NS7
MCID: NNN020
MIFTS: 39

Noonan Syndrome 7 (NS7)

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 7

Summaries for Noonan Syndrome 7

UniProtKB/Swiss-Prot : 72 Noonan syndrome 7: 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 7, also known as ns7, is related to microphthalmia, syndromic 10 and nonparalytic poliomyelitis. An important gene associated with Noonan Syndrome 7 is BRAF (B-Raf Proto-Oncogene, Serine/Threonine Kinase), and among its related pathways/superpathways are Translation Factors and PIWI-interacting RNA (piRNA) biogenesis. Affiliated tissues include eye and heart, and related phenotypes are macrocephaly and intellectual disability

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

OMIM® : 57 Noonan syndrome is a developmental disorder characterized by reduced postnatal growth, dysmorphic facial features, cardiac defects, and variable cognitive defects (summary by Sarkozy et al., 2009). (613706) (Updated 20-May-2021)

Related Diseases for Noonan Syndrome 7

Graphical network of the top 20 diseases related to Noonan Syndrome 7:



Diseases related to Noonan Syndrome 7

Symptoms & Phenotypes for Noonan Syndrome 7

Human phenotypes related to Noonan Syndrome 7:

31 (show all 43)
# Description HPO Frequency HPO Source Accession
1 macrocephaly 31 very rare (1%) HP:0000256
2 intellectual disability 31 very rare (1%) HP:0001249
3 scoliosis 31 very rare (1%) HP:0002650
4 hyperhidrosis 31 very rare (1%) HP:0000975
5 short neck 31 very rare (1%) HP:0000470
6 depressed nasal bridge 31 very rare (1%) HP:0005280
7 hypertelorism 31 very rare (1%) HP:0000316
8 thick vermilion border 31 very rare (1%) HP:0012471
9 short stature 31 very rare (1%) HP:0004322
10 prominent forehead 31 very rare (1%) HP:0011220
11 strabismus 31 very rare (1%) HP:0000486
12 cubitus valgus 31 very rare (1%) HP:0002967
13 low-set ears 31 very rare (1%) HP:0000369
14 webbed neck 31 very rare (1%) HP:0000465
15 shield chest 31 very rare (1%) HP:0000914
16 low posterior hairline 31 very rare (1%) HP:0002162
17 pectus excavatum 31 very rare (1%) HP:0000767
18 atrial septal defect 31 very rare (1%) HP:0001631
19 joint hypermobility 31 very rare (1%) HP:0001382
20 downslanted palpebral fissures 31 very rare (1%) HP:0000494
21 pulmonic stenosis 31 very rare (1%) HP:0001642
22 large earlobe 31 very rare (1%) HP:0009748
23 thickened helices 31 very rare (1%) HP:0000391
24 large for gestational age 31 very rare (1%) HP:0001520
25 deep palmar crease 31 very rare (1%) HP:0006191
26 poor suck 31 very rare (1%) HP:0002033
27 generalized hypotonia 31 very rare (1%) HP:0001290
28 impaired oropharyngeal swallow response 31 very rare (1%) HP:0031162
29 curly hair 31 very rare (1%) HP:0002212
30 narrow forehead 31 very rare (1%) HP:0000341
31 numerous nevi 31 very rare (1%) HP:0001054
32 abnormal esophagus morphology 31 very rare (1%) HP:0002031
33 abnormality of the chin 31 very rare (1%) HP:0000306
34 nasogastric tube feeding in infancy 31 very rare (1%) HP:0011470
35 seizure 31 very rare (1%) HP:0001250
36 palpebral thickening 31 very rare (1%) HP:0030939
37 lentigo maligna melanoma 31 very rare (1%) HP:0012059
38 dysphagia 31 HP:0002015
39 pectus carinatum 31 HP:0000768
40 feeding difficulties in infancy 31 HP:0008872
41 cognitive impairment 31 HP:0100543
42 dolichocephaly 31 HP:0000268
43 hypotonia 31 HP:0001252

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Neck:
short neck
webbed neck

Chest Ribs Sternum Clavicles And Scapulae:
pectus carinatum
pectus carinatum (in some patients)

Head And Neck Face:
prominent forehead
bitemporal narrowing

Abdomen Gastrointestinal:
feeding difficulties
poor suck
poor swallowing

Cardiovascular Heart:
congenital heart defects (in some patients)

Head And Neck Head:
dolicocephaly

Chest External Features:
broad chest

Skeletal Hands:
small joint hyperextensibility

Head And Neck Eyes:
hypertelorism

Growth Height:
short stature

Head And Neck Ears:
low-set ears
thick helix

Neurologic Central Nervous System:
hypotonia
cognitive deficits, mild to moderate

Head And Neck Nose:
flat nasal bridge

Skeletal Spine:
scoliosis (in some patients)

Growth Other:
neonatal growth failure

Skin Nails Hair Skin:
hyperpigmented cutaneous lesions (in some patients)

Clinical features from OMIM®:

613706 (Updated 20-May-2021)

GenomeRNAi Phenotypes related to Noonan Syndrome 7 according to GeneCards Suite gene sharing:

26 (show all 15)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-109 9.55 GADD45G
2 Increased shRNA abundance (Z-score > 2) GR00366-A-132 9.55 GADD45G
3 Increased shRNA abundance (Z-score > 2) GR00366-A-149 9.55 BRAF
4 Increased shRNA abundance (Z-score > 2) GR00366-A-174 9.55 GADD45G
5 Increased shRNA abundance (Z-score > 2) GR00366-A-184 9.55 POLR2B
6 Increased shRNA abundance (Z-score > 2) GR00366-A-19 9.55 EIF4E EIF4G1
7 Increased shRNA abundance (Z-score > 2) GR00366-A-196 9.55 GADD45G
8 Increased shRNA abundance (Z-score > 2) GR00366-A-198 9.55 GADD45G
9 Increased shRNA abundance (Z-score > 2) GR00366-A-212 9.55 EIF4E
10 Increased shRNA abundance (Z-score > 2) GR00366-A-215 9.55 POLR2B
11 Increased shRNA abundance (Z-score > 2) GR00366-A-23 9.55 GADD45G
12 Increased shRNA abundance (Z-score > 2) GR00366-A-47 9.55 BRAF
13 Increased shRNA abundance (Z-score > 2) GR00366-A-60 9.55 EIF4E EIF4G1
14 Increased shRNA abundance (Z-score > 2) GR00366-A-68 9.55 EIF4G1
15 Increased shRNA abundance (Z-score > 2) GR00366-A-94 9.55 EIF4G1

Drugs & Therapeutics for Noonan Syndrome 7

Search Clinical Trials , NIH Clinical Center for Noonan Syndrome 7

Genetic Tests for Noonan Syndrome 7

Genetic tests related to Noonan Syndrome 7:

# Genetic test Affiliating Genes
1 Noonan Syndrome 7 29 BRAF

Anatomical Context for Noonan Syndrome 7

MalaCards organs/tissues related to Noonan Syndrome 7:

40
Eye, Heart

Publications for Noonan Syndrome 7

Articles related to Noonan Syndrome 7:

# Title Authors PMID Year
1
Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum. 6 57
19206169 2009

Variations for Noonan Syndrome 7

ClinVar genetic disease variations for Noonan Syndrome 7:

6 (show top 50) (show all 59)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 BRAF NM_004333.6(BRAF):c.722C>G (p.Thr241Arg) SNV Pathogenic 29806 rs387906660 GRCh37: 7:140501350-140501350
GRCh38: 7:140801550-140801550
2 BRAF NM_004333.6(BRAF):c.1593G>C (p.Trp531Cys) SNV Pathogenic 29808 rs606231228 GRCh37: 7:140476813-140476813
GRCh38: 7:140777013-140777013
3 BRAF NM_001374258.1(BRAF):c.1909C>G (p.Leu637Val) SNV Pathogenic 13969 rs121913369 GRCh37: 7:140453146-140453146
GRCh38: 7:140753346-140753346
4 BRAF NM_001374258.1(BRAF):c.721A>C (p.Thr241Pro) SNV Pathogenic 29807 rs387906661 GRCh37: 7:140501351-140501351
GRCh38: 7:140801551-140801551
5 BRAF NM_001374258.1(BRAF):c.722C>T (p.Thr241Met) SNV Pathogenic 29805 rs387906660 GRCh37: 7:140501350-140501350
GRCh38: 7:140801550-140801550
6 BRAF NM_001374258.1(BRAF):c.1712G>C (p.Trp571Ser) SNV Pathogenic 666569 rs397507478 GRCh37: 7:140476814-140476814
GRCh38: 7:140777014-140777014
7 BRAF NM_001374258.1(BRAF):c.770A>G (p.Gln257Arg) SNV Pathogenic 13973 rs180177035 GRCh37: 7:140501302-140501302
GRCh38: 7:140801502-140801502
8 BRAF NM_001374258.1(BRAF):c.770A>G (p.Gln257Arg) SNV Pathogenic 13973 rs180177035 GRCh37: 7:140501302-140501302
GRCh38: 7:140801502-140801502
9 BRAF NM_001374258.1(BRAF):c.735A>C (p.Leu245Phe) SNV Likely pathogenic 40347 rs397507466 GRCh37: 7:140501337-140501337
GRCh38: 7:140801537-140801537
10 BRAF NM_001374258.1(BRAF):c.2255C>A (p.Ala752Asp) SNV Likely pathogenic 162795 rs727502904 GRCh37: 7:140434563-140434563
GRCh38: 7:140734763-140734763
11 BRAF NM_004333.6(BRAF):c.1387A>G (p.Ile463Val) SNV Likely pathogenic 587514 rs1562957000 GRCh37: 7:140481421-140481421
GRCh38: 7:140781621-140781621
12 BRAF NM_004333.6(BRAF):c.1914T>A (p.Asp638Glu) SNV Likely pathogenic 13981 rs180177042 GRCh37: 7:140449165-140449165
GRCh38: 7:140749365-140749365
13 BRAF NM_001374258.1(BRAF):c.1863T>A (p.Asn621Lys) SNV Likely pathogenic 44811 rs397516895 GRCh37: 7:140453192-140453192
GRCh38: 7:140753392-140753392
14 BRAF NM_001374258.1(BRAF):c.722C>T (p.Thr241Met) SNV Likely pathogenic 29805 rs387906660 GRCh37: 7:140501350-140501350
GRCh38: 7:140801550-140801550
15 BRAF NM_004333.6(BRAF):c.1024A>G (p.Ile342Val) SNV Uncertain significance 359048 rs201481342 GRCh37: 7:140494224-140494224
GRCh38: 7:140794424-140794424
16 BRAF NM_004333.6(BRAF):c.*3C>T SNV Uncertain significance 359043 rs746680490 GRCh37: 7:140434394-140434394
GRCh38: 7:140734594-140734594
17 BRAF NM_004333.6(BRAF):c.437G>A (p.Arg146Gln) SNV Uncertain significance 372564 rs557241012 GRCh37: 7:140534476-140534476
GRCh38: 7:140834676-140834676
18 BRAF NM_004333.6(BRAF):c.981-14C>A SNV Uncertain significance 359049 rs200002171 GRCh37: 7:140494281-140494281
GRCh38: 7:140794481-140794481
19 BRAF NM_001374258.1(BRAF):c.1814+14G>A SNV Uncertain significance 44809 rs184144181 GRCh37: 7:140476698-140476698
GRCh38: 7:140776898-140776898
20 BRAF NM_001374258.1(BRAF):c.2401+27T>C SNV Uncertain significance 162794 rs727502903 GRCh37: 7:140434390-140434390
GRCh38: 7:140734590-140734590
21 BRAF NM_004333.6(BRAF):c.2196C>G (p.Ser732=) SNV Uncertain significance 417227 rs142592480 GRCh37: 7:140434502-140434502
GRCh38: 7:140734702-140734702
22 BRAF NM_001374258.1(BRAF):c.2063A>G (p.Glu688Gly) SNV Uncertain significance 908790 GRCh37: 7:140449136-140449136
GRCh38: 7:140749336-140749336
23 BRAF NM_001374258.1(BRAF):c.563G>C (p.Arg188Thr) SNV Uncertain significance 908852 GRCh37: 7:140508737-140508737
GRCh38: 7:140808937-140808937
24 BRAF NM_001374258.1(BRAF):c.469G>A (p.Val157Ile) SNV Uncertain significance 503529 rs1258111302 GRCh37: 7:140534444-140534444
GRCh38: 7:140834644-140834644
25 BRAF NM_001374258.1(BRAF):c.2401+236T>C SNV Uncertain significance 909590 GRCh37: 7:140434181-140434181
GRCh38: 7:140734381-140734381
26 BRAF NM_001374258.1(BRAF):c.1689A>G (p.Pro563=) SNV Uncertain significance 909644 GRCh37: 7:140476837-140476837
GRCh38: 7:140777037-140777037
27 BRAF NM_001374258.1(BRAF):c.316G>A (p.Gly106Arg) SNV Uncertain significance 505121 rs749247588 GRCh37: 7:140534597-140534597
GRCh38: 7:140834797-140834797
28 BRAF NM_004333.6(BRAF):c.72G>C (p.Glu24Asp) SNV Uncertain significance 133720 rs587778114 GRCh37: 7:140624432-140624432
GRCh38: 7:140924632-140924632
29 BRAF NM_001374258.1(BRAF):c.64G>A (p.Asp22Asn) SNV Uncertain significance 40335 rs397507456 GRCh37: 7:140624440-140624440
GRCh38: 7:140924640-140924640
30 BRAF NM_001374258.1(BRAF):c.2401+223A>G SNV Uncertain significance 910513 GRCh37: 7:140434194-140434194
GRCh38: 7:140734394-140734394
31 BRAF NM_001374258.1(BRAF):c.2401+163A>G SNV Uncertain significance 910514 GRCh37: 7:140434254-140434254
GRCh38: 7:140734454-140734454
32 BRAF NM_001374258.1(BRAF):c.2401+144G>C SNV Uncertain significance 910515 GRCh37: 7:140434273-140434273
GRCh38: 7:140734473-140734473
33 BRAF NM_001374258.1(BRAF):c.1300T>C (p.Ser434Pro) SNV Uncertain significance 910575 GRCh37: 7:140482955-140482955
GRCh38: 7:140783155-140783155
34 BRAF NM_001374258.1(BRAF):c.1066C>G (p.Gln356Glu) SNV Uncertain significance 910576 GRCh37: 7:140494182-140494182
GRCh38: 7:140794382-140794382
35 BRAF NM_001374258.1(BRAF):c.-12C>T SNV Uncertain significance 910631 GRCh37: 7:140624515-140624515
GRCh38: 7:140924715-140924715
36 BRAF NM_001374258.1(BRAF):c.-56C>T SNV Uncertain significance 910632 GRCh37: 7:140624559-140624559
GRCh38: 7:140924759-140924759
37 BRAF NM_001374258.1(BRAF):c.1056T>A (p.Asp352Glu) SNV Uncertain significance 910577 GRCh37: 7:140494192-140494192
GRCh38: 7:140794392-140794392
38 BRAF NM_004333.6(BRAF):c.1023A>G (p.Pro341=) SNV Uncertain significance 512959 rs56092510 GRCh37: 7:140494225-140494225
GRCh38: 7:140794425-140794425
39 BRAF NM_001374258.1(BRAF):c.1357G>A (p.Val453Met) SNV Uncertain significance 44799 rs377093637 GRCh37: 7:140482898-140482898
GRCh38: 7:140783098-140783098
40 BRAF NM_001374258.1(BRAF):c.1819T>G (p.Leu607Val) SNV Uncertain significance 945231 GRCh37: 7:140454029-140454029
GRCh38: 7:140754229-140754229
41 BRAF NM_001374258.1(BRAF):c.708C>T (p.Asn236=) SNV Uncertain significance 44827 rs138333692 GRCh37: 7:140507763-140507763
GRCh38: 7:140807963-140807963
42 BRAF NM_001374258.1(BRAF):c.1068A>G (p.Gln356=) SNV Uncertain significance 44788 rs143335467 GRCh37: 7:140494180-140494180
GRCh38: 7:140794380-140794380
43 BRAF NM_004333.6(BRAF):c.1166G>A (p.Arg389His) SNV Uncertain significance 372627 rs577372072 GRCh37: 7:140487359-140487359
GRCh38: 7:140787559-140787559
44 BRAF NM_001374258.1(BRAF):c.1357G>A (p.Val453Met) SNV Uncertain significance 44799 rs377093637 GRCh37: 7:140482898-140482898
GRCh38: 7:140783098-140783098
45 BRAF NM_004333.6(BRAF):c.1940A>G (p.Tyr647Cys) SNV Uncertain significance 561797 rs1562939198 GRCh37: 7:140449139-140449139
GRCh38: 7:140749339-140749339
46 BRAF NM_001374258.1(BRAF):c.1452G>A (p.Arg484=) SNV Uncertain significance 40362 rs56101602 GRCh37: 7:140481476-140481476
GRCh38: 7:140781676-140781676
47 BRAF NM_004333.6(BRAF):c.36G>A (p.Ala12=) SNV Likely benign 40333 rs397507454 GRCh37: 7:140624468-140624468
GRCh38: 7:140924668-140924668
48 BRAF NM_001374258.1(BRAF):c.2355A>G (p.Leu785=) SNV Likely benign 40399 rs56046546 GRCh37: 7:140434463-140434463
GRCh38: 7:140734663-140734663
49 BRAF NM_001374258.1(BRAF):c.375T>G (p.Ser125=) SNV Likely benign 44825 rs201507202 GRCh37: 7:140534538-140534538
GRCh38: 7:140834738-140834738
50 BRAF NM_001374258.1(BRAF):c.1503A>G (p.Gln501=) SNV Likely benign 40363 rs56216404 GRCh37: 7:140481425-140481425
GRCh38: 7:140781625-140781625

UniProtKB/Swiss-Prot genetic disease variations for Noonan Syndrome 7:

72
# Symbol AA change Variation ID SNP ID
1 BRAF p.Leu597Val VAR_018627 rs121913369
2 BRAF p.Thr241Met VAR_058620 rs387906660
3 BRAF p.Thr241Arg VAR_058622 rs387906660
4 BRAF p.Trp531Cys VAR_058627 rs606231228

Expression for Noonan Syndrome 7

Search GEO for disease gene expression data for Noonan Syndrome 7.

Pathways for Noonan Syndrome 7

Pathways related to Noonan Syndrome 7 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.58 EIF4G1 EIF4E EIF3B
2 10.42 POLR2B ASZ1

GO Terms for Noonan Syndrome 7

Cellular components related to Noonan Syndrome 7 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.44 SCN5A PPP1CA ITPA IFIH1 GADD45G EIF4G1
2 eukaryotic translation initiation factor 4F complex GO:0016281 8.96 EIF4G1 EIF4E

Biological processes related to Noonan Syndrome 7 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 translational initiation GO:0006413 9.58 EIF4G1 EIF4E EIF3B
2 regulation of translational initiation GO:0006446 9.48 EIF4G1 EIF3B
3 behavioral fear response GO:0001662 9.46 EIF4G1 EIF4E
4 positive regulation of interferon-alpha production GO:0032727 9.43 IFIH1 DDX58
5 cellular response to exogenous dsRNA GO:0071360 9.37 IFIH1 DDX58
6 positive regulation of response to cytokine stimulus GO:0060760 9.32 IFIH1 DDX58
7 detection of virus GO:0009597 9.26 IFIH1 DDX58
8 viral process GO:0016032 9.17 VAPA PPP1CA IFIH1 EIF4G1 EIF4E DYNLT1
9 cytoplasmic pattern recognition receptor signaling pathway in response to virus GO:0039528 9.16 IFIH1 DDX58
10 regulation of type III interferon production GO:0034344 8.96 IFIH1 DDX58

Molecular functions related to Noonan Syndrome 7 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 translation initiation factor binding GO:0031369 8.96 EIF4G1 EIF3B
2 translation initiation factor activity GO:0003743 8.8 EIF4G1 EIF4E EIF3B

Sources for Noonan Syndrome 7

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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