NS1
MCID: NNN008
MIFTS: 76

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 noonan syndrome with multiple lentigines 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 carinatum

Disease Ontology : 12 A RASopathy 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 636)
# Related Disease Score Top Affiliating Genes
1 noonan syndrome with multiple lentigines 36.4 SOS2 SOS1 SHOC2 RRAS RASA2 RAF1
2 neurofibromatosis-noonan syndrome 36.0 SOS2 SOS1 SHOC2 PTPN11 MAP2K2 MAP2K1
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 leopard syndrome 2 34.1 RAF1 PTPN11
6 cardiofaciocutaneous syndrome 1 34.1 SOS2 SOS1 SHOC2 RRAS RASA2 RAF1
7 hypertelorism 34.0 RIT1 RAF1 PTPN11 LZTR1 CBL BRAF
8 noonan syndrome 3 33.4 SOS1 SHOC2 RAF1 PTPN11 KRAS HRAS
9 hypertrophic cardiomyopathy 33.3 SOS2 SOS1 SHOC2 RAF1 PTPN11 MRAS
10 juvenile myelomonocytic leukemia 33.1 SOS2 SOS1 SHOC2 RRAS2 RRAS RIT1
11 rasopathy 32.9 SOS1 SHOC2 RAF1 PTPN11 NRAS MRAS
12 noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia 32.8 PTPN11 CBL
13 pulmonary valve stenosis 32.7 SOS2 SOS1 SHOC2 RASA2 PTPN11 MAP2K2
14 lentigines 32.5 RAF1 PTPN11 MAP2K2 MAP2K1 BRAF
15 neurofibromatosis 32.5 RASA2 PTPN11 KRAS HRAS
16 pulmonic stenosis 32.4 SOS1 RAF1 PTPN11 MAP2K2 MAP2K1 KRAS
17 atrial heart septal defect 32.3 SOS1 SHOC2 PTPN11 LZTR1 HRAS
18 leukemia 32.3 SOS1 RAF1 PTPN11 NRAS KRAS HRAS
19 cryptorchidism, unilateral or bilateral 32.3 SOS1 SHOC2 PTPN11 HRAS
20 heart septal defect 32.2 SOS1 SHOC2 PTPN11
21 myeloid leukemia 32.0 RAF1 PTPN11 NRAS MAP2K1 KRAS HRAS
22 ptosis 31.9 SOS1 SHOC2 PTPN11 CBL
23 leukemia, acute myeloid 31.8 PTPN11 NRAS MAP2K1 KRAS HRAS CBL
24 neurofibromatosis, type i 31.7 RASA2 PTPN11 HRAS
25 glioblastoma multiforme 31.5 RRAS RAF1 NRAS MAP2K1 KRAS HRAS
26 patent ductus arteriosus 1 31.5 SOS1 SHOC2 PTPN11
27 melanoma 31.4 RAF1 NRAS MAP2K2 MAP2K1 KRAS HRAS
28 embryonal rhabdomyosarcoma 31.4 PTPN11 KRAS HRAS
29 chronic myelomonocytic leukemia 31.4 PTPN11 NRAS KRAS CBL
30 arteriovenous malformations of the brain 31.3 RASA2 MRAS KRAS BRAF
31 arteriovenous malformation 31.3 MAP2K1 KRAS HRAS
32 villonodular synovitis 31.3 SOS1 PTPN11
33 lung cancer susceptibility 3 31.2 RAF1 NRAS MAP2K1 KRAS HRAS BRAF
34 tetralogy of fallot 31.2 SOS1 PTPN11 LZTR1 HRAS
35 pilomyxoid astrocytoma 31.1 RAF1 KRAS BRAF
36 noonan syndrome-like disorder with loose anagen hair 1 12.7
37 noonan syndrome 4 12.7
38 noonan syndrome 6 12.7
39 noonan syndrome 5 12.7
40 noonan syndrome 7 12.7
41 noonan syndrome-like disorder with loose anagen hair 2 12.6
42 leopard syndrome 1 11.9
43 leopard syndrome 3 11.9
44 short-rib thoracic dysplasia 3 with or without polydactyly 11.9
45 pseudo-turner syndrome 11.8
46 multiple pterygium syndrome, escobar variant 11.7
47 legius syndrome 11.6
48 medulloblastoma 11.6
49 cystic lymphangioma 11.5
50 noonan syndrome 11 11.5

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

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

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

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 Vascular:
patent ductus arteriosus
aortic coarctation

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

Muscle Soft Tissue:
lymphedema

Skeletal Limbs:
cubitus valgus
brachydactyly
clinodactyly
blunt fingertips
polyarticular villonodular synovitis (knees, ankles, wrists, elbows - in some patients)

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

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

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 55)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-100 10.63 SOS1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-110 10.63 BRAF
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-115 10.63 NRAS
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-116 10.63 CBL
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-118 10.63 PTPN11
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-119 10.63 RASA2
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-120 10.63 RASA2 SOS1
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-121 10.63 PTPN11
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-122 10.63 CBL
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-126 10.63 NRAS
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-138 10.63 PTPN11
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-145 10.63 CBL
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-148 10.63 A2ML1 CBL NRAS
14 Decreased shRNA abundance (Z-score < -2) GR00366-A-149 10.63 RAF1 PTPN11 SOS1
15 Decreased shRNA abundance (Z-score < -2) GR00366-A-153 10.63 A2ML1
16 Decreased shRNA abundance (Z-score < -2) GR00366-A-161 10.63 NRAS RAF1
17 Decreased shRNA abundance (Z-score < -2) GR00366-A-166 10.63 BRAF
18 Decreased shRNA abundance (Z-score < -2) GR00366-A-171 10.63 A2ML1
19 Decreased shRNA abundance (Z-score < -2) GR00366-A-177 10.63 BRAF
20 Decreased shRNA abundance (Z-score < -2) GR00366-A-190 10.63 PTPN11
21 Decreased shRNA abundance (Z-score < -2) GR00366-A-194 10.63 BRAF
22 Decreased shRNA abundance (Z-score < -2) GR00366-A-203 10.63 SOS1
23 Decreased shRNA abundance (Z-score < -2) GR00366-A-204 10.63 A2ML1 NRAS RAF1 RASA2
24 Decreased shRNA abundance (Z-score < -2) GR00366-A-208 10.63 NRAS
25 Decreased shRNA abundance (Z-score < -2) GR00366-A-214 10.63 RASA2
26 Decreased shRNA abundance (Z-score < -2) GR00366-A-28 10.63 NRAS
27 Decreased shRNA abundance (Z-score < -2) GR00366-A-29 10.63 BRAF
28 Decreased shRNA abundance (Z-score < -2) GR00366-A-31 10.63 BRAF
29 Decreased shRNA abundance (Z-score < -2) GR00366-A-32 10.63 BRAF
30 Decreased shRNA abundance (Z-score < -2) GR00366-A-37 10.63 PTPN11
31 Decreased shRNA abundance (Z-score < -2) GR00366-A-40 10.63 CBL
32 Decreased shRNA abundance (Z-score < -2) GR00366-A-43 10.63 CBL
33 Decreased shRNA abundance (Z-score < -2) GR00366-A-47 10.63 PTPN11
34 Decreased shRNA abundance (Z-score < -2) GR00366-A-48 10.63 A2ML1
35 Decreased shRNA abundance (Z-score < -2) GR00366-A-54 10.63 NRAS
36 Decreased shRNA abundance (Z-score < -2) GR00366-A-63 10.63 NRAS
37 Decreased shRNA abundance (Z-score < -2) GR00366-A-65 10.63 SOS1
38 Decreased shRNA abundance (Z-score < -2) GR00366-A-68 10.63 A2ML1
39 Decreased shRNA abundance (Z-score < -2) GR00366-A-72 10.63 BRAF
40 Decreased shRNA abundance (Z-score < -2) GR00366-A-89 10.63 RASA2
41 Decreased shRNA abundance (Z-score < -2) GR00366-A-91 10.63 A2ML1
42 Decreased viability GR00055-A-1 10.02 BRAF CBL HRAS KRAS
43 Decreased viability GR00055-A-2 10.02 BRAF CBL HRAS KRAS
44 Decreased viability GR00055-A-3 10.02 KRAS
45 Decreased viability GR00106-A-0 10.02 KRAS
46 Decreased viability GR00221-A-1 10.02 HRAS KRAS
47 Decreased viability GR00221-A-2 10.02 CBL HRAS KRAS
48 Decreased viability GR00221-A-3 10.02 CBL HRAS
49 Decreased viability GR00221-A-4 10.02 BRAF
50 Decreased viability GR00249-S 10.02 BRAF

MGI Mouse Phenotypes related to Noonan Syndrome 1:

45 (show all 18)
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.48 BRAF CBL GJB2 HRAS KRAS LZTR1
2 growth/size/body region MP:0005378 10.39 BRAF CBL GJB2 HRAS KRAS LZTR1
3 craniofacial MP:0005382 10.37 BRAF CBL GJB2 HRAS KRAS LZTR1
4 cellular MP:0005384 10.35 BRAF CBL GJB2 KRAS LZTR1 MAP2K1
5 homeostasis/metabolism MP:0005376 10.33 BRAF CBL GJB2 HRAS KRAS LZTR1
6 hematopoietic system MP:0005397 10.26 BRAF CBL KRAS LZTR1 MRAS NRAS
7 endocrine/exocrine gland MP:0005379 10.22 BRAF CBL HRAS KRAS MAP2K1 MAP2K2
8 immune system MP:0005387 10.21 BRAF CBL GJB2 KRAS MRAS NRAS
9 mortality/aging MP:0010768 10.21 BRAF CBL GJB2 HRAS KRAS LZTR1
10 digestive/alimentary MP:0005381 10.2 BRAF HRAS KRAS MAP2K1 MAP2K2 NRAS
11 embryo MP:0005380 10.19 BRAF GJB2 KRAS MAP2K1 NRAS PTPN11
12 integument MP:0010771 10.18 BRAF CBL GJB2 HRAS KRAS MAP2K1
13 hearing/vestibular/ear MP:0005377 10.1 BRAF CBL GJB2 KRAS MAP2K1 MAP2K2
14 normal MP:0002873 10.03 BRAF GJB2 HRAS KRAS MAP2K1 MAP2K2
15 neoplasm MP:0002006 10.02 BRAF HRAS KRAS MAP2K1 MAP2K2 NRAS
16 skeleton MP:0005390 9.73 BRAF CBL GJB2 HRAS KRAS LZTR1
17 pigmentation MP:0001186 9.55 BRAF CBL KRAS NRAS PTPN11
18 vision/eye MP:0005391 9.32 BRAF GJB2 KRAS MAP2K1 MAP2K2 NRAS

Drugs & Therapeutics for Noonan Syndrome 1

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

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

Interventional clinical trials:

(show all 18)
# 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 Vosoritide for Selected Genetic Causes of Short Stature Recruiting NCT04219007 Phase 2 Vosoritide
8 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
9 An Open Label Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MEK162 in Noonan Syndrome Hypertrophic Cardiomyopathy Withdrawn NCT01556568 Phase 2 MEK162
10 Consequences of Noonan Syndrome/LEOPARD Syndrome Associated Shp2 Mutations on Different Signaling Pathways Activation: Relationship With Hormonal Sensitivity Unknown status NCT02486731
11 Study of Metabolic Modifications in Children With Noonan Syndrome Completed NCT02383316
12 NordiNet® International Outcome Study-Observational Prospective Study on Patients Treated With Norditropin® Completed NCT00960128 somatropin;somatropin
13 Evaluation of an Oral Health Intervention Program for Children With Congenital Heart Defects Completed NCT03311438
14 Effects of Physical Training on Bone and Muscle Quality, Muscle Strength, and Motor Coordination in Children With Neurofibromatosis Type 1 Completed NCT01058330
15 Investigation Into the Natural History and Metabolic and Molecular Basis of RASopathies. Recruiting NCT04395495
16 Familial Investigations of Childhood Cancer Predisposition Recruiting NCT03050268
17 Post Marketing Surveillance on Long-term Use With Norditropin® (Short Stature Due to Noonan Syndrome) Enrolling by invitation NCT03435627 Somatropin
18 Hematological Anomalies in Children With Rasopathy Not yet recruiting NCT04286360

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 1668)
# Title Authors PMID Year
1
Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. 54 24 6 56 61
17143282 2007
2
Germline gain-of-function mutations in SOS1 cause Noonan syndrome. 61 56 54 24 6
17143285 2007
3
Germline KRAS mutations cause Noonan syndrome. 6 56 24 54 61
16474405 2006
4
Protein-tyrosine phosphatase, nonreceptor type 11 mutation analysis and clinical assessment in 45 patients with Noonan syndrome. 24 6 56 61 54
15240615 2004
5
Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. 61 54 24 56 6
12717436 2003
6
PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. 24 6 56 54 61
11992261 2002
7
Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. 56 24 6 61 54
11704759 2001
8
Neurofibromatosis-Noonan syndrome: molecular evidence of the concurrence of both disorders in a patient. 61 56 24 6
15948193 2005
9
Clinical variability in a Noonan syndrome family with a new PTPN11 gene mutation. 6 56 54 61
15384080 2004
10
Genomic duplication of PTPN11 is an uncommon cause of Noonan syndrome. 61 54 56 24
19760651 2009
11
Independent NF1 and PTPN11 mutations in a family with neurofibromatosis-Noonan syndrome. 56 6 61
19449407 2009
12
Craniosynostosis in patients with Noonan syndrome caused by germline KRAS mutations. 24 54 61 6
19396835 2009
13
Clinical and molecular characterization of 40 patients with Noonan syndrome. 61 56 6
18678287 2008
14
Duplication of chromosome band 12q24.11q24.23 results in apparent Noonan syndrome. 24 56 54 61
18348260 2008
15
Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. 61 24 6 54
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. 24 54 56 61
16263833 2006
18
PTPN11 mutations are associated with mild growth hormone resistance in individuals with Noonan syndrome. 24 56 61 54
15985475 2005
19
PTPN11 (protein tyrosine phosphatase, nonreceptor type 11) mutations and response to growth hormone therapy in children with Noonan syndrome. 56 54 24 61
15956085 2005
20
Genotypic and phenotypic characterization of Noonan syndrome: new data and review of the literature. 61 6 56
15723289 2005
21
Noonan syndrome with leukaemoid reaction and overproduction of catecholamines: a case report. 61 56 6
12739139 2003
22
PTPN11 mutation in a large family with Noonan syndrome and dizygous twinning. 56 61 6
12529711 2003
23
Mutations in LZTR1 drive human disease by dysregulating RAS ubiquitination. 61 6 24
30442762 2018
24
Autosomal recessive Noonan syndrome associated with biallelic LZTR1 variants. 61 24 6
29469822 2018
25
Mutation in NRAS in familial Noonan syndrome--case report and review of the literature. 24 6 61
26467218 2015
26
Rare variants in SOS2 and LZTR1 are associated with Noonan syndrome. 61 6 24
25795793 2015
27
Further evidence of the importance of RIT1 in Noonan syndrome. 6 24 61
25124994 2014
28
Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome. 61 6 24
23791108 2013
29
Age-dependent germline mosaicism of the most common noonan syndrome mutation shows the signature of germline selection. 61 6 24
23726368 2013
30
Clinical and hematologic findings in Noonan syndrome patients with PTPN11 gene mutations. 24 56 61
20954246 2010
31
Noonan syndrome: clinical features, diagnosis, and management guidelines. 61 6 24
20876176 2010
32
A restricted spectrum of NRAS mutations causes Noonan syndrome. 24 6 61
19966803 2010
33
Adult height in Noonan syndrome. 24 56 61
14556249 2003
34
Germ-line mutation of the NRAS gene may be responsible for the development of juvenile myelomonocytic leukaemia. 6 24
19775298 2009
35
GH therapy in Noonan syndrome: Review of final height data. 61 52 24
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 61 54
18203203 2008
38
Germline gain-of-function mutations in RAF1 cause Noonan syndrome. 61 6 54
17603482 2007
39
Germline missense mutations affecting KRAS Isoform B are associated with a severe Noonan syndrome phenotype. 61 54 6
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. 61 54 6
12325025 2002
43
PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) mutations in seven Japanese patients with Noonan syndrome. 6 61 54
12161469 2002
44
Noonan syndrome in diverse populations. 56 61
28748642 2017
45
Motor performance in children with Noonan syndrome. 56 61
28627718 2017
46
Juvenile myelomonocytic leukaemia and Noonan syndrome. 61 56
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 61 24
20461756 2010
50
Prenatal detection of Noonan syndrome by mutation analysis of the PTPN11 and the KRAS genes. 24 61 54
20112233 2010

Variations for Noonan Syndrome 1

ClinVar genetic disease variations for Noonan Syndrome 1:

6 (show top 50) (show all 602) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 RIT1 NM_006912.6(RIT1):c.69A>C (p.Lys23Asn)SNV Pathogenic 581105 rs1557962794 1:155880484-155880484 1:155910693-155910693
2 RRAS2 NM_012250.6(RRAS2):c.208G>A (p.Ala70Thr)SNV Pathogenic 626912 11:14316397-14316397 11:14294851-14294851
3 RRAS2 NM_012250.6(RRAS2):c.70_78dup (p.Gly24_Gly26dup)duplication Pathogenic 626913 11:14380338-14380339 11:14358792-14358793
4 RRAS2 NM_012250.6(RRAS2):c.65_73dup (p.Gly22_Gly24dup)duplication Pathogenic 626910 11:14380343-14380344 11:14358797-14358798
5 RRAS2 NM_012250.6(RRAS2):c.68G>T (p.Gly23Val)SNV Pathogenic 626911 11:14380349-14380349 11:14358803-14358803
6 GJB2 NM_004004.6(GJB2):c.205T>C (p.Phe69Leu)SNV Pathogenic 804361 13:20763516-20763516 13:20189377-20189377
7 RIT1 NM_006912.6(RIT1):c.245T>C (p.Phe82Ser)SNV Pathogenic 694696 1:155874286-155874286 1:155904495-155904495
8 RIT1 NM_006912.6(RIT1):c.91G>C (p.Gly31Arg)SNV Pathogenic 694723 1:155880462-155880462 1:155910671-155910671
9 SHOC2 NM_007373.4(SHOC2):c.4A>G (p.Ser2Gly)SNV Pathogenic 6821 rs267607048 10:112724120-112724120 10:110964362-110964362
10 RRAS2 NM_012250.6(RRAS2):c.215A>T (p.Gln72Leu)SNV Pathogenic 9447 rs113954997 11:14316390-14316390 11:14294844-14294844
11 KRAS NM_033360.4(KRAS):c.178G>C (p.Gly60Arg)SNV Pathogenic 12586 rs104894359 12:25380280-25380280 12:25227346-25227346
12 KRAS NM_033360.4(KRAS):c.*12A>TSNV Pathogenic 12587 rs104894360 12:25362838-25362838 12:25209904-25209904
13 KRAS NM_033360.4(KRAS):c.173C>T (p.Thr58Ile)SNV Pathogenic 12588 rs104894364 12:25380285-25380285 12:25227351-25227351
14 KRAS NM_033360.4(KRAS):c.40G>A (p.Val14Ile)SNV Pathogenic 12589 rs104894365 12:25398279-25398279 12:25245345-25245345
15 KRAS NM_033360.4(KRAS):c.15A>T (p.Lys5Asn)SNV Pathogenic 12594 rs104894361 12:25398304-25398304 12:25245370-25245370
16 HRAS NM_005343.4(HRAS):c.37G>T (p.Gly13Cys)SNV Pathogenic 12606 rs104894228 11:534286-534286 11:534286-534286
17 SOS1 NM_005633.3(SOS1):c.797C>A (p.Thr266Lys)SNV Pathogenic 12869 rs137852812 2:39278352-39278352 2:39051211-39051211
18 SOS1 NM_005633.3(SOS1):c.806T>G (p.Met269Arg)SNV Pathogenic 12870 rs137852813 2:39278343-39278343 2:39051202-39051202
19 SOS1 NM_005633.3(SOS1):c.1654A>G (p.Arg552Gly)SNV Pathogenic 12871 rs137852814 2:39249915-39249915 2:39022774-39022774
20 SOS1 NM_005633.3(SOS1):c.1656G>C (p.Arg552Ser)SNV Pathogenic 12872 rs267607079 2:39249913-39249913 2:39022772-39022772
21 SOS1 NM_005633.3(SOS1):c.1294T>C (p.Trp432Arg)SNV Pathogenic 12873 rs267607080 2:39250275-39250275 2:39023134-39023134
22 PTPN11 NM_002834.5(PTPN11):c.214G>T (p.Ala72Ser)SNV Pathogenic 13324 rs121918453 12:112888198-112888198 12:112450394-112450394
23 PTPN11 NM_002834.5(PTPN11):c.184T>G (p.Tyr62Asp)SNV Pathogenic 13329 rs121918460 12:112888168-112888168 12:112450364-112450364
24 PTPN11 NM_002834.5(PTPN11):c.1403C>T (p.Thr468Met)SNV Pathogenic 13331 rs121918457 12:112926270-112926270 12:112488466-112488466
25 PTPN11 NM_002834.5(PTPN11):c.1504T>A (p.Ser502Thr)SNV Pathogenic 13332 rs121918458 12:112926884-112926884 12:112489080-112489080
26 PTPN11 NM_002834.5(PTPN11):c.188A>G (p.Tyr63Cys)SNV Pathogenic 13333 rs121918459 12:112888172-112888172 12:112450368-112450368
27 PTPN11 NM_002834.5(PTPN11):c.218C>T (p.Thr73Ile)SNV Pathogenic 13334 rs121918462 12:112888202-112888202 12:112450398-112450398
28 PTPN11 NM_002834.5(PTPN11):c.854T>C (p.Phe285Ser)SNV Pathogenic 13335 rs121918463 12:112915455-112915455 12:112477651-112477651
29 PTPN11 NM_002834.4(PTPN11):c.226G>A (p.Glu76Lys)SNV Pathogenic 13336 rs121918464 12:112888210-112888210 12:112450406-112450406
30 PTPN11 NM_002834.5(PTPN11):c.236A>G (p.Gln79Arg)SNV Pathogenic 13340 rs121918466 12:112888220-112888220 12:112450416-112450416
31 PTPN11 NM_002834.5(PTPN11):c.922A>G (p.Asn308Asp)SNV Pathogenic 13326 rs28933386 12:112915523-112915523 12:112477719-112477719
32 PTPN11 NM_002834.5(PTPN11):c.182A>G (p.Asp61Gly)SNV Pathogenic 13330 rs121918461 12:112888166-112888166 12:112450362-112450362
33 PTPN11 NM_002834.5(PTPN11):c.923A>G (p.Asn308Ser)SNV Pathogenic 13327 rs121918455 12:112915524-112915524 12:112477720-112477720
34 PTPN11 NM_002834.5(PTPN11):c.1381G>A (p.Ala461Thr)SNV Pathogenic 13342 rs121918468 12:112926248-112926248 12:112488444-112488444
35 PTPN11 NM_002834.5(PTPN11):c.1391G>C (p.Gly464Ala)SNV Pathogenic 13343 rs121918469 12:112926258-112926258 12:112488454-112488454
36 PTPN11 NM_002834.5(PTPN11):c.1529A>C (p.Gln510Pro)SNV Pathogenic 13344 rs121918470 12:112926909-112926909 12:112489105-112489105
37 PTPN11 NM_002834.3(PTPN11):c.179_181delGTG (p.Gly60del)deletion Pathogenic 13346 rs80338836 12:112888161-112888163 12:112450357-112450359
38 PTPN11 NM_002834.5(PTPN11):c.5C>T (p.Thr2Ile)SNV Pathogenic 13349 rs267606990 12:112856920-112856920 12:112419116-112419116
39 MAP2K1 NM_002755.4(MAP2K1):c.389A>G (p.Tyr130Cys)SNV Pathogenic 13351 rs121908595 15:66729181-66729181 15:66436843-66436843
40 NRAS NM_002524.5(NRAS):c.149C>T (p.Thr50Ile)SNV Pathogenic 13902 rs267606921 1:115256562-115256562 1:114713941-114713941
41 NRAS NM_002524.5(NRAS):c.179G>A (p.Gly60Glu)SNV Pathogenic 13903 rs267606920 1:115256532-115256532 1:114713911-114713911
42 RAF1 NM_001354689.3(RAF1):c.770C>T (p.Ser257Leu)SNV Pathogenic 13957 rs80338796 3:12645699-12645699 3:12604200-12604200
43 RAF1 NM_001354689.3(RAF1):c.781C>T (p.Pro261Ser)SNV Pathogenic 13958 rs121434594 3:12645688-12645688 3:12604189-12604189
44 RAF1 NM_001354689.3(RAF1):c.1897C>G (p.Leu633Val)SNV Pathogenic 13960 rs80338797 3:12626123-12626123 3:12584624-12584624
45 BRAF NM_001374258.1(BRAF):c.1511G>A (p.Gly504Glu)SNV Pathogenic 13964 rs121913348 7:140481417-140481417 7:140781617-140781617
46 BRAF NM_001374258.1(BRAF):c.736G>C (p.Ala246Pro)SNV Pathogenic 13965 rs180177034 7:140501336-140501336 7:140801536-140801536
47 BRAF NM_001374258.1(BRAF):c.1909C>G (p.Leu637Val)SNV Pathogenic 13969 rs121913369 7:140453146-140453146 7:140753346-140753346
48 BRAF NM_001374258.1(BRAF):c.1575G>C (p.Leu525Phe)SNV Pathogenic 13975 rs180177036 7:140477853-140477853 7:140778053-140778053
49 RAF1 NM_001354689.3(RAF1):c.1532C>T (p.Thr511Ile)SNV Pathogenic 21342 rs80338799 3:12627244-12627244 3:12585745-12585745
50 BRAF NM_004333.6(BRAF):c.722C>G (p.Thr241Arg)SNV Pathogenic 29806 rs387906660 7:140501350-140501350 7:140801550-140801550

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 218)
# 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
13.83 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
10
Show member pathways
13.78 SOS2 SOS1 RRAS RASA2 RAF1 PTPN11
11
Show member pathways
13.72 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 RRAS2 RRAS RAF1 NRAS
19
Show member pathways
13.38 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
20
Show member pathways
13.35 RAF1 NRAS MAP2K2 MAP2K1 KRAS HRAS
21
Show member pathways
13.34 SOS2 SOS1 RAF1 NRAS MAP2K2 MAP2K1
22
Show member pathways
13.34 SOS2 SOS1 RAF1 NRAS MAP2K2 MAP2K1
23
Show member pathways
13.34 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
24
Show member pathways
13.26 RRAS2 RRAS RAF1 NRAS MRAS MAP2K2
25
Show member pathways
13.26 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
26
Show member pathways
13.25 SOS2 SOS1 RAF1 NRAS MAP2K2 MAP2K1
27
Show member pathways
13.25 SOS2 SOS1 RAF1 PTPN11 NRAS MAP2K2
28
Show member pathways
13.23 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 NRAS MAP2K2 MAP2K1
31
Show member pathways
13.21 SOS2 SOS1 RAF1 PTPN11 NRAS MAP2K2
32
Show member pathways
13.19 SOS2 SOS1 RAF1 NRAS MAP2K2 MAP2K1
33
Show member pathways
13.19 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
34 13.18 SOS2 SOS1 RAF1 NRAS MAP2K2 MAP2K1
35
Show member pathways
13.18 SOS2 SOS1 RAF1 NRAS MAP2K2 MAP2K1
36
Show member pathways
13.14 RAF1 NRAS MAP2K2 MAP2K1 KRAS HRAS
37
Show member pathways
13.13 SOS2 SOS1 RAF1 PTPN11 MAP2K2 MAP2K1
38
Show member pathways
13.09 SOS2 SOS1 RAF1 NRAS MAP2K2 MAP2K1
39
Show member pathways
13.09 SOS2 SOS1 RRAS2 RRAS RAF1 NRAS
40
Show member pathways
13.07 SOS2 SOS1 RAF1 PTPN11 NRAS MAP2K2
41
Show member pathways
13.03 SOS2 SOS1 RAF1 NRAS MAP2K2 MAP2K1
42
Show member pathways
13.01 RRAS2 RRAS RAF1 NRAS MRAS MAP2K2
43
Show member pathways
12.99 SOS2 SOS1 RAF1 NRAS MAP2K2 MAP2K1
44
Show member pathways
12.98 SOS1 PTPN11 NRAS KRAS HRAS
45
Show member pathways
12.97 SOS2 SOS1 RAF1 NRAS MAP2K2 MAP2K1
46 12.97 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 HRAS
49
Show member pathways
12.94 SOS2 SOS1 RAF1 MAP2K2 MAP2K1 KRAS
50
Show member pathways
12.94 SOS2 SOS1 RAF1 PTPN11 NRAS MAP2K2

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 plasma membrane GO:0005886 9.97 SOS1 RRAS2 RRAS RIT1 RAF1 NRAS
2 Golgi apparatus GO:0005794 9.8 RAF1 NRAS MAP2K2 MAP2K1 LZTR1 HRAS
3 cytosol GO:0005829 9.77 SOS2 SOS1 SHOC2 RASA2 RAF1 PTPN11
4 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 20)
# Name GO ID Score Top Affiliating Genes
1 signal transduction GO:0007165 10 SOS1 SHOC2 RRAS2 RRAS RIT1 RASA2
2 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.86 PTPN11 MAP2K1 HRAS BRAF
3 fibroblast growth factor receptor signaling pathway GO:0008543 9.76 SHOC2 PTPN11 CBL
4 stimulatory C-type lectin receptor signaling pathway GO:0002223 9.73 RAF1 NRAS KRAS HRAS
5 thymus development GO:0048538 9.67 RAF1 MAP2K1 BRAF
6 MAPK cascade GO:0000165 9.61 SOS1 RASA2 RAF1 NRAS MAP2K2 MAP2K1
7 positive regulation of production of miRNAs involved in gene silencing by miRNA GO:1903800 9.59 MAP2K2 MAP2K1
8 regulation of stress-activated MAPK cascade GO:0032872 9.58 MAP2K2 MAP2K1
9 thyroid gland development GO:0030878 9.58 RAF1 MAP2K1 BRAF
10 Bergmann glial cell differentiation GO:0060020 9.57 PTPN11 MAP2K1
11 epidermal growth factor receptor signaling pathway GO:0007173 9.56 SOS1 PTPN11 CBL BRAF
12 regulation of early endosome to late endosome transport GO:2000641 9.55 MAP2K2 MAP2K1
13 positive regulation of small GTPase mediated signal transduction GO:0051057 9.54 SOS2 SOS1
14 neurotrophin TRK receptor signaling pathway GO:0048011 9.54 SOS1 RAF1 PTPN11
15 regulation of axon regeneration GO:0048679 9.52 MAP2K1 BRAF
16 response to isolation stress GO:0035900 9.51 KRAS HRAS
17 face development GO:0060324 9.5 RAF1 MAP2K1 BRAF
18 regulation of Golgi inheritance GO:0090170 9.48 MAP2K2 MAP2K1
19 cerebellar cortex formation GO:0021697 9.46 PTPN11 MAP2K1
20 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 nucleotide binding GO:0000166 10 RRAS2 RRAS RIT1 RAF1 NRAS MRAS
2 protein-containing complex binding GO:0044877 9.8 RRAS RAF1 NRAS KRAS HRAS BRAF
3 GTP binding GO:0005525 9.7 RRAS2 RRAS RIT1 NRAS MRAS KRAS
4 scaffold protein binding GO:0097110 9.58 MAP2K2 MAP2K1 BRAF
5 Ras GTPase binding GO:0017016 9.54 RAF1 LZTR1 BRAF
6 GTPase activity GO:0003924 9.5 RRAS2 RRAS RIT1 NRAS MRAS KRAS
7 mitogen-activated protein kinase kinase binding GO:0031434 9.46 RAF1 BRAF
8 MAP-kinase scaffold activity GO:0005078 9.43 MAP2K2 MAP2K1
9 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
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