NS7
MCID: NNN020
MIFTS: 36

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 : 73 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 gastroenteritis and exocervical carcinoma. An important gene associated with Noonan Syndrome 7 is BRAF (B-Raf Proto-Oncogene, Serine/Threonine Kinase), and among its related pathways/superpathways is PIWI-interacting RNA (piRNA) biogenesis. Affiliated tissues include heart and skin, and related phenotypes are scoliosis and intellectual disability

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

OMIM : 56 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)

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 44)
# Description HPO Frequency HPO Source Accession
1 scoliosis 31 occasional (7.5%) HP:0002650
2 intellectual disability 31 very rare (1%) HP:0001249
3 depressed nasal bridge 31 very rare (1%) HP:0005280
4 hypertelorism 31 very rare (1%) HP:0000316
5 macrocephaly 31 very rare (1%) HP:0000256
6 pectus carinatum 31 very rare (1%) HP:0000768
7 thick vermilion border 31 very rare (1%) HP:0012471
8 short stature 31 very rare (1%) HP:0004322
9 hyperhidrosis 31 very rare (1%) HP:0000975
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 hyperpigmentation of the skin 31 very rare (1%) HP:0000953
31 narrow forehead 31 very rare (1%) HP:0000341
32 numerous nevi 31 very rare (1%) HP:0001054
33 abnormal esophagus morphology 31 very rare (1%) HP:0002031
34 abnormality of the chin 31 very rare (1%) HP:0000306
35 nasogastric tube feeding in infancy 31 very rare (1%) HP:0011470
36 seizure 31 very rare (1%) HP:0001250
37 palpebral thickening 31 very rare (1%) HP:0030939
38 lentigo maligna melanoma 31 very rare (1%) HP:0012059
39 short neck 31 HP:0000470
40 muscular hypotonia 31 HP:0001252
41 feeding difficulties in infancy 31 HP:0008872
42 cognitive impairment 31 HP:0100543
43 dysphagia 31 HP:0002015
44 dolichocephaly 31 HP:0000268

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
hypertelorism

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

Head And Neck Face:
prominent forehead
bitemporal narrowing

Head And Neck Ears:
low-set ears
thick helix

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 Neck:
short neck
webbed neck

Growth Height:
short stature

Abdomen Gastrointestinal:
feeding difficulties
poor suck
poor swallowing

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

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

26 (show all 14)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-109 9.47 GADD45G
2 Increased shRNA abundance (Z-score > 2) GR00366-A-132 9.47 GADD45G
3 Increased shRNA abundance (Z-score > 2) GR00366-A-149 9.47 BRAF
4 Increased shRNA abundance (Z-score > 2) GR00366-A-174 9.47 GADD45G
5 Increased shRNA abundance (Z-score > 2) GR00366-A-184 9.47 POLR2B
6 Increased shRNA abundance (Z-score > 2) GR00366-A-19 9.47 EIF4G1
7 Increased shRNA abundance (Z-score > 2) GR00366-A-196 9.47 GADD45G
8 Increased shRNA abundance (Z-score > 2) GR00366-A-198 9.47 GADD45G
9 Increased shRNA abundance (Z-score > 2) GR00366-A-215 9.47 POLR2B
10 Increased shRNA abundance (Z-score > 2) GR00366-A-23 9.47 GADD45G
11 Increased shRNA abundance (Z-score > 2) GR00366-A-47 9.47 BRAF
12 Increased shRNA abundance (Z-score > 2) GR00366-A-60 9.47 EIF4G1
13 Increased shRNA abundance (Z-score > 2) GR00366-A-68 9.47 EIF4G1
14 Increased shRNA abundance (Z-score > 2) GR00366-A-94 9.47 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
Heart, Skin

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 56
19206169 2009
2
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
3
Noonan syndrome: clinical features, diagnosis, and management guidelines. 6
20876176 2010
4
Leopard syndrome. 6
18505544 2008
5
Noonan Syndrome 6
20301303 2001

Variations for Noonan Syndrome 7

ClinVar genetic disease variations for Noonan Syndrome 7:

6 (show top 50) (show all 53) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 BRAF NM_001374258.1(BRAF):c.1712G>C (p.Trp571Ser)SNV Pathogenic 666569 7:140476814-140476814 7:140777014-140777014
2 BRAF NM_001374258.1(BRAF):c.1909C>G (p.Leu637Val)SNV Pathogenic 13969 rs121913369 7:140453146-140453146 7:140753346-140753346
3 BRAF NM_001374258.1(BRAF):c.770A>G (p.Gln257Arg)SNV Pathogenic 13973 rs180177035 7:140501302-140501302 7:140801502-140801502
4 BRAF NM_004333.6(BRAF):c.722C>G (p.Thr241Arg)SNV Pathogenic 29806 rs387906660 7:140501350-140501350 7:140801550-140801550
5 BRAF NM_001374258.1(BRAF):c.735A>C (p.Leu245Phe)SNV Pathogenic 40347 rs397507466 7:140501337-140501337 7:140801537-140801537
6 BRAF NM_004333.6(BRAF):c.1593G>C (p.Trp531Cys)SNV Pathogenic 29808 rs606231228 7:140476813-140476813 7:140777013-140777013
7 BRAF NM_001374258.1(BRAF):c.1863T>A (p.Asn621Lys)SNV Pathogenic/Likely pathogenic 44811 rs397516895 7:140453192-140453192 7:140753392-140753392
8 BRAF NM_001374258.1(BRAF):c.721A>C (p.Thr241Pro)SNV Pathogenic/Likely pathogenic 29807 rs387906661 7:140501351-140501351 7:140801551-140801551
9 BRAF NM_001374258.1(BRAF):c.722C>T (p.Thr241Met)SNV Pathogenic/Likely pathogenic 29805 rs387906660 7:140501350-140501350 7:140801550-140801550
10 BRAF NM_004333.6(BRAF):c.1914T>A (p.Asp638Glu)SNV Pathogenic/Likely pathogenic 13981 rs180177042 7:140449165-140449165 7:140749365-140749365
11 BRAF NM_004333.6(BRAF):c.1387A>G (p.Ile463Val)SNV Likely pathogenic 587514 rs1562957000 7:140481421-140481421 7:140781621-140781621
12 BRAF NM_001374258.1(BRAF):c.1814+14G>ASNV Conflicting interpretations of pathogenicity 44809 rs184144181 7:140476698-140476698 7:140776898-140776898
13 BRAF NM_004333.6(BRAF):c.2196C>G (p.Ser732=)SNV Conflicting interpretations of pathogenicity 417227 rs142592480 7:140434502-140434502 7:140734702-140734702
14 BRAF NM_004333.6(BRAF):c.1023A>G (p.Pro341=)SNV Conflicting interpretations of pathogenicity 512959 rs56092510 7:140494225-140494225 7:140794425-140794425
15 BRAF NM_004333.6(BRAF):c.72G>C (p.Glu24Asp)SNV Conflicting interpretations of pathogenicity 133720 rs587778114 7:140624432-140624432 7:140924632-140924632
16 BRAF NM_004333.6(BRAF):c.981-14C>ASNV Conflicting interpretations of pathogenicity 359049 rs200002171 7:140494281-140494281 7:140794481-140794481
17 BRAF NM_004333.6(BRAF):c.*3C>TSNV Uncertain significance 359043 rs746680490 7:140434394-140434394 7:140734594-140734594
18 BRAF NM_004333.6(BRAF):c.1166G>A (p.Arg389His)SNV Uncertain significance 372627 rs577372072 7:140487359-140487359 7:140787559-140787559
19 BRAF NM_004333.6(BRAF):c.437G>A (p.Arg146Gln)SNV Uncertain significance 372564 rs557241012 7:140534476-140534476 7:140834676-140834676
20 BRAF NM_004333.6(BRAF):c.1024A>G (p.Ile342Val)SNV Uncertain significance 359048 rs201481342 7:140494224-140494224 7:140794424-140794424
21 BRAF NM_004333.6(BRAF):c.1940A>G (p.Tyr647Cys)SNV Uncertain significance 561797 rs1562939198 7:140449139-140449139 7:140749339-140749339
22 BRAF NM_001374258.1(BRAF):c.469G>A (p.Val157Ile)SNV Uncertain significance 503529 rs1258111302 7:140534444-140534444 7:140834644-140834644
23 BRAF NM_001374258.1(BRAF):c.316G>A (p.Gly106Arg)SNV Uncertain significance 505121 rs749247588 7:140534597-140534597 7:140834797-140834797
24 BRAF NM_001374258.1(BRAF):c.1357G>A (p.Val453Met)SNV Uncertain significance 44799 rs377093637 7:140482898-140482898 7:140783098-140783098
25 BRAF NM_001374258.1(BRAF):c.2401+236T>CSNV Uncertain significance 909590 7:140434181-140434181 7:140734381-140734381
26 BRAF NM_001374258.1(BRAF):c.2401+223A>GSNV Uncertain significance 910513 7:140434194-140434194 7:140734394-140734394
27 BRAF NM_001374258.1(BRAF):c.2401+163A>GSNV Uncertain significance 910514 7:140434254-140434254 7:140734454-140734454
28 BRAF NM_001374258.1(BRAF):c.2401+144G>CSNV Uncertain significance 910515 7:140434273-140434273 7:140734473-140734473
29 BRAF NM_001374258.1(BRAF):c.2063A>G (p.Glu688Gly)SNV Uncertain significance 908790 7:140449136-140449136 7:140749336-140749336
30 BRAF NM_001374258.1(BRAF):c.1689A>G (p.Pro563=)SNV Uncertain significance 909644 7:140476837-140476837 7:140777037-140777037
31 BRAF NM_001374258.1(BRAF):c.1300T>C (p.Ser434Pro)SNV Uncertain significance 910575 7:140482955-140482955 7:140783155-140783155
32 BRAF NM_001374258.1(BRAF):c.1066C>G (p.Gln356Glu)SNV Uncertain significance 910576 7:140494182-140494182 7:140794382-140794382
33 BRAF NM_001374258.1(BRAF):c.1056T>A (p.Asp352Glu)SNV Uncertain significance 910577 7:140494192-140494192 7:140794392-140794392
34 BRAF NM_001374258.1(BRAF):c.563G>C (p.Arg188Thr)SNV Uncertain significance 908852 7:140508737-140508737 7:140808937-140808937
35 BRAF NM_001374258.1(BRAF):c.-12C>TSNV Uncertain significance 910631 7:140624515-140624515 7:140924715-140924715
36 BRAF NM_001374258.1(BRAF):c.-56C>TSNV Uncertain significance 910632 7:140624559-140624559 7:140924759-140924759
37 BRAF NM_001374258.1(BRAF):c.2401+27T>CSNV Likely benign 162794 rs727502903 7:140434390-140434390 7:140734590-140734590
38 BRAF NM_004333.6(BRAF):c.*111C>TSNV Benign/Likely benign 359042 rs539860876 7:140434286-140434286 7:140734486-140734486
39 BRAF NM_004333.6(BRAF):c.-5A>GSNV Benign/Likely benign 136536 rs71645936 7:140624508-140624508 7:140924708-140924708
40 BRAF NM_004333.6(BRAF):c.*387G>ASNV Benign/Likely benign 359041 rs114105685 7:140434010-140434010 7:140734210-140734210
41 BRAF NM_001374258.1(BRAF):c.78G>T (p.Glu26Asp)SNV Benign/Likely benign 40337 rs371877084 7:140624426-140624426 7:140924626-140924626
42 BRAF NM_001374258.1(BRAF):c.-19C>TSNV Benign/Likely benign 41445 rs71645935 7:140624522-140624522 7:140924722-140924722
43 BRAF NM_001374258.1(BRAF):c.2247+3A>GSNV Benign 41447 rs371976102 7:140439609-140439609 7:140739809-140739809
44 BRAF NM_001374258.1(BRAF):c.1068A>G (p.Gln356=)SNV Benign 44788 rs143335467 7:140494180-140494180 7:140794380-140794380
45 BRAF NM_004333.6(BRAF):c.36G>A (p.Ala12=)SNV Benign 40333 rs397507454 7:140624468-140624468 7:140924668-140924668
46 BRAF NM_001374258.1(BRAF):c.64G>A (p.Asp22Asn)SNV Benign 40335 rs397507456 7:140624440-140624440 7:140924640-140924640
47 BRAF NM_001374258.1(BRAF):c.375T>G (p.Ser125=)SNV Benign 44825 rs201507202 7:140534538-140534538 7:140834738-140834738
48 BRAF NM_001374258.1(BRAF):c.708C>T (p.Asn236=)SNV Benign 44827 rs138333692 7:140507763-140507763 7:140807963-140807963
49 BRAF NM_001374258.1(BRAF):c.1347A>G (p.Ser449=)SNV Benign 40360 rs145035762 7:140482908-140482908 7:140783108-140783108
50 BRAF NM_001374258.1(BRAF):c.1452G>A (p.Arg484=)SNV Benign 40362 rs56101602 7:140481476-140481476 7:140781676-140781676

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

73
# 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 10.09 POLR2B ASZ1

GO Terms for Noonan Syndrome 7

Sources for Noonan Syndrome 7

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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