NS2
MCID: NNN009
MIFTS: 53

Noonan Syndrome 2 (NS2)

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 2

MalaCards integrated aliases for Noonan Syndrome 2:

Name: Noonan Syndrome 2 58 12 54 76 30 6 15 74
Ns2 58 12 54 76
Noonan Syndrome 2, Autosomal Recessive 76
Noonan Syndrome, Autosomal Recessive 58
Autosomal Recessive Noonan Syndrome 54
Noonan Syndrome Autosomal Recessive 54

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive


Classifications:



Summaries for Noonan Syndrome 2

UniProtKB/Swiss-Prot : 76 Noonan syndrome 2: 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. NS2 inheritance is autosomal recessive.

MalaCards based summary : Noonan Syndrome 2, also known as ns2, is related to hepatitis c virus and influenza. An important gene associated with Noonan Syndrome 2 is LZTR1 (Leucine Zipper Like Transcription Regulator 1), and among its related pathways/superpathways are Interferon gamma signaling and NF-kappaB Signaling. The drugs Methylprednisolone and Prednisolone phosphate have been mentioned in the context of this disorder. Affiliated tissues include skin, t cells and b cells, and related phenotypes are hypertelorism and ptosis

Disease Ontology : 12 A Noonan syndrome characterized by hypertrophic obstructive cardiomyopathy and that has material basis in an autosomal recessive inheritance.

OMIM : 58 Noonan syndrome (NS) is a multiple congenital anomalies syndrome characterized by a typical face, congenital heart disease, and short stature (summary by van der Burgt and Brunner, 2000). For a general phenotypic description and a discussion of genetic heterogeneity of Noonan syndrome, see NS1 (163950). (605275)

Related Diseases for Noonan Syndrome 2

Graphical network of the top 20 diseases related to Noonan Syndrome 2:



Diseases related to Noonan Syndrome 2

Symptoms & Phenotypes for Noonan Syndrome 2

Human phenotypes related to Noonan Syndrome 2:

33 (show all 10)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 33 very rare (1%) HP:0000316
2 ptosis 33 very rare (1%) HP:0000508
3 short stature 33 very rare (1%) HP:0004322
4 global developmental delay 33 HP:0001263
5 coarctation of aorta 33 HP:0001680
6 cardiomyopathy 33 HP:0001638
7 downslanted palpebral fissures 33 HP:0000494
8 pulmonic stenosis 33 HP:0001642
9 mitral stenosis 33 HP:0001718
10 abnormal cardiac septum morphology 33 HP:0001671

Symptoms via clinical synopsis from OMIM:

58
Cardiovascular Heart:
cardiomyopathy
pulmonary valve stenosis
septal defects
coarctation of the aorta
mitral valve stenosis

Head And Neck Ears:
posteriorly rotated ears

Head And Neck Eyes:
downslanting palpebral fissures
hypertelorism (in some patients)
ptosis (in some patients)

Genitourinary Internal Genitalia Male:
cryptorchidism (in some patients)

Chest Breasts:
widely spaced nipples (in some patients)

Head And Neck Head:
normal to increased occipitofrontal circumference (ofc)

Chest External Features:
broad chest (in some patients)

Skeletal:
arthrogryposis (in some patients)

Neoplasia:
leukemia (in 2 families)

Skin Nails Hair Hair:
curly hair

Neurologic Central Nervous System:
developmental delay
impaired intellectual development

Growth Height:
short stature (in some patients)
normal to increased birth length

Prenatal Manifestations Amniotic Fluid:
polyhydramnios (in some patients)

Growth Weight:
normal to increased birth weight

Head And Neck Neck:
broad, short neck

Chest Ribs Sternum Clavicles And Scapulae:
pectus deformity

Hematology:
coagulation defects (in some patients)

Clinical features from OMIM:

605275

GenomeRNAi Phenotypes related to Noonan Syndrome 2 according to GeneCards Suite gene sharing:

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased interferon-beta reporter expression GR00307-A 9.26 IRF3 LZTR1 MAVS XPO1
2 Upregulation of RLR pathway after Sendai virus (SeV) infection GR00302-A 8.92 DDX58 IRF3 MAVS XPO1

Drugs & Therapeutics for Noonan Syndrome 2

Drugs for Noonan Syndrome 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 24)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Methylprednisolone Approved, Vet_approved Phase 2 83-43-2 6741
2
Prednisolone phosphate Approved, Vet_approved Phase 2 302-25-0
3
Prednisolone Approved, Vet_approved Phase 2 50-24-8 5755
4
Methylprednisolone hemisuccinate Approved Phase 2 2921-57-5
5
Ethanol Approved Phase 2 64-17-5 702
6
Prednisolone hemisuccinate Experimental Phase 2 2920-86-7
7 Neuroprotective Agents Phase 2
8 glucocorticoids Phase 2
9 Protective Agents Phase 2
10 Ophthalmic Solutions Phase 2
11 Anti-Inflammatory Agents Phase 2
12 Gastrointestinal Agents Phase 2
13 Pharmaceutical Solutions Phase 2
14 Antiemetics Phase 2
15 Prednisolone acetate Phase 2
16 Hormones Phase 2
17 Methylprednisolone Acetate Phase 2
18 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 2
19 Peripheral Nervous System Agents Phase 2
20 Autonomic Agents Phase 2
21 Hormone Antagonists Phase 2
22 Antineoplastic Agents, Hormonal Phase 2
23 Immunologic Factors Phase 1
24 Vaccines Phase 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Short Term Effectiveness Study of Juxta-Fit Versus Trico Bandages in the Treatment of Leg Lymphedema Completed NCT01068431 Phase 4
2 A Safety and Efficacy Study of NS2 in Patients With Anterior Uveitis Completed NCT02406209 Phase 2 NS2;Prednisolone acetate ophthalmic suspension (1%)
3 A Safety and Activity Study of NS2 in Subjects With Allergic Conjunctivitis Completed NCT02578914 Phase 2 NS2 Ophthalmic Drops (0.5%);NS2 Ophthalmic Drops Vehicle (0.0%)
4 A Study of Topical NS2 Cream to Treat Ichthyosis in Sjögren-Larsson Syndrome (SLS) Completed NCT02402309 Phase 2 Active topical NS2 1% dermatologic cream;Vehicle placebo 0.0% NS2 dermatologic cream
5 Evaluating the Infectivity, Safety, and Immunogenicity of a Respiratory Syncytial Virus Vaccine (RSV 6120/∆NS2/1030s) in RSV-Seropositive Children and RSV-Seronegative Infants and Children Recruiting NCT03387137 Phase 1
6 Evaluating the Infectivity, Safety, and Immunogenicity of a Single Dose of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine (D46/NS2/N/ΔM2-2-HindIII) in RSV-Seronegative Infants 6 to 24 Months of Age Completed NCT03102034 Phase 1
7 Infectivity, Safety and Immunogenicity of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine (D46/NS2/N/ΔM2-2-HindIII) in RSV-Seronegative Infants and Children 6 to 24 Months of Age Completed NCT03099291 Phase 1
8 Effect of Coccinia Cordifolia Extract on Blood Sugar of Newly Diagnosed Diabetics Completed NCT00502008 Not Applicable Coccinia Cordifolia (herbal extract)
9 Study of Human Epidermal Growth Receptor (HER2) Status Evaluation in Breast Cancer Pathology Samples Completed NCT02580799

Search NIH Clinical Center for Noonan Syndrome 2

Genetic Tests for Noonan Syndrome 2

Genetic tests related to Noonan Syndrome 2:

# Genetic test Affiliating Genes
1 Noonan Syndrome 2 30

Anatomical Context for Noonan Syndrome 2

MalaCards organs/tissues related to Noonan Syndrome 2:

42
Skin, T Cells, B Cells, Eye

Publications for Noonan Syndrome 2

Articles related to Noonan Syndrome 2:

(show top 50) (show all 231)
# Title Authors Year
1
Polycrystal Synthesis, Crystal Growth, Structure, and Optical Properties of AgGaGe nS2( n+1) ( n = 2, 3, 4, and 5) Single Crystals for Mid-IR Laser Applications. ( 30977358 )
2019
2
Dengue virus NS2 and NS4: Minor proteins, mammoth roles. ( 29674002 )
2018
3
NS2 proteases from hepatitis C virus and related hepaciviruses share composite active sites and previously unrecognized intrinsic proteolytic activities. ( 29415072 )
2018
4
Autosomal recessive Noonan syndrome associated with biallelic LZTR1 variants. ( 29469822 )
2018
5
Easily reduced bis-pincer (NS2)2molybdenum(iv) to (NHS2)2Mo(ii) by alcohols vs. redox-inert (NS2)(NHS2)iron(iii) complexes. ( 29951680 )
2018
6
Gelatin nanoparticles enhance delivery of hepatitis C virus recombinant NS2 gene. ( 28746382 )
2017
7
Loss of Drosophila nucleostemin 2 (NS2) blocks nucleolar release of the 60S subunit leading to ribosome stress. ( 27150106 )
2017
8
Lineage A Betacoronavirus NS2 Proteins and the Homologous Torovirus Berne pp1a Carboxy-Terminal Domain Are Phosphodiesterases That Antagonize Activation of RNase L. ( 28003490 )
2017
9
Feline Panleucopenia Virus NS2 Suppresses the Host IFN-β Induction by Disrupting the Interaction between TBK1 and STING. ( 28125002 )
2017
10
Toward the laboratory identification of the not-so-simple NS2 neutral and anion isomers. ( 28830189 )
2017
11
Naringenin and quercetin--potential anti-HCV agents for NS2 protease targets. ( 25774442 )
2016
12
Correction: A Conserved NS3 Surface Patch Orchestrates NS2 Protease Stimulation, NS5A Hyperphosphorylation and HCV Genome Replication. ( 26745726 )
2016
13
Crystal structure of the mouse hepatitis virus ns2 phosphodiesterase domain that antagonizes RNase L activation. ( 26757803 )
2016
14
Infection of Common Marmosets with GB Virus B Chimeric Virus Encoding the Major Nonstructural Proteins NS2 to NS4A of Hepatitis C Virus. ( 27384651 )
2016
15
Multiscale simulations on conformational dynamics and membrane interactions of the non-structural 2 (NS2) transmembrane domain. ( 27444387 )
2016
16
Theoretical study of the interactions between the first transmembrane segment of NS2 protein and a POPC lipid bilayer. ( 27455027 )
2016
17
Beyond methylammonium lead iodide: prospects for the emergent field of ns2 containing solar absorbers. ( 27722664 )
2016
18
CHD3 facilitates vRNP nuclear export by interacting with NES1 of influenza A virus NS2. ( 25213355 )
2015
19
Interaction of NS2 with AIMP2 facilitates the switch from ubiquitination to SUMOylation of M1 in influenza A virus-infected cells. ( 25320310 )
2015
20
Phosphatidylserine-specific phospholipase A1 involved in hepatitis C virus assembly through NS2 complex formation. ( 25505071 )
2015
21
Electrocatalytic proton reduction by dimeric nickel complex of a sterically demanding pincer-type NS2 aminobis(thiophenolate) ligand. ( 25539022 )
2015
22
Detergent-resistant membrane association of NS2 and E2 during hepatitis C virus replication. ( 25673706 )
2015
23
A conserved NS3 surface patch orchestrates NS2 protease stimulation, NS5A hyperphosphorylation and HCV genome replication. ( 25774920 )
2015
24
A single NS2 mutation of K86R promotes PR8 vaccine donor virus growth in Vero cells. ( 25817403 )
2015
25
Adaptive Mutations Enhance Assembly and Cell-to-Cell Transmission of a High-Titer Hepatitis C Virus Genotype 5a Core-NS2 JFH1-Based Recombinant. ( 25995244 )
2015
26
Characterization of the Determinants of NS2-3-Independent Virion Morphogenesis of Pestiviruses. ( 26355097 )
2015
27
Identification of a lead like inhibitor of the hepatitis C virus non-structural NS2 autoprotease. ( 26518228 )
2015
28
Inhibition of hepatitis C virus infection by DNA aptamer against NS2 protein. ( 24587329 )
2014
29
Determinants for membrane association of the hepatitis C virus NS2 protease domain. ( 24648458 )
2014
30
RSV-encoded NS2 promotes epithelial cell shedding and distal airway obstruction. ( 24713657 )
2014
31
NS2 proteins of GB virus B and hepatitis C virus share common protease activities and membrane topologies. ( 24741107 )
2014
32
Visual quality assessment after network transmission incorporating NS2 and Evalvid. ( 24883370 )
2014
33
Quantitative proteomic analysis of the influenza A virus nonstructural proteins NS1 and NS2 during natural cell infection identifies PACT as an NS1 target protein and antiviral host factor. ( 24899174 )
2014
34
Murine AKAP7 has a 2',5'-phosphodiesterase domain that can complement an inactive murine coronavirus ns2 gene. ( 24987090 )
2014
35
NS2 is dispensable for efficient assembly of hepatitis C virus-like particles in a bipartite trans-encapsidation system. ( 25024280 )
2014
36
Nuclear export of the influenza virus ribonucleoprotein complex: Interaction of Hsc70 with viral proteins M1 and NS2. ( 25161876 )
2014
37
The Minute Virus of Mice NS2 proteins are not essential for productive infection of embryonic murine cells in utero. ( 25310499 )
2014
38
Effects of hepatitis C virus gene NS2 on the expressions of Bcl-2 and Bax in HepG2 cells. ( 25823150 )
2014
39
Hepatitis C virus NS2 protease inhibits host cell antiviral response by inhibiting IKKε and TBK1 functions. ( 23096996 )
2013
40
A second CRM1-dependent nuclear export signal in the influenza A virus NS2 protein contributes to the nuclear export of viral ribonucleoproteins. ( 23115280 )
2013
41
Respiratory syncytial virus modified by deletions of the NS2 gene and amino acid S1313 of the L polymerase protein is a temperature-sensitive, live-attenuated vaccine candidate that is phenotypically stable at physiological temperature. ( 23236065 )
2013
42
Genetic and functional characterization of the N-terminal region of the hepatitis C virus NS2 protein. ( 23408609 )
2013
43
Identification of specific regions in hepatitis C virus core, NS2 and NS5A that genetically interact with p7 and co-ordinate infectious virus production. ( 23490391 )
2013
44
Hepatitis C virus NS2 protein inhibits DNA damage pathway by sequestering p53 to the cytoplasm. ( 23638118 )
2013
45
Identification of a linear B-cell epitope within the Bluetongue virus serotype 8 NS2 protein using a phage-displayed random peptide library. ( 23747319 )
2013
46
The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and provide insights for ADAR1 playing a supportive role in virus replication. ( 23853584 )
2013
47
Analysis of hepatitis C virus core/NS5A protein co-localization using novel cell culture systems expressing core-NS2 and NS5A of genotypes 1-7. ( 23907394 )
2013
48
Signal peptidase complex subunit 1 participates in the assembly of hepatitis C virus through an interaction with E2 and NS2. ( 24009510 )
2013
49
An adaptive mutation in NS2 is essential for efficient production of infectious 1b/2a chimeric hepatitis C virus in cell culture. ( 22099378 )
2012
50
Identification of residues involved in NS2 homodimerization and elucidation of their impact on the HCV life cycle. ( 22329373 )
2012

Variations for Noonan Syndrome 2

ClinVar genetic disease variations for Noonan Syndrome 2:

6 (show all 22)
# Gene Variation Type Significance SNP ID Assembly Location
1 LZTR1 NM_006767.4(LZTR1): c.1943-256C> T single nucleotide variant Conflicting interpretations of pathogenicity rs761685529 GRCh37 Chromosome 22, 21349779: 21349779
2 LZTR1 NM_006767.4(LZTR1): c.1943-256C> T single nucleotide variant Conflicting interpretations of pathogenicity rs761685529 GRCh38 Chromosome 22, 20995490: 20995490
3 LZTR1 NM_006767.3(LZTR1): c.-38T> A single nucleotide variant Pathogenic GRCh37 Chromosome 22, 21336623: 21336623
4 LZTR1 NM_006767.3(LZTR1): c.-38T> A single nucleotide variant Pathogenic GRCh38 Chromosome 22, 20982334: 20982334
5 LZTR1 NM_006767.3(LZTR1): c.1311G> A (p.Trp437Ter) single nucleotide variant Pathogenic rs770933647 GRCh38 Chromosome 22, 20993712: 20993712
6 LZTR1 NM_006767.3(LZTR1): c.1311G> A (p.Trp437Ter) single nucleotide variant Pathogenic rs770933647 GRCh37 Chromosome 22, 21348001: 21348001
7 LZTR1 NM_006767.3(LZTR1): c.1382C> A (p.Ala461Asp) single nucleotide variant Uncertain significance GRCh37 Chromosome 22, 21348241: 21348241
8 LZTR1 NM_006767.3(LZTR1): c.1382C> A (p.Ala461Asp) single nucleotide variant Uncertain significance GRCh38 Chromosome 22, 20993952: 20993952
9 LZTR1 NM_006767.3(LZTR1): c.1385T> C (p.Ile462Thr) single nucleotide variant Uncertain significance rs147684991 GRCh37 Chromosome 22, 21348244: 21348244
10 LZTR1 NM_006767.3(LZTR1): c.1385T> C (p.Ile462Thr) single nucleotide variant Uncertain significance rs147684991 GRCh38 Chromosome 22, 20993955: 20993955
11 LZTR1 NM_006767.3(LZTR1): c.1407G> A (p.Trp469Ter) single nucleotide variant Pathogenic rs777243508 GRCh37 Chromosome 22, 21348266: 21348266
12 LZTR1 NM_006767.3(LZTR1): c.1407G> A (p.Trp469Ter) single nucleotide variant Pathogenic rs777243508 GRCh38 Chromosome 22, 20993977: 20993977
13 LZTR1 NM_006767.3(LZTR1): c.2246A> G (p.Tyr749Cys) single nucleotide variant Uncertain significance rs755260815 GRCh38 Chromosome 22, 20996722: 20996722
14 LZTR1 NM_006767.3(LZTR1): c.2246A> G (p.Tyr749Cys) single nucleotide variant Uncertain significance rs755260815 GRCh37 Chromosome 22, 21351011: 21351011
15 LZTR1 NM_006767.4(LZTR1): c.2220-17C> A single nucleotide variant Pathogenic GRCh38 Chromosome 22, 20996679: 20996679
16 LZTR1 NM_006767.4(LZTR1): c.2220-17C> A single nucleotide variant Pathogenic GRCh37 Chromosome 22, 21350968: 21350968
17 LZTR1 NM_006767.4(LZTR1): c.628C> T (p.Arg210Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 22, 21343948: 21343948
18 LZTR1 NM_006767.4(LZTR1): c.628C> T (p.Arg210Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 22, 20989659: 20989659
19 LZTR1 NM_006767.4(LZTR1): c.2264G> A (p.Arg755Gln) single nucleotide variant Pathogenic GRCh37 Chromosome 22, 21351029: 21351029
20 LZTR1 NM_006767.4(LZTR1): c.2264G> A (p.Arg755Gln) single nucleotide variant Pathogenic GRCh38 Chromosome 22, 20996740: 20996740
21 LZTR1 NM_006767.4(LZTR1): c.361C> G (p.His121Asp) single nucleotide variant Pathogenic GRCh37 Chromosome 22, 21341833: 21341833
22 LZTR1 NM_006767.4(LZTR1): c.361C> G (p.His121Asp) single nucleotide variant Pathogenic GRCh38 Chromosome 22, 20987544: 20987544

Expression for Noonan Syndrome 2

Search GEO for disease gene expression data for Noonan Syndrome 2.

Pathways for Noonan Syndrome 2

Pathways related to Noonan Syndrome 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.95 DDX58 IRF3 RNASEL STAT2
2 11.87 DDX58 IRF3 MAVS RNASEL STAT2
3 10.82 DDX58 MAVS
4
Show member pathways
10.29 DDX58 IRF3 MAVS STAT2

GO Terms for Noonan Syndrome 2

Biological processes related to Noonan Syndrome 2 according to GeneCards Suite gene sharing:

(show all 19)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription by RNA polymerase II GO:0045944 9.98 CD81 DDX58 IRF3 MAVS RNASEL
2 type I interferon signaling pathway GO:0060337 9.63 IRF3 RNASEL STAT2
3 viral process GO:0016032 9.63 CD81 DDX58 IRF3 MAVS STAT2 XPO1
4 negative regulation of viral genome replication GO:0045071 9.58 MAVS RNASEL
5 positive regulation of interleukin-8 production GO:0032757 9.56 DDX58 MAVS
6 positive regulation of defense response to virus by host GO:0002230 9.55 DDX58 MAVS
7 positive regulation of interleukin-6 secretion GO:2000778 9.54 DDX58 MAVS
8 cellular response to exogenous dsRNA GO:0071360 9.52 DDX58 MAVS
9 positive regulation of tumor necrosis factor secretion GO:1904469 9.51 DDX58 MAVS
10 negative regulation of type I interferon production GO:0032480 9.5 DDX58 IRF3 MAVS
11 positive regulation of interferon-alpha secretion GO:1902741 9.48 DDX58 MAVS
12 positive regulation of myeloid dendritic cell cytokine production GO:0002735 9.43 DDX58 MAVS
13 positive regulation of interferon-beta production GO:0032728 9.43 DDX58 IRF3 MAVS
14 positive regulation of response to cytokine stimulus GO:0060760 9.4 DDX58 MAVS
15 positive regulation of interferon-beta secretion GO:0035549 9.37 DDX58 MAVS
16 defense response to virus GO:0051607 9.35 DDX58 IRF3 MAVS RNASEL STAT2
17 response to exogenous dsRNA GO:0043330 9.27 DDX58
18 positive regulation of type I interferon-mediated signaling pathway GO:0060340 9.19 MAVS
19 positive regulation of interferon-alpha production GO:0032727 8.8 DDX58 IRF3 MAVS

Sources for Noonan Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
Content
Loading form....