MCID: NNN010
MIFTS: 38

Noonan Syndrome 3

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

Aliases & Classifications for Noonan Syndrome 3

MalaCards integrated aliases for Noonan Syndrome 3:

Name: Noonan Syndrome 3 54 12 50 71 29 13 69
Ns3 12 50 71
Kras Gene Related Noonan Syndrome 50

Characteristics:

OMIM:

54
Inheritance:
autosomal dominant

Miscellaneous:
variable features present


HPO:

32
noonan syndrome 3:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Noonan Syndrome 3

UniProtKB/Swiss-Prot : 71 Noonan syndrome 3: 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.

MalaCards based summary : Noonan Syndrome 3, also known as ns3, is related to kras-related noonan syndrome and hepatitis, and has symptoms including short stature, low-set ears and hypertelorism. An important gene associated with Noonan Syndrome 3 is KRAS (KRAS Proto-Oncogene, GTPase). The drugs Ribavirin and Peginterferon alfa-2a have been mentioned in the context of this disorder. Affiliated tissues include heart, skin and liver.

Disease Ontology : 12 A Noonan syndrome that has material basis in heterozygous mutation in the KRAS gene.

OMIM : 54
Noonan syndrome is an autosomal dominant dysmorphic syndrome characterized primarily by dysmorphic facial features, cardiac abnormalities, and short stature, among other features (summary by Shah et al., 1999). For a phenotypic description and a discussion of genetic heterogeneity of Noonan syndrome, see NS1 (163950), which is caused by mutations in the PTPN11 gene (176876). Approximately 50% of cases of Noonan syndrome are caused by mutations in PTPN11. (609942)

Related Diseases for Noonan Syndrome 3

Graphical network of the top 20 diseases related to Noonan Syndrome 3:



Diseases related to Noonan Syndrome 3

Symptoms & Phenotypes for Noonan Syndrome 3

Symptoms via clinical synopsis from OMIM:

54

Growth- Height:
short stature

Head And Neck- Eyes:
downslanting palpebral fissures
epicanthal folds

Cardiovascular- Heart:
atrial septal defect
patent ductus arteriosus
hypertrophic cardiomyopathy
ventricular septal defect
pulmonic stenosis
more
Head And Neck- Face:
frontal bossing

Head And Neck- Head:
macrocephaly
scaphocephaly
dolichocephaly

Chest- Ribs Sternum Clavicles And Scapulae:
pectus excavatum, mild

Head And Neck- Neck:
webbed neck (in some patients)
cystic hygroma (in some patients)

Neurologic- Central Nervous System:
developmental delay, mild to severe (in some patients)

Skeletal:
delayed bone age

Head And Neck- Ears:
low-set ears
posteriorly rotated ears

Prenatal Manifestations- Amniotic Fluid:
polyhydramnios

Head And Neck- Nose:
hypoplastic nasal bridge
short nose
anteverted nares

Head And Neck- Mouth:
high palate

Genitourinary- Internal Genitalia Male:
cryptorchidism (in some patients)

Skeletal- Skull:
craniosynostosis (in some patients)


Clinical features from OMIM:

609942

Human phenotypes related to Noonan Syndrome 3:

32 (show all 13)
id Description HPO Frequency HPO Source Accession
1 short stature 32 HP:0004322
2 low-set ears 32 HP:0000369
3 hypertelorism 32 HP:0000316
4 frontal bossing 32 HP:0002007
5 short nose 32 HP:0003196
6 anteverted nares 32 HP:0000463
7 global developmental delay 32 HP:0001263
8 ventricular septal defect 32 HP:0001629
9 webbed neck 32 HP:0000465
10 pulmonic stenosis 32 HP:0001642
11 sagittal craniosynostosis 32 HP:0004442
12 juvenile myelomonocytic leukemia 32 HP:0012209
13 atrial septal dilatation 32 HP:0011995

Drugs & Therapeutics for Noonan Syndrome 3

Drugs for Noonan Syndrome 3 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 67)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Ribavirin Approved Phase 4,Phase 3,Phase 2,Phase 1 36791-04-5 37542
2
Peginterferon alfa-2a Approved, Investigational Phase 4,Phase 3,Phase 2 198153-51-4 5360545
3
Sofosbuvir Approved Phase 4,Phase 3,Phase 2 1190307-88-0 45375808
4 interferons Phase 4,Phase 3,Phase 2,Phase 1
5 Anti-Infective Agents Phase 4,Phase 2,Phase 3,Phase 1
6 Interferon-alpha Phase 4,Phase 2,Phase 3,Phase 1
7 Antimetabolites Phase 4,Phase 3,Phase 2,Phase 1
8 Antiviral Agents Phase 4,Phase 3,Phase 2,Phase 1
9
Ivermectin Approved, Vet_approved Phase 2, Phase 3 70288-86-7 6474909 46936176
10
Ritonavir Approved, Investigational Phase 2, Phase 3 155213-67-5 392622
11
Interferon beta-1a Approved, Investigational Phase 3 145258-61-3 6438354
12
Peginterferon alfa-2b Approved Phase 2, Phase 3,Phase 1 99210-65-8, 215647-85-1
13
Interferon beta-1b Approved Phase 3 145155-23-3
14
Simeprevir Approved Phase 3,Phase 2,Phase 1 923604-59-5 66576988
15
Ledipasvir Approved Phase 2, Phase 3 1256388-51-8 67505836
16
Simvastatin Approved Phase 3 79902-63-9 54454
17
Entecavir Approved, Investigational Phase 2, Phase 3 142217-69-4 153941
18
Efavirenz Approved, Investigational Phase 3 154598-52-4 64139
19 Antiparasitic Agents Phase 2, Phase 3
20
protease inhibitors Phase 3,Phase 2,Phase 1
21 Adjuvants, Immunologic Phase 3
22 Hepatitis C Antibodies Phase 2, Phase 3,Phase 1
23 Cytochrome P-450 CYP3A Inhibitors Phase 2, Phase 3
24 HIV Protease Inhibitors Phase 3,Phase 2,Phase 1
25 Cytochrome P-450 Enzyme Inhibitors Phase 2, Phase 3
26 Hormone Antagonists Phase 3
27 Hormones Phase 3
28 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 3
29 Anti-HIV Agents Phase 2, Phase 3
30 Interferon-beta Phase 3
31 Anti-Retroviral Agents Phase 2, Phase 3
32 Ledipasvir, sofosbuvir drug combination Phase 2, Phase 3
33 Liver Extracts Phase 3,Phase 2
34
Tenofovir Phase 2, Phase 3 147127-20-6 464205
35 Reverse Transcriptase Inhibitors Phase 2, Phase 3
36 Nucleic Acid Synthesis Inhibitors Phase 2, Phase 3
37 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 3
38 Hypolipidemic Agents Phase 3
39 Immunoglobulins Phase 2, Phase 3
40 Anticholesteremic Agents Phase 3
41 Lipid Regulating Agents Phase 3
42 Antibodies Phase 2, Phase 3
43 Raltegravir Potassium Phase 3
44 Atazanavir Sulfate Phase 3
45
Tacrolimus Approved, Investigational Phase 2 104987-11-3 445643 439492
46
Miconazole Approved, Investigational, Vet_approved Phase 2 22916-47-8 4189
47
Zinc Approved Phase 2 7440-66-6 32051 23994
48
Triamcinolone Approved, Vet_approved Phase 2 124-94-7 31307
49 Vaccines Phase 2,Phase 1
50 Pharmaceutical Solutions Phase 2,Phase 1

Interventional clinical trials:

(show all 50)

id Name Status NCT ID Phase Drugs
1 A Study for G1b CHC Patients With CKD-3 Treated With Grazoprevir Plus Elbasvir Recruiting NCT03144635 Phase 4 Grazoprevir plus Elbasvir
2 Telaprevir, Peg-IFN-alfa-2a, and RBV in Treatment-Experienced Black/African American and Non-Black/African American Subjects With Genotype 1 Chronic Hepatitis C Terminated NCT01467492 Phase 4 Telaprevir;Ribavirin
3 A Clinical Trial of 16 Weeks of Duration to Evaluate Retreatment With Elbasvir/Grazoprevir Plus Sofosbuvir and Ribavirin in Patients With Chronic Hepatitis C Genotypes 1,4 Who Have Failed to Treat With a Regime Based on an Inhibitor of the NS5A Withdrawn NCT03105349 Phase 4 elbasvir/grazoprevir;Sofosbuvir;Ribavirin
4 Efficacy and Safety of Ivermectin Against Dengue Infection Unknown status NCT02045069 Phase 2, Phase 3 2 days Ivermectin;3 days Ivermectin;Placebo
5 3-year Follow-up Study in Patients Previously Treated With TMC435-Containing Regimen for the Treatment of Hepatitis C Virus Infection Completed NCT01349465 Phase 3 No treatment
6 Efficacy and Safety of MP-424, Interferon Beta (IFN Beta), and Ribavirin(RBV) in Treatment-Naïve or Having Received Interferon Based Therapy With Chronic Hepatitis C (CHC) Completed NCT01753570 Phase 3 MP-424;RBV;IFN beta
7 Efficacy and Safety Study of Simeprevir in Combination With Sofosbuvir in Participants With Genotype 1 Chronic Hepatitis C Virus Infection and Cirrhosis Completed NCT02114151 Phase 3 Simeprevir;Sofosbuvir
8 Somatropin Effect on Linear Growth and Final Height in Subjects With Noonan Syndrome Completed NCT01529840 Phase 3 somatropin;somatropin
9 Effect of MAXOMAT ® on the Growth of Small Children to NOONAN's Syndrome Completed NCT00452725 Phase 3 MAXOMAT ®, biosynthetic growth hormone
10 Genetic Testing of Noonan Subjects Previously Treated With Norditropin®. An Extension to Trial GHNOO-1658 Completed NCT01529944 Phase 3 somatropin;somatropin
11 8 Weeks Versus 12 Weeks of Elbasvir/Grazoprevir in Treatment-naïve CHC With Mild Fibrosis Recruiting NCT03186365 Phase 3 Zepatier Oral Product
12 Treatment With HMG-COA Reductase Inhibitor of Growth and Bone Abnormalities in Children With Noonan Syndrome Recruiting NCT02713945 Phase 3 Simvastatin;Placebo
13 DAAs Treatment for Chronic HCV/HBV Co-infection Patients(DASCO) Recruiting NCT02555943 Phase 2, Phase 3 Ledipasvir/Sofosbuvir;Sofosbuvir and Daclatasvir;Ombitasvir, Paritaprevir, Ritonavir, Dasabuvir;Entecavir;Tenofovir disoproxil
14 Investigating the Long-term Efficacy and Safety of Two Doses of NN-220 (Somatropin) in Short Stature Due to Noonan Syndrome Active, not recruiting NCT01927861 Phase 3 somatropin
15 Three-year Follow-up of Participants After Administration of Boceprevir or Narlaprevir for the Treatment of Chronic Hepatitis C (P05063) Terminated NCT00689390 Phase 2, Phase 3 Ribavirin
16 A Study to Treat Subjects With Telaprevir, Ribavirin, and Peginterferon Who Are Coinfected With HIV and Hepatitis C Virus (HCV) Terminated NCT01467479 Phase 3 Telaprevir;Ribavirin;Highly Active Antiretroviral Therapy (HAART)
17 CHRONVAC-C Study Followed by Standard of Care in Chronic Hepatitis C Virus (HCV) Subjects Unknown status NCT01335711 Phase 2 ChronVac-C + SOC;SOC
18 Phase I-II Vaccination of Autologous Dendritic Cells Transduced With Adenoviral Vector Encoding NS3 in Hepatitis C Encoding NS3 in Hepatitis C Completed NCT02309086 Phase 1, Phase 2
19 Pilot Study to Assess Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-dose Combination in Treatment Experienced Subjects With Hepatitis C Virus (HCV) Genotype 1 - HIV Co-infection Completed NCT02125500 Phase 2 Sofosbuvir/Ledipasvir fixed dose
20 Safety and Efficacy of the Therapeutic Vaccine GI-5005 Combined With Pegylated Interferon Plus Ribavirin Standard of Care Therapy Versus Standard of Care Alone in Patients With Genotype 1 Chronic Hepatitis C Infection Completed NCT00606086 Phase 2 GI-5005;Pegylated Interferon and Ribavirin
21 A Pharmacokinetics/Pharmacodynamics Study of SCH 900518 in Previously Untreated Subjects With Genotype 1 Chronic Hepatitis C (Protocol No. P05104AM2)(COMPLETED) Completed NCT00797745 Phase 2 ribavirin;SCH 900518;ritonavir
22 A Phase 2b, Safety and Efficacy Study of Boceprevir in Patients Coinfected With HIV and Hepatitis C (P05411 AM4) Completed NCT00959699 Phase 2 PegIFN-2b;RBV;Placebo to Boceprevir;Boceprevir
23 Safety, Tolerability and Efficacy of 12-weeks of Sovaprevir, ACH-3102 and Ribavirin in Treatment-naive GT-1 HCV Subjects Completed NCT01849562 Phase 2 Sovaprevir;ACH-3102;RBV;Placebo
24 Simeprevir in Combination With Sofosbuvir in Treatment-Naïve or -Experienced Adults With Chronic Genotype 4 Hepatitis C Virus Infection Completed NCT02253550 Phase 2 Simeprevir;Sofosbuvir
25 Safety Study of Pegylated Interferon Lambda Plus Single or 2 Direct Antiviral Agents With Ribavirin Completed NCT01309932 Phase 2 BMS-790052 (NS5A Inhibitor);Ribavirin (RBV);BMS-650032 (NS3 Protease Inhibitor);Ribavirin (RBV);Ribavirin (RBV);BMS-790052 (NS5A Inhibitor);BMS-650032 (NS3 Protease Inhibitor);Placebo (PBO) for BMS-650032 (Placebo for NS3 Protease Inhibitor);Placebo (PBO) for BMS-790052 (Placebo for NS5A Inhibitor);Placebo for Ribavirin (RBV);Placebo for Ribavirin (RBV)
26 Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of Simeprevir, Daclatasvir and Sofosbuvir in Treatment-naive Participants With Chronic Hepatitis C Virus Genotype 1 Infection Completed NCT02349048 Phase 2 Simeprevir 150 mg;Daclatasvir 60 mg;Sofosbuvir 400 mg
27 A Study to Investigate the Pharmacokinetic Interactions Between Simeprevir and Ledipasvir in a Treatment Regimen Consisting of Simeprevir, Sofosbuvir, and Ledipasvir in Treatment-naive Participants With Chronic Hepatitis C Virus Genotype 1 Infection Completed NCT02421211 Phase 2 Simeprevir (SMV);Ledipasvir (LDV);Sofosbuvir (SOF)
28 A Study of Pharmacokinetics, Efficacy, Safety, Tolerability, of the Combination of Simeprevir (TMC435), Daclatasvir (BMS-790052), and Ribavirin (RBV) in Patients With Recurrent Chronic Hepatitis C Genotype 1b Infection After Orthotopic Liver Transplantati Completed NCT01938625 Phase 2 Simeprevir;Daclatasvir;Ribavirin;Cyclosporine;Tacrolimus
29 Autologous Dendritic Cell Vaccine for Treatment of Patients With Chronic HCV-Infection Recruiting NCT03119025 Phase 1, Phase 2
30 Efficacy and Safety of Combinations of AL-335, Odalasvir (ODV) and Simeprevir (SMV) in the Treatment of Chronic Hepatitis C Infection Active, not recruiting NCT02765490 Phase 2 AL-335;Odalasvir;Simeprevir
31 An Efficacy, Safety and Pharmacokinetics Study of Simeprevir, Daclatasvir and Sofosbuvir in Participants With Chronic Hepatitis C Virus Genotype 1 or 4 Infection and Decompensated Liver Disease Active, not recruiting NCT02262728 Phase 2 Simeprevir;Daclatasvir;Sofosbuvir
32 Research Study Using Recombinant Human Insulin-Like Growth Factor-1/Recombinant Human Insulin-Like Growth Factor Binding Protein-3 for Children With Noonan Syndrome Terminated NCT00351221 Phase 2 rhIGF-1/rhIGFBP-3
33 GS-5885, GS-9451 With Peginterferon Alfa 2a (PEG) and Ribavirin in Treatment-Naïve Subjects With Chronic Genotype 1 Hep C Virus Infection and IL28B CC Genotype Terminated NCT01384383 Phase 2 GS-5885;GS-9451;RBV;PEG
34 An Open-Label Study of the Effect of Telaprevir in Combination With Peginterferon Alfa-2b and Ribavirin in Pediatric Subjects Infected With Hepatitis C Virus Terminated NCT01701063 Phase 1, Phase 2 Telaprevir;Peginterferon alfa-2b;Ribavirin
35 An Open Label Study of the Effect of Telaprevir in Combination With Ribavirin and Peginterferon on HCV Infection in Stable Liver Transplant Patients Terminated NCT01467505 Phase 2 Telaprevir;Ribavirin;Pegylated Interferon Alfa-2a;Immunosuppressant Regimen
36 An Efficacy, Safety, Tolerability and Pharmacokinetics Study of 12 Weeks Treatment With Simeprevir and Daclatasvir in Participants With Chronic Hepatitis C Virus Genotype 1b or 4 Infection and Either Severe Renal Impairment or End-stage Renal Disease on H Withdrawn NCT02397395 Phase 2 Simeprevir (SMV) 150 mg;Daclatasvir (DCV) 60 mg
37 Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MEK162 in Noonan Syndrome Hypertrophic Cardiomyopathy Withdrawn NCT01556568 Phase 2 MEK162
38 Safety and Efficacy of the Therapeutic Vaccine GI-5005 Versus Placebo for the Treatment of Chronic Hepatitis C Infection Completed NCT00124215 Phase 1
39 A Study to Evaluate the Effect of ACH-3102 and Simeprevir on AL-335 Pharmacokinetics in Healthy Volunteers Completed NCT02512562 Phase 1 AL-335;ACH-3102;Simeprevir
40 A Drug Interaction Study of Boceprevir in Combination With Amlodipine or Diltiazem in Healthy Volunteers Withdrawn NCT01549496 Phase 1 Amlodipine;Diltiazem
41 TG4040 in Patients With Chronic HCV Withdrawn NCT00449124 Phase 1 Placebo
42 Examining the Immune Response in Patients With Gaucher Disease and Hepatitis C Unknown status NCT01274208
43 An Observational/Non-interventional, Study of NS3/4a Protease and NS5A Protein of Hepatitis C Virus in Brazilian Participants With Chronic HCV Infection Completed NCT02597270
44 Evaluating the Role of Immune Responses in the Emergence of Protease Inhibitor Mutations Completed NCT01517529
45 Effect of Teleprevir in Triple Therapy on Intrahepatic Immunological Mechanisms Completed NCT01641094
46 Study the Usefulness of Bio-impedance Spectroscopy in the Early Assessment of Breast Cancer Related Lymphoedema Completed NCT01599039
47 Comparative Trial in Compression Therapy in Leg Lymphedema Completed NCT00665379
48 Eliminating Hepatitis C Transmission by Enhancing Care and Treatment Among HIV Co-infected Individuals Recruiting NCT02786758
49 The Durability of Response and Persistence of Resistance to AbbVie's 2 Direct-acting Antiviral Agent (2D) Therapy in Japanese Subjects Active, not recruiting NCT02581020
50 Hormonal Sensitivity in Patients With Noonan and LEOPARD Syndromes Not yet recruiting NCT02486731

Search NIH Clinical Center for Noonan Syndrome 3

Genetic Tests for Noonan Syndrome 3

Genetic tests related to Noonan Syndrome 3:

id Genetic test Affiliating Genes
1 Noonan Syndrome 3 29

Anatomical Context for Noonan Syndrome 3

MalaCards organs/tissues related to Noonan Syndrome 3:

39
Heart, Skin, Liver, Testes, Bone, Breast

Publications for Noonan Syndrome 3

Variations for Noonan Syndrome 3

UniProtKB/Swiss-Prot genetic disease variations for Noonan Syndrome 3:

71
id Symbol AA change Variation ID SNP ID
1 KRAS p.Val14Ile VAR_026109 rs104894365
2 KRAS p.Thr58Ile VAR_026111 rs104894364
3 KRAS p.Gln22Arg VAR_064851 rs727503110
4 KRAS p.Pro34Leu VAR_064852 rs104894366
5 KRAS p.Pro34Gln VAR_064853
6 KRAS p.Ile36Met VAR_064854 rs727503109
7 KRAS p.Lys5Glu VAR_065144 rs193929331
8 KRAS p.Gly60Ser VAR_065146 rs104894359

ClinVar genetic disease variations for Noonan Syndrome 3:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 KRAS NM_004985.4(KRAS): c.458A> T (p.Asp153Val) single nucleotide variant Pathogenic rs104894360 GRCh37 Chromosome 12, 25362838: 25362838
2 KRAS NM_004985.4(KRAS): c.173C> T (p.Thr58Ile) single nucleotide variant Pathogenic rs104894364 GRCh37 Chromosome 12, 25380285: 25380285
3 KRAS NM_004985.4(KRAS): c.40G> A (p.Val14Ile) single nucleotide variant Pathogenic rs104894365 GRCh37 Chromosome 12, 25398279: 25398279
4 KRAS NM_004985.4(KRAS): c.455T> G (p.Val152Gly) single nucleotide variant Pathogenic rs104894367 GRCh37 Chromosome 12, 25362841: 25362841
5 KRAS NM_033360.3(KRAS): c.13A> G (p.Lys5Glu) single nucleotide variant Pathogenic/Likely pathogenic rs193929331 GRCh37 Chromosome 12, 25398306: 25398306
6 KRAS NM_004985.4(KRAS): c.178G> A (p.Gly60Ser) single nucleotide variant Pathogenic rs104894359 GRCh37 Chromosome 12, 25380280: 25380280
7 KRAS NM_033360.3(KRAS): c.440A> G (p.Lys147Arg) single nucleotide variant Pathogenic rs1135401776 GRCh37 Chromosome 12, 25378558: 25378558

Cosmic variations for Noonan Syndrome 3:

9
id Cosmic Mut ID Gene Symbol COSMIC Disease Classification
(Primary site, Site subtype, Primary histology, Histology subtype)
Mutation CDS Mutation AA Conf
1 COSM584 NRAS skin,neck,benign melanocytic nevus,congenital c.182A>G p.Q61R 3

Expression for Noonan Syndrome 3

Search GEO for disease gene expression data for Noonan Syndrome 3.

Pathways for Noonan Syndrome 3

GO Terms for Noonan Syndrome 3

Sources for Noonan Syndrome 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
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42 MeSH
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60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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