NS5
MCID: NNN012
MIFTS: 39

Noonan Syndrome 5 (NS5)

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 5

Summaries for Noonan Syndrome 5

UniProtKB/Swiss-Prot : 73 Noonan syndrome 5: 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 5, also known as ns5, is related to dengue virus and encephalitis. An important gene associated with Noonan Syndrome 5 is RAF1 (Raf-1 Proto-Oncogene, Serine/Threonine Kinase). Affiliated tissues include skin, heart and eye, and related phenotypes are intellectual disability and depressed nasal bridge

Disease Ontology : 12 A Noonan syndrome that has material basis in mutation in the RAF1 gene.

More information from OMIM: 611553 PS163950

Related Diseases for Noonan Syndrome 5

Graphical network of the top 20 diseases related to Noonan Syndrome 5:



Diseases related to Noonan Syndrome 5

Symptoms & Phenotypes for Noonan Syndrome 5

Human phenotypes related to Noonan Syndrome 5:

31 (show all 27)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 very rare (1%) HP:0001249
2 depressed nasal bridge 31 very rare (1%) HP:0005280
3 thick vermilion border 31 very rare (1%) HP:0012471
4 short stature 31 very rare (1%) HP:0004322
5 cryptorchidism 31 very rare (1%) HP:0000028
6 polyhydramnios 31 very rare (1%) HP:0001561
7 hypertrophic cardiomyopathy 31 very rare (1%) HP:0001639
8 webbed neck 31 very rare (1%) HP:0000465
9 atrial septal defect 31 very rare (1%) HP:0001631
10 nevus 31 very rare (1%) HP:0003764
11 pulmonic stenosis 31 very rare (1%) HP:0001642
12 curly hair 31 very rare (1%) HP:0002212
13 macrocephaly 31 HP:0000256
14 hypertelorism 31 HP:0000316
15 low-set ears 31 HP:0000369
16 short neck 31 HP:0000470
17 ptosis 31 HP:0000508
18 global developmental delay 31 HP:0001263
19 mandibular prognathia 31 HP:0000303
20 abnormal facial shape 31 HP:0001999
21 downslanted palpebral fissures 31 HP:0000494
22 prominent forehead 31 HP:0011220
23 arrhythmia 31 HP:0011675
24 epicanthus 31 HP:0000286
25 cubitus valgus 31 HP:0002967
26 wide mouth 31 HP:0000154
27 abnormality of the sternum 31 HP:0000766

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Head:
macrocephaly
dolicocephaly (in some patients)

Head And Neck Ears:
low-set ears
thickened helix
large thick ear lobe (in some patients)

Growth Height:
short stature

Skeletal Limbs:
cubitus valgus

Genitourinary Internal Genitalia Male:
cryptorchidism (in some patients)

Prenatal Manifestations Amniotic Fluid:
polyhydramnios (in some patients)

Cardiovascular Heart:
hypertrophic cardiomyopathy (in some patients)
pulmonary valve stenosis (in some patients)
arrhythmia, variable

Skin Nails Hair Skin:
nevi (in some patients)

Head And Neck Eyes:
hypertelorism
downslanting palpebral fissures
epicanthal folds
palpebral ptosis

Head And Neck Neck:
short neck
webbed neck

Head And Neck Face:
prominent forehead
prominent chin

Neurologic Central Nervous System:
mental retardation (in some patients)
developmental delay ( in some patients)

Head And Neck Nose:
flat nasal bridge (in some patients)

Head And Neck Mouth:
thick lips (in some patients)
macrostomia (uncommon)

Chest Ribs Sternum Clavicles And Scapulae:
pectus anomaly

Skin Nails Hair Hair:
curly hair (in some patients)

Clinical features from OMIM:

611553

GenomeRNAi Phenotypes related to Noonan Syndrome 5 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00221-A-1 9.44 CIT RAF1
2 Decreased viability GR00221-A-2 9.44 CIT RAF1
3 Decreased viability GR00221-A-3 9.44 CIT DGKA
4 Decreased viability GR00231-A 9.44 RAF1
5 Decreased viability GR00301-A 9.44 CIT DGKA RAF1
6 Decreased viability GR00402-S-2 9.44 CIT DGKA RAF1
7 Decreased substrate adherent cell growth GR00193-A-1 9.35 BRSK1 CIT RAF1
8 Decreased substrate adherent cell growth GR00193-A-2 9.35 CIT RAF1

Drugs & Therapeutics for Noonan Syndrome 5

Search Clinical Trials , NIH Clinical Center for Noonan Syndrome 5

Genetic Tests for Noonan Syndrome 5

Genetic tests related to Noonan Syndrome 5:

# Genetic test Affiliating Genes
1 Noonan Syndrome 5 29 RAF1

Anatomical Context for Noonan Syndrome 5

MalaCards organs/tissues related to Noonan Syndrome 5:

40
Skin, Heart, Eye, Liver

Publications for Noonan Syndrome 5

Articles related to Noonan Syndrome 5:

# Title Authors PMID Year
1
Germline gain-of-function mutations in RAF1 cause Noonan syndrome. 56 6
17603482 2007
2
Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. 56 6
17603483 2007
3
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
4
Noonan syndrome: clinical features, diagnosis, and management guidelines. 6
20876176 2010
5
Leopard syndrome. 6
18505544 2008
6
Noonan Syndrome 6
20301303 2001
7
Congenital chylothorax: a prospective nationwide epidemiological study in Germany. 61
25480460 2015

Variations for Noonan Syndrome 5

ClinVar genetic disease variations for Noonan Syndrome 5:

6 (show all 13) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 RAF1 NM_002880.3(RAF1):c.1837C>G (p.Leu613Val)SNV Pathogenic 13960 rs80338797 3:12626123-12626123 3:12584624-12584624
2 RAF1 NM_002880.3(RAF1):c.770C>T (p.Ser257Leu)SNV Pathogenic 13957 rs80338796 3:12645699-12645699 3:12604200-12604200
3 RAF1 NM_002880.3(RAF1):c.781C>T (p.Pro261Ser)SNV Pathogenic 13958 rs121434594 3:12645688-12645688 3:12604189-12604189
4 RAF1 NM_002880.3(RAF1):c.782C>T (p.Pro261Leu)SNV Pathogenic 120246 rs397516828 3:12645687-12645687 3:12604188-12604188
5 RAF1 NM_002880.3(RAF1):c.505G>C (p.Gly169Arg)SNV Pathogenic/Likely pathogenic 265535 rs886039607 3:12650341-12650341 3:12608842-12608842
6 RAF1 NM_002880.3(RAF1):c.776C>G (p.Ser259Cys)SNV Pathogenic/Likely pathogenic 40602 rs397516827 3:12645693-12645693 3:12604194-12604194
7 RAF1 NM_002880.3(RAF1):c.781C>G (p.Pro261Ala)SNV Pathogenic/Likely pathogenic 40605 rs121434594 3:12645688-12645688 3:12604189-12604189
8 RAF1 NM_002880.3(RAF1):c.782C>G (p.Pro261Arg)SNV Pathogenic/Likely pathogenic 40606 rs397516828 3:12645687-12645687 3:12604188-12604188
9 RAF1 NM_002880.3(RAF1):c.788T>A (p.Val263Asp)SNV Pathogenic/Likely pathogenic 496189 rs397516830 3:12645681-12645681 3:12604182-12604182
10 RAF1 NM_002880.3(RAF1):c.1472C>G (p.Thr491Arg)SNV Likely pathogenic 13959 rs80338799 3:12627244-12627244 3:12585745-12585745
11 RAF1 NM_002880.3(RAF1):c.601A>G (p.Ile201Val)SNV Uncertain significance 432929 rs757700986 3:12647779-12647779 3:12606280-12606280
12 RAF1 NM_002880.3(RAF1):c.1467G>C (p.Leu489Phe)SNV Uncertain significance 40619 rs1553610155 3:12627249-12627249 3:12585750-12585750
13 RAF1 NM_002880.3(RAF1):c.1814C>T (p.Ser605Phe)SNV Uncertain significance 181512 rs730881004 3:12626146-12626146 3:12584647-12584647

UniProtKB/Swiss-Prot genetic disease variations for Noonan Syndrome 5:

73 (show all 14)
# Symbol AA change Variation ID SNP ID
1 RAF1 p.Arg256Ser VAR_037807 rs397516826
2 RAF1 p.Ser257Leu VAR_037808 rs80338796
3 RAF1 p.Ser259Phe VAR_037809 rs397516827
4 RAF1 p.Thr260Arg VAR_037811
5 RAF1 p.Pro261Ala VAR_037812 rs121434594
6 RAF1 p.Pro261Leu VAR_037813 rs397516828
7 RAF1 p.Pro261Ser VAR_037814 rs121434594
8 RAF1 p.Val263Ala VAR_037815 rs397516830
9 RAF1 p.Asp486Gly VAR_037816 rs397516815
10 RAF1 p.Asp486Asn VAR_037817 rs80338798
11 RAF1 p.Thr491Ile VAR_037818 rs80338799
12 RAF1 p.Thr491Arg VAR_037819 rs80338799
13 RAF1 p.Ser612Thr VAR_037820 rs144839246
14 RAF1 p.Leu613Val VAR_037821 rs80338797

Expression for Noonan Syndrome 5

Search GEO for disease gene expression data for Noonan Syndrome 5.

Pathways for Noonan Syndrome 5

GO Terms for Noonan Syndrome 5

Biological processes related to Noonan Syndrome 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitotic cytokinesis GO:0000281 9.26 KIF23 CIT
2 positive regulation of cytokinesis GO:0032467 9.16 KIF23 CIT
3 regulation of neuron projection development GO:0010975 8.96 CHODL BRSK1
4 intracellular signal transduction GO:0035556 8.92 RAF1 DGKA CIT BRSK1

Sources for Noonan Syndrome 5

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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