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MCID: NNN026
MIFTS: 51

Noonan Syndrome with Multiple Lentigines

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 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
Orphanet: 60  
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 : 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 noonan syndrome 1, 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, eye and kidney, 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
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 71)
# Related Disease Score Top Affiliating Genes
1 leopard syndrome 32.0 BRAF PTPN11 RAF1
2 noonan syndrome 1 31.9 BRAF PTPN11 RAF1 RPL6
3 lentigines 30.8 BRAF PTPN11 RAF1
4 hypertrophic cardiomyopathy 30.1 BRAF PTPN11 RAF1
5 leopard syndrome 2 12.6
6 leopard syndrome 3 12.6
7 lentiginosis, inherited patterned 11.9
8 legius syndrome 11.1
9 pseudo-turner syndrome 10.7
10 leopard syndrome 1 10.4
11 orthostatic intolerance 10.3
12 myoblastoma 10.3
13 muscle hypertrophy 10.2
14 neuropathy 10.2
15 craniosynostosis 10.1
16 keratosis 10.1
17 granular cell tumor 10.1
18 neurofibroma 10.1
19 melanoma 10.0
20 pilomyxoid astrocytoma 10.0 BRAF RAF1
21 metachondromatosis 10.0 PTPN11 RPL6
22 cardiofaciocutaneous syndrome 1 10.0 BRAF PTPN11
23 atrial standstill 1 9.9
24 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 9.9
25 leukemia 9.9
26 heart disease 9.9
27 leukemia, chronic lymphocytic 2 9.9 BRAF PTPN11
28 pulmonic stenosis 9.9 BRAF PTPN11 RAF1
29 dyschromatosis universalis hereditaria 1 9.9
30 neurofibromatosis, type i 9.9
31 neurofibromatosis, type iv, of riccardi 9.9
32 teeth, supernumerary 9.9
33 renal hypodysplasia/aplasia 1 9.9
34 neurofibromatosis-noonan syndrome 9.9
35 renal hypodysplasia/aplasia 3 9.9
36 dermatitis 9.9
37 rhabdomyosarcoma 9.9
38 aorto-right ventricular tunnel 9.9
39 hypertelorism 9.9 BRAF PTPN11 RAF1
40 juvenile myelomonocytic leukemia 9.8 BRAF PTPN11 RAF1
41 noonan syndrome 3 9.8 PTPN11 RAF1
42 acroosteolysis 9.8
43 cardiac conduction defect 9.8
44 marfan syndrome 9.8
45 steatocystoma multiplex 9.8
46 wolff-parkinson-white syndrome 9.8
47 alopecia-epilepsy-oligophrenia syndrome of moynahan 9.8
48 autism 9.8
49 schizencephaly 9.8
50 werner syndrome 9.8

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



Diseases related to Noonan Syndrome with Multiple Lentigines
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Symptoms & Phenotypes for Noonan Syndrome with Multiple Lentigines

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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
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 30
Sources

Anatomical Context for Noonan Syndrome with Multiple Lentigines

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

42
Skin, Eye, Kidney, Bone, Bone Marrow, Myeloid
Sources

Publications for Noonan Syndrome with Multiple Lentigines

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Articles related to Noonan Syndrome with Multiple Lentigines:

(show top 50) (show all 164)
# Title Authors Year
1
Importance of cardiovascular examination in patients with multiple lentigines: two cases of LEOPARD syndrome with hypertrophic cardiomyopathy. ( 29717636 )
2019
2
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 )
2019
3
Noonan syndrome with multiple lentigines and associated craniosynostosis. ( 29356064 )
2018
4
Widespread keratosis pilaris in a patient with Noonan syndrome with multiple lentigines. ( 30152106 )
2018
5
A Rare Case of Left Ventricular Noncompaction in LEOPARD Syndrome. ( 29629024 )
2018
6
Clinical, pathological and dermoscopic characteristics of cutaneous lesions in LEOPARD syndrome. ( 28862807 )
2018
7
Patient with confirmed LEOPARD syndrome developing multiple melanoma. ( 29445579 )
2018
8
Accelerated Cardiomyocyte Proliferation in the Heart of a Neonate With LEOPARD Syndrome-Associated Fatal Cardiomyopathy. ( 29602897 )
2018
9
Generalised lentiginosis and café noir spots leading to a diagnosis of LEOPARD syndrome. ( 29891643 )
2018
10
Noonan syndrome with multiple lentigines with PTPN11 (T468M) gene mutation accompanied with solitary granular cell tumor. ( 28681392 )
2017
11
In vivo efficacy of the AKT inhibitor ARQ 092 in Noonan Syndrome with multiple lentigines-associated hypertrophic cardiomyopathy. ( 28582432 )
2017
12
Cochlear implantation and clinical features in patients with Noonan syndrome and Noonan syndrome with multiple lentigines caused by a mutation in PTPN11. ( 28483241 )
2017
13
Heterozygous deletion of AKT1 rescues cardiac contractility, but not hypertrophy, in a mouse model of Noonan Syndrome with Multiple Lentigines. ( 28911943 )
2017
14
Do you know this syndrome? Leopard syndrome. ( 28225973 )
2017
15
Paraspinal neurofibromas and hypertrophic neuropathy in Noonan syndrome with multiple lentigines. ( 26337637 )
2016
16
Hypertrophic neuropathy in Noonan syndrome with multiple lentigines. ( 26952712 )
2016
17
Multiple giant cell lesions in a patient with Noonan syndrome with multiple lentigines. ( 27238887 )
2016
18
Developmental SHP2 dysfunction underlies cardiac hypertrophy in Noonan syndrome with multiple lentigines. ( 27348588 )
2016
19
LEOPARD syndrome and multiple granular cell tumors: An underreported association? ( 26728819 )
2016
20
Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling. ( 26742426 )
2016
21
Erratum: LEOPARD syndrome and multiple granular cell tumors: An underreported association? ( 26924415 )
2016
22
Identification of a PTPN11 hot spot mutation in a child with atypical LEOPARD syndrome. ( 27484170 )
2016
23
The experience of bilateral cochlear implantation in a child with LEOPARD syndrome. ( 27729118 )
2016
24
LEOPARD Syndrome with Patent Ductus Arteriosus and Hypertrophic Cardiomyopathy. ( 26591153 )
2015
25
Rapidly progressive hypertrophic cardiomyopathy in an infant with Noonan syndrome with multiple lentigines: palliative treatment with a rapamycin analog. ( 25708222 )
2015
26
A novel heterozygous MAP2K1 mutation in a patient with Noonan syndrome with multiple lentigines. ( 25423878 )
2015
27
Elevated Ca2+ transients and increased myofibrillar power generation cause cardiac hypercontractility in a model of Noonan syndrome with multiple lentigines. ( 25724491 )
2015
28
Pathogenesis of multiple lentigines in LEOPARD syndrome with PTPN11 gene mutation. ( 25917897 )
2015
29
LEOPARD syndrome: you could be the first one to diagnose! ( 25572376 )
2015
30
PTPN11 mutation manifesting as LEOPARD syndrome associated with hypertrophic plexi and neuropathic pain. ( 25884655 )
2015
31
Phenotypical diversity of patients with LEOPARD syndrome carrying the worldwide recurrent p.Tyr279Cys PTPN11 mutation. ( 26377839 )
2015
32
LEOPARD Syndrome. ( 26632807 )
2015
33
LEOPARD syndrome without hearing loss or pulmonary stenosis: a report of 2 cases. ( 25544017 )
2015
34
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). ( 25173338 )
2014
35
Leopard syndrome: a report of five cases from one family in two generations. ( 24401936 )
2014
36
Anesthesia and LEOPARD syndrome: a review of forty-nine anesthetic exposures. ( 24461361 )
2014
37
Structural insights into Noonan/LEOPARD syndrome-related mutants of protein-tyrosine phosphatase SHP2 (PTPN11). ( 24628801 )
2014
38
LEOPARD syndrome: maxillofacial care. ( 24705231 )
2014
39
Noonan and LEOPARD syndrome Shp2 variants induce heart displacement defects in zebrafish. ( 24718990 )
2014
40
LEOPARD syndrome: clinical dilemmas in differential diagnosis of RASopathies. ( 24767283 )
2014
41
Leopard syndrome caused by heterozygous missense mutation of Tyr 279 Cys in the PTPN11 gene in a sporadic case of Chinese Han. ( 24820750 )
2014
42
PZR coordinates Shp2 Noonan and LEOPARD syndrome signaling in zebrafish and mice. ( 24865967 )
2014
43
Molecular basis of gain-of-function LEOPARD syndrome-associated SHP2 mutations. ( 24935154 )
2014
44
Phosphoproteomics-mediated identification of Fer kinase as a target of mutant Shp2 in Noonan and LEOPARD syndrome. ( 25184253 )
2014
45
LEOPARD syndrome-associated SHP2 mutation confers leanness and protection from diet-induced obesity. ( 25288766 )
2014
46
LEOPARD syndrome: a variant of Noonan syndrome strongly associated with hypertrophic cardiomyopathy. ( 24775816 )
2013
47
Delayed primary diagnosis of LEOPARD syndrome type 1. ( 23317994 )
2013
48
Structural and mechanistic insights into LEOPARD syndrome-associated SHP2 mutations. ( 23457302 )
2013
49
New approaches to prevent LEOPARD syndrome-associated cardiac hypertrophy by specifically targeting Shp2-dependent signaling. ( 23673659 )
2013
50
Syndromic Hearing Loss in Association with PTPN11-Related Disorder: The Experience of Cochlear Implantation in a Child with LEOPARD Syndrome. ( 23799168 )
2013
Sources

Variations for Noonan Syndrome with Multiple Lentigines

About this section

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_004333.5(BRAF): c.36G> A (p.Ala12=) single nucleotide variant Benign rs397507454 GRCh37 Chromosome 7, 140624468: 140624468
20 BRAF NM_004333.5(BRAF): c.36G> A (p.Ala12=) single nucleotide variant Benign rs397507454 GRCh38 Chromosome 7, 140924668: 140924668
21 BRAF NM_004333.5(BRAF): c.78G> T (p.Glu26Asp) single nucleotide variant Benign/Likely benign rs371877084 GRCh37 Chromosome 7, 140624426: 140624426
22 BRAF NM_004333.5(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_004333.5(BRAF): c.1227A> G (p.Ser409=) single nucleotide variant Benign rs145035762 GRCh37 Chromosome 7, 140482908: 140482908
26 BRAF NM_004333.5(BRAF): c.1227A> G (p.Ser409=) single nucleotide variant Benign rs145035762 GRCh38 Chromosome 7, 140783108: 140783108
27 BRAF NM_004333.5(BRAF): c.1332G> A (p.Arg444=) single nucleotide variant Benign rs56101602 GRCh37 Chromosome 7, 140481476: 140481476
28 BRAF NM_004333.5(BRAF): c.1332G> A (p.Arg444=) single nucleotide variant Benign rs56101602 GRCh38 Chromosome 7, 140781676: 140781676
29 BRAF NM_004333.5(BRAF): c.1383A> G (p.Gln461=) single nucleotide variant Benign rs56216404 GRCh37 Chromosome 7, 140481425: 140481425
30 BRAF NM_004333.5(BRAF): c.1383A> G (p.Gln461=) single nucleotide variant Benign rs56216404 GRCh38 Chromosome 7, 140781625: 140781625
31 BRAF NM_004333.5(BRAF): c.1929A> G (p.Gly643=) single nucleotide variant Benign rs9648696 GRCh37 Chromosome 7, 140449150: 140449150
32 BRAF NM_004333.5(BRAF): c.1929A> G (p.Gly643=) single nucleotide variant Benign rs9648696 GRCh38 Chromosome 7, 140749350: 140749350
33 BRAF NM_004333.5(BRAF): c.2235A> G (p.Leu745=) single nucleotide variant Benign rs56046546 GRCh37 Chromosome 7, 140434463: 140434463
34 BRAF NM_004333.5(BRAF): c.2235A> G (p.Leu745=) single nucleotide variant Benign rs56046546 GRCh38 Chromosome 7, 140734663: 140734663
35 PTPN11 NM_002834.4(PTPN11): c.1381G> T (p.Ala461Ser) single nucleotide variant Pathogenic rs121918468 GRCh37 Chromosome 12, 112926248: 112926248
36 PTPN11 NM_002834.4(PTPN11): c.1093-9C> A single nucleotide variant Benign/Likely benign rs12301915 GRCh37 Chromosome 12, 112919869: 112919869
37 PTPN11 NM_002834.4(PTPN11): c.1093-9C> A single nucleotide variant Benign/Likely benign rs12301915 GRCh38 Chromosome 12, 112482065: 112482065
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 66
Show member pathways
 12.49 BRAF PTPN11 RAF1
2
Ras signaling pathway 38
Show member pathways
 12.45 BRAF PTPN11 RAF1
3
Development HGF signaling pathway 23
Show member pathways
 12.43 BRAF PTPN11 RAF1
4
ErbB signaling pathway 1 38
Show member pathways
 12.24 BRAF PTPN11 RAF1
5
Immune response Role of DAP12 receptors in NK cells 23
Show member pathways
 12.18 BRAF PTPN11 RAF1
6
Development VEGF signaling via VEGFR2 - generic cascades 23
Show member pathways
 12.02 BRAF PTPN11 RAF1
7
B cell receptor signaling pathway (KEGG) 38
Show member pathways
 11.95 BRAF PTPN11 RAF1
8
G-protein signaling Ras family GTPases in kinase cascades (scheme) 23
Show member pathways
 11.69 BRAF PTPN11 RAF1
9
Proteoglycans in cancer 38
11.64 BRAF PTPN11 RAF1
10
VEGF Pathway (Tocris) 62
Show member pathways
 11.56 BRAF RAF1
11
Bladder cancer 1 38
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
 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 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
 10.97 BRAF RAF1
26
Development_Leptin signaling via JAK/STAT and MAPK cascades 23
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 23
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 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 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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