NS6
MCID: NNN013
MIFTS: 45

Noonan Syndrome 6 (NS6)

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 6

Summaries for Noonan Syndrome 6

UniProtKB/Swiss-Prot : 76 Noonan syndrome 6: 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 6, also known as ns6, is related to noonan syndrome 7 and noonan syndrome 4. An important gene associated with Noonan Syndrome 6 is NRAS (NRAS Proto-Oncogene, GTPase), and among its related pathways/superpathways are Toll-like Receptor Signaling Pathway and PI3K-Akt signaling pathway. The drugs Miconazole and Monensin have been mentioned in the context of this disorder. Affiliated tissues include skin, eye and myeloid, and related phenotypes are hypertelorism and low-set ears

Disease Ontology : 12 A Noonan syndrome that has_material_basis in heterozygous mutation in the NRAS gene on chromosome 1p13.

Description from OMIM: 613224

Related Diseases for Noonan Syndrome 6

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

Diseases related to Noonan Syndrome 6 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 noonan syndrome 7 10.1
2 noonan syndrome 4 9.9 CTTNBP2 ITPA
3 noonan syndrome 2 9.8 IRF3 MAVS
4 retinitis pigmentosa 33 9.6 IRF3 TBK1
5 herpes simplex encephalitis 9.5 IRF3 TBK1
6 viral infectious disease 9.4 IRF3 MAVS TBK1
7 noonan syndrome 3 9.1 IRF3 ITPA MAVS TBK1
8 noonan syndrome 1 9.0 CTTNBP2 IRF3 MAVS NRAS TBK1

Graphical network of the top 20 diseases related to Noonan Syndrome 6:



Diseases related to Noonan Syndrome 6

Symptoms & Phenotypes for Noonan Syndrome 6

Human phenotypes related to Noonan Syndrome 6:

33 (show all 27)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 33 obligate (100%) HP:0000316
2 low-set ears 33 obligate (100%) HP:0000369
3 short stature 33 obligate (100%) HP:0004322
4 hyperkeratosis 33 obligate (100%) HP:0000962
5 cryptorchidism 33 obligate (100%) HP:0000028
6 webbed neck 33 obligate (100%) HP:0000465
7 curly hair 33 obligate (100%) HP:0002212
8 generalized hypotonia 33 obligate (100%) HP:0001290
9 asymmetry of the thorax 33 obligate (100%) HP:0001555
10 macrocephaly 33 very rare (1%) HP:0000256
11 global developmental delay 33 very rare (1%) HP:0001263
12 delayed speech and language development 33 very rare (1%) HP:0000750
13 intellectual disability, mild 33 very rare (1%) HP:0001256
14 hypertrophic cardiomyopathy 33 very rare (1%) HP:0001639
15 myopia 33 very rare (1%) HP:0000545
16 pulmonic stenosis 33 very rare (1%) HP:0001642
17 depressed nasal bridge 33 HP:0005280
18 wide nasal bridge 33 HP:0000431
19 sensorineural hearing impairment 33 HP:0000407
20 edema 33 HP:0000969
21 epicanthus 33 HP:0000286
22 motor delay 33 HP:0001270
23 downslanted palpebral fissures 33 HP:0000494
24 sparse hair 33 HP:0008070
25 cafe-au-lait spot 33 HP:0000957
26 keratosis pilaris 33 HP:0032152
27 long eyebrows 33 HP:0004523

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Head:
macrocephaly

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum

Growth Height:
short stature

Skin Nails Hair Skin:
hyperkeratosis
lentigines
keratosis pilaris
cafe-au-lait spots

Head And Neck Neck:
webbed neck
nuchal edema

Neurologic Central Nervous System:
motor delay
hypotonia
learning difficulties (in some patients)
developmental delay (in some patients)

Head And Neck Face:
high forehead

Prenatal Manifestations Placenta And Umbilical Cord:
single umbilical artery

Hematology:
juvenile myelomonocytic leukemia (in 1 patient)

Head And Neck Ears:
low-set ears
hearing loss, sensorineural (in 1 patient)

Head And Neck Nose:
depressed nasal bridge
broad nasal bridge

Cardiovascular Heart:
hypertrophic cardiomyopathy
pulmonic stenosis
supraventricular extrasystoles

Genitourinary Internal Genitalia Male:
cryptorchidism

Head And Neck Eyes:
myopia
downslanting palpebral fissures
epicanthal folds
long eyebrows

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Skin Nails Hair Hair:
curly hair
sparse hair

Chest External Features:
thorax deformity

Clinical features from OMIM:

613224

GenomeRNAi Phenotypes related to Noonan Syndrome 6 according to GeneCards Suite gene sharing:

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased interferon-beta reporter expression GR00307-A 8.8 IRF3 ITPA MAVS

MGI Mouse Phenotypes related to Noonan Syndrome 6:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 integument MP:0010771 8.92 ITPA MAVS NRAS TBK1

Drugs & Therapeutics for Noonan Syndrome 6

Drugs for Noonan Syndrome 6 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 7)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Miconazole Approved, Investigational, Vet_approved Not Applicable 22916-47-8 4189
2
Monensin Experimental, Vet_approved Not Applicable 17090-79-8
3 Antiparasitic Agents Not Applicable
4 Anti-Infective Agents Not Applicable
5 Antifungal Agents Not Applicable
6 Antiprotozoal Agents Not Applicable
7 Ionophores Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Comparative Trial to Monitor Interface Pressure in Relation to Volume Change in Leg Lymphoedema Completed NCT01828606 Not Applicable

Search NIH Clinical Center for Noonan Syndrome 6

Genetic Tests for Noonan Syndrome 6

Genetic tests related to Noonan Syndrome 6:

# Genetic test Affiliating Genes
1 Noonan Syndrome 6 30 NRAS

Anatomical Context for Noonan Syndrome 6

MalaCards organs/tissues related to Noonan Syndrome 6:

42
Skin, Eye, Myeloid

Publications for Noonan Syndrome 6

Articles related to Noonan Syndrome 6:

(show all 14)
# Title Authors Year
1
Porcine Deltacoronavirus Accessory Protein NS6 Antagonizes Interferon Beta Production by Interfering with the Binding of RIG-I/MDA5 to Double-Stranded RNA. ( 29769346 )
2018
2
Identification and subcellular localization of porcine deltacoronavirus accessory protein NS6. ( 27661736 )
2016
3
Mutation in NRAS in familial Noonan syndrome--case report and review of the literature. ( 26467218 )
2015
4
Structure determination of Murine Norovirus NS6 proteases with C-terminal extensions designed to probe protease-substrate interactions. ( 25755927 )
2015
5
Structure of a murine norovirus NS6 protease-product complex revealed by adventitious crystallisation. ( 22685603 )
2012
6
Nucleolin interacts with the feline calicivirus 3' untranslated region and the protease-polymerase NS6 and NS7 proteins, playing a role in virus replication. ( 21680514 )
2011
7
Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis. ( 21079152 )
2011
8
Noonan syndrome: clinical features, diagnosis, and management guidelines. ( 20876176 )
2010
9
A restricted spectrum of NRAS mutations causes Noonan syndrome. ( 19966803 )
2010
10
Germ-line mutation of the NRAS gene may be responsible for the development of juvenile myelomonocytic leukaemia. ( 19775298 )
2009
11
NRAS mutation causes a human autoimmune lymphoproliferative syndrome. ( 17517660 )
2007
12
Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations. ( 17332249 )
2007
13
N-ras gene point mutations in childhood acute lymphocytic leukemia correlate with a poor prognosis. ( 2407301 )
1990
14
Amino-acid substitutions at codon 13 of the N-ras oncogene in human acute myeloid leukaemia. ( 2989702 )
1985

Variations for Noonan Syndrome 6

UniProtKB/Swiss-Prot genetic disease variations for Noonan Syndrome 6:

76
# Symbol AA change Variation ID SNP ID
1 NRAS p.Thr50Ile VAR_063085 rs267606921
2 NRAS p.Gly60Glu VAR_063086 rs267606920

ClinVar genetic disease variations for Noonan Syndrome 6:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 NRAS NM_002524.3(NRAS): c.38G> A (p.Gly13Asp) single nucleotide variant Pathogenic rs121434596 GRCh37 Chromosome 1, 115258744: 115258744
2 NRAS NM_002524.3(NRAS): c.38G> A (p.Gly13Asp) single nucleotide variant Pathogenic rs121434596 GRCh38 Chromosome 1, 114716123: 114716123
3 NRAS NM_002524.4(NRAS): c.149C> T (p.Thr50Ile) single nucleotide variant Pathogenic rs267606921 GRCh37 Chromosome 1, 115256562: 115256562
4 NRAS NM_002524.4(NRAS): c.149C> T (p.Thr50Ile) single nucleotide variant Pathogenic rs267606921 GRCh38 Chromosome 1, 114713941: 114713941
5 NRAS NM_002524.4(NRAS): c.179G> A (p.Gly60Glu) single nucleotide variant Pathogenic rs267606920 GRCh37 Chromosome 1, 115256532: 115256532
6 NRAS NM_002524.4(NRAS): c.179G> A (p.Gly60Glu) single nucleotide variant Pathogenic rs267606920 GRCh38 Chromosome 1, 114713911: 114713911
7 NRAS NM_002524.4(NRAS): c.317C> T (p.Ser106Leu) single nucleotide variant Uncertain significance rs797045795 GRCh37 Chromosome 1, 115252323: 115252323
8 NRAS NM_002524.4(NRAS): c.317C> T (p.Ser106Leu) single nucleotide variant Uncertain significance rs797045795 GRCh38 Chromosome 1, 114709702: 114709702

Expression for Noonan Syndrome 6

Search GEO for disease gene expression data for Noonan Syndrome 6.

Pathways for Noonan Syndrome 6

Pathways related to Noonan Syndrome 6 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.57 IRF3 MAVS TBK1
2
Show member pathways
12.44 IRF3 NRAS TBK1
3
Show member pathways
12.25 IRF3 MAVS TBK1
4 12.01 IRF3 MAVS TBK1
5
Show member pathways
11.81 IRF3 NRAS TBK1
6
Show member pathways
11.74 IRF3 MAVS TBK1
7
Show member pathways
11.72 IRF3 MAVS NRAS TBK1
8 11.18 NRAS TBK1
9
Show member pathways
10.32 IRF3 MAVS

GO Terms for Noonan Syndrome 6

Biological processes related to Noonan Syndrome 6 according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 immune system process GO:0002376 9.7 IRF3 MAVS TBK1
2 innate immune response GO:0045087 9.69 IRF3 MAVS TBK1
3 viral process GO:0016032 9.67 IRF3 MAVS TBK1
4 defense response to virus GO:0051607 9.58 IRF3 MAVS TBK1
5 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0043123 9.54 IRF3 MAVS TBK1
6 positive regulation of type I interferon production GO:0032481 9.48 IRF3 TBK1
7 TRIF-dependent toll-like receptor signaling pathway GO:0035666 9.46 IRF3 TBK1
8 activation of innate immune response GO:0002218 9.43 MAVS TBK1
9 negative regulation of type I interferon production GO:0032480 9.33 IRF3 MAVS TBK1
10 regulation of type I interferon production GO:0032479 9.32 IRF3 TBK1
11 positive regulation of interferon-beta production GO:0032728 9.13 IRF3 MAVS TBK1
12 positive regulation of type I interferon-mediated signaling pathway GO:0060340 8.96 MAVS
13 positive regulation of interferon-alpha production GO:0032727 8.8 IRF3 MAVS TBK1

Sources for Noonan Syndrome 6

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
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