MCID: NNN011
MIFTS: 32

Noonan Syndrome 4

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Cardiovascular diseases, Nephrological diseases, Reproductive diseases, Skin diseases, Endocrine diseases, Fetal diseases

Aliases & Classifications for Noonan Syndrome 4

Summaries for Noonan Syndrome 4

UniProtKB/Swiss-Prot : 75 Noonan syndrome 4: 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. Some patients with NS4 have polyarticular villonodular synovitis.

MalaCards based summary : Noonan Syndrome 4, also known as ns4, is related to hepatitis and hepatitis c. An important gene associated with Noonan Syndrome 4 is SOS1 (SOS Ras/Rac Guanine Nucleotide Exchange Factor 1). The drugs Interferon-alpha and Vaccines have been mentioned in the context of this disorder. Affiliated tissues include heart, skin and bone, and related phenotypes are macrocephaly and hypertelorism

Disease Ontology : 12 A Noonan syndrome that has material basis in heterozygous mutation in the SOS1 gene on chromosome 2p22.

Description from OMIM: 610733

Related Diseases for Noonan Syndrome 4

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 4 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hepatitis 10.2
2 hepatitis c 10.2
3 hepatitis c virus 10.2
4 liver cirrhosis 9.9
5 vaccinia 9.9
6 hepatocellular carcinoma 9.9

Graphical network of the top 20 diseases related to Noonan Syndrome 4:



Diseases related to Noonan Syndrome 4

Symptoms & Phenotypes for Noonan Syndrome 4

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Head:
macrocephaly

Head And Neck Neck:
short neck
webbed neck

Head And Neck Teeth:
dental malocclusion

Cardiovascular Heart:
hypertrophic cardiomyopathy
pulmonic stenosis
congenital heart defect
ventricular septal defects

Skeletal Limbs:
cubitus valgus
blunt fingertips
polyarticular villonodular synovitis in knees, ankles, wrists, and/or elbows (in some patients)

Head And Neck Mouth:
thick lips

Head And Neck Nose:
flat nasal bridge

Head And Neck Ears:
low-set posteriorly rotated ears

Neoplasia:
multiple giant cell granulomas (bones, joints, soft tissues)

Hematology:
prolonged bleeding time (less common)

Head And Neck Eyes:
hypertelorism
ptosis
downslanting palpebral fissures
epicanthal folds
blue eyes
more
Skeletal Spine:
scoliosis

Growth Height:
short stature

GenitourinaryInternal GenitaliaMale:
cryptorchidism

Skin Nails Hair Hair:
curly hair
high anterior hairline
sparse eyebrows

Chest Breasts:
widely spaced nipples

Skin Nails Hair Skin:
keratosis pilaris
ectodermal symptoms

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum inferiorly

Neurologic Central Nervous System:
mild cognitive impairment (less common)

Laboratory Abnormalities:
partial deficiency of factor xi (less common)
partial deficiency of factor xiii (less common)


Clinical features from OMIM:

610733

Human phenotypes related to Noonan Syndrome 4:

32 (show all 25)
# Description HPO Frequency HPO Source Accession
1 macrocephaly 32 HP:0000256
2 hypertelorism 32 HP:0000316
3 short neck 32 HP:0000470
4 ptosis 32 HP:0000508
5 scoliosis 32 HP:0002650
6 dental malocclusion 32 HP:0000689
7 depressed nasal bridge 32 HP:0005280
8 short stature 32 HP:0004322
9 hypertrophic cardiomyopathy 32 HP:0001639
10 thick lower lip vermilion 32 HP:0000179
11 epicanthus 32 HP:0000286
12 cryptorchidism 32 HP:0000028
13 cubitus valgus 32 HP:0002967
14 wide intermamillary distance 32 HP:0006610
15 webbed neck 32 HP:0000465
16 blue irides 32 HP:0000635
17 low-set, posteriorly rotated ears 32 HP:0000368
18 downslanted palpebral fissures 32 HP:0000494
19 ventricular septal defect 32 HP:0001629
20 prolonged bleeding time 32 occasional (7.5%) HP:0003010
21 pulmonic stenosis 32 HP:0001642
22 curly hair 32 HP:0002212
23 high anterior hairline 32 HP:0009890
24 sparse and thin eyebrow 32 HP:0000535
25 pectus excavatum of inferior sternum 32 HP:0000915

Drugs & Therapeutics for Noonan Syndrome 4

Drugs for Noonan Syndrome 4 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 8)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Interferon-alpha Phase 1, Phase 2
2 Vaccines Phase 1, Phase 2
3
Histamine Approved, Investigational 75614-87-8, 51-45-6 774
4 Histamine Antagonists
5 Histamine H1 Antagonists
6 Histamine H2 Antagonists
7
Histamine Phosphate 51-74-1 65513
8 Neurotransmitter Agents

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Autologous Dendritic Cell Vaccine for Treatment of Patients With Chronic HCV-Infection Recruiting NCT03119025 Phase 1, Phase 2
2 TG4040 in Patients With Chronic HCV Withdrawn NCT00449124 Phase 1 Placebo
3 Physical Condition in Lipedema and Obesity Completed NCT01759004 Not Applicable
4 Efficacy of Antihistamine Dosing-up and add-on Treatment With H2-receptor Antagonist Recruiting NCT03293225

Search NIH Clinical Center for Noonan Syndrome 4

Genetic Tests for Noonan Syndrome 4

Genetic tests related to Noonan Syndrome 4:

# Genetic test Affiliating Genes
1 Noonan Syndrome 4 29 SOS1

Anatomical Context for Noonan Syndrome 4

MalaCards organs/tissues related to Noonan Syndrome 4:

41
Heart, Skin, Bone, Eye

Publications for Noonan Syndrome 4

Variations for Noonan Syndrome 4

UniProtKB/Swiss-Prot genetic disease variations for Noonan Syndrome 4:

75 (show all 37)
# Symbol AA change Variation ID SNP ID
1 SOS1 p.Glu108Lys VAR_030423 rs397517164
2 SOS1 p.Thr266Lys VAR_030424 rs137852812
3 SOS1 p.Met269Arg VAR_030425 rs137852813
4 SOS1 p.Asp309Tyr VAR_030426 rs397517180
5 SOS1 p.Tyr337Cys VAR_030427 rs724160007
6 SOS1 p.Trp432Arg VAR_030428 rs267607080
7 SOS1 p.Glu433Lys VAR_030429 rs397517147
8 SOS1 p.Gly434Arg VAR_030430 rs397517148
9 SOS1 p.Cys441Tyr VAR_030431 rs727504295
10 SOS1 p.Ser548Arg VAR_030432 rs397517149
11 SOS1 p.Leu550Pro VAR_030433 rs397517153
12 SOS1 p.Arg552Gly VAR_030434 rs137852814
13 SOS1 p.Arg552Lys VAR_030435 rs397517154
14 SOS1 p.Arg552Ser VAR_030436 rs267607079
15 SOS1 p.Tyr702His VAR_030438 rs727505381
16 SOS1 p.Trp729Leu VAR_030439
17 SOS1 p.Ile733Phe VAR_030440 rs574088829
18 SOS1 p.Glu846Lys VAR_030441 rs397517159
19 SOS1 p.Met269Thr VAR_064504 rs137852813
20 SOS1 p.Gln477Arg VAR_064505 rs730881044
21 SOS1 p.Arg497Gln VAR_064506 rs371314838
22 SOS1 p.Pro102Arg VAR_066032
23 SOS1 p.Pro112Arg VAR_066033 rs397517166
24 SOS1 p.Lys170Glu VAR_066034 rs397517172
25 SOS1 p.Ile252Thr VAR_066035 rs142094234
26 SOS1 p.Met422Val VAR_066037
27 SOS1 p.Glu424Lys VAR_066038 rs730881041
28 SOS1 p.Gly434Lys VAR_066041 rs730881048
29 SOS1 p.Ile437Thr VAR_066042 rs397517150
30 SOS1 p.Pro478Arg VAR_066044
31 SOS1 p.Gly482Arg VAR_066045
32 SOS1 p.Leu490Arg VAR_066046
33 SOS1 p.Thr549Lys VAR_066047 rs730881046
34 SOS1 p.Arg552Met VAR_066048
35 SOS1 p.Arg552Thr VAR_066049 rs397517154
36 SOS1 p.Phe623Ile VAR_066052
37 SOS1 p.Pro894Arg VAR_066055

ClinVar genetic disease variations for Noonan Syndrome 4:

6
(show all 24)
# Gene Variation Type Significance SNP ID Assembly Location
1 SOS1 NM_005633.3(SOS1): c.797C> A (p.Thr266Lys) single nucleotide variant Pathogenic rs137852812 GRCh37 Chromosome 2, 39278352: 39278352
2 SOS1 NM_005633.3(SOS1): c.797C> A (p.Thr266Lys) single nucleotide variant Pathogenic rs137852812 GRCh38 Chromosome 2, 39051211: 39051211
3 SOS1 NM_005633.3(SOS1): c.806T> G (p.Met269Arg) single nucleotide variant Pathogenic rs137852813 GRCh37 Chromosome 2, 39278343: 39278343
4 SOS1 NM_005633.3(SOS1): c.806T> G (p.Met269Arg) single nucleotide variant Pathogenic rs137852813 GRCh38 Chromosome 2, 39051202: 39051202
5 SOS1 NM_005633.3(SOS1): c.1654A> G (p.Arg552Gly) single nucleotide variant Pathogenic rs137852814 GRCh37 Chromosome 2, 39249915: 39249915
6 SOS1 NM_005633.3(SOS1): c.1654A> G (p.Arg552Gly) single nucleotide variant Pathogenic rs137852814 GRCh38 Chromosome 2, 39022774: 39022774
7 SOS1 NM_005633.3(SOS1): c.1656G> C (p.Arg552Ser) single nucleotide variant Pathogenic rs267607079 GRCh37 Chromosome 2, 39249913: 39249913
8 SOS1 NM_005633.3(SOS1): c.1656G> C (p.Arg552Ser) single nucleotide variant Pathogenic rs267607079 GRCh38 Chromosome 2, 39022772: 39022772
9 SOS1 NM_005633.3(SOS1): c.1294T> C (p.Trp432Arg) single nucleotide variant Pathogenic rs267607080 GRCh37 Chromosome 2, 39250275: 39250275
10 SOS1 NM_005633.3(SOS1): c.1294T> C (p.Trp432Arg) single nucleotide variant Pathogenic rs267607080 GRCh38 Chromosome 2, 39023134: 39023134
11 SOS1 NM_005633.3(SOS1): c.806T> C (p.Met269Thr) single nucleotide variant Pathogenic rs137852813 GRCh37 Chromosome 2, 39278343: 39278343
12 SOS1 NM_005633.3(SOS1): c.806T> C (p.Met269Thr) single nucleotide variant Pathogenic rs137852813 GRCh38 Chromosome 2, 39051202: 39051202
13 SOS1 NM_005633.3(SOS1): c.1655G> A (p.Arg552Lys) single nucleotide variant Pathogenic rs397517154 GRCh37 Chromosome 2, 39249914: 39249914
14 SOS1 NM_005633.3(SOS1): c.1655G> A (p.Arg552Lys) single nucleotide variant Pathogenic rs397517154 GRCh38 Chromosome 2, 39022773: 39022773
15 SOS1 NM_005633.3(SOS1): c.1656G> T (p.Arg552Ser) single nucleotide variant Pathogenic rs267607079 GRCh37 Chromosome 2, 39249913: 39249913
16 SOS1 NM_005633.3(SOS1): c.1656G> T (p.Arg552Ser) single nucleotide variant Pathogenic rs267607079 GRCh38 Chromosome 2, 39022772: 39022772
17 SOS1 NM_005633.3(SOS1): c.2183A> T (p.Lys728Ile) single nucleotide variant Pathogenic/Likely pathogenic rs397517156 GRCh37 Chromosome 2, 39239474: 39239474
18 SOS1 NM_005633.3(SOS1): c.2183A> T (p.Lys728Ile) single nucleotide variant Pathogenic/Likely pathogenic rs397517156 GRCh38 Chromosome 2, 39012333: 39012333
19 SOS1 NM_005633.3(SOS1): c.1310T> C (p.Ile437Thr) single nucleotide variant Pathogenic rs397517150 GRCh37 Chromosome 2, 39250259: 39250259
20 SOS1 NM_005633.3(SOS1): c.1310T> C (p.Ile437Thr) single nucleotide variant Pathogenic rs397517150 GRCh38 Chromosome 2, 39023118: 39023118
21 SOS1 NM_005633.3(SOS1): c.1574T> C (p.Ile525Thr) single nucleotide variant Uncertain significance rs146722878 GRCh37 Chromosome 2, 39249995: 39249995
22 SOS1 NM_005633.3(SOS1): c.1574T> C (p.Ile525Thr) single nucleotide variant Uncertain significance rs146722878 GRCh38 Chromosome 2, 39022854: 39022854
23 SOS1 NM_005633.3(SOS1): c.979A> G (p.Ile327Val) single nucleotide variant Uncertain significance rs758546951 GRCh37 Chromosome 2, 39262448: 39262448
24 SOS1 NM_005633.3(SOS1): c.979A> G (p.Ile327Val) single nucleotide variant Uncertain significance rs758546951 GRCh38 Chromosome 2, 39035307: 39035307

Expression for Noonan Syndrome 4

Search GEO for disease gene expression data for Noonan Syndrome 4.

Pathways for Noonan Syndrome 4

GO Terms for Noonan Syndrome 4

Sources for Noonan Syndrome 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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