NS1
MCID: NNN008
MIFTS: 76

Noonan Syndrome 1 (NS1)

Categories: Bone diseases, Cardiovascular diseases, Ear diseases, Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Mental diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Reproductive diseases, Skin diseases
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Aliases & Classifications for Noonan Syndrome 1

MalaCards integrated aliases for Noonan Syndrome 1:

Name: Noonan Syndrome 1 57 11 73 28 12 5 14
Noonan Syndrome 57 11 24 19 42 58 75 73 28 53 5 43 14 38 71 33
Turner Phenotype with Normal Karyotype 57 42 73
Female Pseudo-Turner Syndrome 57 42 73
Male Turner Syndrome 57 42 73
Ns1 57 11 73
Noonan Syndrome with Pigmented Villonodular Synovitis 73 5
Noonan Syndrome-Like Disorder with Multiple Giant Cell Lesions 73
Noonan-Like/multiple Giant Cell Lesion Syndrome 73
Turner Syndrome in Female with X Chromosome 42
Turner's Phenotype, Karyotype Normal 11
Pseudo-Ullrich-Turner Syndrome 42
Pterygium Colli Syndrome 73
Familial Turner Syndrome 42
Ullrich-Noonan Syndrome 42
Noonan Syndrome, Type 1 38
Noonan-Ehmke Syndrome 42
Turner Syndrome, Male 71
Turner-Like Syndrome 42
Noonan's Syndrome 42
Ns 42

Characteristics:


Inheritance:

Noonan Syndrome 1: Autosomal dominant 57
Noonan Syndrome: Autosomal dominant,Autosomal recessive 58

Prevelance:

Noonan Syndrome: 6-9/10000 (United States) 1-5/10000 (Worldwide) 58

Age Of Onset:

Noonan Syndrome: Antenatal,Childhood,Infancy,Neonatal 58

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
genetic heterogeneity
allelic to leopard syndrome


Classifications:

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


Summaries for Noonan Syndrome 1

MedlinePlus Genetics: 42 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 Apoptotic Pathways in Synovial Fibroblasts and ERK Signaling. The drugs Simvastatin and Antimetabolites have been mentioned in the context of this disorder. Affiliated tissues include heart, bone and skin, and related phenotypes are ptosis and dysarthria

GARD: 19 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. It is typically inherited in an autosomal dominant manner, but many cases are due to a new genetic change and are not inherited from either parent. 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

UniProtKB/Swiss-Prot: 73 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.

OMIM®: 57 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) (Updated 08-Dec-2022)

Disease Ontology 11 Noonan syndrome 1: A Noonan syndrome that has material basis in the PTPN11 gene on chromosome 12q24.

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

Orphanet: 58 A rare, highly variable, multisystemic disorder mainly characterized by short stature, distinctive facial features, congenital heart defects, cardiomyopathy and an increased risk to develop tumors in childhood.

Wikipedia: 75 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 Noonan Syndrome 13
Noonan Syndrome 14

Diseases related to Noonan Syndrome 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 856)
# Related Disease Score Top Affiliating Genes
1 noonan syndrome with multiple lentigines 34.4 SOS2 SOS1 SHOC2 RRAS2 RIT1 RASA2
2 neurofibromatosis-noonan syndrome 34.0 SOS2 SOS1 SHOC2 RRAS2 RASA2 PTPN11
3 noonan syndrome-like disorder with loose anagen hair 33.6 SOS2 SOS1 SHOC2 RASA2 PTPN11 PPP1CB
4 noonan syndrome-like disorder with loose anagen hair 1 33.5 SHOC2 PTPN11 KRAS HRAS
5 pseudo-turner syndrome 33.4 SPRED2 SOS2 SOS1 SHOC2 RRAS2 RIT1
6 juvenile myelomonocytic leukemia 33.4 SOS2 SOS1 SHOC2 RRAS2 RIT1 RASA2
7 noonan syndrome 7 33.3 SHOC2 BRAF
8 costello syndrome 33.3 SOS2 SOS1 SHOC2 RASA2 RAF1 PTPN11
9 noonan syndrome and noonan-related syndrome 33.2 SOS1 SHOC2 RIT1 RAF1 PTPN11 NRAS
10 rasopathy 33.0 SPRED2 SOS2 SOS1 SHOC2 RRAS2 RIT1
11 cardiofaciocutaneous syndrome 1 32.9 SOS2 SOS1 SHOC2 RRAS2 RIT1 RASA2
12 hypertrophic cardiomyopathy 32.8 SOS2 SOS1 SHOC2 RRAS2 RIT1 RAF1
13 noonan syndrome 3 32.5 SOS1 RAF1 PTPN11 LRRC56 KRAS HRAS
14 noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia 32.3 PTPN11 CBL
15 neurofibromatosis 32.2 SOS1 RASA2 PTPN11 NRAS LZTR1 KRAS
16 pulmonary valve stenosis 32.1 SOS2 SOS1 SHOC2 RASA2 PTPN11 MAP2K1
17 neurofibromatosis, type i 32.1 SOS1 RASA2 RAF1 PTPN11 NRAS MAP2K1
18 lentigines 32.0 RAF1 PTPN11 BRAF
19 atrial heart septal defect 31.9 SOS2 SOS1 SHOC2 PTPN11 LZTR1
20 heart septal defect 31.8 SOS1 SHOC2 PTPN11
21 pulmonic stenosis 31.8 SOS1 RAF1 PTPN11 MAP2K1 KRAS HRAS
22 ptosis 31.7 SOS1 SHOC2 PTPN11 PPP1CB CBL
23 cystic lymphangioma 31.6 SOS1 SHOC2 PTPN11 LZTR1
24 rhabdomyosarcoma 31.5 SOS1 PTPN11 NRAS MAP2K1 LRRC56 KRAS
25 leukemia, acute myeloid 31.5 PTPN11 NRAS MAP2K1 LRRC56 KRAS HRAS
26 lymphangioma 31.4 KRAS HRAS BRAF
27 pilocytic astrocytoma 31.3 SOS1 RAF1 PTPN11 NRAS KRAS HRAS
28 villonodular synovitis 31.2 SOS1 PTPN11
29 neurilemmomatosis 31.2 RIT1 MRAS LZTR1
30 hydrops fetalis, nonimmune 31.2 RIT1 PTPN11 LRRC56 KRAS HRAS
31 keratosis pilaris atrophicans faciei 31.1 SOS1 PTPN11 MAP2K1
32 myelodysplastic syndrome 31.1 PTPN11 NRAS LRRC56 KRAS HRAS CBL
33 hashimoto thyroiditis 31.0 NRAS KRAS HRAS BRAF
34 pigmented villonodular synovitis 31.0 SOS1 PTPN11
35 patent ductus arteriosus 1 31.0 SOS1 SHOC2 PTPN11
36 leukemia, chronic lymphocytic 31.0 PTPN11 NRAS LRRC56 KRAS HRAS BRAF
37 myeloma, multiple 31.0 PTPN11 NRAS LRRC56 KRAS HRAS BRAF
38 nuchal bleb, familial 30.9 SOS1 LZTR1
39 lung cancer susceptibility 3 30.9 SOS1 RAF1 PTPN11 NRAS MAP2K1 LRRC56
40 chronic myelomonocytic leukemia 30.9 PTPN11 NRAS KRAS HRAS
41 arteriovenous malformation 30.9 RASA2 MAP2K1 LRRC56 HRAS BRAF
42 melanoma 30.9 SOS1 RAF1 NRAS MAP2K1 LRRC56 KRAS
43 glioblastoma 30.8 RAF1 NRAS MAP2K1 LRRC56 KRAS HRAS
44 arteriovenous malformations of the brain 30.8 RASA2 KRAS HRAS BRAF
45 schimmelpenning-feuerstein-mims syndrome 30.7 SOS1 NRAS LRRC56 KRAS HRAS
46 lymphatic malformation 12 30.6 SOS2 RRAS2 RASA2
47 ras-associated autoimmune leukoproliferative disorder 30.6 NRAS KRAS HRAS
48 pilomyxoid astrocytoma 30.6 RAF1 KRAS BRAF
49 legius syndrome 30.5 SPRED2 HRAS
50 noonan syndrome 4 11.7

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 30 (show top 50) (show all 95)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ptosis 58 30 Very rare (1%) Very frequent (99-80%)
HP:0000508
2 dysarthria 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001260
3 high palate 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000218
4 muscle weakness 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001324
5 hypertelorism 58 30 Very rare (1%) Very frequent (99-80%)
HP:0000316
6 pectus carinatum 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000768
7 short stature 58 30 Very rare (1%) Very frequent (99-80%)
HP:0004322
8 thick lower lip vermilion 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000179
9 aplasia/hypoplasia of the abdominal wall musculature 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0010318
10 enlarged thorax 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0100625
11 wide intermamillary distance 58 30 Very rare (1%) Very frequent (99-80%)
HP:0006610
12 micrognathia 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000347
13 webbed neck 58 30 Very rare (1%) Very frequent (99-80%)
HP:0000465
14 thickened nuchal skin fold 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000474
15 cystic hygroma 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000476
16 pectus excavatum 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000767
17 downslanted palpebral fissures 58 30 Very rare (1%) Very frequent (99-80%)
HP:0000494
18 low-set, posteriorly rotated ears 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000368
19 joint hyperflexibility 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0005692
20 proptosis 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000520
21 high forehead 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000348
22 midface retrusion 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0011800
23 triangular face 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000325
24 thickened helices 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000391
25 pulmonary artery stenosis 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0004415
26 hypogonadotropic hypogonadism 30 Hallmark (90%) HP:0000044
27 scoliosis 58 30 Frequent (33%) Frequent (79-30%)
HP:0002650
28 hypotonia 58 30 Frequent (33%) Frequent (79-30%)
HP:0001252
29 hepatomegaly 58 30 Frequent (33%) Frequent (79-30%)
HP:0002240
30 delayed skeletal maturation 58 30 Frequent (33%) Frequent (79-30%)
HP:0002750
31 coarse hair 58 30 Frequent (33%) Frequent (79-30%)
HP:0002208
32 feeding difficulties in infancy 58 30 Very rare (1%) Frequent (79-30%)
HP:0008872
33 strabismus 58 30 Frequent (33%) Frequent (79-30%)
HP:0000486
34 cryptorchidism 58 30 Very rare (1%) Frequent (79-30%)
HP:0000028
35 low posterior hairline 58 30 Very rare (1%) Frequent (79-30%)
HP:0002162
36 abnormal dermatoglyphics 58 30 Frequent (33%) Frequent (79-30%)
HP:0007477
37 arrhythmia 58 30 Frequent (33%) Frequent (79-30%)
HP:0011675
38 abnormal pulmonary valve morphology 58 30 Frequent (33%) Frequent (79-30%)
HP:0001641
39 abnormal platelet function 58 30 Frequent (33%) Frequent (79-30%)
HP:0011869
40 abnormal hair quantity 58 30 Frequent (33%) Frequent (79-30%)
HP:0011362
41 abnormality of the spleen 58 30 Frequent (33%) Frequent (79-30%)
HP:0001743
42 abnormal bleeding 58 30 Frequent (33%) Frequent (79-30%)
HP:0001892
43 abnormality of coagulation 58 30 Frequent (33%) Frequent (79-30%)
HP:0001928
44 nystagmus 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000639
45 sensorineural hearing impairment 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000407
46 lymphedema 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001004
47 melanocytic nevus 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000995
48 brachydactyly 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001156
49 clinodactyly of the 5th finger 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0004209
50 radioulnar synostosis 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002974

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Head And Neck Eyes:
ptosis
hypertelorism
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 (Updated 08-Dec-2022)

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

25 (show all 48)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-1 10.58 CBL HRAS BRAF KRAS
2 Decreased viability GR00055-A-2 10.58 CBL HRAS BRAF KRAS
3 Decreased viability GR00055-A-3 10.58 KRAS
4 Decreased viability GR00106-A-0 10.58 KRAS
5 Decreased viability GR00107-A-1 10.58 MAP2K1
6 Decreased viability GR00221-A-1 10.58 HRAS NRAS KRAS
7 Decreased viability GR00221-A-2 10.58 CBL HRAS KRAS
8 Decreased viability GR00221-A-3 10.58 CBL HRAS MAP2K1 NRAS
9 Decreased viability GR00221-A-4 10.58 BRAF
10 Decreased viability GR00249-S 10.58 BRAF
11 Decreased viability GR00301-A 10.58 BRAF KRAS
12 Increased shRNA abundance (Z-score > 2) GR00366-A-116 10.58 RAF1 SPRED2
13 Increased shRNA abundance (Z-score > 2) GR00366-A-118 10.58 RASA2 SPRED2
14 Increased shRNA abundance (Z-score > 2) GR00366-A-126 10.58 SOS1
15 Increased shRNA abundance (Z-score > 2) GR00366-A-130 10.58 CBL SOS1
16 Increased shRNA abundance (Z-score > 2) GR00366-A-142 10.58 RASA2
17 Increased shRNA abundance (Z-score > 2) GR00366-A-148 10.58 SOS1
18 Increased shRNA abundance (Z-score > 2) GR00366-A-149 10.58 CBL BRAF
19 Increased shRNA abundance (Z-score > 2) GR00366-A-150 10.58 RAF1
20 Increased shRNA abundance (Z-score > 2) GR00366-A-151 10.58 CBL RAF1
21 Increased shRNA abundance (Z-score > 2) GR00366-A-153 10.58 CBL
22 Increased shRNA abundance (Z-score > 2) GR00366-A-16 10.58 SPRED2
23 Increased shRNA abundance (Z-score > 2) GR00366-A-165 10.58 SOS1
24 Increased shRNA abundance (Z-score > 2) GR00366-A-178 10.58 PTPN11
25 Increased shRNA abundance (Z-score > 2) GR00366-A-186 10.58 CBL
26 Increased shRNA abundance (Z-score > 2) GR00366-A-19 10.58 SPRED2
27 Increased shRNA abundance (Z-score > 2) GR00366-A-201 10.58 CBL
28 Increased shRNA abundance (Z-score > 2) GR00366-A-203 10.58 SPRED2
29 Increased shRNA abundance (Z-score > 2) GR00366-A-204 10.58 CBL SPRED2
30 Increased shRNA abundance (Z-score > 2) GR00366-A-210 10.58 CBL
31 Increased shRNA abundance (Z-score > 2) GR00366-A-3 10.58 NRAS
32 Increased shRNA abundance (Z-score > 2) GR00366-A-47 10.58 BRAF
33 Increased shRNA abundance (Z-score > 2) GR00366-A-52 10.58 RAF1
34 Increased shRNA abundance (Z-score > 2) GR00366-A-53 10.58 SPRED2
35 Increased shRNA abundance (Z-score > 2) GR00366-A-57 10.58 RASA2
36 Increased shRNA abundance (Z-score > 2) GR00366-A-68 10.58 SOS1
37 Increased shRNA abundance (Z-score > 2) GR00366-A-7 10.58 PTPN11
38 Increased shRNA abundance (Z-score > 2) GR00366-A-72 10.58 NRAS RAF1
39 Increased shRNA abundance (Z-score > 2) GR00366-A-77 10.58 RASA2
40 Increased shRNA abundance (Z-score > 2) GR00366-A-78 10.58 PTPN11
41 Increased shRNA abundance (Z-score > 2) GR00366-A-81 10.58 CBL
42 Increased shRNA abundance (Z-score > 2) GR00366-A-91 10.58 RASA2 SOS1
43 Decreased viability GR00381-A-1 10.58 BRAF KRAS
44 no effect GR00402-S-1 10.18 BRAF CBL GJB2 HRAS KRAS LRRC56
45 no effect GR00402-S-2 10.18 BRAF CBL HRAS KRAS LRRC56 MAP2K1
46 Reduced mammosphere formation GR00396-S 9.61 BRAF HRAS KRAS NRAS PPP1CB PTPN11
47 Increased cell migration GR00055-A-1 9.56 SPRED2
48 Increased cell migration GR00055-A-3 9.56 SPRED2

MGI Mouse Phenotypes related to Noonan Syndrome 1:

45 (show all 18)
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.41 BRAF CBL GJB2 HRAS KRAS LRRC56
2 homeostasis/metabolism MP:0005376 10.38 BRAF CBL GJB2 HRAS KRAS LRRC56
3 cardiovascular system MP:0005385 10.34 BRAF CBL GJB2 HRAS KRAS LRRC56
4 normal MP:0002873 10.31 BRAF GJB2 HRAS KRAS MAP2K1 MRAS
5 craniofacial MP:0005382 10.23 BRAF CBL GJB2 HRAS KRAS LZTR1
6 immune system MP:0005387 10.22 BRAF CBL GJB2 KRAS LRRC56 MRAS
7 muscle MP:0005369 10.16 BRAF CBL HRAS KRAS LZTR1 PTPN11
8 embryo MP:0005380 10.15 BRAF GJB2 KRAS MAP2K1 NRAS PTPN11
9 digestive/alimentary MP:0005381 10.13 BRAF HRAS KRAS MAP2K1 NRAS PTPN11
10 neoplasm MP:0002006 10.12 BRAF HRAS KRAS MAP2K1 NRAS PTPN11
11 skeleton MP:0005390 10.1 BRAF CBL GJB2 HRAS KRAS LZTR1
12 limbs/digits/tail MP:0005371 10.09 BRAF CBL GJB2 KRAS NRAS PTPN11
13 hearing/vestibular/ear MP:0005377 10.07 BRAF CBL GJB2 KRAS MAP2K1 PTPN11
14 vision/eye MP:0005391 10 BRAF GJB2 KRAS MAP2K1 NRAS PTPN11
15 respiratory system MP:0005388 9.97 BRAF CBL HRAS KRAS LRRC56 PTPN11
16 hematopoietic system MP:0005397 9.93 BRAF CBL KRAS LZTR1 MRAS NRAS
17 mortality/aging MP:0010768 9.83 BRAF CBL GJB2 HRAS KRAS LRRC56
18 integument MP:0010771 9.44 BRAF CBL GJB2 HRAS KRAS LRRC56

Drugs & Therapeutics for Noonan Syndrome 1

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

(show all 12)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Simvastatin Approved Phase 3 79902-63-9 54454
2 Antimetabolites Phase 3
3 Hypolipidemic Agents Phase 3
4 Anticholesteremic Agents Phase 3
5 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 3
6 Lipid Regulating Agents Phase 3
7 Hormones Phase 3
8 Hormone Antagonists Phase 3
9
Mecasermin Approved, Investigational Phase 2 68562-41-4
10 Insulin, Globin Zinc Phase 2
11
Insulin Phase 2
12 Mitogens Phase 2

Interventional clinical trials:

(show all 19)
# Name Status NCT ID Phase Drugs
1 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
2 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 Completed NCT02713945 Phase 3 Simvastatin;Placebo
3 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
4 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
5 Genetic Testing of Noonan Subjects Previously Treated With Norditropin® in the GHNOO-1658 Trial Completed NCT01529944 Phase 3 somatropin
6 A Study Comparing the Effect and Safety of Once Weekly Dosing of Somapacitan With Daily Norditropin® as Well as Evaluating Long-term Safety of Somapacitan in a Basket Study Design in Children With Short Stature Either Born Small for Gestational Age or With Turner Syndrome, Noonan Syndrome, or Idiopathic Short Stature Recruiting NCT05330325 Phase 3 Somapacitan;Norditropin®
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 Completed NCT02486731
10 Study of Metabolic Modifications in Children With Noonan Syndrome Completed NCT02383316
11 Post Marketing Surveillance on Long-term Use With Norditropin® (Short Stature Due to Noonan Syndrome) Completed NCT03435627 Somatropin
12 NordiNet® International Outcome Study-Observational Prospective Study on Patients Treated With Norditropin® Completed NCT00960128 somatropin
13 Investigation Into the Natural History and Metabolic and Molecular Basis of RASopathies. Recruiting NCT04395495
14 Constitution of a Biological Collection to Study the Pathophysiology in Noonan Syndrome and to Identify Predictive Factors of Disease Progression Recruiting NCT05202210
15 Familial Investigations of Childhood Cancer Predisposition Recruiting NCT03050268
16 GROWing Up With Rare GENEtic Syndromes ….When Children With Complex Genetic Syndromes Reach Adult Age Recruiting NCT04463316
17 Clinical, Genetic, and Epidemiologic Study of Children and Adults With RASopathies Recruiting NCT04888936
18 Acceptance and Commitment Therapy for Caregivers of Children With a RASopathy: An Internal Pilot Feasibility Study and Follow-up Phase III Randomized Controlled Trial Recruiting NCT05361811
19 French Registry of Children Treated With Norditropin® for Short Stature Associated With Noonan Syndrome Enrolling by invitation NCT05308927 Norditropin

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 28 BRAF MAP2K1 PTPN11
2 Noonan Syndrome 28 MAP2K1 PTPN11

Anatomical Context for Noonan Syndrome 1

Organs/tissues related to Noonan Syndrome 1:

MalaCards : Heart, Bone, Skin, Eye, Testes, Breast, Spleen
ODiseA: Blood And Bone Marrow, Brain, Heart-Atrium, Heart-Ventricle, Heart, Skin

Publications for Noonan Syndrome 1

Articles related to Noonan Syndrome 1:

(show top 50) (show all 2423)
# Title Authors PMID Year
1
Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. 53 62 24 57 5
17143282 2007
2
Germline gain-of-function mutations in SOS1 cause Noonan syndrome. 53 62 24 57 5
17143285 2007
3
Germline KRAS mutations cause Noonan syndrome. 53 62 24 57 5
16474405 2006
4
Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. 53 62 24 57 5
12717436 2003
5
PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. 53 62 24 57 5
11992261 2002
6
Clinical and hematologic findings in Noonan syndrome patients with PTPN11 gene mutations. 62 24 57 5
20954246 2010
7
Neurofibromatosis-Noonan syndrome: molecular evidence of the concurrence of both disorders in a patient. 62 24 57 5
15948193 2005
8
Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease. 53 62 57 5
16358218 2006
9
Noonan syndrome: relationships between genotype, growth, and growth factors. 53 62 57 5
16263833 2006
10
PTPN11 mutations are associated with mild growth hormone resistance in individuals with Noonan syndrome. 53 62 57 5
15985475 2005
11
PTPN11 (protein tyrosine phosphatase, nonreceptor type 11) mutations and response to growth hormone therapy in children with Noonan syndrome. 53 62 57 5
15956085 2005
12
Clinical variability in a Noonan syndrome family with a new PTPN11 gene mutation. 53 62 57 5
15384080 2004
13
Protein-tyrosine phosphatase, nonreceptor type 11 mutation analysis and clinical assessment in 45 patients with Noonan syndrome. 53 62 57 5
15240615 2004
14
Spectrum of mutations in PTPN11 and genotype-phenotype correlation in 96 patients with Noonan syndrome and five patients with cardio-facio-cutaneous syndrome. 53 62 57 5
12634870 2003
15
Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. 53 62 57 5
11704759 2001
16
Juvenile myelomonocytic leukaemia and Noonan syndrome. 62 57 5
25097206 2014
17
Germinal mosaicism in Noonan syndrome: A family with two affected siblings of normal parents. 62 57 5
20979190 2010
18
Noonan syndrome, the SOS1 gene and embryonal rhabdomyosarcoma. 53 62 24 5
20461756 2010
19
Tumor spectrum in children with Noonan syndrome and SOS1 or RAF1 mutations. 53 62 24 5
19953625 2010
20
SOS1 and PTPN11 mutations in five cases of Noonan syndrome with multiple giant cell lesions. 53 62 24 5
19352411 2009
21
Genomic duplication of PTPN11 is an uncommon cause of Noonan syndrome. 53 62 24 57
19760651 2009
22
Independent NF1 and PTPN11 mutations in a family with neurofibromatosis-Noonan syndrome. 62 57 5
19449407 2009
23
Craniosynostosis in patients with Noonan syndrome caused by germline KRAS mutations. 53 62 24 5
19396835 2009
24
Clinical and molecular characterization of 40 patients with Noonan syndrome. 62 57 5
18678287 2008
25
Long-term GH treatment improves adult height in children with Noonan syndrome with and without mutations in protein tyrosine phosphatase, non-receptor-type 11. 53 62 24 5
18562489 2008
26
Duplication of chromosome band 12q24.11q24.23 results in apparent Noonan syndrome. 53 62 24 57
18348260 2008
27
Mediating ERK 1/2 signaling rescues congenital heart defects in a mouse model of Noonan syndrome. 62 57 5
17641779 2007
28
Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. 53 62 24 5
17603483 2007
29
Early fetal death associated with compound heterozygosity for Noonan syndrome-causative PTPN11 mutations. 62 57 5
17497712 2007
30
Expansion of the genotypic and phenotypic spectrum in patients with KRAS germline mutations. 53 62 24 5
17056636 2007
31
PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects. 62 57 5
16377799 2006
32
Genotypic and phenotypic characterization of Noonan syndrome: new data and review of the literature. 62 57 5
15723289 2005
33
Activating mutations of the noonan syndrome-associated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia. 53 62 24 5
15604238 2004
34
Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia. 53 62 24 5
14982869 2004
35
Genetics and variation in phenotype in Noonan syndrome. 53 62 24 5
15539800 2004
36
Noonan syndrome with leukaemoid reaction and overproduction of catecholamines: a case report. 62 57 5
12739139 2003
37
PTPN11 mutation in a large family with Noonan syndrome and dizygous twinning. 62 57 5
12529711 2003
38
Juvenile myelomonocytic leukemia and Noonan syndrome. 62 57 5
10598665 1999
39
Cochlear implantation and clinical features in patients with Noonan syndrome and Noonan syndrome with multiple lentigines caused by a mutation in PTPN11. 62 24 5
28483241 2017
40
Spectrum of mutations and genotype-phenotype analysis in Noonan syndrome patients with RIT1 mutations. 62 24 5
26714497 2016
41
Activating Mutations Affecting the Dbl Homology Domain of SOS2 Cause Noonan Syndrome. 62 24 5
26173643 2015
42
Molecular Diversity and Associated Phenotypic Spectrum of Germline CBL Mutations. 62 24 5
25952305 2015
43
[Arnold-Chiari malformation in Noonan syndrome and other syndromes of the RAS/MAPK pathway]. 62 24 5
25912702 2015
44
Neonatal pulmonary arterial hypertension and Noonan syndrome: two fatal cases with a specific RAF1 mutation. 62 24 5
25706034 2015
45
Further evidence of the importance of RIT1 in Noonan syndrome. 62 24 5
25124994 2014
46
Next-generation sequencing identifies rare variants associated with Noonan syndrome. 62 24 5
25049390 2014
47
Unique cerebrovascular anomalies in Noonan syndrome with RAF1 mutation. 62 24 5
23877478 2014
48
Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome. 62 24 5
23791108 2013
49
Age-dependent germline mosaicism of the most common noonan syndrome mutation shows the signature of germline selection. 62 24 5
23726368 2013
50
Cancer risk in patients with Noonan syndrome carrying a PTPN11 mutation. 62 24 5
21407260 2011

Variations for Noonan Syndrome 1

ClinVar genetic disease variations for Noonan Syndrome 1:

5 (show top 50) (show all 1012)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PTPN11 NM_002834.5(PTPN11):c.217_218delinsCT (p.Thr73Leu) INDEL Pathogenic
44604 rs397516802 GRCh37: 12:112888201-112888202
GRCh38: 12:112450397-112450398
2 RAF1 NM_002880.4(RAF1):c.786T>A (p.Asn262Lys) SNV Pathogenic
44634 rs397516829 GRCh37: 3:12645683-12645683
GRCh38: 3:12604184-12604184
3 RIT1 NM_006912.6(RIT1):c.241G>C (p.Glu81Gln) SNV Pathogenic
183404 rs869025192 GRCh37: 1:155874290-155874290
GRCh38: 1:155904499-155904499
4 RRAS2 NM_012250.6(RRAS2):c.65_73dup (p.Gly22_Gly24dup) DUP Pathogenic
626910 rs1591495776 GRCh37: 11:14380343-14380344
GRCh38: 11:14358797-14358798
5 RRAS2 NM_012250.6(RRAS2):c.68G>T (p.Gly23Val) SNV Pathogenic
626911 rs1591495779 GRCh37: 11:14380349-14380349
GRCh38: 11:14358803-14358803
6 RRAS2 NM_012250.6(RRAS2):c.208G>A (p.Ala70Thr) SNV Pathogenic
626912 rs782457908 GRCh37: 11:14316397-14316397
GRCh38: 11:14294851-14294851
7 RRAS2 NM_012250.6(RRAS2):c.215A>T (p.Gln72Leu) SNV Pathogenic
9447 rs113954997 GRCh37: 11:14316390-14316390
GRCh38: 11:14294844-14294844
8 RRAS2 NM_012250.6(RRAS2):c.70_78dup (p.Gly24_Gly26dup) DUP Pathogenic
626913 rs1591495767 GRCh37: 11:14380338-14380339
GRCh38: 11:14358792-14358793
9 RIT1 NM_006912.6(RIT1):c.245T>C (p.Phe82Ser) SNV Pathogenic
694696 rs868208063 GRCh37: 1:155874286-155874286
GRCh38: 1:155904495-155904495
10 RIT1 NM_006912.6(RIT1):c.91G>C (p.Gly31Arg) SNV Pathogenic
694723 rs1571999498 GRCh37: 1:155880462-155880462
GRCh38: 1:155910671-155910671
11 GJB2 NM_004004.6(GJB2):c.205T>C (p.Phe69Leu) SNV Pathogenic
804361 rs1593351503 GRCh37: 13:20763516-20763516
GRCh38: 13:20189377-20189377
12 SOS1 NM_005633.4(SOS1):c.3134C>G (p.Pro1045Arg) SNV Pathogenic
932923 rs1668859370 GRCh37: 2:39222476-39222476
GRCh38: 2:38995335-38995335
13 RIT1 NM_006912.6(RIT1):c.244T>A (p.Phe82Ile) SNV Pathogenic
183406 rs869025194 GRCh37: 1:155874287-155874287
GRCh38: 1:155904496-155904496
14 SPRED2 NM_181784.3(SPRED2):c.187C>T (p.Arg63Ter) SNV Pathogenic
1210167 GRCh37: 2:65571870-65571870
GRCh38: 2:65344736-65344736
15 SPRED2 NM_181784.3(SPRED2):c.1142_1143del (p.Leu381fs) DEL Pathogenic
1209657 GRCh37: 2:65540749-65540750
GRCh38: 2:65313615-65313616
16 SPRED2 NM_181784.3(SPRED2):c.299T>C (p.Leu100Pro) SNV Pathogenic
1209658 GRCh37: 2:65561813-65561813
GRCh38: 2:65334679-65334679
17 PTPN11 NM_002834.5(PTPN11):c.209A>G (p.Lys70Arg) SNV Pathogenic
44603 rs397516801 GRCh37: 12:112888193-112888193
GRCh38: 12:112450389-112450389
18 CBL NM_005188.4(CBL):c.1096-1G>C SNV Pathogenic
45196 rs397517076 GRCh37: 11:119148875-119148875
GRCh38: 11:119278165-119278165
19 PTPN11 NM_002834.5(PTPN11):c.598A>T (p.Asn200Tyr) SNV Pathogenic
164998 rs727503381 GRCh37: 12:112892440-112892440
GRCh38: 12:112454636-112454636
20 RAF1 NM_002880.4(RAF1):c.781C>G (p.Pro261Ala) SNV Pathogenic
40605 rs121434594 GRCh37: 3:12645688-12645688
GRCh38: 3:12604189-12604189
21 CBL NM_005188.4(CBL):c.1096-1G>T SNV Pathogenic
180815 rs397517076 GRCh37: 11:119148875-119148875
GRCh38: 11:119278165-119278165
22 RIT1 NM_006912.6(RIT1):c.104G>C (p.Ser35Thr) SNV Pathogenic
183401 rs869025189 GRCh37: 1:155880449-155880449
GRCh38: 1:155910658-155910658
23 RAF1 NM_002880.4(RAF1):c.768G>T (p.Arg256Ser) SNV Pathogenic
40599 rs397516826 GRCh37: 3:12645701-12645701
GRCh38: 3:12604202-12604202
24 SOS1 NM_005633.4(SOS1):c.1294T>C (p.Trp432Arg) SNV Pathogenic
Pathogenic
12873 rs267607080 GRCh37: 2:39250275-39250275
GRCh38: 2:39023134-39023134
25 PTPN11 NM_002834.5(PTPN11):c.172A>C (p.Asn58His) SNV Pathogenic
40486 rs397507505 GRCh37: 12:112888156-112888156
GRCh38: 12:112450352-112450352
26 RAF1 NM_002880.4(RAF1):c.524A>G (p.His175Arg) SNV Pathogenic
40594 rs397516822 GRCh37: 3:12650322-12650322
GRCh38: 3:12608823-12608823
27 PTPN11 NM_002834.5(PTPN11):c.854T>G (p.Phe285Cys) SNV Pathogenic
40533 rs121918463 GRCh37: 12:112915455-112915455
GRCh38: 12:112477651-112477651
28 SOS1 NM_005633.4(SOS1):c.1649T>C (p.Leu550Pro) SNV Pathogenic
40680 rs397517153 GRCh37: 2:39249920-39249920
GRCh38: 2:39022779-39022779
29 SOS1 NM_005633.4(SOS1):c.2183A>T (p.Lys728Ile) SNV Pathogenic
Likely Pathogenic
40699 rs397517156 GRCh37: 2:39239474-39239474
GRCh38: 2:39012333-39012333
30 KRAS NM_004985.5(KRAS):c.214A>T (p.Met72Leu) SNV Pathogenic
179141 rs727504662 GRCh37: 12:25380244-25380244
GRCh38: 12:25227310-25227310
31 PTPN11 NM_002834.5(PTPN11):c.1471C>A (p.Pro491Thr) SNV Pathogenic
Pathogenic/Likely Pathogenic
40549 rs397507539 GRCh37: 12:112926851-112926851
GRCh38: 12:112489047-112489047
32 KRAS NM_004985.5(KRAS):c.173C>T (p.Thr58Ile) SNV Pathogenic
12588 rs104894364 GRCh37: 12:25380285-25380285
GRCh38: 12:25227351-25227351
33 KRAS NM_004985.5(KRAS):c.101C>T (p.Pro34Leu) SNV Pathogenic
40454 rs104894366 GRCh37: 12:25398218-25398218
GRCh38: 12:25245284-25245284
34 PTPN11 NM_002834.5(PTPN11):c.178G>A (p.Gly60Ser) SNV Pathogenic
40490 rs397507507 GRCh37: 12:112888162-112888162
GRCh38: 12:112450358-112450358
35 PTPN11 NM_002834.5(PTPN11):c.417G>T (p.Glu139Asp) SNV Pathogenic
Pathogenic
40512 rs397507520 GRCh37: 12:112891083-112891083
GRCh38: 12:112453279-112453279
36 RIT1 NM_006912.6(RIT1):c.229G>A (p.Ala77Thr) SNV Pathogenic
Likely Pathogenic
183403 rs869025191 GRCh37: 1:155874530-155874530
GRCh38: 1:155904739-155904739
37 RIT1 NM_006912.6(RIT1):c.246T>A (p.Phe82Leu) SNV Pathogenic
370035 rs730881014 GRCh37: 1:155874285-155874285
GRCh38: 1:155904494-155904494
38 PTPN11 NM_002834.5(PTPN11):c.802G>T (p.Gly268Cys) SNV Pathogenic
Likely Pathogenic
40523 rs397507527 GRCh37: 12:112910793-112910793
GRCh38: 12:112472989-112472989
39 SOS1 NM_005633.4(SOS1):c.2197A>T (p.Ile733Phe) SNV Pathogenic
40701 rs574088829 GRCh37: 2:39239460-39239460
GRCh38: 2:39012319-39012319
40 KRAS NM_004985.5(KRAS):c.466T>A (p.Phe156Ile) SNV Pathogenic
163758 rs397517042 GRCh37: 12:25362830-25362830
GRCh38: 12:25209896-25209896
41 BRAF NM_004333.6(BRAF):c.722C>A (p.Thr241Lys) SNV Pathogenic
44829 rs387906660 GRCh37: 7:140501350-140501350
GRCh38: 7:140801550-140801550
42 KRAS NM_004985.5(KRAS):c.178G>C (p.Gly60Arg) SNV Pathogenic
12586 rs104894359 GRCh37: 12:25380280-25380280
GRCh38: 12:25227346-25227346
43 BRAF NM_004333.6(BRAF):c.736G>C (p.Ala246Pro) SNV Pathogenic
Pathogenic
13965 rs180177034 GRCh37: 7:140501336-140501336
GRCh38: 7:140801536-140801536
44 BRAF NM_004333.6(BRAF):c.1501G>A (p.Glu501Lys) SNV Pathogenic
13977 rs180177038 GRCh37: 7:140477807-140477807
GRCh38: 7:140778007-140778007
45 BRAF NM_004333.6(BRAF):c.1455G>T (p.Leu485Phe) SNV Pathogenic
Uncertain Significance
177844 rs180177036 GRCh37: 7:140477853-140477853
GRCh38: 7:140778053-140778053
46 BRAF NM_004333.6(BRAF):c.722C>T (p.Thr241Met) SNV Pathogenic
Pathogenic
Pathogenic
29805 rs387906660 GRCh37: 7:140501350-140501350
GRCh38: 7:140801550-140801550
47 PTPN11 NM_002834.5(PTPN11):c.179_181del (p.Gly60del) DEL Pathogenic
13346 rs80338836 GRCh37: 12:112888161-112888163
GRCh38: 12:112450357-112450359
48 NRAS NM_002524.5(NRAS):c.149C>T (p.Thr50Ile) SNV Pathogenic
Not Provided
13902 rs267606921 GRCh37: 1:115256562-115256562
GRCh38: 1:114713941-114713941
49 NRAS NM_002524.5(NRAS):c.35G>T (p.Gly12Val) SNV Pathogenic
40470 rs121913237 GRCh37: 1:115258747-115258747
GRCh38: 1:114716126-114716126
50 BRAF NM_004333.6(BRAF):c.1802A>C (p.Lys601Thr) SNV Pathogenic
44818 rs397507484 GRCh37: 7:140453133-140453133
GRCh38: 7:140753333-140753333

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

73 (show all 39)
# 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.Phe71Leu VAR_015995 rs397507512
24 PTPN11 p.Gly503Arg VAR_016003 rs397507545
25 PTPN11 p.Thr2Ile VAR_027183 rs267606990
26 PTPN11 p.Asn58Lys VAR_027184 rs397507506
27 PTPN11 p.Glu69Gln VAR_027185 rs397507511
28 PTPN11 p.Gln79Pro VAR_027186
29 PTPN11 p.Gln256Arg VAR_027187 rs397507523
30 PTPN11 p.Thr411Met VAR_027189 rs121918467
31 PTPN11 p.Gln506Arg VAR_027195
32 PTPN11 p.Thr59Ala VAR_066060 rs886043790
33 PTPN11 p.Pro491Ser VAR_071706 rs397507539
34 PTPN11 p.Gln510Glu VAR_076499 rs397507549
35 PTPN11 p.Leu261Phe VAR_078101 rs397507525
36 PTPN11 p.Leu261His VAR_078102 rs765642157
37 PTPN11 p.Leu262Phe VAR_078103
38 PTPN11 p.Leu262Arg VAR_078104 rs397507526
39 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 directly related to Noonan Syndrome 1:

# Pathway Source
1 Signaling by RAS mutants Reactome 66
2 Signaling by RAF1 mutants Reactome 66
3 SHOC2 M1731 mutant abolishes MRAS complex function Reactome 66
4 Gain-of-function MRAS complexes activate RAF signaling Reactome 66
5 Signaling by MRAS-complex mutants Reactome 66

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

(show top 50) (show all 200)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
14.03 BRAF HRAS KRAS MAP2K1 MRAS NRAS
2
Show member pathways
14.02 BRAF CBL HRAS KRAS MAP2K1 MRAS
3
Show member pathways
14.02 SPRED2 SOS1 SHOC2 RAF1 PTPN11 PPP1CB
4 13.93 BRAF CBL HRAS KRAS MAP2K1 MRAS
5
Show member pathways
13.89 BRAF HRAS KRAS MAP2K1 MRAS NRAS
6
Show member pathways
13.82 SOS2 SOS1 RRAS2 RAF1 NRAS MRAS
7
Show member pathways
13.77 SOS2 SOS1 RRAS2 RAF1 PTPN11 NRAS
8
Show member pathways
13.76 SOS2 SOS1 RRAS2 RAF1 NRAS MRAS
9
Show member pathways
13.71 BRAF CBL HRAS KRAS MAP2K1 MRAS
10
Show member pathways
13.65 SOS2 SOS1 RRAS2 RASA2 RAF1 PPP1CB
11
Show member pathways
13.58 SOS2 SOS1 RRAS2 RAF1 NRAS MRAS
12
Show member pathways
13.57 SPRED2 SOS1 SHOC2 RASA2 RAF1 PTPN11
13
Show member pathways
13.56 SOS2 SOS1 RRAS2 RAF1 PPP1CB NRAS
14
Show member pathways
13.53 SOS2 SOS1 RRAS2 RAF1 NRAS MRAS
15
Show member pathways
13.5 SOS2 SOS1 PTPN11 NRAS MAP2K1 KRAS
16
Show member pathways
13.48 BRAF HRAS KRAS MAP2K1 MRAS NRAS
17
Show member pathways
13.44 RRAS2 PTPN11 PPP1CB NRAS MRAS KRAS
18
Show member pathways
13.32 SOS2 SOS1 RRAS2 RAF1 PPP1CB NRAS
19
Show member pathways
13.3 HRAS KRAS MAP2K1 MRAS NRAS RAF1
20
Show member pathways
13.18 SOS2 SOS1 RRAS2 RAF1 NRAS MRAS
21
Show member pathways
13.17 RRAS2 RAF1 NRAS MRAS MAP2K1 KRAS
22
Show member pathways
13.16 SOS2 SOS1 RAF1 NRAS MAP2K1 KRAS
23
Show member pathways
13.13 BRAF HRAS KRAS MAP2K1 MRAS NRAS
24
Show member pathways
13.12 SOS2 SOS1 RRAS2 RAF1 NRAS MRAS
25
Show member pathways
13.11 SOS2 SOS1 RAF1 NRAS MAP2K1 KRAS
26
Show member pathways
13.1 SOS2 SOS1 RAF1 NRAS MAP2K1 KRAS
27 13.1 BRAF CBL HRAS KRAS MAP2K1 NRAS
28
Show member pathways
13.09 BRAF CBL HRAS KRAS MAP2K1 MRAS
29
Show member pathways
13.06 SOS2 SOS1 RAF1 MAP2K1 HRAS CBL
30
Show member pathways
13.03 BRAF CBL HRAS KRAS MAP2K1 MRAS
31
Show member pathways
13.02 RAF1 NRAS MAP2K1 KRAS HRAS BRAF
32
Show member pathways
13.01 SOS1 PTPN11 NRAS KRAS HRAS
33
Show member pathways
13.01 SOS2 SOS1 RAF1 PTPN11 PPP1CB MAP2K1
34
Show member pathways
13.01 CBL HRAS KRAS MAP2K1 MRAS NRAS
35
Show member pathways
12.99 BRAF CBL HRAS KRAS MAP2K1 NRAS
36
Show member pathways
12.95 RRAS2 RAF1 NRAS MRAS MAP2K1 KRAS
37
Show member pathways
12.94 RAF1 NRAS MAP2K1 KRAS HRAS BRAF
38
Show member pathways
12.94 SHOC2 RAF1 PPP1CB NRAS MRAS MAP2K1
39
Show member pathways
12.91 BRAF HRAS KRAS MAP2K1 MRAS NRAS
40
Show member pathways
12.9 RRAS2 NRAS MRAS KRAS HRAS
41
Show member pathways
12.9 SOS2 SOS1 RRAS2 RAF1 NRAS MRAS
42
Show member pathways
12.88 SOS2 SOS1 RAF1 MAP2K1 KRAS BRAF
43
Show member pathways
12.88 SOS2 SOS1 RAF1 PTPN11 MAP2K1 KRAS
44
Show member pathways
12.87 BRAF CBL HRAS KRAS NRAS PTPN11
45
Show member pathways
12.87 BRAF GJB2 HRAS KRAS MAP2K1 MRAS
46
Show member pathways
12.85 SOS1 PTPN11 NRAS KRAS HRAS
47
Show member pathways
12.84 SOS1 RIT1 PTPN11 NRAS MAP2K1 KRAS
48
Show member pathways
12.83 SOS2 SOS1 RAF1 PPP1CB MAP2K1 HRAS
49
Show member pathways
12.81 RAF1 PTPN11 NRAS MAP2K1 KRAS HRAS
50
Show member pathways
12.81 SOS2 SOS1 PTPN11 NRAS KRAS HRAS

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 GTPase complex GO:1905360 8.92 SOS1 HRAS

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

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 signal transduction GO:0007165 10.2 BRAF CBL HRAS KRAS MAP2K1 MRAS
2 thymus development GO:0048538 10 RAF1 MAP2K1 BRAF
3 thyroid gland development GO:0030878 9.95 BRAF MAP2K1 RAF1
4 face development GO:0060324 9.91 RAF1 MAP2K1 BRAF
5 epidermal growth factor receptor signaling pathway GO:0007173 9.86 SOS1 PTPN11 CBL BRAF
6 regulation of T cell differentiation in thymus GO:0033081 9.85 SOS2 SOS1
7 regulation of pro-B cell differentiation GO:2000973 9.81 SOS2 SOS1
8 cerebellar cortex formation GO:0021697 9.8 PTPN11 MAP2K1
9 positive regulation of protein serine/threonine kinase activity GO:0071902 9.8 SOS1 RAF1 MAP2K1 KRAS
10 neurotrophin TRK receptor signaling pathway GO:0048011 9.8 SOS1 RAF1 PTPN11
11 MAPK cascade GO:0000165 9.8 BRAF HRAS KRAS MAP2K1 NRAS PPP1CB
12 regulation of axon regeneration GO:0048679 9.71 BRAF MAP2K1
13 insulin receptor signaling pathway GO:0008286 9.67 HRAS RAF1 SOS1 SOS2
14 insulin-like growth factor receptor signaling pathway GO:0048009 9.63 SOS1 RAF1 MAP2K1
15 Ras protein signal transduction GO:0007265 9.58 SOS2 SOS1 SHOC2 RRAS2 RIT1 NRAS
16 lymphocyte homeostasis GO:0002260 9.56 SOS2 SOS1

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

# Name GO ID Score Top Affiliating Genes
1 GTP binding GO:0005525 10.15 RRAS2 RIT1 NRAS MRAS KRAS HRAS
2 GTPase activity GO:0003924 10.1 RRAS2 RIT1 NRAS MRAS KRAS HRAS
3 hydrolase activity GO:0016787 10.01 RRAS2 RIT1 PTPN11 PPP1CB NRAS MRAS
4 nucleotide binding GO:0000166 9.91 BRAF HRAS KRAS MAP2K1 MRAS NRAS
5 G protein activity GO:0003925 9.65 RIT1 NRAS MRAS KRAS HRAS
6 protein serine/threonine kinase activator activity GO:0043539 9.63 SOS1 RAF1 MAP2K1 KRAS HRAS
7 GDP binding GO:0019003 9.4 RRAS2 RIT1 NRAS MRAS KRAS HRAS

Sources for Noonan Syndrome 1

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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