NS2
MCID: NNN009
MIFTS: 39

Noonan Syndrome 2 (NS2)

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 2

MalaCards integrated aliases for Noonan Syndrome 2:

Name: Noonan Syndrome 2 57 12 20 72 29 6 15 70
Ns2 57 12 20 72
Noonan Syndrome 2, Autosomal Recessive 72
Noonan Syndrome, Autosomal Recessive 57
Autosomal Recessive Noonan Syndrome 20
Noonan Syndrome Autosomal Recessive 20
Syndrome, Noonan, Type 2 39

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive


HPO:

31
noonan syndrome 2:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Noonan Syndrome 2

UniProtKB/Swiss-Prot : 72 Noonan syndrome 2: 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. NS2 inheritance is autosomal recessive.

MalaCards based summary : Noonan Syndrome 2, also known as ns2, is related to noonan syndrome 1 and hepatitis c virus. An important gene associated with Noonan Syndrome 2 is LZTR1 (Leucine Zipper Like Transcription Regulator 1). Affiliated tissues include eye and liver, and related phenotypes are ptosis and hypertelorism

Disease Ontology : 12 A Noonan syndrome characterized by hypertrophic obstructive cardiomyopathy and that has material basis in an autosomal recessive inheritance.

OMIM® : 57 Noonan syndrome (NS) is a multiple congenital anomalies syndrome characterized by a typical face, congenital heart disease, and short stature (summary by van der Burgt and Brunner, 2000). For a general phenotypic description and a discussion of genetic heterogeneity of Noonan syndrome, see NS1 (163950). (605275) (Updated 20-May-2021)

Related Diseases for Noonan Syndrome 2

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

(show top 50) (show all 55)
# Related Disease Score Top Affiliating Genes
1 noonan syndrome 1 28.2 SH2D3C SH2D3A RNASEL PDE12 MT-TI MRPL58
2 hepatitis c virus 10.7
3 hepatitis c 10.6
4 hepatitis 10.4
5 influenza 10.4
6 diarrhea 10.3
7 blue toe syndrome 10.2 SH2D3C SH2D3A
8 western equine encephalitis 10.2 SH2D3C SH2D3A
9 vaccinia 10.2
10 eastern equine encephalitis 10.2 SH2D3C SH2D3A
11 acute diarrhea 10.1 SH2D3A ASZ1
12 deafness, nonsyndromic sensorineural, mitochondrial 10.1 MT-TI MT-TH
13 microphthalmia with limb anomalies 10.1 RNASEL PDE12 IFIH1
14 hemorrhagic disease 10.1
15 avian influenza 10.1
16 retinitis pigmentosa 12 10.0 MT-TI MT-TH
17 noonan syndrome 3 10.0 SH2D3C SH2D3A LNP1
18 weiss-kruszka syndrome 10.0
19 pthirus pubis infestation 10.0 MT-TI MT-TH
20 paralytic poliomyelitis 10.0 RNASEL MT-TI IFIH1
21 atrial septal defect 1 10.0
22 human immunodeficiency virus type 1 10.0
23 dengue virus 10.0
24 disseminated intravascular coagulation 10.0
25 liver cirrhosis 10.0
26 cytokine deficiency 10.0
27 lice infestation 10.0 MT-TI MT-TH
28 croup 9.9 SH2D3A PLP2 IFIH1
29 pseudo-turner syndrome 9.9
30 parasitic ectoparasitic infectious disease 9.8 MT-TI MT-TH
31 triiodothyronine receptor auxiliary protein 9.8
32 ataxia-telangiectasia 9.8
33 ataxia and polyneuropathy, adult-onset 9.8
34 cervical cancer 9.8
35 west nile virus 9.8
36 middle east respiratory syndrome 9.8
37 rapidly involuting congenital hemangioma 9.8
38 mumps 9.8
39 common cold 9.8
40 japanese encephalitis 9.8
41 rabies 9.8
42 dengue disease 9.8
43 telangiectasis 9.8
44 viral hepatitis 9.8
45 newcastle disease 9.8
46 aleutian mink disease 9.8
47 bronchiolitis 9.8
48 severe acute respiratory syndrome 9.8
49 plague 9.8
50 pneumonia 9.8

Graphical network of the top 20 diseases related to Noonan Syndrome 2:



Diseases related to Noonan Syndrome 2

Symptoms & Phenotypes for Noonan Syndrome 2

Human phenotypes related to Noonan Syndrome 2:

31 (show all 20)
# Description HPO Frequency HPO Source Accession
1 ptosis 31 very rare (1%) HP:0000508
2 hypertelorism 31 very rare (1%) HP:0000316
3 short stature 31 very rare (1%) HP:0004322
4 cryptorchidism 31 very rare (1%) HP:0000028
5 wide intermamillary distance 31 very rare (1%) HP:0006610
6 shield chest 31 very rare (1%) HP:0000914
7 polyhydramnios 31 very rare (1%) HP:0001561
8 arthrogryposis multiplex congenita 31 very rare (1%) HP:0002804
9 short neck 31 HP:0000470
10 global developmental delay 31 HP:0001263
11 coarctation of aorta 31 HP:0001680
12 downslanted palpebral fissures 31 HP:0000494
13 abnormal cardiac septum morphology 31 HP:0001671
14 leukemia 31 HP:0001909
15 pulmonic stenosis 31 HP:0001642
16 cardiomyopathy 31 HP:0001638
17 posteriorly rotated ears 31 HP:0000358
18 mitral stenosis 31 HP:0001718
19 curly hair 31 HP:0002212
20 abnormal sternum morphology 31 HP:0000766

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Cardiovascular Heart:
cardiomyopathy
pulmonary valve stenosis
septal defects
coarctation of the aorta
mitral valve stenosis

Skin Nails Hair Hair:
curly hair

Neurologic Central Nervous System:
developmental delay
impaired intellectual development

Growth Height:
short stature (in some patients)
normal to increased birth length

Chest Breasts:
widely spaced nipples (in some patients)

Head And Neck Head:
normal to increased occipitofrontal circumference (ofc)

Chest External Features:
broad chest (in some patients)

Skeletal:
arthrogryposis (in some patients)

Neoplasia:
leukemia (in 2 families)

Head And Neck Ears:
posteriorly rotated ears

Genitourinary Internal Genitalia Male:
cryptorchidism (in some patients)

Head And Neck Eyes:
downslanting palpebral fissures
hypertelorism (in some patients)
ptosis (in some patients)

Prenatal Manifestations Amniotic Fluid:
polyhydramnios (in some patients)

Growth Weight:
normal to increased birth weight

Head And Neck Neck:
broad, short neck

Chest Ribs Sternum Clavicles And Scapulae:
pectus deformity

Hematology:
coagulation defects (in some patients)

Clinical features from OMIM®:

605275 (Updated 20-May-2021)

Drugs & Therapeutics for Noonan Syndrome 2

Search Clinical Trials , NIH Clinical Center for Noonan Syndrome 2

Genetic Tests for Noonan Syndrome 2

Genetic tests related to Noonan Syndrome 2:

# Genetic test Affiliating Genes
1 Noonan Syndrome 2 29

Anatomical Context for Noonan Syndrome 2

MalaCards organs/tissues related to Noonan Syndrome 2:

40
Eye, Liver

Publications for Noonan Syndrome 2

Articles related to Noonan Syndrome 2:

# Title Authors PMID Year
1
Autosomal recessive Noonan syndrome associated with biallelic LZTR1 variants. 6 57
29469822 2018
2
Intronic CRISPR Repair in a Preclinical Model of Noonan Syndrome-Associated Cardiomyopathy. 6
32623905 2020
3
Delineation of LZTR1 mutation-positive patients with Noonan syndrome and identification of LZTR1 binding to RAF1-PPP1CB complexes. 57
30368668 2019
4
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. 6
25741868 2015
5
Genetic heterogeneity in Noonan syndrome: evidence for an autosomal recessive form. 57
10982482 2000
6
A syndrome of mental retardation, short stature, craniofacial anomalies with palpebral ptosis and pulmonary stenosis in three siblings with normal parents. An example of autosomal recessive inheritance of the Noonan phenotype? 57
1642809 1992
7
Familial Turner phenotype. 57
5782826 1969
8
The investigation of quality of life in 87 Chinese patients with disorders of sex development. 61
26075230 2015
9
Orofacial aspects in Noonan syndrome: 2 case report. 61
18505655 2008
10
Pulmonary lymphangiectasia revisited. 61
10813353 2000

Variations for Noonan Syndrome 2

ClinVar genetic disease variations for Noonan Syndrome 2:

6 (show all 23)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 LZTR1 NM_006767.4(LZTR1):c.2264G>A (p.Arg755Gln) SNV Pathogenic 599032 rs762834512 GRCh37: 22:21351029-21351029
GRCh38: 22:20996740-20996740
2 LZTR1 NM_006767.4(LZTR1):c.361C>G (p.His121Asp) SNV Pathogenic 599033 rs1569154492 GRCh37: 22:21341833-21341833
GRCh38: 22:20987544-20987544
3 LZTR1 NM_006767.4(LZTR1):c.1311G>A (p.Trp437Ter) SNV Pathogenic 549751 rs770933647 GRCh37: 22:21348001-21348001
GRCh38: 22:20993712-20993712
4 LZTR1 NM_006767.4(LZTR1):c.-38T>A SNV Pathogenic 549752 rs1459786357 GRCh37: 22:21336623-21336623
GRCh38: 22:20982334-20982334
5 LZTR1 NM_006767.4(LZTR1):c.1407G>A (p.Trp469Ter) SNV Pathogenic 549753 rs777243508 GRCh37: 22:21348266-21348266
GRCh38: 22:20993977-20993977
6 LZTR1 NM_006767.4(LZTR1):c.2178C>A (p.Tyr726Ter) SNV Pathogenic 522799 rs1034395178 GRCh37: 22:21350360-21350360
GRCh38: 22:20996071-20996071
7 LZTR1 NM_006767.4(LZTR1):c.2220-17C>A SNV Pathogenic 599029 rs1249726034 GRCh37: 22:21350968-21350968
GRCh38: 22:20996679-20996679
8 LZTR1 NM_006767.4(LZTR1):c.628C>T (p.Arg210Ter) SNV Pathogenic 599030 rs150419186 GRCh37: 22:21343948-21343948
GRCh38: 22:20989659-20989659
9 LZTR1 NM_006767.4(LZTR1):c.993+1G>A SNV Pathogenic 973830 GRCh37: 22:21346119-21346119
GRCh38: 22:20991830-20991830
10 LZTR1 NM_006767.4(LZTR1):c.2407-2A>G SNV Pathogenic 809337 rs1158550690 GRCh37: 22:21351519-21351519
GRCh38: 22:20997230-20997230
11 LZTR1 NM_006767.4(LZTR1):c.510-2A>G SNV Likely pathogenic 692086 rs1458682620 GRCh37: 22:21343076-21343076
GRCh38: 22:20988787-20988787
12 LZTR1 NM_006767.4(LZTR1):c.2044A>G (p.Lys682Glu) SNV Likely pathogenic 449911 rs758472207 GRCh37: 22:21350136-21350136
GRCh38: 22:20995847-20995847
13 LZTR1 NM_006767.4(LZTR1):c.722T>C (p.Phe241Ser) SNV Likely pathogenic 978716 GRCh37: 22:21344745-21344745
GRCh38: 22:20990456-20990456
14 LZTR1 NM_006767.4(LZTR1):c.1030del (p.Ser344fs) Deletion Likely pathogenic 523986 rs1555928249 GRCh37: 22:21346538-21346538
GRCh38: 22:20992249-20992249
15 LZTR1 NM_006767.4(LZTR1):c.273G>A (p.Met91Ile) SNV Likely pathogenic 998256 GRCh37: 22:21340139-21340139
GRCh38: 22:20985850-20985850
16 LZTR1 NM_006767.4(LZTR1):c.1943-256C>T SNV Conflicting interpretations of pathogenicity 522800 rs761685529 GRCh37: 22:21349779-21349779
GRCh38: 22:20995490-20995490
17 LZTR1 NM_006767.4(LZTR1):c.1055A>C (p.Tyr352Ser) SNV Uncertain significance 1028561 GRCh37: 22:21346564-21346564
GRCh38: 22:20992275-20992275
18 LZTR1 NM_006767.4(LZTR1):c.594-3C>T SNV Uncertain significance 984472 GRCh37: 22:21343911-21343911
GRCh38: 22:20989622-20989622
19 LZTR1 NM_006767.4(LZTR1):c.2246A>G (p.Tyr749Cys) SNV Uncertain significance 549754 rs755260815 GRCh37: 22:21351011-21351011
GRCh38: 22:20996722-20996722
20 LZTR1 NM_006767.4(LZTR1):c.1382C>A (p.Ala461Asp) SNV Uncertain significance 549755 rs1569156890 GRCh37: 22:21348241-21348241
GRCh38: 22:20993952-20993952
21 LZTR1 NM_006767.4(LZTR1):c.1385T>C (p.Ile462Thr) SNV Uncertain significance 549756 rs147684991 GRCh37: 22:21348244-21348244
GRCh38: 22:20993955-20993955
22 LZTR1 NM_006767.4(LZTR1):c.2462T>C (p.Ile821Thr) SNV Uncertain significance 635756 rs1275511136 GRCh37: 22:21351576-21351576
GRCh38: 22:20997287-20997287
23 LZTR1 NM_006767.4(LZTR1):c.2245T>C (p.Tyr749His) SNV Uncertain significance 634900 rs1601723615 GRCh37: 22:21351010-21351010
GRCh38: 22:20996721-20996721

UniProtKB/Swiss-Prot genetic disease variations for Noonan Syndrome 2:

72
# Symbol AA change Variation ID SNP ID
1 LZTR1 p.Arg170Trp VAR_081299 rs757502214
2 LZTR1 p.Arg697Gln VAR_081324 rs370638947
3 LZTR1 p.Pro701His VAR_081326 rs132757982

Expression for Noonan Syndrome 2

Search GEO for disease gene expression data for Noonan Syndrome 2.

Pathways for Noonan Syndrome 2

GO Terms for Noonan Syndrome 2

Cellular components related to Noonan Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial matrix GO:0005759 9.02 RNASEL PDE12 MRPL58 GFM2 ABCE1

Biological processes related to Noonan Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleic acid phosphodiester bond hydrolysis GO:0090305 9.43 RNASEL PDE12 ISG20L2
2 RNA phosphodiester bond hydrolysis, exonucleolytic GO:0090503 9.32 PDE12 ISG20L2
3 regulation of type I interferon-mediated signaling pathway GO:0060338 9.16 RNASEL ABCE1
4 translational termination GO:0006415 8.96 MRPL58 ABCE1
5 defense response to virus GO:0051607 8.92 RNASEL PDE12 IFIH1 ABCE1

Molecular functions related to Noonan Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 3'-5'-exoribonuclease activity GO:0000175 9.16 PDE12 ISG20L2
2 nuclease activity GO:0004518 9.13 RNASEL PDE12 ISG20L2
3 ribonucleoprotein complex binding GO:0043021 8.8 RNASEL PPP1CA IFIH1

Sources for Noonan Syndrome 2

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
Content
Loading form....