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 : 73 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 neuropathy and amyotrophic lateral sclerosis 1. An important gene associated with Noonan Syndrome 6 is NRAS (NRAS Proto-Oncogene, GTPase), and among its related pathways/superpathways are Regulation of lipid metabolism Insulin signaling-generic cascades and Interferon gamma signaling. Affiliated tissues include heart, skin and myeloid, and related phenotypes are hypertelorism and short stature

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

More information from OMIM: 613224 PS163950

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 Noonan Syndrome 11
Noonan Syndrome 12

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

(show all 25)
# Related Disease Score Top Affiliating Genes
1 neuropathy 10.3
2 amyotrophic lateral sclerosis 1 10.2
3 polyneuropathy 10.2
4 lateral sclerosis 10.2
5 gastroenteritis 10.2
6 demyelinating polyneuropathy 10.2
7 noonan syndrome 8 10.1 POLR2B ARMC9
8 singleton-merten syndrome 9.9 IFIH1 DDX58
9 sting-associated vasculopathy with onset in infancy 9.8 IFIH1 DDX58
10 diabetes mellitus, insulin-dependent, 20 9.8 IFIH1 DDX58
11 noonan syndrome 4 9.7 POLR2B ITPA DDX58 CTTNBP2 ASZ1
12 chilblain lupus 1 9.7 IFIH1 DDX58
13 western equine encephalitis 9.6 SH2D3C SH2D3A
14 noonan syndrome 3 9.5 SH2D3C SH2D3A ITPA
15 lassa fever 9.5 IFIH1 DDX58
16 eastern equine encephalitis 9.4 SH2D3C SH2D3A
17 mouth disease 9.4 IFIH1 G3BP1 EIF4G1 DDX58
18 acute diarrhea 9.4 SPECC1 SH2D3C SH2D3A ASZ1
19 croup 9.3 SH2D3A IFIH1 DDX58
20 severe acute respiratory syndrome 9.3 SH2D3A IFIH1 DDX58
21 noonan syndrome 1 9.0 SH2D3C SH2D3A NRAS EIF4G1 DDX58
22 middle east respiratory syndrome 8.9 SH2D3C SH2D3A PPP1CA IFIH1 ASZ1
23 noonan syndrome 2 8.8 SH2D3C SH2D3A IFIH1 ASZ1 ARMC9
24 noonan syndrome 7 8.6 SPECC1 SCN5A PPP1CA POLR2B ITPA EIF4G1
25 coronavirus infectious disease 8.5 SPECC1 SH2D3C SH2D3A PPP1CA IFIH1 DDX58

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:

31 (show all 32)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 31 obligate (100%) HP:0000316
2 short stature 31 obligate (100%) HP:0004322
3 hyperkeratosis 31 obligate (100%) HP:0000962
4 cryptorchidism 31 obligate (100%) HP:0000028
5 low-set ears 31 obligate (100%) HP:0000369
6 webbed neck 31 obligate (100%) HP:0000465
7 asymmetry of the thorax 31 obligate (100%) HP:0001555
8 generalized hypotonia 31 obligate (100%) HP:0001290
9 curly hair 31 obligate (100%) HP:0002212
10 global developmental delay 31 very rare (1%) HP:0001263
11 macrocephaly 31 very rare (1%) HP:0000256
12 delayed speech and language development 31 very rare (1%) HP:0000750
13 intellectual disability, mild 31 very rare (1%) HP:0001256
14 hypertrophic cardiomyopathy 31 very rare (1%) HP:0001639
15 myopia 31 very rare (1%) HP:0000545
16 pulmonic stenosis 31 very rare (1%) HP:0001642
17 depressed nasal bridge 31 HP:0005280
18 wide nasal bridge 31 HP:0000431
19 sensorineural hearing impairment 31 HP:0000407
20 edema 31 HP:0000969
21 epicanthus 31 HP:0000286
22 pectus excavatum 31 HP:0000767
23 motor delay 31 HP:0001270
24 downslanted palpebral fissures 31 HP:0000494
25 polyhydramnios 31 HP:0001561
26 high forehead 31 HP:0000348
27 sparse hair 31 HP:0008070
28 single umbilical artery 31 HP:0001195
29 cafe-au-lait spot 31 HP:0000957
30 long eyebrows 31 HP:0004523
31 keratosis pilaris 31 HP:0032152
32 juvenile myelomonocytic leukemia 31 HP:0012209

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Nose:
depressed nasal bridge
broad nasal bridge

Growth Height:
short stature

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

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

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

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 Head:
macrocephaly

Cardiovascular Heart:
hypertrophic cardiomyopathy
pulmonic stenosis
supraventricular extrasystoles

Genitourinary Internal Genitalia Male:
cryptorchidism

Head And Neck Neck:
webbed neck
nuchal edema

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Skin Nails Hair Hair:
sparse hair
curly hair

Chest External Features:
thorax deformity

Clinical features from OMIM:

613224

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

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00221-A-1 9.77 NRAS
2 Decreased viability GR00221-A-3 9.77 NRAS
3 Decreased viability GR00240-S-1 9.77 ARMC9 EIF4A1 EIF4A2 POLR2B
4 Decreased viability GR00249-S 9.77 ARMC9 CTTNBP2 EIF4A1 EIF4G1 G3BP1 POLR2B
5 Decreased viability GR00381-A-1 9.77 CTTNBP2 SH2D3C
6 Decreased viability GR00386-A-1 9.77 ARMC9 CD300LF EIF4A1 EIF4G1 ITPA POLR2B
7 Decreased viability GR00402-S-2 9.77 ARMC9 EIF4A1 EIF4G1 ITPA POLR2B SCN5A

Drugs & Therapeutics for Noonan Syndrome 6

Search Clinical Trials , 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 29 NRAS

Anatomical Context for Noonan Syndrome 6

MalaCards organs/tissues related to Noonan Syndrome 6:

40
Heart, Skin, Myeloid

Publications for Noonan Syndrome 6

Articles related to Noonan Syndrome 6:

(show all 12)
# Title Authors PMID Year
1
Mutation in NRAS in familial Noonan syndrome--case report and review of the literature. 56 6
26467218 2015
2
A restricted spectrum of NRAS mutations causes Noonan syndrome. 6 56
19966803 2010
3
Germ-line mutation of the NRAS gene may be responsible for the development of juvenile myelomonocytic leukaemia. 56 6
19775298 2009
4
2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). 6
25173338 2014
5
Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis. 6
21079152 2011
6
Noonan syndrome: clinical features, diagnosis, and management guidelines. 6
20876176 2010
7
Leopard syndrome. 6
18505544 2008
8
Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations. 6
17332249 2007
9
NRAS mutation causes a human autoimmune lymphoproliferative syndrome. 6
17517660 2007
10
Noonan Syndrome 6
20301303 2001
11
N-ras gene point mutations in childhood acute lymphocytic leukemia correlate with a poor prognosis. 6
2407301 1990
12
Amino-acid substitutions at codon 13 of the N-ras oncogene in human acute myeloid leukaemia. 6
2989702 1985

Variations for Noonan Syndrome 6

ClinVar genetic disease variations for Noonan Syndrome 6:

6 (show top 50) (show all 78) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 NRAS NM_002524.5(NRAS):c.38G>A (p.Gly13Asp)SNV Pathogenic 13901 rs121434596 1:115258744-115258744 1:114716123-114716123
2 NRAS NM_002524.5(NRAS):c.149C>T (p.Thr50Ile)SNV Pathogenic 13902 rs267606921 1:115256562-115256562 1:114713941-114713941
3 NRAS NM_002524.5(NRAS):c.179G>A (p.Gly60Glu)SNV Pathogenic 13903 rs267606920 1:115256532-115256532 1:114713911-114713911
4 NRAS NM_002524.5(NRAS):c.360G>A (p.Leu120=)SNV Conflicting interpretations of pathogenicity 40476 rs143020946 1:115252280-115252280 1:114709659-114709659
5 NRAS NM_002524.5(NRAS):c.112-8A>GSNV Conflicting interpretations of pathogenicity 138538 rs9724626 1:115256607-115256607 1:114713986-114713986
6 NRAS NM_002524.5(NRAS):c.553C>T (p.Pro185Ser)SNV Conflicting interpretations of pathogenicity 179025 rs374061873 1:115251173-115251173 1:114708552-114708552
7 NRAS NM_002524.5(NRAS):c.317C>T (p.Ser106Leu)SNV Uncertain significance 211686 rs797045795 1:115252323-115252323 1:114709702-114709702
8 NRAS NM_002524.5(NRAS):c.*3404T>CSNV Uncertain significance 291940 rs185234485 1:115247311-115247311 1:114704690-114704690
9 NRAS NM_002524.5(NRAS):c.*2811C>ASNV Uncertain significance 874295 1:115247904-115247904 1:114705283-114705283
10 NRAS NM_002524.5(NRAS):c.*2589G>ASNV Uncertain significance 875228 1:115248126-115248126 1:114705505-114705505
11 NRAS NM_002524.5(NRAS):c.*2523A>GSNV Uncertain significance 875229 1:115248192-115248192 1:114705571-114705571
12 NRAS NM_002524.5(NRAS):c.*3103G>TSNV Uncertain significance 876282 1:115247612-115247612 1:114704991-114704991
13 NRAS NM_002524.5(NRAS):c.*3020A>GSNV Uncertain significance 876283 1:115247695-115247695 1:114705074-114705074
14 NRAS NM_002524.5(NRAS):c.*651C>TSNV Uncertain significance 875280 1:115250064-115250064 1:114707443-114707443
15 NRAS NM_002524.5(NRAS):c.*340G>ASNV Uncertain significance 876239 1:115250375-115250375 1:114707754-114707754
16 NRAS NM_002524.5(NRAS):c.112-6C>GSNV Uncertain significance 876240 1:115256605-115256605 1:114713984-114713984
17 NRAS NM_002524.5(NRAS):c.250A>G (p.Ile84Val)SNV Uncertain significance 424299 rs376177995 1:115256461-115256461 1:114713840-114713840
18 NRAS NM_002524.5(NRAS):c.*2767C>TSNV Uncertain significance 874296 1:115247948-115247948 1:114705327-114705327
19 NRAS NM_002524.5(NRAS):c.*2618A>GSNV Uncertain significance 875227 1:115248097-115248097 1:114705476-114705476
20 NRAS NM_002524.5(NRAS):c.*3430T>ASNV Uncertain significance 876142 1:115247285-115247285 1:114704664-114704664
21 NRAS NM_002524.5(NRAS):c.*3362T>CSNV Uncertain significance 876279 1:115247353-115247353 1:114704732-114704732
22 NRAS NM_002524.5(NRAS):c.*3341A>TSNV Uncertain significance 876280 1:115247374-115247374 1:114704753-114704753
23 NRAS NM_002524.5(NRAS):c.*2412G>ASNV Uncertain significance 876187 1:115248303-115248303 1:114705682-114705682
24 NRAS NM_002524.5(NRAS):c.*2328G>ASNV Uncertain significance 876188 1:115248387-115248387 1:114705766-114705766
25 NRAS NM_002524.5(NRAS):c.*2226G>CSNV Uncertain significance 876189 1:115248489-115248489 1:114705868-114705868
26 NRAS NM_002524.5(NRAS):c.*2188C>ASNV Uncertain significance 876190 1:115248527-115248527 1:114705906-114705906
27 NRAS NM_002524.5(NRAS):c.*1974T>CSNV Uncertain significance 876327 1:115248741-115248741 1:114706120-114706120
28 NRAS NM_002524.5(NRAS):c.*1936C>GSNV Uncertain significance 876328 1:115248779-115248779 1:114706158-114706158
29 NRAS NM_002524.5(NRAS):c.*1914A>GSNV Uncertain significance 876329 1:115248801-115248801 1:114706180-114706180
30 NRAS NM_002524.5(NRAS):c.*1887T>CSNV Uncertain significance 876330 1:115248828-115248828 1:114706207-114706207
31 NRAS NM_002524.5(NRAS):c.*1845T>CSNV Uncertain significance 876331 1:115248870-115248870 1:114706249-114706249
32 NRAS NM_002524.5(NRAS):c.*1629C>GSNV Uncertain significance 874356 1:115249086-115249086 1:114706465-114706465
33 NRAS NM_002524.5(NRAS):c.*1571A>GSNV Uncertain significance 874357 1:115249144-115249144 1:114706523-114706523
34 NRAS NM_002524.5(NRAS):c.*1509A>GSNV Uncertain significance 874358 1:115249206-115249206 1:114706585-114706585
35 NRAS NM_002524.5(NRAS):c.*1466A>TSNV Uncertain significance 874359 1:115249249-115249249 1:114706628-114706628
36 NRAS NM_002524.5(NRAS):c.*1105C>TSNV Uncertain significance 874360 1:115249610-115249610 1:114706989-114706989
37 NRAS NM_002524.5(NRAS):c.*2860G>ASNV Uncertain significance 291947 rs886045099 1:115247855-115247855 1:114705234-114705234
38 NRAS NM_002524.5(NRAS):c.*2630G>ASNV Uncertain significance 291955 rs886045102 1:115248085-115248085 1:114705464-114705464
39 NRAS NM_002524.5(NRAS):c.*2178G>ASNV Uncertain significance 291961 rs886045103 1:115248537-115248537 1:114705916-114705916
40 NRAS NM_002524.5(NRAS):c.*3392T>CSNV Uncertain significance 291941 rs886045097 1:115247323-115247323 1:114704702-114704702
41 NRAS NM_002524.5(NRAS):c.*3062C>TSNV Uncertain significance 291945 rs886045098 1:115247653-115247653 1:114705032-114705032
42 NRAS NM_002524.5(NRAS):c.*2546C>TSNV Uncertain significance 291956 rs778203603 1:115248169-115248169 1:114705548-114705548
43 NRAS NM_002524.5(NRAS):c.*536C>TSNV Uncertain significance 291971 rs886045108 1:115250179-115250179 1:114707558-114707558
44 NRAS NM_002524.5(NRAS):c.-106G>TSNV Uncertain significance 291977 rs755583487 1:115259367-115259367 1:114716746-114716746
45 NRAS NM_002524.5(NRAS):c.*2677A>TSNV Uncertain significance 291952 rs886045101 1:115248038-115248038 1:114705417-114705417
46 NRAS NM_002524.5(NRAS):c.*2513T>ASNV Uncertain significance 291958 rs150969241 1:115248202-115248202 1:114705581-114705581
47 NRAS NM_002524.5(NRAS):c.*1656C>TSNV Uncertain significance 291962 rs886045104 1:115249059-115249059 1:114706438-114706438
48 NRAS NM_002524.5(NRAS):c.*774A>GSNV Uncertain significance 291968 rs886045107 1:115249941-115249941 1:114707320-114707320
49 NRAS NM_002524.5(NRAS):c.*344A>GSNV Uncertain significance 291974 rs746680042 1:115250371-115250371 1:114707750-114707750
50 NRAS NM_002524.5(NRAS):c.*2805T>CSNV Uncertain significance 291949 rs776606789 1:115247910-115247910 1:114705289-114705289

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

73
# Symbol AA change Variation ID SNP ID
1 NRAS p.Thr50Ile VAR_063085 rs267606921
2 NRAS p.Gly60Glu VAR_063086 rs267606920

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
12.13 PPP1CA NRAS EIF4G1 EIF4A2 EIF4A1
2
Show member pathways
11.95 EIF4G1 EIF4A2 EIF4A1 DDX58
3
Show member pathways
11.52 EIF4G1 EIF4A2 EIF4A1
4 10.78 POLR2B ASZ1
5
Show member pathways
10.58 EIF4G1 EIF4A2 EIF4A1

GO Terms for Noonan Syndrome 6

Cellular components related to Noonan Syndrome 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 eukaryotic translation initiation factor 4F complex GO:0016281 8.8 EIF4G1 EIF4A2 EIF4A1

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

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 translational initiation GO:0006413 9.69 EIF4G1 EIF4A2 EIF4A1
2 positive regulation of peptidyl-serine phosphorylation GO:0033138 9.61 SH2D3C SH2D3A EIF4G1
3 regulation of translational initiation GO:0006446 9.55 EIF4G1 EIF4A2
4 positive regulation of interferon-beta production GO:0032728 9.54 IFIH1 DDX58
5 positive regulation of tumor necrosis factor secretion GO:1904469 9.52 IFIH1 DDX58
6 cellular response to exogenous dsRNA GO:0071360 9.49 IFIH1 DDX58
7 cytoplasmic translational initiation GO:0002183 9.48 EIF4A2 EIF4A1
8 positive regulation of interferon-alpha production GO:0032727 9.46 IFIH1 DDX58
9 positive regulation of interferon-alpha secretion GO:1902741 9.4 IFIH1 DDX58
10 positive regulation of response to cytokine stimulus GO:0060760 9.37 IFIH1 DDX58
11 detection of virus GO:0009597 9.32 IFIH1 DDX58
12 positive regulation of interferon-beta secretion GO:0035549 9.26 IFIH1 DDX58
13 viral process GO:0016032 9.17 PPP1CA IFIH1 G3BP1 EIF4G1 EIF4A2 EIF4A1
14 cytoplasmic pattern recognition receptor signaling pathway in response to virus GO:0039528 9.16 IFIH1 DDX58
15 regulation of type III interferon production GO:0034344 8.96 IFIH1 DDX58

Molecular functions related to Noonan Syndrome 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 10.27 SPECC1 SH2D3C SH2D3A SCN5A PPP1CA POLR2B
2 nucleotide binding GO:0000166 10 NRAS ITPA IFIH1 G3BP1 EIF4A2 EIF4A1
3 hydrolase activity GO:0016787 9.95 PPP1CA ITPA IFIH1 G3BP1 EIF4A2 EIF4A1
4 RNA binding GO:0003723 9.87 POLR2B IFIH1 G3BP1 EIF4G1 EIF4A2 EIF4A1
5 translation factor activity, RNA binding GO:0008135 9.43 EIF4G1 EIF4A1
6 double-stranded RNA binding GO:0003725 9.43 IFIH1 EIF4A1 DDX58
7 helicase activity GO:0004386 9.35 IFIH1 G3BP1 EIF4A2 EIF4A1 DDX58
8 translation initiation factor activity GO:0003743 9.33 EIF4G1 EIF4A2 EIF4A1
9 RNA helicase activity GO:0003724 9.02 IFIH1 G3BP1 EIF4A2 EIF4A1 DDX58

Sources for Noonan Syndrome 6

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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