NS5
MCID: NNN012
MIFTS: 37

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 heart and skin, 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 hypertrophic cardiomyopathy 31 very rare (1%) HP:0001639
6 cryptorchidism 31 very rare (1%) HP:0000028
7 webbed neck 31 very rare (1%) HP:0000465
8 atrial septal defect 31 very rare (1%) HP:0001631
9 nevus 31 very rare (1%) HP:0003764
10 polyhydramnios 31 very rare (1%) HP:0001561
11 pulmonic stenosis 31 very rare (1%) HP:0001642
12 curly hair 31 very rare (1%) HP:0002212
13 global developmental delay 31 HP:0001263
14 hypertelorism 31 HP:0000316
15 short neck 31 HP:0000470
16 macrocephaly 31 HP:0000256
17 mandibular prognathia 31 HP:0000303
18 abnormal facial shape 31 HP:0001999
19 prominent forehead 31 HP:0011220
20 arrhythmia 31 HP:0011675
21 cubitus valgus 31 HP:0002967
22 low-set ears 31 HP:0000369
23 epicanthus 31 HP:0000286
24 ptosis 31 HP:0000508
25 wide mouth 31 HP:0000154
26 downslanted palpebral fissures 31 HP:0000494
27 abnormality of the sternum 31 HP:0000766

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
hypertelorism
downslanting palpebral fissures
epicanthal folds
palpebral ptosis

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

Head And Neck Face:
prominent forehead
prominent chin

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

Neurologic Central Nervous System:
mental retardation (in some patients)
developmental delay ( 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 Neck:
short neck
webbed neck

Growth Height:
short stature

Skeletal Limbs:
cubitus valgus

Genitourinary Internal Genitalia Male:
cryptorchidism (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

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
Heart, Skin

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. 6 56
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 top 50) (show all 77) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 RAF1 NM_001354689.3(RAF1):c.770C>T (p.Ser257Leu)SNV Pathogenic 13957 rs80338796 3:12645699-12645699 3:12604200-12604200
2 RAF1 NM_001354689.3(RAF1):c.781C>T (p.Pro261Ser)SNV Pathogenic 13958 rs121434594 3:12645688-12645688 3:12604189-12604189
3 RAF1 NM_001354689.3(RAF1):c.1897C>G (p.Leu633Val)SNV Pathogenic 13960 rs80338797 3:12626123-12626123 3:12584624-12584624
4 RAF1 NM_001354689.3(RAF1):c.782C>T (p.Pro261Leu)SNV Pathogenic 120246 rs397516828 3:12645687-12645687 3:12604188-12604188
5 RAF1 NM_001354689.3(RAF1):c.505G>C (p.Gly169Arg)SNV Pathogenic/Likely pathogenic 265535 rs886039607 3:12650341-12650341 3:12608842-12608842
6 RAF1 NM_001354689.3(RAF1):c.776C>G (p.Ser259Cys)SNV Pathogenic/Likely pathogenic 40602 rs397516827 3:12645693-12645693 3:12604194-12604194
7 RAF1 NM_001354689.3(RAF1):c.781C>G (p.Pro261Ala)SNV Pathogenic/Likely pathogenic 40605 rs121434594 3:12645688-12645688 3:12604189-12604189
8 RAF1 NM_001354689.3(RAF1):c.782C>G (p.Pro261Arg)SNV Pathogenic/Likely pathogenic 40606 rs397516828 3:12645687-12645687 3:12604188-12604188
9 RAF1 NM_001354689.3(RAF1):c.788T>A (p.Val263Asp)SNV Pathogenic/Likely pathogenic 496189 rs397516830 3:12645681-12645681 3:12604182-12604182
10 RAF1 NM_001354689.3(RAF1):c.1532C>G (p.Thr511Arg)SNV Likely pathogenic 13959 rs80338799 3:12627244-12627244 3:12585745-12585745
11 RAF1 NM_001354689.3(RAF1):c.993C>T (p.Pro331=)SNV Conflicting interpretations of pathogenicity 477681 rs1553613022 3:12641708-12641708 3:12600209-12600209
12 RAF1 NM_001354689.3(RAF1):c.994G>A (p.Val332Met)SNV Conflicting interpretations of pathogenicity 477682 rs555034652 3:12641707-12641707 3:12600208-12600208
13 RAF1 NM_001354689.3(RAF1):c.600T>C (p.Thr200=)SNV Conflicting interpretations of pathogenicity 508664 rs779808613 3:12647780-12647780 3:12606281-12606281
14 RAF1 NM_001354689.3(RAF1):c.231C>T (p.Ser77=)SNV Conflicting interpretations of pathogenicity 509193 rs1450510914 3:12653538-12653538 3:12612039-12612039
15 RAF1 NM_001354689.3(RAF1):c.*190G>ASNV Conflicting interpretations of pathogenicity 343099 rs528863135 3:12625823-12625823 3:12584324-12584324
16 RAF1 NM_001354689.3(RAF1):c.21T>C (p.Ala7=)SNV Conflicting interpretations of pathogenicity 343104 rs886057915 3:12660200-12660200 3:12618701-12618701
17 RAF1 NM_001354689.3(RAF1):c.462C>G (p.Ile154Met)SNV Conflicting interpretations of pathogenicity 220830 rs367732360 3:12650384-12650384 3:12608885-12608885
18 RAF1 NM_001354689.3(RAF1):c.1781A>G (p.Tyr594Cys)SNV Conflicting interpretations of pathogenicity 177842 rs370242565 3:12626428-12626428 3:12584929-12584929
19 RAF1 NM_001354689.3(RAF1):c.-201C>ASNV Conflicting interpretations of pathogenicity 40577 rs532668125 3:12705486-12705486 3:12663987-12663987
20 RAF1 NM_001354689.3(RAF1):c.122G>A (p.Arg41Gln)SNV Conflicting interpretations of pathogenicity 40586 rs145611571 3:12660099-12660099 3:12618600-12618600
21 RAF1 NM_001354689.3(RAF1):c.-27+7G>ASNV Uncertain significance 40578 rs886057916 3:12705305-12705305 3:12663806-12663806
22 RAF1 NM_001354689.3(RAF1):c.-209G>ASNV Uncertain significance 177838 rs727504351 3:12705494-12705494 3:12663995-12663995
23 RAF1 NM_001354689.3(RAF1):c.1874C>T (p.Ser625Phe)SNV Uncertain significance 181512 rs730881004 3:12626146-12626146 3:12584647-12584647
24 RAF1 NM_001354689.3(RAF1):c.1527G>C (p.Leu509Phe)SNV Uncertain significance 40619 rs1553610155 3:12627249-12627249 3:12585750-12585750
25 RAF1 NM_001354689.3(RAF1):c.-139T>GSNV Uncertain significance 343106 rs886057918 3:12705424-12705424 3:12663925-12663925
26 RAF1 NM_001354689.3(RAF1):c.-181T>CSNV Uncertain significance 343108 rs886057920 3:12705466-12705466 3:12663967-12663967
27 RAF1 NM_001354689.3(RAF1):c.*640T>CSNV Uncertain significance 343093 rs759464247 3:12625373-12625373 3:12583874-12583874
28 RAF1 NM_001354689.3(RAF1):c.*627C>TSNV Uncertain significance 343094 rs879160471 3:12625386-12625386 3:12583887-12583887
29 RAF1 NM_001354689.3(RAF1):c.-110G>ASNV Uncertain significance 343105 rs886057917 3:12705395-12705395 3:12663896-12663896
30 RAF1 NM_001354689.3(RAF1):c.-146C>GSNV Uncertain significance 343107 rs886057919 3:12705431-12705431 3:12663932-12663932
31 RAF1 NM_001354689.3(RAF1):c.*162T>CSNV Uncertain significance 343100 rs886057913 3:12625851-12625851 3:12584352-12584352
32 RAF1 NM_001354689.3(RAF1):c.*113T>GSNV Uncertain significance 343102 rs886057914 3:12625900-12625900 3:12584401-12584401
33 RAF1 NM_001354689.3(RAF1):c.659_660del (p.Ser220fs)deletion Uncertain significance 828171 3:12647720-12647721 3:12606221-12606222
34 RAF1 NM_001354689.3(RAF1):c.*841C>TSNV Uncertain significance 902116 3:12625172-12625172 3:12583673-12583673
35 RAF1 NM_001354689.3(RAF1):c.*840A>TSNV Uncertain significance 903003 3:12625173-12625173 3:12583674-12583674
36 RAF1 NM_001354689.3(RAF1):c.*706C>TSNV Uncertain significance 903004 3:12625307-12625307 3:12583808-12583808
37 RAF1 NM_001354689.3(RAF1):c.*647G>TSNV Uncertain significance 903005 3:12625366-12625366 3:12583867-12583867
38 RAF1 NM_001354689.3(RAF1):c.*643C>GSNV Uncertain significance 899385 3:12625370-12625370 3:12583871-12583871
39 RAF1 NM_001354689.3(RAF1):c.*630A>GSNV Uncertain significance 899386 3:12625383-12625383 3:12583884-12583884
40 RAF1 NM_001354689.3(RAF1):c.*628G>TSNV Uncertain significance 899387 3:12625385-12625385 3:12583886-12583886
41 RAF1 NM_001354689.3(RAF1):c.*410A>GSNV Uncertain significance 900510 3:12625603-12625603 3:12584104-12584104
42 RAF1 NM_001354689.3(RAF1):c.*73T>ASNV Uncertain significance 899432 3:12625940-12625940 3:12584441-12584441
43 RAF1 NM_001354689.3(RAF1):c.1352A>C (p.Lys451Thr)SNV Uncertain significance 902234 3:12632375-12632375 3:12590876-12590876
44 RAF1 NM_001354689.3(RAF1):c.903T>A (p.Ile301=)SNV Uncertain significance 903109 3:12641906-12641906 3:12600407-12600407
45 RAF1 NM_001354689.3(RAF1):c.654A>G (p.Arg218=)SNV Uncertain significance 899635 3:12647726-12647726 3:12606227-12606227
46 RAF1 NM_001354689.3(RAF1):c.-53G>ASNV Uncertain significance 903300 3:12705338-12705338 3:12663839-12663839
47 RAF1 NM_001354689.3(RAF1):c.-59C>GSNV Uncertain significance 903301 3:12705344-12705344 3:12663845-12663845
48 RAF1 NM_001354689.3(RAF1):c.-107C>TSNV Uncertain significance 903302 3:12705392-12705392 3:12663893-12663893
49 RAF1 NM_001354689.3(RAF1):c.-264C>GSNV Uncertain significance 900848 3:12705549-12705549 3:12664050-12664050
50 RAF1 NC_000003.12:g.12664140G>CSNV Uncertain significance 902521 3:12705639-12705639 3:12664140-12664140

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 positive regulation of cytokinesis GO:0032467 8.62 KIF23 CIT

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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