43 RAF1 NM_002880.3(RAF1): c.-281C> G single nucleotide variant Benign/Likely benign rs61761285 GRCh37 Chromosome 3, 12705566: 12705566
44 RAF1 NM_002880.3(RAF1): c.-281C> G single nucleotide variant Benign/Likely benign rs61761285 GRCh38 Chromosome 3, 12664067: 12664067
45 RAF1 NM_002880.3(RAF1): c.-267G> A single nucleotide variant Conflicting interpretations of pathogenicity rs116247741 GRCh37 Chromosome 3, 12705552: 12705552
46 RAF1 NM_002880.3(RAF1): c.-267G> A single nucleotide variant Conflicting interpretations of pathogenicity rs116247741 GRCh38 Chromosome 3, 12664053: 12664053
47 RAF1 NM_002880.3(RAF1): c.-204G> C single nucleotide variant Conflicting interpretations of pathogenicity rs547543588 GRCh37 Chromosome 3, 12705489: 12705489
48 RAF1 NM_002880.3(RAF1): c.-204G> C single nucleotide variant Conflicting interpretations of pathogenicity rs547543588 GRCh38 Chromosome 3, 12663990: 12663990
49 RAF1 NM_002880.3(RAF1): c.-27+7G> A single nucleotide variant Uncertain significance rs886057916 GRCh37 Chromosome 3, 12705305: 12705305
50 RAF1 NM_002880.3(RAF1): c.-27+7G> A single nucleotide variant Uncertain significance rs886057916 GRCh38 Chromosome 3, 12663806: 12663806
Sources

Expression for Noonan Syndrome with Multiple Lentigines

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

Pathways for Noonan Syndrome with Multiple Lentigines

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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 65
Show member pathways
 12.49 BRAF PTPN11 RAF1
2
Ras signaling pathway 37
Show member pathways
 12.45 BRAF PTPN11 RAF1
3
Development HGF signaling pathway 22
Show member pathways
 12.43 BRAF PTPN11 RAF1
4
Immune response Role of DAP12 receptors in NK cells 22
Show member pathways
 12.18 BRAF PTPN11 RAF1
5
ErbB signaling pathway 1 37
Show member pathways
 12.13 BRAF PTPN11 RAF1
6
Development VEGF signaling via VEGFR2 - generic cascades 22
Show member pathways
 12.02 BRAF PTPN11 RAF1
7
B cell receptor signaling pathway (KEGG) 37
Show member pathways
 11.95 BRAF PTPN11 RAF1
8
G-protein signaling Ras family GTPases in kinase cascades (scheme) 22
Show member pathways
 11.69 BRAF PTPN11 RAF1
9
Proteoglycans in cancer 37
11.64 BRAF PTPN11 RAF1
10
VEGF Pathway (Tocris) 61
Show member pathways
 11.56 BRAF RAF1
11
Bladder cancer 37 1
11.5 BRAF RAF1
12
Human Thyroid Stimulating Hormone (TSH) signaling pathway 1
11.45 BRAF RAF1
13
Negative regulation of MAPK pathway 66
Show member pathways
 11.42 BRAF RAF1
14
Downstream signaling in naive CD8+ T cells 1
Show member pathways
 11.38 BRAF RAF1
15
mTOR signaling pathway (Pathway Interaction Database) 1
11.38 BRAF RAF1
16
Long-term depression 37
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 22
11.27 BRAF RAF1
20
Semaphorin Signaling 64
11.26 BRAF RAF1
21
Immune response_Role of integrins in NK cells cytotoxicity 22
11.2 PTPN11 RAF1
22
Interleukin-11 Signaling Pathway 1
11.19 PTPN11 RAF1
23
Vemurafenib Pathway, Pharmacodynamics 61
11.16 BRAF RAF1
24
Immune response_IL-6 signaling pathway 22
11.01 PTPN11 RAF1
25
Trk receptor signaling mediated by the MAPK pathway 1
Show member pathways
 10.97 BRAF RAF1
26
Development_Leptin signaling via JAK/STAT and MAPK cascades 22
Show member pathways
 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 22
10.75 BRAF RAF1
Sources

GO Terms for Noonan Syndrome with Multiple Lentigines

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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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3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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