NS1
MCID: NNN008
MIFTS: 77

Noonan Syndrome 1 (NS1)

Categories: Cardiovascular diseases, Ear diseases, Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Reproductive diseases, Skin diseases

Aliases & Classifications for Noonan Syndrome 1

MalaCards integrated aliases for Noonan Syndrome 1:

Name: Noonan Syndrome 1 56 12 52 73 29 13 6 15
Noonan Syndrome 56 12 74 24 52 25 58 73 36 29 54 6 43 15 71
Female Pseudo-Turner Syndrome 56 52 25 73
Male Turner Syndrome 56 52 25 73
Turner Phenotype with Normal Karyotype 56 25 73
Ns1 56 12 73
Pseudo-Ullrich-Turner Syndrome 52 25
Ullrich-Noonan Syndrome 52 25
Noonan-Ehmke Syndrome 52 25
Noonan Syndrome-Like Disorder with Multiple Giant Cell Lesions 73
Noonan Syndrome with Pigmented Villonodular Synovitis 73
Noonan-Like/multiple Giant Cell Lesion Syndrome 73
Turner Syndrome in Female with X Chromosome 25
Turner's Phenotype, Karyotype Normal 12
Pterygium Colli Syndrome 73
Familial Turner Syndrome 25
Syndrome, Noonan, Type 1 39
Turner Syndrome, Male 71
Turner-Like Syndrome 25
Noonan's Syndrome 25
Syndrome, Noonan 39
Ns 25

Characteristics:

Orphanet epidemiological data:

58
noonan syndrome
Inheritance: Autosomal dominant; Prevalence: 6-9/10000 (Europe); Age of onset: Neonatal; Age of death: normal life expectancy;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
genetic heterogeneity
allelic to leopard syndrome


HPO:

31
noonan syndrome 1:
Inheritance autosomal dominant inheritance heterogeneous


GeneReviews:

24
Penetrance Penetrance of ns is difficult to determine because of ascertainment bias and variable expressivity with frequent subtlety of features. many affected adults are diagnosed only after the birth of a more obviously affected infant.

Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Rare circulatory system diseases
Rare cardiac malformations
Rare renal diseases
Rare infertility disorders
Rare skin diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


Summaries for Noonan Syndrome 1

Genetics Home Reference : 25 Noonan syndrome is a condition that affects many areas of the body. It is characterized by mildly unusual facial features, short stature, heart defects, bleeding problems, skeletal malformations, and many other signs and symptoms. People with Noonan syndrome have distinctive facial features such as a deep groove in the area between the nose and mouth (philtrum), widely spaced eyes that are usually pale blue or blue-green in color, and low-set ears that are rotated backward. Affected individuals may have a high arch in the roof of the mouth (high-arched palate), poor teeth alignment, and a small lower jaw (micrognathia). Many children with Noonan syndrome have a short neck, and both children and adults may have excess neck skin (also called webbing) and a low hairline at the back of the neck. Between 50 and 70 percent of individuals with Noonan syndrome have short stature. At birth, they are usually a normal length and weight, but growth slows over time. Abnormal levels of growth hormone, a protein that is necessary for the normal growth of the body's bones and tissues, may contribute to the slow growth. Individuals with Noonan syndrome often have either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum). Some affected people may also have an abnormal side-to-side curvature of the spine (scoliosis). Most people with Noonan syndrome have some form of critical congenital heart disease. The most common heart defect in these individuals is a narrowing of the valve that controls blood flow from the heart to the lungs (pulmonary valve stenosis). Some have hypertrophic cardiomyopathy, which enlarges and weakens the heart muscle. A variety of bleeding disorders have been associated with Noonan syndrome. Some affected individuals have excessive bruising, nosebleeds, or prolonged bleeding following injury or surgery. Rarely, women with Noonan syndrome who have a bleeding disorder have excessive bleeding during menstruation (menorrhagia) or childbirth. Adolescent males with Noonan syndrome typically experience delayed puberty. They go through puberty starting at age 13 or 14 and have a reduced pubertal growth spurt that results in shortened stature. Most males with Noonan syndrome have undescended testes (cryptorchidism), which may contribute to infertility (inability to father a child) later in life. Females with Noonan syndrome can experience delayed puberty but most have normal puberty and fertility. Noonan syndrome can cause a variety of other signs and symptoms. Most children diagnosed with Noonan syndrome have normal intelligence, but a few have special educational needs, and some have intellectual disability. Some affected individuals have vision or hearing problems. Affected infants may have feeding problems, which typically get better by age 1 or 2 years. Infants with Noonan syndrome may be born with puffy hands and feet caused by a buildup of fluid (lymphedema), which can go away on its own. Older individuals can also develop lymphedema, usually in the ankles and lower legs. Some people with Noonan syndrome develop cancer, particularly those involving the blood-forming cells (leukemia). It has been estimated that children with Noonan syndrome have an eightfold increased risk of developing leukemia or other cancers over age-matched peers. Noonan syndrome is one of a group of related conditions, collectively known as RASopathies. These conditions all have similar signs and symptoms and are caused by changes in the same cell signaling pathway. In addition to Noonan syndrome, the RASopathies include cardiofaciocutaneous syndrome, Costello syndrome, neurofibromatosis type 1, Legius syndrome, and Noonan syndrome with multiple lentigines.

MalaCards based summary : Noonan Syndrome 1, also known as noonan syndrome, is related to leopard syndrome and neurofibromatosis-noonan syndrome. An important gene associated with Noonan Syndrome 1 is PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11), and among its related pathways/superpathways are Ras signaling pathway and MAPK signaling pathway. The drugs Simvastatin and Hormone Antagonists have been mentioned in the context of this disorder. Affiliated tissues include heart, bone and eye, and related phenotypes are hypertelorism and pectus excavatum

Disease Ontology : 12 A syndrome that is characterized by mildly unusual facial features, short stature, heart defects, bleeding problems, skeletal malformations, and many other signs and symptoms.

NIH Rare Diseases : 52 Noonan syndrome is a genetic disorder that causes abnormal development of multiple parts of the body. Features of Noonan syndrome may include a distinctive facial appearance, short stature , a broad or webbed neck, congenital heart defects , bleeding problems, problems with bone structure (skeletal malformations), and developmental delay . Noonan syndrome may be caused by a mutation in any of several genes , and can be classified into subtypes based on the responsible gene . It is typically inherited in an autosomal dominant manner, but many cases are due to a new mutation and are not inherited from either parent. Treatment depends on the symptoms present in each person. Noonan syndrome belongs to a group of related conditions called the RASopathies . These conditions have some overlapping features and are all caused by genetic changes that disrupt the body's RAS pathway, affecting growth and development. Other conditions in this group include: neurofibromatosis type 1 LEOPARD syndrome , also called Noonan syndrome with multiple lentigines Costello syndrome cardiofaciocutaneous syndrome Legius syndrome capillary malformation-arteriovenous malformation syndrome

OMIM : 56 Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, facial dysmorphism, and a wide spectrum of congenital heart defects. The distinctive facial features consist of a broad forehead, hypertelorism, downslanting palpebral fissures, a high-arched palate, and low-set, posteriorly rotated ears. Cardiac involvement is present in up to 90% of patients. Pulmonic stenosis and hypertrophic cardiomyopathy are the most common forms of cardiac disease, but a variety of other lesions are also observed. Additional relatively frequent features include multiple skeletal defects (chest and spine deformities), webbed neck, mental retardation, cryptorchidism, and bleeding diathesis (summary by Tartaglia et al., 2002). (163950)

KEGG : 36 Noonan syndrome (NS) is an autosomal dominant disorder characterised by short stature, craniofacial dysmorphism, congenital cardiac defects, cryptorchidism in men, coagulation defects, and neurocognitive delay. In addition, individuals with NS have an increased risk of developing cancer. NS is caused by germline mutations in genes that encode components or regulators of the Ras/MAPK pathway. Heterozygous, pathogenic variants in 9 known genes account for approximately 80% of cases. The most common gene associated with NS is PTPN11, which accounts for approximately 50% of all cases.

UniProtKB/Swiss-Prot : 73 Noonan syndrome 1: 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. Some patients with NS1 develop multiple giant cell lesions of the jaw or other bony or soft tissues, which are classified as pigmented villonodular synovitis (PVNS) when occurring in the jaw or joints.

Wikipedia : 74 Noonan syndrome (NS) is a genetic disorder that may present with mildly unusual facial features, short... more...

GeneReviews: NBK1124

Related Diseases for Noonan Syndrome 1

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 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 621)
# Related Disease Score Top Affiliating Genes
1 leopard syndrome 35.7 SOS2 SOS1 SHOC2 RASA2 RAF1 PTPN11
2 neurofibromatosis-noonan syndrome 35.0 PTPN11 MAP2K2
3 noonan syndrome and noonan-related syndrome 34.9 SOS1 RAF1 PTPN11 MAP2K2 BRAF
4 costello syndrome 34.3 SOS1 SHOC2 PTPN11 MAP2K2 MAP2K1 KRAS
5 cardiofaciocutaneous syndrome 1 34.0 SOS2 SOS1 SHOC2 RRAS RIT1 RASA2
6 hypertelorism 33.9 RIT1 RAF1 PTPN11 LZTR1 BRAF
7 noonan syndrome 3 33.4 SOS1 SHOC2 RAF1 PTPN11 KRAS HRAS
8 noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia 33.0 PTPN11 CBL
9 hypertrophic cardiomyopathy 33.0 SOS1 RAF1 PTPN11 MAP2K2 MAP2K1 KRAS
10 rasopathy 32.9 SOS1 SHOC2 RRAS RAF1 PTPN11 NRAS
11 juvenile myelomonocytic leukemia 32.9 SOS2 SOS1 SHOC2 RRAS RIT1 RASA2
12 neurofibromatosis, type iv, of riccardi 32.6 RASA2 PTPN11 LZTR1 KRAS HRAS
13 pulmonary valve stenosis 32.5 SOS2 SOS1 SHOC2 PTPN11 MAP2K2 MAP2K1
14 leukemia 32.4 SOS1 RAF1 PTPN11 NRAS KRAS KAT6B
15 lentigines 32.4 RAF1 PTPN11 BRAF
16 cryptorchidism, unilateral or bilateral 32.3 SOS1 SHOC2 PTPN11 HRAS
17 atrial heart septal defect 32.3 SOS1 SHOC2 PTPN11 LZTR1 HRAS
18 heart septal defect 32.2 SOS1 SHOC2 PTPN11
19 pulmonic stenosis 32.1 SOS1 KRAS HRAS BRAF
20 ptosis 32.0 SOS1 SHOC2 KAT6B CBL
21 myeloid leukemia 31.8 RAF1 PTPN11 NRAS MAP2K1 KRAS HRAS
22 leukemia, acute myeloid 31.7 PTPN11 NRAS MAP2K1 KRAS HRAS CBL
23 glioblastoma multiforme 31.5 RRAS RAF1 NRAS MAP2K1 KRAS HRAS
24 chronic myelomonocytic leukemia 31.4 PTPN11 NRAS KRAS CBL
25 embryonal rhabdomyosarcoma 31.4 SOS1 PTPN11 HRAS
26 villonodular synovitis 31.4 SOS1 PTPN11
27 tetralogy of fallot 31.3 SOS1 PTPN11 LZTR1 HRAS
28 lung cancer susceptibility 3 31.2 RAF1 NRAS MAP2K1 KRAS HRAS BRAF
29 pilomyxoid astrocytoma 31.0 RAF1 KRAS BRAF
30 noonan syndrome 4 12.7
31 noonan syndrome 6 12.7
32 noonan syndrome 5 12.7
33 noonan syndrome-like disorder with loose anagen hair 1 12.7
34 noonan syndrome 7 12.7
35 noonan syndrome-like disorder with loose anagen hair 2 12.6
36 short-rib thoracic dysplasia 3 with or without polydactyly 11.9
37 pseudo-turner syndrome 11.8
38 multiple pterygium syndrome, escobar variant 11.7
39 legius syndrome 11.6
40 medulloblastoma 11.6
41 cystic lymphangioma 11.5
42 cherubism 11.5
43 noonan syndrome 11 11.5
44 pectus carinatum 11.5
45 cardiofaciocutaneous syndrome 2 11.5
46 pulmonary valve disease 11.2 SOS2 SOS1 SHOC2 RASA2 PTPN11 MAP2K2
47 melanoma 11.2 RAF1 NRAS MAP2K2 MAP2K1 KRAS HRAS
48 kousseff nichols syndrome 11.1
49 noonan syndrome 2 11.1
50 noonan syndrome 8 11.1

Graphical network of the top 20 diseases related to Noonan Syndrome 1:



Diseases related to Noonan Syndrome 1

Symptoms & Phenotypes for Noonan Syndrome 1

Human phenotypes related to Noonan Syndrome 1:

58 31 (show top 50) (show all 86)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertelorism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000316
2 pectus excavatum 58 31 hallmark (90%) Very frequent (99-80%) HP:0000767
3 high palate 58 31 hallmark (90%) Very frequent (99-80%) HP:0000218
4 ptosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000508
5 dysarthria 58 31 hallmark (90%) Very frequent (99-80%) HP:0001260
6 muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0001324
7 pectus carinatum 58 31 hallmark (90%) Very frequent (99-80%) HP:0000768
8 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
9 micrognathia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000347
10 downslanted palpebral fissures 58 31 hallmark (90%) Very frequent (99-80%) HP:0000494
11 midface retrusion 58 31 hallmark (90%) Very frequent (99-80%) HP:0011800
12 aplasia/hypoplasia of the abdominal wall musculature 58 31 hallmark (90%) Very frequent (99-80%) HP:0010318
13 thick lower lip vermilion 58 31 hallmark (90%) Very frequent (99-80%) HP:0000179
14 joint hyperflexibility 58 31 hallmark (90%) Very frequent (99-80%) HP:0005692
15 enlarged thorax 58 31 hallmark (90%) Very frequent (99-80%) HP:0100625
16 wide intermamillary distance 58 31 hallmark (90%) Very frequent (99-80%) HP:0006610
17 webbed neck 58 31 hallmark (90%) Very frequent (99-80%) HP:0000465
18 thickened nuchal skin fold 58 31 hallmark (90%) Very frequent (99-80%) HP:0000474
19 cystic hygroma 58 31 hallmark (90%) Very frequent (99-80%) HP:0000476
20 hypogonadotrophic hypogonadism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000044
21 proptosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000520
22 high forehead 58 31 hallmark (90%) Very frequent (99-80%) HP:0000348
23 low-set, posteriorly rotated ears 58 31 hallmark (90%) Very frequent (99-80%) HP:0000368
24 triangular face 58 31 hallmark (90%) Very frequent (99-80%) HP:0000325
25 thickened helices 58 31 hallmark (90%) Very frequent (99-80%) HP:0000391
26 pulmonary artery stenosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0004415
27 muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001252
28 scoliosis 58 31 frequent (33%) Frequent (79-30%) HP:0002650
29 hepatomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0002240
30 delayed skeletal maturation 58 31 frequent (33%) Frequent (79-30%) HP:0002750
31 cryptorchidism 58 31 frequent (33%) Frequent (79-30%) HP:0000028
32 coarse hair 58 31 frequent (33%) Frequent (79-30%) HP:0002208
33 feeding difficulties in infancy 58 31 frequent (33%) Frequent (79-30%) HP:0008872
34 arrhythmia 58 31 frequent (33%) Frequent (79-30%) HP:0011675
35 abnormal bleeding 58 31 frequent (33%) Frequent (79-30%) HP:0001892
36 strabismus 58 31 frequent (33%) Frequent (79-30%) HP:0000486
37 low posterior hairline 58 31 frequent (33%) Frequent (79-30%) HP:0002162
38 abnormal dermatoglyphics 58 31 frequent (33%) Frequent (79-30%) HP:0007477
39 abnormal hair quantity 58 31 frequent (33%) Frequent (79-30%) HP:0011362
40 abnormality of the spleen 58 31 frequent (33%) Frequent (79-30%) HP:0001743
41 abnormal platelet function 58 31 frequent (33%) Frequent (79-30%) HP:0011869
42 abnormality of coagulation 58 31 frequent (33%) Frequent (79-30%) HP:0001928
43 abnormal pulmonary valve morphology 31 frequent (33%) HP:0001641
44 nystagmus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000639
45 brachydactyly 58 31 occasional (7.5%) Occasional (29-5%) HP:0001156
46 sensorineural hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000407
47 lymphedema 58 31 occasional (7.5%) Occasional (29-5%) HP:0001004
48 melanocytic nevus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000995
49 clinodactyly of the 5th finger 58 31 occasional (7.5%) Occasional (29-5%) HP:0004209
50 radioulnar synostosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002974

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
hypertelorism
ptosis
myopia
downslanting palpebral fissures
epicanthal folds
more
Skeletal Limbs:
clinodactyly
brachydactyly
cubitus valgus
blunt fingertips
polyarticular villonodular synovitis (knees, ankles, wrists, elbows - in some patients)

Genitourinary Internal Genitalia Male:
cryptorchidism
occasional hypogonadism
male infertility (in individuals with bilateral cryptorchidism)

Cardiovascular Vascular:
patent ductus arteriosus
aortic coarctation

Chest Ribs Sternum Clavicles And Scapulae:
shield chest
pectus carinatum superiorly
pectus excavatum inferiorly

Skin Nails Hair Hair:
low posterior hairline
woolly-like hair

Skeletal Spine:
kyphoscoliosis
vertebral abnormalities

Hematology:
amegakaryocytic thrombocytopenia
von willebrand disease
bleeding tendency

Head And Neck Ears:
hearing loss, sensorineural
low-set posteriorly rotated ears

Neurologic Central Nervous System:
articulation difficulties
mental retardation (25%)

Head And Neck Neck:
short neck
webbed neck
cystic hygroma

Head And Neck Teeth:
dental malocclusion

Head And Neck Face:
micrognathia
triangular face (with age)

Muscle Soft Tissue:
lymphedema

Growth Other:
failure to thrive in infancy
specific growth curves are available

Laboratory Abnormalities:
thrombocytopenia
partial deficiency of factor xi(c)
partial deficiency of factor xii(c)
partial deficiency of factor xiii(c)

Cardiovascular Heart:
pulmonic stenosis
congenital heart defect
atrial septal defects
ventricular septal defects
hypertrophic obstructive cardiomyopathy

Head And Neck Mouth:
high arched palate
deeply grooved philtrum
high peaks of upper lip vermilion border

Growth Height:
short stature (postnatal onset)

Neoplasia:
malignant schwannoma
multiple giant cell granulomas (bones, joints, soft tissues)

Clinical features from OMIM:

163950

GenomeRNAi Phenotypes related to Noonan Syndrome 1 according to GeneCards Suite gene sharing:

26 (show top 50) (show all 58)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-116 10.45 CBL RAF1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-119 10.45 RASA2
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-130 10.45 CBL
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-142 10.45 RASA2
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-145 10.45 CBL
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-148 10.45 A2ML1 CBL NRAS
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-150 10.45 RAF1
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-153 10.45 A2ML1 CBL
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-171 10.45 A2ML1
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-204 10.45 A2ML1 CBL NRAS RAF1 RASA2
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-28 10.45 NRAS
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-40 10.45 CBL
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-48 10.45 A2ML1
14 Decreased shRNA abundance (Z-score < -2) GR00366-A-68 10.45 A2ML1
15 Decreased shRNA abundance (Z-score < -2) GR00366-A-72 10.45 NRAS RAF1
16 Decreased shRNA abundance (Z-score < -2) GR00366-A-89 10.45 RASA2
17 Decreased shRNA abundance (Z-score < -2) GR00366-A-91 10.45 A2ML1 RASA2
18 Decreased viability GR00055-A-2 10.28 BRAF CBL HRAS KRAS
19 Decreased viability GR00106-A-0 10.28 KRAS
20 Decreased viability GR00221-A-1 10.28 HRAS KRAS
21 Decreased viability GR00221-A-2 10.28 CBL HRAS KRAS
22 Decreased viability GR00221-A-3 10.28 CBL HRAS
23 Decreased viability GR00221-A-4 10.28 BRAF
24 Decreased viability GR00301-A 10.28 BRAF KRAS
25 Decreased viability GR00381-A-1 10.28 BRAF KRAS
26 Decreased viability GR00402-S-2 10.28 BRAF CBL HRAS KRAS
27 Increased shRNA abundance (Z-score > 2) GR00366-A-100 10.2 SOS1
28 Increased shRNA abundance (Z-score > 2) GR00366-A-110 10.2 BRAF
29 Increased shRNA abundance (Z-score > 2) GR00366-A-118 10.2 PTPN11
30 Increased shRNA abundance (Z-score > 2) GR00366-A-120 10.2 SOS1
31 Increased shRNA abundance (Z-score > 2) GR00366-A-121 10.2 PTPN11
32 Increased shRNA abundance (Z-score > 2) GR00366-A-122 10.2 CBL
33 Increased shRNA abundance (Z-score > 2) GR00366-A-126 10.2 SOS1
34 Increased shRNA abundance (Z-score > 2) GR00366-A-138 10.2 PTPN11
35 Increased shRNA abundance (Z-score > 2) GR00366-A-149 10.2 BRAF CBL PTPN11 RAF1 SOS1
36 Increased shRNA abundance (Z-score > 2) GR00366-A-151 10.2 CBL RAF1
37 Increased shRNA abundance (Z-score > 2) GR00366-A-161 10.2 RAF1
38 Increased shRNA abundance (Z-score > 2) GR00366-A-166 10.2 BRAF
39 Increased shRNA abundance (Z-score > 2) GR00366-A-177 10.2 BRAF
40 Increased shRNA abundance (Z-score > 2) GR00366-A-178 10.2 PTPN11
41 Increased shRNA abundance (Z-score > 2) GR00366-A-186 10.2 CBL
42 Increased shRNA abundance (Z-score > 2) GR00366-A-190 10.2 PTPN11
43 Increased shRNA abundance (Z-score > 2) GR00366-A-194 10.2 BRAF
44 Increased shRNA abundance (Z-score > 2) GR00366-A-201 10.2 CBL
45 Increased shRNA abundance (Z-score > 2) GR00366-A-210 10.2 CBL
46 Increased shRNA abundance (Z-score > 2) GR00366-A-29 10.2 BRAF
47 Increased shRNA abundance (Z-score > 2) GR00366-A-31 10.2 BRAF
48 Increased shRNA abundance (Z-score > 2) GR00366-A-32 10.2 BRAF
49 Increased shRNA abundance (Z-score > 2) GR00366-A-37 10.2 PTPN11
50 Increased shRNA abundance (Z-score > 2) GR00366-A-43 10.2 CBL

MGI Mouse Phenotypes related to Noonan Syndrome 1:

45 (show all 17)
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.44 BRAF CBL HRAS KRAS LZTR1 MAP2K1
2 growth/size/body region MP:0005378 10.36 BRAF CBL HRAS KRAS LZTR1 MAP2K1
3 craniofacial MP:0005382 10.33 BRAF CBL HRAS KRAS LZTR1 MAP2K1
4 cellular MP:0005384 10.3 BRAF CBL KRAS LZTR1 MAP2K1 MAP2K2
5 homeostasis/metabolism MP:0005376 10.3 BRAF CBL HRAS KRAS LZTR1 MAP2K1
6 endocrine/exocrine gland MP:0005379 10.22 BRAF CBL HRAS KRAS MAP2K1 MAP2K2
7 hematopoietic system MP:0005397 10.22 BRAF CBL KRAS MRAS NRAS PTPN11
8 digestive/alimentary MP:0005381 10.19 BRAF HRAS KRAS MAP2K1 MAP2K2 NRAS
9 mortality/aging MP:0010768 10.18 BRAF CBL HRAS KRAS LZTR1 MAP2K1
10 immune system MP:0005387 10.17 BRAF CBL KRAS MRAS NRAS PTPN11
11 integument MP:0010771 10.14 BRAF CBL HRAS KRAS MAP2K1 MAP2K2
12 hearing/vestibular/ear MP:0005377 10.04 BRAF CBL KRAS MAP2K1 MAP2K2 PTPN11
13 neoplasm MP:0002006 10.02 BRAF HRAS KRAS MAP2K1 MAP2K2 NRAS
14 normal MP:0002873 10 BRAF HRAS KRAS MAP2K1 MAP2K2 MRAS
15 skeleton MP:0005390 9.7 BRAF CBL HRAS KRAS LZTR1 MAP2K1
16 pigmentation MP:0001186 9.55 BRAF CBL KRAS NRAS PTPN11
17 vision/eye MP:0005391 9.28 BRAF KRAS MAP2K1 MAP2K2 NRAS PTPN11

Drugs & Therapeutics for Noonan Syndrome 1

Drugs for Noonan Syndrome 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 31)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Simvastatin Approved Phase 3 79902-63-9 54454
2 Hormone Antagonists Phase 3
3 Hypolipidemic Agents Phase 3
4 Anticholesteremic Agents Phase 3
5 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 3
6 Antimetabolites Phase 3
7 Lipid Regulating Agents Phase 3
8
Lovastatin Approved, Investigational Phase 2 75330-75-5 53232
9
Lamotrigine Approved, Investigational Phase 2 84057-84-1 3878
10
Zinc Approved, Investigational Phase 2 7440-66-6 32051
11
Mecasermin Approved, Investigational Phase 2 68562-41-4
12
Calcium Approved, Nutraceutical Phase 2 7440-70-2 271
13 Hormones Phase 2
14 Tranquilizing Agents Phase 2
15 Anticonvulsants Phase 2
16 Antipsychotic Agents Phase 2
17 Sodium Channel Blockers Phase 2
18 Psychotropic Drugs Phase 2
19 L 647318 Phase 2
20 Dihydromevinolin Phase 2
21 Diuretics, Potassium Sparing Phase 2
22 Central Nervous System Depressants Phase 2
23 Calcium, Dietary Phase 2
24 calcium channel blockers Phase 2
25 Hypoglycemic Agents Phase 2
26 insulin Phase 2
27 Insulin, Globin Zinc Phase 2
28 Mitogens Phase 2
29 Protective Agents
30 Fluorides
31 Cariostatic Agents

Interventional clinical trials:

(show all 15)
# Name Status NCT ID Phase Drugs
1 Effect of the Growth Hormone MAXOMAT ® on the Growth of Small Children and Adolescents (<-2 SD) Due to NOONAN's Syndrome Completed NCT00452725 Phase 3 MAXOMAT ®, biosynthetic growth hormone
2 A 52-week, Multi-centre, Randomised, Double-blind, Parallel-group, no Treatment Controlled (Open-label) Trial Investigating the Efficacy and Safety of Two Doses of NN-220 in Short Stature With Noonan Syndrome Completed NCT01927861 Phase 3 somatropin
3 Genetic Testing of Noonan Subjects Previously Treated With Norditropin® in the GHNOO-1658 Trial Completed NCT01529944 Phase 3 somatropin;somatropin
4 Norditropin Treatment in Subjects With Noonan Syndrome. Effects on Linear Growth and Final Height - Data Collection and Follow-up Visit Completed NCT01529840 Phase 3 somatropin;somatropin
5 Treatment With HMG-COA Reductase Inhibitor (Simvastatin) of Growth and Bone Abnormalities in Children With Noonan Syndrome: A Phase III Randomised, Double Blind, Placebo-controlled Therapeutic Trial Recruiting NCT02713945 Phase 3 Simvastatin;Placebo
6 Improvement of Synaptic Plasticity and Cognitive Function in RAS Pathway Disorders Recruiting NCT03504501 Phase 2 Lovastatin;Lamotrigine
7 A Phase 2, Open-Label, Multicenter, Clinical Trial to Evaluate the Pharmacokinetics, Safety and Efficacy of Recombinant Human Insulin-Like Growth Factor-1/Recombinant Human Insulin-Like Growth Factor Binding Protein-3 in Children With Growth Failure Due to Noonan Syndrome Terminated NCT00351221 Phase 2 rhIGF-1/rhIGFBP-3
8 An Open Label Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MEK162 in Noonan Syndrome Hypertrophic Cardiomyopathy Withdrawn NCT01556568 Phase 2 MEK162
9 Consequences of Noonan Syndrome/LEOPARD Syndrome Associated Shp2 Mutations on Different Signaling Pathways Activation: Relationship With Hormonal Sensitivity Unknown status NCT02486731
10 Study of Metabolic Modifications in Children With Noonan Syndrome Completed NCT02383316
11 Evaluation of an Oral Health Intervention Program for Children With Congenital Heart Defects Completed NCT03311438
12 NordiNet® International Outcome Study-Observational Prospective Study on Patients Treated With Norditropin® Completed NCT00960128 somatropin;somatropin
13 Effects of Physical Training on Bone and Muscle Quality, Muscle Strength, and Motor Coordination in Children With Neurofibromatosis Type 1 Completed NCT01058330
14 Familial Investigations of Childhood Cancer Predisposition Recruiting NCT03050268
15 Post Marketing Surveillance on Long-term Use With Norditropin® (Short Stature Due to Noonan Syndrome) Enrolling by invitation NCT03435627 Somatropin

Search NIH Clinical Center for Noonan Syndrome 1

Cochrane evidence based reviews: noonan syndrome

Genetic Tests for Noonan Syndrome 1

Genetic tests related to Noonan Syndrome 1:

# Genetic test Affiliating Genes
1 Noonan Syndrome 1 29 BRAF MAP2K1 PTPN11
2 Noonan Syndrome 29 MAP2K1 PTPN11

Anatomical Context for Noonan Syndrome 1

MalaCards organs/tissues related to Noonan Syndrome 1:

40
Heart, Bone, Eye, Skin, Testes, Lung, Breast

Publications for Noonan Syndrome 1

Articles related to Noonan Syndrome 1:

(show top 50) (show all 1610)
# Title Authors PMID Year
1
Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. 61 56 54 24 6
17143282 2007
2
Germline gain-of-function mutations in SOS1 cause Noonan syndrome. 6 54 24 61 56
17143285 2007
3
Germline KRAS mutations cause Noonan syndrome. 61 54 6 56 24
16474405 2006
4
Protein-tyrosine phosphatase, nonreceptor type 11 mutation analysis and clinical assessment in 45 patients with Noonan syndrome. 61 54 56 24 6
15240615 2004
5
Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. 54 24 56 6 61
12717436 2003
6
PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. 24 61 54 6 56
11992261 2002
7
Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. 54 24 56 6 61
11704759 2001
8
Neurofibromatosis-Noonan syndrome: molecular evidence of the concurrence of both disorders in a patient. 61 6 56 24
15948193 2005
9
Clinical variability in a Noonan syndrome family with a new PTPN11 gene mutation. 54 6 56 61
15384080 2004
10
Genomic duplication of PTPN11 is an uncommon cause of Noonan syndrome. 54 61 24 56
19760651 2009
11
Independent NF1 and PTPN11 mutations in a family with neurofibromatosis-Noonan syndrome. 61 6 56
19449407 2009
12
Craniosynostosis in patients with Noonan syndrome caused by germline KRAS mutations. 61 6 54 24
19396835 2009
13
Clinical and molecular characterization of 40 patients with Noonan syndrome. 56 6 61
18678287 2008
14
Duplication of chromosome band 12q24.11q24.23 results in apparent Noonan syndrome. 24 54 56 61
18348260 2008
15
Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. 61 54 6 24
17603483 2007
16
Early fetal death associated with compound heterozygosity for Noonan syndrome-causative PTPN11 mutations. 56 6 61
17497712 2007
17
Noonan syndrome: relationships between genotype, growth, and growth factors. 61 24 54 56
16263833 2006
18
PTPN11 (protein tyrosine phosphatase, nonreceptor type 11) mutations and response to growth hormone therapy in children with Noonan syndrome. 24 61 54 56
15956085 2005
19
PTPN11 mutations are associated with mild growth hormone resistance in individuals with Noonan syndrome. 54 61 24 56
15985475 2005
20
Genotypic and phenotypic characterization of Noonan syndrome: new data and review of the literature. 6 56 61
15723289 2005
21
Noonan syndrome with leukaemoid reaction and overproduction of catecholamines: a case report. 6 56 61
12739139 2003
22
PTPN11 mutation in a large family with Noonan syndrome and dizygous twinning. 61 6 56
12529711 2003
23
Mutations in LZTR1 drive human disease by dysregulating RAS ubiquitination. 24 6 61
30442762 2018
24
Autosomal recessive Noonan syndrome associated with biallelic LZTR1 variants. 6 24 61
29469822 2018
25
Mutation in NRAS in familial Noonan syndrome--case report and review of the literature. 6 24 61
26467218 2015
26
Rare variants in SOS2 and LZTR1 are associated with Noonan syndrome. 24 6 61
25795793 2015
27
Further evidence of the importance of RIT1 in Noonan syndrome. 24 6 61
25124994 2014
28
Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome. 61 24 6
23791108 2013
29
Age-dependent germline mosaicism of the most common noonan syndrome mutation shows the signature of germline selection. 6 61 24
23726368 2013
30
Clinical and hematologic findings in Noonan syndrome patients with PTPN11 gene mutations. 56 24 61
20954246 2010
31
Noonan syndrome: clinical features, diagnosis, and management guidelines. 61 24 6
20876176 2010
32
A restricted spectrum of NRAS mutations causes Noonan syndrome. 6 24 61
19966803 2010
33
Adult height in Noonan syndrome. 61 24 56
14556249 2003
34
Germ-line mutation of the NRAS gene may be responsible for the development of juvenile myelomonocytic leukaemia. 24 6
19775298 2009
35
GH therapy in Noonan syndrome: Review of final height data. 52 24 61
20029237 2009
36
Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum. 6 24
19206169 2009
37
Electrocardiography in Noonan syndrome PTPN11 gene mutation--phenotype characterization. 56 54 61
18203203 2008
38
Germline gain-of-function mutations in RAF1 cause Noonan syndrome. 6 54 61
17603482 2007
39
Germline missense mutations affecting KRAS Isoform B are associated with a severe Noonan syndrome phenotype. 6 61 54
16773572 2006
40
Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease. 56 54 61
16358218 2006
41
Spectrum of mutations in PTPN11 and genotype-phenotype correlation in 96 patients with Noonan syndrome and five patients with cardio-facio-cutaneous syndrome. 54 56 61
12634870 2003
42
PTPN11 mutations in Noonan syndrome type I: detection of recurrent mutations in exons 3 and 13. 54 6 61
12325025 2002
43
PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) mutations in seven Japanese patients with Noonan syndrome. 54 61 6
12161469 2002
44
Motor performance in children with Noonan syndrome. 56 61
28627718 2017
45
Noonan syndrome in diverse populations. 56 61
28748642 2017
46
Juvenile myelomonocytic leukaemia and Noonan syndrome. 56 61
25097206 2014
47
Contribution of RIT1 mutations to the pathogenesis of Noonan syndrome: four new cases and further evidence of heterogeneity. 6 61
24939608 2014
48
Germinal mosaicism in Noonan syndrome: A family with two affected siblings of normal parents. 56 61
20979190 2010
49
Noonan syndrome, the SOS1 gene and embryonal rhabdomyosarcoma. 54 24 61
20461756 2010
50
Prenatal detection of Noonan syndrome by mutation analysis of the PTPN11 and the KRAS genes. 54 24 61
20112233 2010

Variations for Noonan Syndrome 1

ClinVar genetic disease variations for Noonan Syndrome 1:

6 (show top 50) (show all 679) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 HRAS NM_005343.4(HRAS):c.37G>T (p.Gly13Cys)SNV Pathogenic 12606 rs104894228 11:534286-534286 11:534286-534286
2 SOS1 NM_005633.3(SOS1):c.797C>A (p.Thr266Lys)SNV Pathogenic 12869 rs137852812 2:39278352-39278352 2:39051211-39051211
3 SOS1 NM_005633.3(SOS1):c.806T>G (p.Met269Arg)SNV Pathogenic 12870 rs137852813 2:39278343-39278343 2:39051202-39051202
4 SOS1 NM_005633.3(SOS1):c.1654A>G (p.Arg552Gly)SNV Pathogenic 12871 rs137852814 2:39249915-39249915 2:39022774-39022774
5 SOS1 NM_005633.3(SOS1):c.1656G>C (p.Arg552Ser)SNV Pathogenic 12872 rs267607079 2:39249913-39249913 2:39022772-39022772
6 SOS1 NM_005633.3(SOS1):c.1294T>C (p.Trp432Arg)SNV Pathogenic 12873 rs267607080 2:39250275-39250275 2:39023134-39023134
7 PTPN11 NM_002834.4(PTPN11):c.214G>T (p.Ala72Ser)SNV Pathogenic 13324 rs121918453 12:112888198-112888198 12:112450394-112450394
8 PTPN11 NM_002834.4(PTPN11):c.215C>G (p.Ala72Gly)SNV Pathogenic 13325 rs121918454 12:112888199-112888199 12:112450395-112450395
9 PTPN11 NM_002834.4(PTPN11):c.922A>G (p.Asn308Asp)SNV Pathogenic 13326 rs28933386 12:112915523-112915523 12:112477719-112477719
10 PTPN11 NM_002834.4(PTPN11):c.923A>G (p.Asn308Ser)SNV Pathogenic 13327 rs121918455 12:112915524-112915524 12:112477720-112477720
11 PTPN11 NM_002834.4(PTPN11):c.184T>G (p.Tyr62Asp)SNV Pathogenic 13329 rs121918460 12:112888168-112888168 12:112450364-112450364
12 PTPN11 NM_002834.4(PTPN11):c.182A>G (p.Asp61Gly)SNV Pathogenic 13330 rs121918461 12:112888166-112888166 12:112450362-112450362
13 PTPN11 NM_002834.4(PTPN11):c.1403C>T (p.Thr468Met)SNV Pathogenic 13331 rs121918457 12:112926270-112926270 12:112488466-112488466
14 PTPN11 NM_002834.4(PTPN11):c.1504T>A (p.Ser502Thr)SNV Pathogenic 13332 rs121918458 12:112926884-112926884 12:112489080-112489080
15 PTPN11 NM_002834.4(PTPN11):c.188A>G (p.Tyr63Cys)SNV Pathogenic 13333 rs121918459 12:112888172-112888172 12:112450368-112450368
16 PTPN11 NM_002834.4(PTPN11):c.218C>T (p.Thr73Ile)SNV Pathogenic 13334 rs121918462 12:112888202-112888202 12:112450398-112450398
17 PTPN11 NM_002834.4(PTPN11):c.854T>C (p.Phe285Ser)SNV Pathogenic 13335 rs121918463 12:112915455-112915455 12:112477651-112477651
18 PTPN11 NM_002834.4(PTPN11):c.226G>A (p.Glu76Lys)SNV Pathogenic 13336 rs121918464 12:112888210-112888210 12:112450406-112450406
19 PTPN11 NM_002834.4(PTPN11):c.236A>G (p.Gln79Arg)SNV Pathogenic 13340 rs121918466 12:112888220-112888220 12:112450416-112450416
20 PTPN11 NM_002834.4(PTPN11):c.1232C>T (p.Thr411Met)SNV Pathogenic 13341 rs121918467 12:112924286-112924286 12:112486482-112486482
21 PTPN11 NM_002834.4(PTPN11):c.1391G>C (p.Gly464Ala)SNV Pathogenic 13343 rs121918469 12:112926258-112926258 12:112488454-112488454
22 PTPN11 NM_002834.4(PTPN11):c.1529A>C (p.Gln510Pro)SNV Pathogenic 13344 rs121918470 12:112926909-112926909 12:112489105-112489105
23 PTPN11 NM_002834.4(PTPN11):c.5C>T (p.Thr2Ile)SNV Pathogenic 13349 rs267606990 12:112856920-112856920 12:112419116-112419116
24 MAP2K1 NM_002755.3(MAP2K1):c.389A>G (p.Tyr130Cys)SNV Pathogenic 13351 rs121908595 15:66729181-66729181 15:66436843-66436843
25 NRAS NM_002524.5(NRAS):c.149C>T (p.Thr50Ile)SNV Pathogenic 13902 rs267606921 1:115256562-115256562 1:114713941-114713941
26 NRAS NM_002524.5(NRAS):c.179G>A (p.Gly60Glu)SNV Pathogenic 13903 rs267606920 1:115256532-115256532 1:114713911-114713911
27 RAF1 NM_002880.3(RAF1):c.770C>T (p.Ser257Leu)SNV Pathogenic 13957 rs80338796 3:12645699-12645699 3:12604200-12604200
28 RAF1 NM_002880.3(RAF1):c.781C>T (p.Pro261Ser)SNV Pathogenic 13958 rs121434594 3:12645688-12645688 3:12604189-12604189
29 RAF1 NM_002880.3(RAF1):c.1837C>G (p.Leu613Val)SNV Pathogenic 13960 rs80338797 3:12626123-12626123 3:12584624-12584624
30 BRAF NM_004333.6(BRAF):c.736G>C (p.Ala246Pro)SNV Pathogenic 13965 rs180177034 7:140501336-140501336 7:140801536-140801536
31 SHOC2 NM_007373.3(SHOC2):c.4A>G (p.Ser2Gly)SNV Pathogenic 6821 rs267607048 10:112724120-112724120 10:110964362-110964362
32 RRAS2 NM_012250.6(RRAS2):c.215A>T (p.Gln72Leu)SNV Pathogenic 9447 rs113954997 11:14316390-14316390 11:14294844-14294844
33 KRAS NM_004985.5(KRAS):c.178G>C (p.Gly60Arg)SNV Pathogenic 12586 rs104894359 12:25380280-25380280 12:25227346-25227346
34 KRAS NM_004985.5(KRAS):c.458A>T (p.Asp153Val)SNV Pathogenic 12587 rs104894360 12:25362838-25362838 12:25209904-25209904
35 KRAS NM_004985.5(KRAS):c.173C>T (p.Thr58Ile)SNV Pathogenic 12588 rs104894364 12:25380285-25380285 12:25227351-25227351
36 KRAS NM_004985.5(KRAS):c.40G>A (p.Val14Ile)SNV Pathogenic 12589 rs104894365 12:25398279-25398279 12:25245345-25245345
37 BRAF NM_004333.6(BRAF):c.1789C>G (p.Leu597Val)SNV Pathogenic 13969 rs121913369 7:140453146-140453146 7:140753346-140753346
38 BRAF NM_004333.6(BRAF):c.1455G>C (p.Leu485Phe)SNV Pathogenic 13975 rs180177036 7:140477853-140477853 7:140778053-140778053
39 KRAS NM_004985.5(KRAS):c.15A>T (p.Lys5Asn)SNV Pathogenic 12594 rs104894361 12:25398304-25398304 12:25245370-25245370
40 RAF1 NM_002880.3(RAF1):c.1472C>T (p.Thr491Ile)SNV Pathogenic 21342 rs80338799 3:12627244-12627244 3:12585745-12585745
41 PTPN11 NM_002834.3(PTPN11):c.179_181delGTG (p.Gly60del)deletion Pathogenic 13346 rs80338836 12:112888163-112888165 12:112450359-112450361
42 BRAF NM_004333.6(BRAF):c.1593G>C (p.Trp531Cys)SNV Pathogenic 29808 rs606231228 7:140476813-140476813 7:140777013-140777013
43 BRAF NM_004333.6(BRAF):c.722C>G (p.Thr241Arg)SNV Pathogenic 29806 rs387906660 7:140501350-140501350 7:140801550-140801550
44 NRAS NM_002524.5(NRAS):c.101C>T (p.Pro34Leu)SNV Pathogenic 39647 rs397514553 1:115258681-115258681 1:114716060-114716060
45 BRAF NM_004333.6(BRAF):c.735A>C (p.Leu245Phe)SNV Pathogenic 40347 rs397507466 7:140501337-140501337 7:140801537-140801537
46 BRAF NM_004333.6(BRAF):c.1513C>T (p.Leu505Phe)SNV Pathogenic 40375 rs397507477 7:140477795-140477795 7:140777995-140777995
47 BRAF NM_004333.6(BRAF):c.1787G>T (p.Gly596Val)SNV Pathogenic 40387 rs397507483 7:140453148-140453148 7:140753348-140753348
48 BRAF NM_004333.6(BRAF):c.1796C>T (p.Thr599Ile)SNV Pathogenic 40388 rs121913375 7:140453139-140453139 7:140753339-140753339
49 KRAS NM_004985.5(KRAS):c.65A>G (p.Gln22Arg)SNV Pathogenic 40452 rs727503110 12:25398254-25398254 12:25245320-25245320
50 KRAS NM_004985.5(KRAS):c.101C>T (p.Pro34Leu)SNV Pathogenic 40454 rs104894366 12:25398218-25398218 12:25245284-25245284

UniProtKB/Swiss-Prot genetic disease variations for Noonan Syndrome 1:

73 (show all 38)
# Symbol AA change Variation ID SNP ID
1 PTPN11 p.Thr42Ala VAR_015601 rs397507501
2 PTPN11 p.Gly60Ala VAR_015602 rs397507509
3 PTPN11 p.Asp61Gly VAR_015603 rs121918461
4 PTPN11 p.Asp61Asn VAR_015604 rs397507510
5 PTPN11 p.Tyr62Asp VAR_015605 rs121918460
6 PTPN11 p.Tyr63Cys VAR_015606 rs121918459
7 PTPN11 p.Ala72Gly VAR_015607 rs121918454
8 PTPN11 p.Ala72Ser VAR_015608 rs121918453
9 PTPN11 p.Thr73Ile VAR_015609 rs121918462
10 PTPN11 p.Glu76Asp VAR_015610 rs397507514
11 PTPN11 p.Gln79Arg VAR_015611 rs121918466
12 PTPN11 p.Asp106Ala VAR_015612 rs397507517
13 PTPN11 p.Glu139Asp VAR_015613 rs397507520
14 PTPN11 p.Tyr279Cys VAR_015614 rs121918456
15 PTPN11 p.Ile282Val VAR_015615 rs397507529
16 PTPN11 p.Phe285Ser VAR_015616 rs121918463
17 PTPN11 p.Phe285Leu VAR_015617 rs397507531
18 PTPN11 p.Asn308Ser VAR_015618 rs121918455
19 PTPN11 p.Asn308Asp VAR_015619 rs28933386
20 PTPN11 p.Arg501Lys VAR_015622 rs397507543
21 PTPN11 p.Ser502Thr VAR_015623 rs121918458
22 PTPN11 p.Met504Val VAR_015624 rs397507547
23 PTPN11 p.Gly503Arg VAR_016003 rs397507545
24 PTPN11 p.Thr2Ile VAR_027183 rs267606990
25 PTPN11 p.Asn58Lys VAR_027184 rs397507506
26 PTPN11 p.Glu69Gln VAR_027185 rs397507511
27 PTPN11 p.Gln79Pro VAR_027186
28 PTPN11 p.Gln256Arg VAR_027187 rs397507523
29 PTPN11 p.Thr411Met VAR_027189 rs121918467
30 PTPN11 p.Gln506Arg VAR_027195
31 PTPN11 p.Thr59Ala VAR_066060 rs886043790
32 PTPN11 p.Pro491Ser VAR_071706 rs397507539
33 PTPN11 p.Gln510Glu VAR_076499 rs397507549
34 PTPN11 p.Leu261Phe VAR_078101 rs397507525
35 PTPN11 p.Leu261His VAR_078102 rs765642157
36 PTPN11 p.Leu262Phe VAR_078103
37 PTPN11 p.Leu262Arg VAR_078104 rs397507526
38 PTPN11 p.Arg265Gln VAR_078105 rs376607329

Expression for Noonan Syndrome 1

Search GEO for disease gene expression data for Noonan Syndrome 1.

Pathways for Noonan Syndrome 1

Pathways related to Noonan Syndrome 1 according to KEGG:

36
# Name Kegg Source Accession
1 Ras signaling pathway hsa04014
2 MAPK signaling pathway hsa04010

Pathways related to Noonan Syndrome 1 according to GeneCards Suite gene sharing:

(show top 50) (show all 215)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
14.35 SOS2 SOS1 RIT1 RASA2 RAF1 PTPN11
2
Show member pathways
14.18 SOS1 RASA2 RAF1 PTPN11 NRAS MAP2K2
3
Show member pathways
14.08 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
4
Show member pathways
14.07 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
5
Show member pathways
13.95 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
6
Show member pathways
13.93 SOS1 RASA2 RAF1 PTPN11 NRAS MAP2K2
7
Show member pathways
13.92 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
8
Show member pathways
13.84 SOS2 SOS1 RRAS2 RRAS RAF1 PTPN11
9
Show member pathways
13.82 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
10
Show member pathways
13.78 SOS2 SOS1 RRAS RASA2 RAF1 PTPN11
11
Show member pathways
13.71 SOS2 SOS1 RRAS2 RRAS RASA2 RAF1
12
Show member pathways
13.64 SOS1 RASA2 RAF1 PTPN11 NRAS MAP2K2
13
Show member pathways
13.63 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
14
Show member pathways
13.61 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
15
Show member pathways
13.6 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
16
Show member pathways
13.52 SOS2 SOS1 RRAS2 RRAS RASA2 RAF1
17
Show member pathways
13.45 RRAS2 RRAS PTPN11 NRAS MRAS KRAS
18
Show member pathways
13.39 SOS2 SOS1 RAF1 NRAS MAP2K2 MAP2K1
19
Show member pathways
13.39 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
20
Show member pathways
13.38 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
21
Show member pathways
13.35 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
22
Show member pathways
13.28 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
23
Show member pathways
13.26 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
24
Show member pathways
13.25 SOS2 SOS1 RAF1 NRAS MAP2K2 MAP2K1
25
Show member pathways
13.25 RRAS2 RRAS RAF1 NRAS MRAS MAP2K2
26
Show member pathways
13.25 SOS2 SOS1 RAF1 PTPN11 NRAS MAP2K2
27
Show member pathways
13.23 SOS2 SOS1 RAF1 NRAS MAP2K2 MAP2K1
28
Show member pathways
13.22 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
29
Show member pathways
13.22 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
30
Show member pathways
13.21 SOS2 SOS1 RAF1 PTPN11 NRAS MAP2K2
31
Show member pathways
13.2 SOS2 SOS1 RAF1 NRAS MAP2K2 MAP2K1
32
Show member pathways
13.19 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
33 13.18 SOS2 SOS1 RAF1 NRAS MAP2K2 MAP2K1
34
Show member pathways
13.18 SOS2 SOS1 RAF1 NRAS MAP2K2 MAP2K1
35
Show member pathways
13.14 RAF1 NRAS MAP2K2 MAP2K1 KRAS HRAS
36
Show member pathways
13.13 SOS2 SOS1 RAF1 PTPN11 MAP2K2 MAP2K1
37
Show member pathways
13.1 SOS2 SOS1 RAF1 NRAS MAP2K2 MAP2K1
38
Show member pathways
13.08 RAF1 NRAS MAP2K2 MAP2K1 KRAS HRAS
39
Show member pathways
13.06 SOS2 SOS1 RAF1 PTPN11 NRAS MAP2K2
40
Show member pathways
13.03 SOS2 SOS1 RAF1 NRAS MAP2K2 MAP2K1
41
Show member pathways
13.01 RAF1 NRAS MAP2K2 MAP2K1 KRAS HRAS
42
Show member pathways
13.01 RRAS2 RRAS RAF1 NRAS MRAS MAP2K2
43
Show member pathways
12.98 SOS1 PTPN11 NRAS KRAS HRAS
44
Show member pathways
12.98 SOS2 SOS1 RAF1 NRAS MAP2K2 MAP2K1
45
Show member pathways
12.97 SOS2 SOS1 RAF1 NRAS MAP2K2 MAP2K1
46 12.96 SOS2 SOS1 RRAS2 RRAS RASA2 RAF1
47
Show member pathways
12.95 SOS1 PTPN11 NRAS KRAS HRAS CBL
48
Show member pathways
12.94 SOS2 SOS1 RAF1 MAP2K2 MAP2K1 KRAS
49
Show member pathways
12.93 SOS2 SOS1 RAF1 PTPN11 NRAS MAP2K2
50
Show member pathways
12.93 SOS2 SOS1 RRAS RAF1 PTPN11 NRAS

GO Terms for Noonan Syndrome 1

Cellular components related to Noonan Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Golgi apparatus GO:0005794 9.5 RAF1 NRAS MAP2K2 MAP2K1 LZTR1 HRAS
2 nucleosome GO:0000786 9.33 SOS2 SOS1 KAT6B
3 focal adhesion GO:0005925 9.1 RRAS2 RRAS MAP2K2 MAP2K1 KRAS CBL

Biological processes related to Noonan Syndrome 1 according to GeneCards Suite gene sharing:

(show all 26)
# Name GO ID Score Top Affiliating Genes
1 signal transduction GO:0007165 9.97 SOS1 RRAS2 RRAS RIT1 RASA2 RAF1
2 heart development GO:0007507 9.92 RAF1 PTPN11 MAP2K2 MAP2K1
3 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.89 PTPN11 MAP2K1 HRAS BRAF
4 regulation of Rho protein signal transduction GO:0035023 9.8 SOS2 SOS1 RAF1
5 fibroblast growth factor receptor signaling pathway GO:0008543 9.79 SHOC2 PTPN11 CBL
6 stimulatory C-type lectin receptor signaling pathway GO:0002223 9.76 RAF1 NRAS KRAS HRAS
7 epidermal growth factor receptor signaling pathway GO:0007173 9.71 SOS1 PTPN11 CBL
8 thymus development GO:0048538 9.71 RAF1 MAP2K2 MAP2K1 BRAF
9 positive regulation of axonogenesis GO:0050772 9.69 MAP2K2 MAP2K1 BRAF
10 thyroid gland development GO:0030878 9.62 RAF1 MAP2K2 MAP2K1 BRAF
11 positive regulation of production of miRNAs involved in gene silencing by miRNA GO:1903800 9.61 MAP2K2 MAP2K1
12 regulation of stress-activated MAPK cascade GO:0032872 9.61 MAP2K2 MAP2K1
13 neurotrophin TRK receptor signaling pathway GO:0048011 9.61 SOS1 RAF1 PTPN11
14 MAPK cascade GO:0000165 9.61 SOS1 RASA2 RAF1 NRAS MAP2K2 MAP2K1
15 regulation of protein heterodimerization activity GO:0043497 9.6 MAP2K2 MAP2K1
16 regulation of early endosome to late endosome transport GO:2000641 9.58 MAP2K2 MAP2K1
17 Bergmann glial cell differentiation GO:0060020 9.58 PTPN11 MAP2K1
18 positive regulation of small GTPase mediated signal transduction GO:0051057 9.57 SOS2 SOS1
19 trachea formation GO:0060440 9.56 MAP2K2 MAP2K1
20 face development GO:0060324 9.56 RAF1 MAP2K2 MAP2K1 BRAF
21 response to isolation stress GO:0035900 9.55 KRAS HRAS
22 regulation of axon regeneration GO:0048679 9.54 MAP2K2 MAP2K1 BRAF
23 regulation of Golgi inheritance GO:0090170 9.52 MAP2K2 MAP2K1
24 epithelial cell proliferation involved in lung morphogenesis GO:0060502 9.49 MAP2K2 MAP2K1
25 cerebellar cortex formation GO:0021697 9.48 PTPN11 MAP2K1
26 Ras protein signal transduction GO:0007265 9.28 SOS1 SHOC2 RRAS2 RRAS RIT1 NRAS

Molecular functions related to Noonan Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 10.32 SOS2 SOS1 SHOC2 RRAS2 RRAS RIT1
2 nucleotide binding GO:0000166 9.8 RAF1 NRAS MAP2K2 MAP2K1 KRAS HRAS
3 GTP binding GO:0005525 9.7 RRAS2 RRAS RIT1 NRAS MRAS KRAS
4 Ras GTPase binding GO:0017016 9.5 RAF1 LZTR1 BRAF
5 GTPase activity GO:0003924 9.5 RRAS2 RRAS RIT1 NRAS MRAS KRAS
6 mitogen-activated protein kinase kinase binding GO:0031434 9.4 RAF1 BRAF
7 GDP binding GO:0019003 9.17 RRAS2 RRAS RIT1 NRAS MRAS KRAS

Sources for Noonan Syndrome 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....