LPRD2
MCID: LPR011
MIFTS: 38

Leopard Syndrome 2 (LPRD2)

Categories: Cardiovascular diseases, Ear diseases, Genetic diseases, Reproductive diseases
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Aliases & Classifications for Leopard Syndrome 2

MalaCards integrated aliases for Leopard Syndrome 2:

Name: Leopard Syndrome 2 57 11 73 28 12 5 71
Noonan Syndrome with Multiple Lentigines 2 11 14
Lprd2 57 73
Leopard Syndrome, Type 2 38
Leopard Syndrome, 2 43

Classifications:



Summaries for Leopard Syndrome 2

UniProtKB/Swiss-Prot: 73 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 cholestasis-lymphedema syndrome and hypotrichosis-lymphedema-telangiectasia-renal defect syndrome. An important gene associated with Leopard Syndrome 2 is RAF1 (Raf-1 Proto-Oncogene, Serine/Threonine Kinase), and among its related pathways/superpathways are Neuropathic Pain-Signaling in Dorsal Horn Neurons and Ion channel transport. Affiliated tissues include skin, heart and testis, and related phenotypes are short neck and depressed nasal bridge

Disease Ontology: 11 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

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:

30 (show all 18)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short neck 30 HP:0000470
2 depressed nasal bridge 30 HP:0005280
3 hypertelorism 30 HP:0000316
4 mandibular prognathia 30 HP:0000303
5 short stature 30 HP:0004322
6 thick lower lip vermilion 30 HP:0000179
7 dry skin 30 HP:0000958
8 cubitus valgus 30 HP:0002967
9 low-set ears 30 HP:0000369
10 webbed neck 30 HP:0000465
11 epicanthus 30 HP:0000286
12 hypertrophic cardiomyopathy 30 HP:0001639
13 dolichocephaly 30 HP:0000268
14 downslanted palpebral fissures 30 HP:0000494
15 multiple lentigines 30 HP:0001003
16 cafe-au-lait spot 30 HP:0000957
17 curly hair 30 HP:0002212
18 abnormal sternum morphology 30 HP:0000766

Clinical features from OMIM®:

611554 (Updated 08-Dec-2022)

MGI Mouse Phenotypes related to Leopard Syndrome 2:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 normal MP:0002873 9.73 CCBE1 CLCA4 CLCN7 GJC2 RAF1 SOX18
2 immune system MP:0005387 9.7 CALCRL CCBE1 CLCN7 GJC2 PTPN14 RAF1
3 mortality/aging MP:0010768 9.5 CALCRL CCBE1 CLCN7 GJC2 PTPN14 RAF1
4 integument MP:0010771 9.02 CALCRL CCBE1 CLCN7 RAF1 SOX18

Drugs & Therapeutics for Leopard Syndrome 2

Search Clinical Trials, NIH Clinical Center for Leopard Syndrome 2

Cochrane evidence based reviews: leopard syndrome, 2

Genetic Tests for Leopard Syndrome 2

Genetic tests related to Leopard Syndrome 2:

# Genetic test Affiliating Genes
1 Leopard Syndrome 2 28 RAF1

Anatomical Context for Leopard Syndrome 2

Organs/tissues related to Leopard Syndrome 2:

MalaCards : Skin, Heart, Testis
ODiseA: Testis, Heart-Atrium, Heart-Ventricle, Heart, Skin

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. 57 5
17603483 2007
2
Germline gain-of-function mutations in RAF1 cause Noonan syndrome. 5
17603482 2007
3
Two cases of LEOPARD syndrome--RAF1 mutations firstly described in children. 62
22389993 2011

Variations for Leopard Syndrome 2

ClinVar genetic disease variations for Leopard Syndrome 2:

5 (show top 50) (show all 80)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 RAF1 NM_002880.4(RAF1):c.788T>A (p.Val263Asp) SNV Pathogenic
496189 rs397516830 GRCh37: 3:12645681-12645681
GRCh38: 3:12604182-12604182
2 RAF1 NM_002880.4(RAF1):c.781C>G (p.Pro261Ala) SNV Pathogenic
40605 rs121434594 GRCh37: 3:12645688-12645688
GRCh38: 3:12604189-12604189
3 RAF1 NM_002880.4(RAF1):c.776C>A (p.Ser259Tyr) SNV Pathogenic
44633 rs397516827 GRCh37: 3:12645693-12645693
GRCh38: 3:12604194-12604194
4 RAF1 NM_002880.4(RAF1):c.505G>C (p.Gly169Arg) SNV Pathogenic
265535 rs886039607 GRCh37: 3:12650341-12650341
GRCh38: 3:12608842-12608842
5 RAF1 NM_002880.4(RAF1):c.770C>T (p.Ser257Leu) SNV Pathogenic
Pathogenic
13957 rs80338796 GRCh37: 3:12645699-12645699
GRCh38: 3:12604200-12604200
6 RAF1 NM_002880.4(RAF1):c.1837C>G (p.Leu613Val) SNV Pathogenic
13960 rs80338797 GRCh37: 3:12626123-12626123
GRCh38: 3:12584624-12584624
7 RAF1 NM_002880.4(RAF1):c.1082G>C (p.Gly361Ala) SNV Likely Pathogenic
40613 rs397516813 GRCh37: 3:12641216-12641216
GRCh38: 3:12599717-12599717
8 RAF1 NM_002880.4(RAF1):c.61G>A (p.Val21Met) SNV Likely Pathogenic
978721 rs752484962 GRCh37: 3:12660160-12660160
GRCh38: 3:12618661-12618661
9 RAF1 NM_002880.4(RAF1):c.773C>G (p.Thr258Arg) SNV Likely Pathogenic
801936 rs1575573330 GRCh37: 3:12645696-12645696
GRCh38: 3:12604197-12604197
10 RAF1 NM_002880.4(RAF1):c.122G>A (p.Arg41Gln) SNV Conflicting Interpretations Of Pathogenicity
40586 rs145611571 GRCh37: 3:12660099-12660099
GRCh38: 3:12618600-12618600
11 RAF1 NM_002880.3(RAF1):c.-354C>G SNV Uncertain Significance
902521 rs964288487 GRCh37: 3:12705639-12705639
GRCh38: 3:12664140-12664140
12 RAF1 NM_002880.4(RAF1):c.332G>A (p.Arg111His) SNV Uncertain Significance
930654 rs996417348 GRCh37: 3:12650823-12650823
GRCh38: 3:12609324-12609324
13 RAF1 NM_002880.4(RAF1):c.1814C>T (p.Ser605Phe) SNV Uncertain Significance
Uncertain Significance
181512 rs730881004 GRCh37: 3:12626146-12626146
GRCh38: 3:12584647-12584647
14 RAF1 NM_002880.4(RAF1):c.601A>G (p.Ile201Val) SNV Uncertain Significance
432929 rs757700986 GRCh37: 3:12647779-12647779
GRCh38: 3:12606280-12606280
15 RAF1 NM_002880.4(RAF1):c.1922C>G (p.Thr641Arg) SNV Uncertain Significance
1696596 GRCh37: 3:12626038-12626038
GRCh38: 3:12584539-12584539
16 RAF1 NM_002880.4(RAF1):c.-27+7G>A SNV Uncertain Significance
40578 rs886057916 GRCh37: 3:12705305-12705305
GRCh38: 3:12663806-12663806
17 RAF1 NM_002880.4(RAF1):c.124G>A (p.Ala42Thr) SNV Uncertain Significance
448930 rs200856000 GRCh37: 3:12660097-12660097
GRCh38: 3:12618598-12618598
18 RAF1 NM_002880.4(RAF1):c.21T>C (p.Ala7=) SNV Uncertain Significance
343104 rs886057915 GRCh37: 3:12660200-12660200
GRCh38: 3:12618701-12618701
19 RAF1 NM_002880.4(RAF1):c.600T>C (p.Thr200=) SNV Uncertain Significance
508664 rs779808613 GRCh37: 3:12647780-12647780
GRCh38: 3:12606281-12606281
20 RAF1 NM_002880.4(RAF1):c.933C>T (p.Pro311=) SNV Uncertain Significance
477681 rs1553613022 GRCh37: 3:12641708-12641708
GRCh38: 3:12600209-12600209
21 RAF1 NM_002880.4(RAF1):c.226A>G (p.Met76Val) SNV Uncertain Significance
181507 rs730880999 GRCh37: 3:12653543-12653543
GRCh38: 3:12612044-12612044
22 RAF1 NM_002880.4(RAF1):c.-204G>C SNV Uncertain Significance
40576 rs547543588 GRCh37: 3:12705489-12705489
GRCh38: 3:12663990-12663990
23 RAF1 NM_002880.4(RAF1):c.1193G>T (p.Arg398Leu) SNV Uncertain Significance
40614 rs730880382 GRCh37: 3:12633207-12633207
GRCh38: 3:12591708-12591708
24 RAF1 NM_002880.4(RAF1):c.*113T>G SNV Uncertain Significance
343102 rs886057914 GRCh37: 3:12625900-12625900
GRCh38: 3:12584401-12584401
25 RAF1 NM_002880.4(RAF1):c.*643C>G SNV Uncertain Significance
899385 rs932173134 GRCh37: 3:12625370-12625370
GRCh38: 3:12583871-12583871
26 RAF1 NM_002880.4(RAF1):c.*630A>G SNV Uncertain Significance
899386 rs975583754 GRCh37: 3:12625383-12625383
GRCh38: 3:12583884-12583884
27 RAF1 NM_002880.4(RAF1):c.*628G>T SNV Uncertain Significance
899387 rs374944110 GRCh37: 3:12625385-12625385
GRCh38: 3:12583886-12583886
28 RAF1 NM_002880.4(RAF1):c.*162T>C SNV Uncertain Significance
343100 rs886057913 GRCh37: 3:12625851-12625851
GRCh38: 3:12584352-12584352
29 RAF1 NM_002880.4(RAF1):c.-146C>G SNV Uncertain Significance
343107 rs886057919 GRCh37: 3:12705431-12705431
GRCh38: 3:12663932-12663932
30 RAF1 NM_002880.4(RAF1):c.*640T>C SNV Uncertain Significance
343093 rs759464247 GRCh37: 3:12625373-12625373
GRCh38: 3:12583874-12583874
31 RAF1 NM_002880.4(RAF1):c.-110G>A SNV Uncertain Significance
343105 rs886057917 GRCh37: 3:12705395-12705395
GRCh38: 3:12663896-12663896
32 RAF1 NM_002880.4(RAF1):c.-181T>C SNV Uncertain Significance
343108 rs886057920 GRCh37: 3:12705466-12705466
GRCh38: 3:12663967-12663967
33 RAF1 NM_002880.4(RAF1):c.*627C>T SNV Uncertain Significance
343094 rs879160471 GRCh37: 3:12625386-12625386
GRCh38: 3:12583887-12583887
34 RAF1 NM_002880.4(RAF1):c.-139T>G SNV Uncertain Significance
343106 rs886057918 GRCh37: 3:12705424-12705424
GRCh38: 3:12663925-12663925
35 RAF1 NM_002880.4(RAF1):c.*73T>A SNV Uncertain Significance
899432 rs932588742 GRCh37: 3:12625940-12625940
GRCh38: 3:12584441-12584441
36 RAF1 NM_002880.4(RAF1):c.654A>G (p.Arg218=) SNV Uncertain Significance
899635 rs898490426 GRCh37: 3:12647726-12647726
GRCh38: 3:12606227-12606227
37 RAF1 NM_002880.4(RAF1):c.-201C>A SNV Uncertain Significance
40577 rs532668125 GRCh37: 3:12705486-12705486
GRCh38: 3:12663987-12663987
38 RAF1 NM_002880.4(RAF1):c.*410A>G SNV Uncertain Significance
900510 rs1055682241 GRCh37: 3:12625603-12625603
GRCh38: 3:12584104-12584104
39 RAF1 NM_002880.4(RAF1):c.231C>T (p.Ser77=) SNV Uncertain Significance
509193 rs1450510914 GRCh37: 3:12653538-12653538
GRCh38: 3:12612039-12612039
40 RAF1 NM_002880.4(RAF1):c.-209G>A SNV Uncertain Significance
177838 rs727504351 GRCh37: 3:12705494-12705494
GRCh38: 3:12663995-12663995
41 RAF1 NM_002880.4(RAF1):c.-264C>G SNV Uncertain Significance
900848 rs894363344 GRCh37: 3:12705549-12705549
GRCh38: 3:12664050-12664050
42 RAF1, MKRN2 NM_002880.4(RAF1):c.*841C>T SNV Uncertain Significance
902116 rs1461713213 GRCh37: 3:12625172-12625172
GRCh38: 3:12583673-12583673
43 RAF1 NM_002880.4(RAF1):c.1292A>C (p.Lys431Thr) SNV Uncertain Significance
902234 rs747632183 GRCh37: 3:12632375-12632375
GRCh38: 3:12590876-12590876
44 RAF1, MKRN2 NM_002880.4(RAF1):c.*840A>T SNV Uncertain Significance
903003 rs2058212896 GRCh37: 3:12625173-12625173
GRCh38: 3:12583674-12583674
45 RAF1 NM_002880.4(RAF1):c.*706C>T SNV Uncertain Significance
903004 rs1466261579 GRCh37: 3:12625307-12625307
GRCh38: 3:12583808-12583808
46 RAF1 NM_002880.4(RAF1):c.*647G>T SNV Uncertain Significance
903005 rs1457071879 GRCh37: 3:12625366-12625366
GRCh38: 3:12583867-12583867
47 RAF1 NM_002880.4(RAF1):c.*120C>A SNV Uncertain Significance
903051 rs1575528605 GRCh37: 3:12625893-12625893
GRCh38: 3:12584394-12584394
48 RAF1 NM_002880.4(RAF1):c.843T>A (p.Ile281=) SNV Uncertain Significance
903109 rs2058826353 GRCh37: 3:12641906-12641906
GRCh38: 3:12600407-12600407
49 RAF1 NM_002880.4(RAF1):c.-53G>A SNV Uncertain Significance
903300 rs985291322 GRCh37: 3:12705338-12705338
GRCh38: 3:12663839-12663839
50 RAF1 NM_002880.4(RAF1):c.-59C>G SNV Uncertain Significance
903301 rs201603517 GRCh37: 3:12705344-12705344
GRCh38: 3:12663845-12663845

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

73
# 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:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.92 RAF1 CLCN7 CLCA4
2
Show member pathways
11.6 RAF1 CLCN7 CLCA4
3
Show member pathways
11.35 CLCN7 CLCA4
4 10.11 RAF1 CALCRL

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 angiogenesis GO:0001525 9.55 SOX18 CCBE1 CALCRL
2 chloride transport GO:0006821 9.26 CLCN7 CLCA4
3 lymphangiogenesis GO:0001946 9.1 SOX18 PTPN14 CCBE1
4 lymph vessel development GO:0001945 8.96 SOX18 CCBE1

Sources for Leopard Syndrome 2

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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