NS6
MCID: NNN013
MIFTS: 34

Noonan Syndrome 6 (NS6)

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 6

Summaries for Noonan Syndrome 6

UniProtKB/Swiss-Prot : 72 Noonan syndrome 6: 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 6, also known as ns6, is related to gastroenteritis and noonan syndrome 10. An important gene associated with Noonan Syndrome 6 is NRAS (NRAS Proto-Oncogene, GTPase). Affiliated tissues include eye and myeloid, and related phenotypes are hypertelorism and short stature

Disease Ontology : 12 A Noonan syndrome that has material basis in heterozygous mutation in the NRAS gene on chromosome 1p13.

More information from OMIM: 613224 PS163950

Related Diseases for Noonan Syndrome 6

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 Noonan Syndrome 11
Noonan Syndrome 12 Noonan Syndrome 13

Diseases related to Noonan Syndrome 6 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 gastroenteritis 10.0
2 noonan syndrome 10 9.7 SLC17A5 KLHDC3

Symptoms & Phenotypes for Noonan Syndrome 6

Human phenotypes related to Noonan Syndrome 6:

31 (show all 32)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 31 obligate (100%) HP:0000316
2 short stature 31 obligate (100%) HP:0004322
3 hyperkeratosis 31 obligate (100%) HP:0000962
4 cryptorchidism 31 obligate (100%) HP:0000028
5 low-set ears 31 obligate (100%) HP:0000369
6 webbed neck 31 obligate (100%) HP:0000465
7 asymmetry of the thorax 31 obligate (100%) HP:0001555
8 generalized hypotonia 31 obligate (100%) HP:0001290
9 curly hair 31 obligate (100%) HP:0002212
10 macrocephaly 31 very rare (1%) HP:0000256
11 global developmental delay 31 very rare (1%) HP:0001263
12 delayed speech and language development 31 very rare (1%) HP:0000750
13 intellectual disability, mild 31 very rare (1%) HP:0001256
14 myopia 31 very rare (1%) HP:0000545
15 hypertrophic cardiomyopathy 31 very rare (1%) HP:0001639
16 pulmonic stenosis 31 very rare (1%) HP:0001642
17 depressed nasal bridge 31 HP:0005280
18 wide nasal bridge 31 HP:0000431
19 sensorineural hearing impairment 31 HP:0000407
20 epicanthus 31 HP:0000286
21 pectus excavatum 31 HP:0000767
22 motor delay 31 HP:0001270
23 downslanted palpebral fissures 31 HP:0000494
24 polyhydramnios 31 HP:0001561
25 high forehead 31 HP:0000348
26 sparse hair 31 HP:0008070
27 single umbilical artery 31 HP:0001195
28 cafe-au-lait spot 31 HP:0000957
29 edema 31 HP:0000969
30 long eyebrows 31 HP:0004523
31 keratosis pilaris 31 HP:0032152
32 juvenile myelomonocytic leukemia 31 HP:0012209

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Head:
macrocephaly

Growth Height:
short stature

Genitourinary Internal Genitalia Male:
cryptorchidism

Head And Neck Neck:
webbed neck
nuchal edema

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum

Neurologic Central Nervous System:
motor delay
hypotonia
learning difficulties (in some patients)
developmental delay (in some patients)

Head And Neck Face:
high forehead

Prenatal Manifestations Placenta And Umbilical Cord:
single umbilical artery

Hematology:
juvenile myelomonocytic leukemia (in 1 patient)

Head And Neck Nose:
depressed nasal bridge
broad nasal bridge

Skin Nails Hair Skin:
hyperkeratosis
keratosis pilaris
cafe-au-lait spots
lentigines

Head And Neck Ears:
low-set ears
hearing loss, sensorineural (in 1 patient)

Head And Neck Eyes:
myopia
long eyebrows
downslanting palpebral fissures
epicanthal folds

Cardiovascular Heart:
hypertrophic cardiomyopathy
pulmonic stenosis
supraventricular extrasystoles

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Skin Nails Hair Hair:
sparse hair
curly hair

Chest External Features:
thorax deformity

Clinical features from OMIM®:

613224 (Updated 20-May-2021)

GenomeRNAi Phenotypes related to Noonan Syndrome 6 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased caspase activity GR00400-S-1 9.1 FAM177B KLHDC3
2 Increased caspase activity GR00400-S-2 9.1 C2CD6 FAM177B KLHDC3 POLR2J3

Drugs & Therapeutics for Noonan Syndrome 6

Search Clinical Trials , NIH Clinical Center for Noonan Syndrome 6

Genetic Tests for Noonan Syndrome 6

Genetic tests related to Noonan Syndrome 6:

# Genetic test Affiliating Genes
1 Noonan Syndrome 6 29 NRAS

Anatomical Context for Noonan Syndrome 6

MalaCards organs/tissues related to Noonan Syndrome 6:

40
Eye, Myeloid

Publications for Noonan Syndrome 6

Articles related to Noonan Syndrome 6:

# Title Authors PMID Year
1
Mutation in NRAS in familial Noonan syndrome--case report and review of the literature. 57 6
26467218 2015
2
A restricted spectrum of NRAS mutations causes Noonan syndrome. 6 57
19966803 2010
3
Germ-line mutation of the NRAS gene may be responsible for the development of juvenile myelomonocytic leukaemia. 6 57
19775298 2009
4
Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis. 6
21079152 2011
5
Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations. 6
17332249 2007
6
NRAS mutation causes a human autoimmune lymphoproliferative syndrome. 6
17517660 2007
7
N-ras gene point mutations in childhood acute lymphocytic leukemia correlate with a poor prognosis. 6
2407301 1990
8
Amino-acid substitutions at codon 13 of the N-ras oncogene in human acute myeloid leukaemia. 6
2989702 1985

Variations for Noonan Syndrome 6

ClinVar genetic disease variations for Noonan Syndrome 6:

6 (show top 50) (show all 78)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NRAS NM_002524.5(NRAS):c.149C>T (p.Thr50Ile) SNV Pathogenic 13902 rs267606921 GRCh37: 1:115256562-115256562
GRCh38: 1:114713941-114713941
2 NRAS NM_002524.5(NRAS):c.179G>A (p.Gly60Glu) SNV Pathogenic 13903 rs267606920 GRCh37: 1:115256532-115256532
GRCh38: 1:114713911-114713911
3 NRAS NM_002524.5(NRAS):c.38G>A (p.Gly13Asp) SNV Pathogenic 13901 rs121434596 GRCh37: 1:115258744-115258744
GRCh38: 1:114716123-114716123
4 NRAS NM_002524.5(NRAS):c.*344A>G SNV Uncertain significance 291974 rs746680042 GRCh37: 1:115250371-115250371
GRCh38: 1:114707750-114707750
5 NRAS NM_002524.5(NRAS):c.380C>G (p.Thr127Arg) SNV Uncertain significance 291976 rs779899354 GRCh37: 1:115252260-115252260
GRCh38: 1:114709639-114709639
6 NRAS NM_002524.5(NRAS):c.*2714G>T SNV Uncertain significance 291951 rs886045100 GRCh37: 1:115248001-115248001
GRCh38: 1:114705380-114705380
7 NRAS NM_002524.5(NRAS):c.*1643G>C SNV Uncertain significance 291963 rs571329214 GRCh37: 1:115249072-115249072
GRCh38: 1:114706451-114706451
8 NRAS NM_002524.5(NRAS):c.-106G>T SNV Uncertain significance 291977 rs755583487 GRCh37: 1:115259367-115259367
GRCh38: 1:114716746-114716746
9 NRAS NM_002524.5(NRAS):c.*3404T>C SNV Uncertain significance 291940 rs185234485 GRCh37: 1:115247311-115247311
GRCh38: 1:114704690-114704690
10 NRAS NM_002524.5(NRAS):c.*2805T>C SNV Uncertain significance 291949 rs776606789 GRCh37: 1:115247910-115247910
GRCh38: 1:114705289-114705289
11 NRAS NM_002524.5(NRAS):c.*2677A>T SNV Uncertain significance 291952 rs886045101 GRCh37: 1:115248038-115248038
GRCh38: 1:114705417-114705417
12 NRAS NM_002524.5(NRAS):c.*536C>T SNV Uncertain significance 291971 rs886045108 GRCh37: 1:115250179-115250179
GRCh38: 1:114707558-114707558
13 NRAS NM_002524.5(NRAS):c.*2513T>A SNV Uncertain significance 291958 rs150969241 GRCh37: 1:115248202-115248202
GRCh38: 1:114705581-114705581
14 NRAS NM_002524.5(NRAS):c.*111A>G SNV Uncertain significance 291975 rs188272768 GRCh37: 1:115250604-115250604
GRCh38: 1:114707983-114707983
15 NRAS NM_002524.5(NRAS):c.*2630G>A SNV Uncertain significance 291955 rs886045102 GRCh37: 1:115248085-115248085
GRCh38: 1:114705464-114705464
16 NRAS NM_002524.5(NRAS):c.*2178G>A SNV Uncertain significance 291961 rs886045103 GRCh37: 1:115248537-115248537
GRCh38: 1:114705916-114705916
17 NRAS NM_002524.5(NRAS):c.*1382G>T SNV Uncertain significance 291964 rs886045105 GRCh37: 1:115249333-115249333
GRCh38: 1:114706712-114706712
18 NRAS NM_002524.5(NRAS):c.*3392T>C SNV Uncertain significance 291941 rs886045097 GRCh37: 1:115247323-115247323
GRCh38: 1:114704702-114704702
19 NRAS NM_002524.5(NRAS):c.*2860G>A SNV Uncertain significance 291947 rs886045099 GRCh37: 1:115247855-115247855
GRCh38: 1:114705234-114705234
20 NRAS NM_002524.5(NRAS):c.553C>T (p.Pro185Ser) SNV Uncertain significance 179025 rs374061873 GRCh37: 1:115251173-115251173
GRCh38: 1:114708552-114708552
21 NRAS NM_002524.5(NRAS):c.*1656C>T SNV Uncertain significance 291962 rs886045104 GRCh37: 1:115249059-115249059
GRCh38: 1:114706438-114706438
22 NRAS NM_002524.5(NRAS):c.*2546C>T SNV Uncertain significance 291956 rs778203603 GRCh37: 1:115248169-115248169
GRCh38: 1:114705548-114705548
23 NRAS NM_002524.5(NRAS):c.*3062C>T SNV Uncertain significance 291945 rs886045098 GRCh37: 1:115247653-115247653
GRCh38: 1:114705032-114705032
24 NRAS NM_002524.5(NRAS):c.*774A>G SNV Uncertain significance 291968 rs886045107 GRCh37: 1:115249941-115249941
GRCh38: 1:114707320-114707320
25 NRAS NM_002524.5(NRAS):c.*2844T>A SNV Uncertain significance 291948 rs530053161 GRCh37: 1:115247871-115247871
GRCh38: 1:114705250-114705250
26 NRAS NM_002524.5(NRAS):c.*2811C>A SNV Uncertain significance 874295 GRCh37: 1:115247904-115247904
GRCh38: 1:114705283-114705283
27 NRAS NM_002524.5(NRAS):c.*2767C>T SNV Uncertain significance 874296 GRCh37: 1:115247948-115247948
GRCh38: 1:114705327-114705327
28 NRAS NM_002524.5(NRAS):c.*1629C>G SNV Uncertain significance 874356 GRCh37: 1:115249086-115249086
GRCh38: 1:114706465-114706465
29 NRAS NM_002524.5(NRAS):c.*1571A>G SNV Uncertain significance 874357 GRCh37: 1:115249144-115249144
GRCh38: 1:114706523-114706523
30 NRAS NM_002524.5(NRAS):c.*1509A>G SNV Uncertain significance 874358 GRCh37: 1:115249206-115249206
GRCh38: 1:114706585-114706585
31 NRAS NM_002524.5(NRAS):c.*1466A>T SNV Uncertain significance 874359 GRCh37: 1:115249249-115249249
GRCh38: 1:114706628-114706628
32 NRAS NM_002524.5(NRAS):c.*1105C>T SNV Uncertain significance 874360 GRCh37: 1:115249610-115249610
GRCh38: 1:114706989-114706989
33 NRAS NM_002524.5(NRAS):c.*2618A>G SNV Uncertain significance 875227 GRCh37: 1:115248097-115248097
GRCh38: 1:114705476-114705476
34 NRAS NM_002524.5(NRAS):c.*2589G>A SNV Uncertain significance 875228 GRCh37: 1:115248126-115248126
GRCh38: 1:114705505-114705505
35 NRAS NM_002524.5(NRAS):c.*2523A>G SNV Uncertain significance 875229 GRCh37: 1:115248192-115248192
GRCh38: 1:114705571-114705571
36 NRAS NM_002524.5(NRAS):c.*2412G>A SNV Uncertain significance 876187 GRCh37: 1:115248303-115248303
GRCh38: 1:114705682-114705682
37 NRAS NM_002524.5(NRAS):c.*2328G>A SNV Uncertain significance 876188 GRCh37: 1:115248387-115248387
GRCh38: 1:114705766-114705766
38 NRAS NM_002524.5(NRAS):c.*2226G>C SNV Uncertain significance 876189 GRCh37: 1:115248489-115248489
GRCh38: 1:114705868-114705868
39 NRAS NM_002524.5(NRAS):c.*2188C>A SNV Uncertain significance 876190 GRCh37: 1:115248527-115248527
GRCh38: 1:114705906-114705906
40 NRAS NM_002524.5(NRAS):c.*340G>A SNV Uncertain significance 876239 GRCh37: 1:115250375-115250375
GRCh38: 1:114707754-114707754
41 NRAS NM_002524.5(NRAS):c.360G>A (p.Leu120=) SNV Uncertain significance 40476 rs143020946 GRCh37: 1:115252280-115252280
GRCh38: 1:114709659-114709659
42 NRAS NM_002524.5(NRAS):c.250A>G (p.Ile84Val) SNV Uncertain significance 424299 rs376177995 GRCh37: 1:115256461-115256461
GRCh38: 1:114713840-114713840
43 NRAS NM_002524.5(NRAS):c.112-6C>G SNV Uncertain significance 876240 GRCh37: 1:115256605-115256605
GRCh38: 1:114713984-114713984
44 NRAS NM_002524.5(NRAS):c.*3362T>C SNV Uncertain significance 876279 GRCh37: 1:115247353-115247353
GRCh38: 1:114704732-114704732
45 NRAS NM_002524.5(NRAS):c.*3341A>T SNV Uncertain significance 876280 GRCh37: 1:115247374-115247374
GRCh38: 1:114704753-114704753
46 NRAS NM_002524.5(NRAS):c.*3103G>T SNV Uncertain significance 876282 GRCh37: 1:115247612-115247612
GRCh38: 1:114704991-114704991
47 NRAS NM_002524.5(NRAS):c.*3020A>G SNV Uncertain significance 876283 GRCh37: 1:115247695-115247695
GRCh38: 1:114705074-114705074
48 NRAS NM_002524.5(NRAS):c.*1974T>C SNV Uncertain significance 876327 GRCh37: 1:115248741-115248741
GRCh38: 1:114706120-114706120
49 NRAS NM_002524.5(NRAS):c.*1936C>G SNV Uncertain significance 876328 GRCh37: 1:115248779-115248779
GRCh38: 1:114706158-114706158
50 NRAS NM_002524.5(NRAS):c.*1914A>G SNV Uncertain significance 876329 GRCh37: 1:115248801-115248801
GRCh38: 1:114706180-114706180

UniProtKB/Swiss-Prot genetic disease variations for Noonan Syndrome 6:

72
# Symbol AA change Variation ID SNP ID
1 NRAS p.Thr50Ile VAR_063085 rs267606921
2 NRAS p.Gly60Glu VAR_063086 rs267606920

Expression for Noonan Syndrome 6

Search GEO for disease gene expression data for Noonan Syndrome 6.

Pathways for Noonan Syndrome 6

GO Terms for Noonan Syndrome 6

Sources for Noonan Syndrome 6

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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