LPRD2
MCID: LPR011
MIFTS: 35

Leopard Syndrome 2 (LPRD2)

Categories: Cardiovascular diseases, Ear diseases, Genetic diseases, Reproductive diseases

Aliases & Classifications for Leopard Syndrome 2

MalaCards integrated aliases for Leopard Syndrome 2:

Name: Leopard Syndrome 2 57 12 72 29 13 6 70
Noonan Syndrome with Multiple Lentigines 2 12 15
Lprd2 57 72
Leopard Syndrome, Type 2 39

Characteristics:

HPO:

31
leopard syndrome 2:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Leopard Syndrome 2

UniProtKB/Swiss-Prot : 72 LEOPARD syndrome 2: A disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness.

MalaCards based summary : Leopard Syndrome 2, also known as noonan syndrome with multiple lentigines 2, is related to noonan syndrome and noonan-related syndrome and lentigines. An important gene associated with Leopard Syndrome 2 is RAF1 (Raf-1 Proto-Oncogene, Serine/Threonine Kinase), and among its related pathways/superpathways are Response to elevated platelet cytosolic Ca2+ and Development FGFR signaling pathway. Related phenotypes are short neck and depressed nasal bridge

Disease Ontology : 12 A Noonan syndrome with multiple lentigines that has material basis in heterozygous mutation in the RAF1 gene on chromosome 3p25.

More information from OMIM: 611554 PS151100

Related Diseases for Leopard Syndrome 2

Diseases in the Leopard Syndrome 1 family:

Leopard Syndrome 2 Leopard Syndrome 3

Diseases related to Leopard Syndrome 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 12)
# Related Disease Score Top Affiliating Genes
1 noonan syndrome and noonan-related syndrome 9.9 RAF1 PTPN11
2 lentigines 9.9 RAF1 PTPN11
3 leopard syndrome 1 9.9 RAF1 PTPN11
4 noonan syndrome 3 9.9 RAF1 PTPN11
5 noonan syndrome with multiple lentigines 9.9 RAF1 PTPN11
6 cardiofaciocutaneous syndrome 1 9.9 RAF1 PTPN11
7 noonan syndrome 5 9.9 RAF1 MKRN2
8 pilocytic astrocytoma 9.9 RAF1 PTPN11
9 neurofibromatosis, type i 9.8 RAF1 PTPN11
10 gastric adenocarcinoma 9.8 RAF1 PTPN11
11 juvenile myelomonocytic leukemia 9.7 RAF1 PTPN11
12 rasopathy 9.6 RAF1 PTPN11

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



Diseases related to Leopard Syndrome 2

Symptoms & Phenotypes for Leopard Syndrome 2

Human phenotypes related to Leopard Syndrome 2:

31 (show all 18)
# Description HPO Frequency HPO Source Accession
1 short neck 31 HP:0000470
2 depressed nasal bridge 31 HP:0005280
3 hypertelorism 31 HP:0000316
4 mandibular prognathia 31 HP:0000303
5 short stature 31 HP:0004322
6 thick lower lip vermilion 31 HP:0000179
7 dry skin 31 HP:0000958
8 cubitus valgus 31 HP:0002967
9 low-set ears 31 HP:0000369
10 webbed neck 31 HP:0000465
11 epicanthus 31 HP:0000286
12 hypertrophic cardiomyopathy 31 HP:0001639
13 dolichocephaly 31 HP:0000268
14 downslanted palpebral fissures 31 HP:0000494
15 multiple lentigines 31 HP:0001003
16 cafe-au-lait spot 31 HP:0000957
17 curly hair 31 HP:0002212
18 abnormal sternum morphology 31 HP:0000766

Clinical features from OMIM®:

611554 (Updated 05-Apr-2021)

MGI Mouse Phenotypes related to Leopard Syndrome 2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 hearing/vestibular/ear MP:0005377 8.8 MKRN2 PTPN11 RAF1

Drugs & Therapeutics for Leopard Syndrome 2

Search Clinical Trials , NIH Clinical Center for Leopard Syndrome 2

Genetic Tests for Leopard Syndrome 2

Genetic tests related to Leopard Syndrome 2:

# Genetic test Affiliating Genes
1 Leopard Syndrome 2 29 RAF1

Anatomical Context for Leopard Syndrome 2

Publications for Leopard Syndrome 2

Articles related to Leopard Syndrome 2:

# Title Authors PMID Year
1
Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. 6 57
17603483 2007
2
Germline gain-of-function mutations in RAF1 cause Noonan syndrome. 6
17603482 2007
3
Two cases of LEOPARD syndrome--RAF1 mutations firstly described in children. 61
22389993 2011

Variations for Leopard Syndrome 2

ClinVar genetic disease variations for Leopard Syndrome 2:

6 (show top 50) (show all 77)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 RAF1 NM_001354689.3(RAF1):c.776C>A (p.Ser259Tyr) SNV Pathogenic 44633 rs397516827 GRCh37: 3:12645693-12645693
GRCh38: 3:12604194-12604194
2 RAF1 NM_001354689.3(RAF1):c.505G>C (p.Gly169Arg) SNV Pathogenic 265535 rs886039607 GRCh37: 3:12650341-12650341
GRCh38: 3:12608842-12608842
3 RAF1 NM_001354689.3(RAF1):c.788T>A (p.Val263Asp) SNV Pathogenic 496189 rs397516830 GRCh37: 3:12645681-12645681
GRCh38: 3:12604182-12604182
4 RAF1 NM_001354689.3(RAF1):c.1897C>G (p.Leu633Val) SNV Pathogenic 13960 rs80338797 GRCh37: 3:12626123-12626123
GRCh38: 3:12584624-12584624
5 RAF1 NM_001354689.3(RAF1):c.770C>T (p.Ser257Leu) SNV Pathogenic 13957 rs80338796 GRCh37: 3:12645699-12645699
GRCh38: 3:12604200-12604200
6 RAF1 NM_001354689.3(RAF1):c.770C>T (p.Ser257Leu) SNV Pathogenic 13957 rs80338796 GRCh37: 3:12645699-12645699
GRCh38: 3:12604200-12604200
7 RAF1 NM_001354689.3(RAF1):c.781C>G (p.Pro261Ala) SNV Pathogenic 40605 rs121434594 GRCh37: 3:12645688-12645688
GRCh38: 3:12604189-12604189
8 RAF1 NM_001354689.3(RAF1):c.1142G>C (p.Gly381Ala) SNV Likely pathogenic 40613 rs397516813 GRCh37: 3:12641216-12641216
GRCh38: 3:12599717-12599717
9 RAF1 NM_001354689.3(RAF1):c.61G>A (p.Val21Met) SNV Likely pathogenic 978721 GRCh37: 3:12660160-12660160
GRCh38: 3:12618661-12618661
10 RAF1 NM_001354689.3(RAF1):c.773C>G (p.Thr258Arg) SNV Likely pathogenic 801936 rs1575573330 GRCh37: 3:12645696-12645696
GRCh38: 3:12604197-12604197
11 RAF1 NM_001354689.3(RAF1):c.122G>A (p.Arg41Gln) SNV Conflicting interpretations of pathogenicity 40586 rs145611571 GRCh37: 3:12660099-12660099
GRCh38: 3:12618600-12618600
12 RAF1 NM_001354689.3(RAF1):c.601A>G (p.Ile201Val) SNV Uncertain significance 432929 rs757700986 GRCh37: 3:12647779-12647779
GRCh38: 3:12606280-12606280
13 RAF1 NM_001354689.3(RAF1):c.226A>G (p.Met76Val) SNV Uncertain significance 181507 rs730880999 GRCh37: 3:12653543-12653543
GRCh38: 3:12612044-12612044
14 RAF1 NM_001354689.3(RAF1):c.600T>C (p.Thr200=) SNV Uncertain significance 508664 rs779808613 GRCh37: 3:12647780-12647780
GRCh38: 3:12606281-12606281
15 RAF1 NM_001354689.3(RAF1):c.231C>T (p.Ser77=) SNV Uncertain significance 509193 rs1450510914 GRCh37: 3:12653538-12653538
GRCh38: 3:12612039-12612039
16 RAF1 NM_001354689.3(RAF1):c.*73T>A SNV Uncertain significance 899432 GRCh37: 3:12625940-12625940
GRCh38: 3:12584441-12584441
17 RAF1 NM_001354689.3(RAF1):c.654A>G (p.Arg218=) SNV Uncertain significance 899635 GRCh37: 3:12647726-12647726
GRCh38: 3:12606227-12606227
18 RAF1 NM_001354689.3(RAF1):c.-27+7G>A SNV Uncertain significance 40578 rs886057916 GRCh37: 3:12705305-12705305
GRCh38: 3:12663806-12663806
19 RAF1 NM_001354689.3(RAF1):c.21T>C (p.Ala7=) SNV Uncertain significance 343104 rs886057915 GRCh37: 3:12660200-12660200
GRCh38: 3:12618701-12618701
20 RAF1 NM_001354689.3(RAF1):c.124G>A (p.Ala42Thr) SNV Uncertain significance 448930 rs200856000 GRCh37: 3:12660097-12660097
GRCh38: 3:12618598-12618598
21 RAF1 NM_001354689.3(RAF1):c.1874C>T (p.Ser625Phe) SNV Uncertain significance 181512 rs730881004 GRCh37: 3:12626146-12626146
GRCh38: 3:12584647-12584647
22 RAF1 NM_001354689.3(RAF1):c.*643C>G SNV Uncertain significance 899385 GRCh37: 3:12625370-12625370
GRCh38: 3:12583871-12583871
23 RAF1 NM_001354689.3(RAF1):c.*630A>G SNV Uncertain significance 899386 GRCh37: 3:12625383-12625383
GRCh38: 3:12583884-12583884
24 RAF1 NM_001354689.3(RAF1):c.*628G>T SNV Uncertain significance 899387 GRCh37: 3:12625385-12625385
GRCh38: 3:12583886-12583886
25 RAF1 NM_001354689.3(RAF1):c.-201C>A SNV Uncertain significance 40577 rs532668125 GRCh37: 3:12705486-12705486
GRCh38: 3:12663987-12663987
26 RAF1 NM_001354689.3(RAF1):c.*410A>G SNV Uncertain significance 900510 GRCh37: 3:12625603-12625603
GRCh38: 3:12584104-12584104
27 RAF1 NM_001354689.3(RAF1):c.-209G>A SNV Uncertain significance 177838 rs727504351 GRCh37: 3:12705494-12705494
GRCh38: 3:12663995-12663995
28 RAF1 NM_001354689.3(RAF1):c.-264C>G SNV Uncertain significance 900848 GRCh37: 3:12705549-12705549
GRCh38: 3:12664050-12664050
29 RAF1 , MKRN2 NM_001354689.3(RAF1):c.*841C>T SNV Uncertain significance 902116 GRCh37: 3:12625172-12625172
GRCh38: 3:12583673-12583673
30 RAF1 NM_001354689.3(RAF1):c.1352A>C (p.Lys451Thr) SNV Uncertain significance 902234 GRCh37: 3:12632375-12632375
GRCh38: 3:12590876-12590876
31 RAF1 NC_000003.12:g.12664140G>C SNV Uncertain significance 902521 GRCh37: 3:12705639-12705639
GRCh38: 3:12664140-12664140
32 RAF1 , MKRN2 NM_001354689.3(RAF1):c.*840A>T SNV Uncertain significance 903003 GRCh37: 3:12625173-12625173
GRCh38: 3:12583674-12583674
33 RAF1 NM_001354689.3(RAF1):c.*706C>T SNV Uncertain significance 903004 GRCh37: 3:12625307-12625307
GRCh38: 3:12583808-12583808
34 RAF1 NM_001354689.3(RAF1):c.*647G>T SNV Uncertain significance 903005 GRCh37: 3:12625366-12625366
GRCh38: 3:12583867-12583867
35 RAF1 NM_001354689.3(RAF1):c.*120C>A SNV Uncertain significance 903051 GRCh37: 3:12625893-12625893
GRCh38: 3:12584394-12584394
36 RAF1 NM_001354689.3(RAF1):c.993C>T (p.Pro331=) SNV Uncertain significance 477681 rs1553613022 GRCh37: 3:12641708-12641708
GRCh38: 3:12600209-12600209
37 RAF1 NM_001354689.3(RAF1):c.903T>A (p.Ile301=) SNV Uncertain significance 903109 GRCh37: 3:12641906-12641906
GRCh38: 3:12600407-12600407
38 RAF1 NM_001354689.3(RAF1):c.-53G>A SNV Uncertain significance 903300 GRCh37: 3:12705338-12705338
GRCh38: 3:12663839-12663839
39 RAF1 NM_001354689.3(RAF1):c.-59C>G SNV Uncertain significance 903301 GRCh37: 3:12705344-12705344
GRCh38: 3:12663845-12663845
40 RAF1 NM_001354689.3(RAF1):c.-107C>T SNV Uncertain significance 903302 GRCh37: 3:12705392-12705392
GRCh38: 3:12663893-12663893
41 RAF1 NM_001354689.3(RAF1):c.332G>A (p.Arg111His) SNV Uncertain significance 930654 GRCh37: 3:12650823-12650823
GRCh38: 3:12609324-12609324
42 RAF1 NM_001354689.3(RAF1):c.-110G>A SNV Uncertain significance 343105 rs886057917 GRCh37: 3:12705395-12705395
GRCh38: 3:12663896-12663896
43 RAF1 NM_001354689.3(RAF1):c.-181T>C SNV Uncertain significance 343108 rs886057920 GRCh37: 3:12705466-12705466
GRCh38: 3:12663967-12663967
44 RAF1 NM_001354689.3(RAF1):c.*627C>T SNV Uncertain significance 343094 rs879160471 GRCh37: 3:12625386-12625386
GRCh38: 3:12583887-12583887
45 RAF1 NM_001354689.3(RAF1):c.-139T>G SNV Uncertain significance 343106 rs886057918 GRCh37: 3:12705424-12705424
GRCh38: 3:12663925-12663925
46 RAF1 NM_001354689.3(RAF1):c.*162T>C SNV Uncertain significance 343100 rs886057913 GRCh37: 3:12625851-12625851
GRCh38: 3:12584352-12584352
47 RAF1 NM_001354689.3(RAF1):c.-146C>G SNV Uncertain significance 343107 rs886057919 GRCh37: 3:12705431-12705431
GRCh38: 3:12663932-12663932
48 RAF1 NM_001354689.3(RAF1):c.*640T>C SNV Uncertain significance 343093 rs759464247 GRCh37: 3:12625373-12625373
GRCh38: 3:12583874-12583874
49 RAF1 NM_001354689.3(RAF1):c.*113T>G SNV Uncertain significance 343102 rs886057914 GRCh37: 3:12625900-12625900
GRCh38: 3:12584401-12584401
50 RAF1 NM_001354689.3(RAF1):c.-204G>C SNV Uncertain significance 40576 rs547543588 GRCh37: 3:12705489-12705489
GRCh38: 3:12663990-12663990

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

72
# Symbol AA change Variation ID SNP ID
1 RAF1 p.Ser257Leu VAR_037808 rs80338796
2 RAF1 p.Leu613Val VAR_037821 rs80338797

Expression for Leopard Syndrome 2

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

Pathways for Leopard Syndrome 2

Pathways related to Leopard Syndrome 2 according to GeneCards Suite gene sharing:

(show all 20)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.84 SERPIND1 RAF1 PTPN11
2
Show member pathways
11.99 RAF1 PTPN11
3 11.9 RAF1 PTPN11
4
Show member pathways
11.88 RAF1 PTPN11
5 11.83 RAF1 PTPN11
6
Show member pathways
11.79 RAF1 PTPN11
7 11.75 RAF1 PTPN11
8
Show member pathways
11.73 RAF1 PTPN11
9
Show member pathways
11.69 RAF1 PTPN11
10 11.65 RAF1 PTPN11
11
Show member pathways
11.6 RAF1 PTPN11
12 11.51 RAF1 PTPN11
13
Show member pathways
11.42 RAF1 PTPN11
14
Show member pathways
11.28 RAF1 PTPN11
15 11.01 RAF1 PTPN11
16 10.97 RAF1 PTPN11
17
Show member pathways
10.73 RAF1 PTPN11
18 10.67 RAF1 PTPN11
19
Show member pathways
10.43 RAF1 PTPN11
20 10.07 RAF1 PTPN11

GO Terms for Leopard Syndrome 2

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

# Name GO ID Score Top Affiliating Genes
1 platelet activation GO:0030168 8.96 RAF1 PTPN11
2 neurotrophin TRK receptor signaling pathway GO:0048011 8.62 RAF1 PTPN11

Sources for Leopard 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 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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