Leopard Syndrome 1 disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

LPRD1 MCID: LPR012 MIFTS: 48	Leopard Syndrome 1 (LPRD1) Categories: Cardiovascular diseases, Ear diseases, Genetic diseases, Reproductive diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Expand all tables

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Aliases & Classifications for Leopard Syndrome 1

MalaCards integrated aliases for Leopard Syndrome 1:

Name: Leopard Syndrome 1 ⁵⁷ ¹² ⁷² ²⁹ ¹³ ⁶ ³⁷

Noonan Syndrome with Multiple Lentigines 1 ¹² ¹⁵

Multiple Lentigines Syndrome ⁵⁷ ⁶

Lprd1 ⁵⁷ ⁷²

Lentiginosis, Cardiomyopathic ⁵⁷

Leopard Syndrome, Type 1 ³⁹

Multiple Lentigines ⁷⁰

Leopard Syndrome ⁷⁰

Characteristics:

OMIM®:

⁵⁷ (Updated 20-May-2021)

Inheritance:
autosomal dominant

Miscellaneous:
leopard is an acronym: lentigines, ekg abnormalities, ocular hypertelorism, obstructive cardiomyopathy, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and deafness
lentigines may be absent
lentigines may be congenital or develop in first months to years of life

HPO:

³¹

leopard syndrome 1:
Inheritance autosomal dominant inheritance

Classifications:

MalaCards categories:
Global: Genetic diseases
Anatomical: Reproductive diseases Ear diseases Cardiovascular diseases

See all MalaCards categories (disease lists)

External Ids:

Disease Ontology ¹² DOID:0080548

OMIM® ⁵⁷ 151100

OMIM Phenotypic Series ⁵⁷ PS151100

MeSH ⁴⁴ D044542

MedGen ⁴¹ C0175704 C4551484 CN074218

UMLS ⁷⁰ C0175704 C1328931

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Summaries for Leopard Syndrome 1

OMIM® : ⁵⁷ LEOPARD is an acronym for the manifestations of this syndrome as listed by Gorlin et al. (1969): multiple lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness. (151100) (Updated 20-May-2021)

MalaCards based summary : Leopard Syndrome 1, also known as noonan syndrome with multiple lentigines 1, is related to noonan syndrome with multiple lentigines and lentigines, and has symptoms including hyposmia An important gene associated with Leopard Syndrome 1 is PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11), and among its related pathways/superpathways are Immune response Role of DAP12 receptors in NK cells and Development Slit-Robo signaling. Affiliated tissues include ovary, heart and cerebellum, and related phenotypes are hypertrophic cardiomyopathy and pulmonic stenosis

Disease Ontology : ¹² A Noonan syndrome with multiple lentigines that has material basis in heterozygous mutation in the PTPN11 gene on chromosome 12q24.

UniProtKB/Swiss-Prot : ⁷² LEOPARD syndrome 1: A disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness.

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Related Diseases for Leopard Syndrome 1

Diseases in the Leopard Syndrome 1 family:

Leopard Syndrome 2

Leopard Syndrome 3

Diseases related to Leopard Syndrome 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 38)

#	Related Disease	Score	Top Affiliating Genes
1	noonan syndrome with multiple lentigines	32.6	RAF1 PTPN11 BRAF
2	lentigines	31.3	RAF1 PTPN11 BRAF
3	noonan syndrome 1	28.7	RPL6 RAF1 PTPN11 PALM3 MIR3193 MAPKAPK5
4	lentiginosis, inherited patterned	11.2
5	hypertelorism	10.2
6	leopard syndrome 2	10.2	RAF1 PTPN11
7	branchiootic syndrome 1	10.2
8	pseudo-turner syndrome	10.2
9	noonan syndrome and noonan-related syndrome	10.2	RAF1 PTPN11 BRAF
10	pilocytic astrocytoma of cerebellum	10.1	CLCN6 BRAF
11	pilomyxoid astrocytoma	10.1	RAF1 CLCN6 BRAF
12	neurofibromatosis	10.1
13	pilocytic astrocytoma	10.1	RAF1 PTPN11 BRAF
14	cerebellar astrocytoma	10.1	CLCN6 BRAF
15	rasopathy	10.0	RPL6 RAF1 PTPN11 BRAF
16	juvenile xanthogranuloma	10.0	PTPN11 BRAF
17	cafe-au-lait spots, multiple	9.9
18	dyschromatosis universalis hereditaria 1	9.9
19	pectus excavatum	9.9
20	dowling-degos disease 1	9.9
21	teeth, supernumerary	9.9
22	renal hypodysplasia/aplasia 1	9.9
23	watson syndrome	9.9
24	alopecia-epilepsy-oligophrenia syndrome of moynahan	9.9
25	cryptorchidism, unilateral or bilateral	9.9
26	neurofibromatosis-noonan syndrome	9.9
27	hypospadias	9.9
28	hypertrophic cardiomyopathy	9.9
29	graves' disease	9.9
30	heart septal defect	9.9
31	atrial heart septal defect	9.9
32	dermatitis	9.9
33	rhabdomyosarcoma	9.9
34	pulmonary valve stenosis	9.9
35	ocular hypertension	9.9
36	aorto-right ventricular tunnel	9.9
37	cardiofaciocutaneous syndrome 1	9.9	SPRED3 RAF1 PTPN11 BRAF
38	metachondromatosis	9.9	RPL6 PTPN11 MIR3193 FAM219B CLCN6

Graphical network of the top 20 diseases related to Leopard Syndrome 1:

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Symptoms & Phenotypes for Leopard Syndrome 1

Human phenotypes related to Leopard Syndrome 1:

³¹ (show all 41)

#	Description	HPO Frequency	HPO Source Accession
1	hypertrophic cardiomyopathy ³¹	very rare (1%)	HP:0001639
2	pulmonic stenosis ³¹	very rare (1%)	HP:0001642
3	ptosis ³¹		HP:0000508
4	short neck ³¹		HP:0000470
5	hypertelorism ³¹		HP:0000316
6	mandibular prognathia ³¹		HP:0000303
7	pectus carinatum ³¹		HP:0000768
8	sensorineural hearing impairment ³¹		HP:0000407
9	short stature ³¹		HP:0004322
10	delayed puberty ³¹		HP:0000823
11	intellectual disability, mild ³¹		HP:0001256
12	strabismus ³¹		HP:0000486
13	cleft palate ³¹		HP:0000175
14	cryptorchidism ³¹		HP:0000028
15	cubitus valgus ³¹		HP:0002967
16	low-set ears ³¹		HP:0000369
17	webbed neck ³¹		HP:0000465
18	epicanthus ³¹		HP:0000286
19	pectus excavatum ³¹		HP:0000767
20	scapular winging ³¹		HP:0003691
21	third degree atrioventricular block ³¹		HP:0001709
22	kyphoscoliosis ³¹		HP:0002751
23	bundle branch block ³¹		HP:0011710
24	limited elbow movement ³¹		HP:0002996
25	depressed nasal ridge ³¹		HP:0000457
26	micropenis ³¹		HP:0000054
27	protruding ear ³¹		HP:0000411
28	hypospadias ³¹		HP:0000047
29	spina bifida occulta ³¹		HP:0003298
30	triangular face ³¹		HP:0000325
31	multiple lentigines ³¹		HP:0001003
32	missing ribs ³¹		HP:0000921
33	hyposmia ³¹		HP:0004409
34	unilateral renal agenesis ³¹		HP:0000122
35	posteriorly rotated ears ³¹		HP:0000358
36	cafe-au-lait spot ³¹		HP:0000957
37	subvalvular aortic stenosis ³¹		HP:0001682
38	hypoplasia of the ovary ³¹		HP:0008724
39	aplasia of the ovary ³¹		HP:0010463
40	delayed menarche ³¹		HP:0012569
41	parietal bossing ³¹		HP:0000242

Symptoms via clinical synopsis from OMIM®:

⁵⁷ (Updated 20-May-2021)

Head And Neck Eyes:
ptosis
hypertelorism
strabismus
epicanthal folds

Chest Ribs Sternum Clavicles And Scapulae:
pectus carinatum
pectus excavatum
winged scapulae
absent ribs

Endocrine Features:
delayed puberty
late menarche

Skeletal Limbs:
cubitus valgus
limited elbow mobility

Skeletal Spine:
kyphoscoliosis
spina bifida occulta

Head And Neck Face:
triangular face
prognathism
biparietal bossing

Genitourinary Kidneys:
unilateral renal agenesis

Neurologic Central Nervous System:
mental retardation, mild

Skin Nails Hair Skin:
cafe-au-lait spots
lentigines, 1-5mm, dark (especially neck and trunk)
cafe-noir spots (trunk)

Genitourinary Internal Genitalia Female:
absent ovary
hypoplastic ovary

Head And Neck Neck:
short neck
pterygium colli

Growth Weight:
short stature

Head And Neck Mouth:
cleft palate

Head And Neck Ears:
low-set ears
posteriorly rotated ears
sensorineural hearing loss
prominent ears

Cardiovascular Heart:
bundle branch block
pulmonic stenosis (40%)
superior ekg axis (-60 degrees to -120 degrees)
hypertrophic cardiomyopathy (20%)
subaortic stenosis
more

Head And Neck Nose:
hyposmia
broad, flat nose

Growth Other:
growth retardation

Genitourinary External Genitalia Male:
small penis
hypospadias (50%)

Genitourinary Internal Genitalia Male:
cryptorchidism (unilateral or bilateral)

Clinical features from OMIM®:

151100 (Updated 20-May-2021)

UMLS symptoms related to Leopard Syndrome 1:

hyposmia

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Drugs & Therapeutics for Leopard Syndrome 1

Interventional clinical trials:

#	Name	Status	NCT ID	Phase	Drugs
1	Consequences of Noonan Syndrome/LEOPARD Syndrome Associated Shp2 Mutations on Different Signaling Pathways Activation: Relationship With Hormonal Sensitivity	Unknown status	NCT02486731
2	Investigation Into the Natural History and Metabolic and Molecular Basis of RASopathies.	Recruiting	NCT04395495

Search NIH Clinical Center for Leopard Syndrome 1

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Genetic Tests for Leopard Syndrome 1

Genetic tests related to Leopard Syndrome 1:

#	Genetic test	Affiliating Genes
1	Leopard Syndrome 1 ²⁹	PTPN11

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Anatomical Context for Leopard Syndrome 1

MalaCards organs/tissues related to Leopard Syndrome 1:

⁴⁰

Ovary, Heart, Cerebellum, Myeloid, Skin

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Publications for Leopard Syndrome 1

Articles related to Leopard Syndrome 1:

(show top 50) (show all 127)

#	Title	Authors	PMID	Year
1	Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome. ⁵⁷ ⁶	Carvajal-Vergara X...Lemischka IR	20535210	2010
2	IMAGE CARDIO MED. A patient with LEOPARD syndrome and PTPN11 mutation. ⁶ ⁵⁷	Lehmann LH...Katus HA	19273734	2009
3	Multiple granular cell tumors are an associated feature of LEOPARD syndrome caused by mutation in PTPN11. ⁶ ⁵⁷	Schrader KA...McGillivray BC	19054014	2009
4	Genotype-phenotype analysis and natural history of left ventricular hypertrophy in LEOPARD syndrome. ⁵⁷ ⁶	Limongelli G...Calabro R	18241070	2008
5	PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects. ⁵⁷ ⁶	Kontaridis MI...Neel BG	16377799	2006
6	Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease. ⁶ ⁵⁷	Tartaglia M...Gelb BD	16358218	2006
7	Genetic heterogeneity in LEOPARD syndrome: two families with no mutations in PTPN11. ⁶ ⁵⁷	Kalidas K...Jeffery S	15690106	2005
8	Two novel and one recurrent PTPN11 mutations in LEOPARD syndrome. ⁵⁷ ⁶	Yoshida R...Ogata T	15389709	2004
9	Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 gene. ⁶ ⁵⁷	Digilio MC...Dallapiccola B	12058348	2002
10	Molecular and clinical studies in 107 Noonan syndrome affected individuals with PTPN11 mutations. ⁶	Athota JP...Shetty S	32164556	2020
11	ClinGen's RASopathy Expert Panel consensus methods for variant interpretation. ⁶	Gelb BD...ClinGen RASopathy Working Group	29493581	2018
12	Novel mutations and their genotype-phenotype correlations in patients with Noonan syndrome, using next-generation sequencing. ⁶	Tafazoli A...Abbaszadegan MR	28957739	2018
13	Craniosynostosis in patients with RASopathies: Accumulating clinical evidence for expanding the phenotype. ⁶	Ueda K...Okamoto N	28650561	2017
14	Cochlear implantation and clinical features in patients with Noonan syndrome and Noonan syndrome with multiple lentigines caused by a mutation in PTPN11. ⁶	van Nierop JWI...Kunst HPM	28483241	2017
15	Ocular Manifestations of Noonan Syndrome: A Prospective Clinical and Genetic Study of 25 Patients. ⁶	van Trier DC...Cruysberg JR	27521173	2016
16	Lentiginous phenotypes caused by diverse pathogenic genes (SASH1 and PTPN11): clinical and molecular discrimination. ⁶	Zhang J...Yao Z	27659786	2016
17	Genomic Classification and Prognosis in Acute Myeloid Leukemia. ⁶	Papaemmanuil E...Campbell PJ	27276561	2016
18	Retrospective study of prenatal ultrasound findings in newborns with a Noonan spectrum disorder. ⁶	Hakami F...Mason-Suares H	26918529	2016
19	The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. ⁶	Arber DA...Vardiman JW	27069254	2016
20	De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies. ⁶	Homsy J...Chung WK	26785492	2015
21	[Arnold-Chiari malformation in Noonan syndrome and other syndromes of the RAS/MAPK pathway]. ⁶	Ejarque I...Perez-Aytes A	25912702	2015
22	Neonatal pulmonary arterial hypertension and Noonan syndrome: two fatal cases with a specific RAF1 mutation. ⁶	Hopper RK...Hudgins L	25706034	2015
23	PTPN11 mutation manifesting as LEOPARD syndrome associated with hypertrophic plexi and neuropathic pain. ⁶	Spatola M...Croquelois A	25884655	2015
24	Subclonal mutations in SETBP1 confer a poor prognosis in juvenile myelomonocytic leukemia. ⁶	Stieglitz E...Loh ML	25395418	2015
25	Juvenile myelomonocytic leukaemia and Noonan syndrome. ⁶	Strullu M...Cave H	25097206	2014
26	Molecular basis of gain-of-function LEOPARD syndrome-associated SHP2 mutations. ⁶	Yu ZH...Zhang ZY	24935154	2014
27	Noonan and LEOPARD syndrome Shp2 variants induce heart displacement defects in zebrafish. ⁶	Bonetti M...den Hertog J	24718990	2014
28	Structure-energy-based predictions and network modelling of RASopathy and cancer missense mutations. ⁶	Kiel C...Serrano L	24803665	2014
29	LEOPARD syndrome: clinical dilemmas in differential diagnosis of RASopathies. ⁶	Santoro C...Perrotta S	24767283	2014
30	Structural insights into Noonan/LEOPARD syndrome-related mutants of protein-tyrosine phosphatase SHP2 (PTPN11). ⁶	Qiu W...Chirgadze NY	24628801	2014
31	Diagnosis of Noonan syndrome and related disorders using target next generation sequencing. ⁶	Lepri FR...Dallapiccola B	24451042	2014
32	Medulloblastoma in a patient with the PTPN11 p.Thr468Met mutation. ⁶	Rankin J...Hanemann CO	23813970	2013
33	Syndromic Hearing Loss in Association with PTPN11-Related Disorder: The Experience of Cochlear Implantation in a Child with LEOPARD Syndrome. ⁶	Chu HS...Hong SH	23799168	2013
34	Age-dependent germline mosaicism of the most common noonan syndrome mutation shows the signature of germline selection. ⁶	Yoon SR...Arnheim N	23726368	2013
35	LEOPARD syndrome: a variant of Noonan syndrome strongly associated with hypertrophic cardiomyopathy. ⁶	Carcavilla A...Ezquieta B	24775816	2013
36	Extensive abdominal lipomatosis in a patient with Noonan/LEOPARD syndrome (Noonan syndrome-Multiple Lentigines). ⁶	Piard J...Leheup B	22528600	2012
37	A rasopathy phenotype with severe congenital hypertrophic obstructive cardiomyopathy associated with a PTPN11 mutation and a novel variant in SOS1. ⁶	Fahrner JA...Gunay-Aygun M	22585553	2012
38	Pediatric cardiomyopathy: importance of genetic and metabolic evaluation. ⁶	Kindel SJ...Ware SM	22555271	2012
39	The PTPN11 loss-of-function mutation Q510E-Shp2 causes hypertrophic cardiomyopathy by dysregulating mTOR signaling. ⁶	Schramm C...Krenz M	22058153	2012
40	LEOPARD-type SHP2 mutant Gln510Glu attenuates cardiomyocyte differentiation and promotes cardiac hypertrophy via dysregulation of Akt/GSK-3β/β-catenin signaling. ⁶	Ishida H...Ozono K	21803945	2011
41	Implantable cardioverter defibrillator for progressive hypertrophic cardiomyopathy in a patient with LEOPARD syndrome and a novel PTPN11 mutation Gln510His. ⁶	Wakabayashi Y...Kosho T	21910226	2011
42	RASopathies: Clinical Diagnosis in the First Year of Life. ⁶	Digilio MC...Dallapiccola B	22190897	2011
43	Cancer risk in patients with Noonan syndrome carrying a PTPN11 mutation. ⁶	Jongmans MC...Hoogerbrugge N	21407260	2011
44	Lethal presentation of neurofibromatosis and Noonan syndrome. ⁶	Prada CE...Hopkin RJ	21567923	2011
45	PTPN11-associated mutations in the heart: has LEOPARD changed Its RASpots? ⁶	Lauriol J...Kontaridis MI	22681964	2011
46	LEOPARD Syndrome with PTPN11 Gene Mutation Showing Six Cardinal Symptoms of LEOPARD. ⁶	Kim J...Lee MG	21747628	2011
47	Rapamycin reverses hypertrophic cardiomyopathy in a mouse model of LEOPARD syndrome-associated PTPN11 mutation. ⁶	Marin TM...Kontaridis MI	21339643	2011
48	LEOPARD syndrome in an infant with severe hypertrophic cardiomyopathy and PTPN11 mutation. ⁶	Ganigara M...Kumar RS	21677813	2011
49	Co-occurring PTPN11 and SOS1 gene mutations in Noonan syndrome: does this predict a more severe phenotype? ⁶	Brasil AS...Bertola DR	21340158	2010
50	Familial cases of atypical clinical features genetically diagnosed as LEOPARD syndrome (multiple lentigines syndrome). ⁶	Kato H...Yoshimura K	20883402	2010

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Genes for Leopard Syndrome 1

Genes related to Leopard Syndrome 1 (3 elite genes):

(show all 20)

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubMed IDs
1	PTPN11	Protein Tyrosine Phosphatase Non-Receptor Type 11	Protein Coding	1349.89	Molecular basis known ⁵⁷ Pathogenic ⁶ Causative variation ⁷² Genetic Tests ²⁹ Likely pathogenic ⁶ DISEASES inferred ¹⁵ GeneCards inferred via : Disorders Variants (show sections)	15690106 20308328
2	BRAF	B-Raf Proto-Oncogene, Serine/Threonine Kinase	Protein Coding	400	Pathogenic ⁶
3	RAF1	Raf-1 Proto-Oncogene, Serine/Threonine Kinase	Protein Coding	400	Pathogenic ⁶	17603482 17603483 25706034 (more) 19933846 19953625 20052757
4	RPL6	Ribosomal Protein L6	Protein Coding	7.61	GeneCards inferred via : Variants (show sections)
5	MIR3193	MicroRNA 3193	RNA Gene	6.23	DISEASES inferred ¹⁵
6	FAM219B	Family With Sequence Similarity 219 Member B	Protein Coding	5.92	DISEASES inferred ¹⁵
7	CLCN6	Chloride Voltage-Gated Channel 6	Protein Coding	5.8	DISEASES inferred ¹⁵
8	PTPN20	Protein Tyrosine Phosphatase Non-Receptor Type 20	Protein Coding	5.38	DISEASES inferred ¹⁵
9	PHETA1	PH Domain Containing Endocytic Trafficking Adaptor 1	Protein Coding	5.36	DISEASES inferred ¹⁵
10	BORCS7	BLOC-1 Related Complex Subunit 7	Protein Coding	5.28	DISEASES inferred ¹⁵
11	PALM3	Paralemmin 3	Protein Coding	5.23	DISEASES inferred ¹⁵
12	ACBD4	Acyl-CoA Binding Domain Containing 4	Protein Coding	5.18	DISEASES inferred ¹⁵
13	MIR4513	MicroRNA 4513	RNA Gene	5.17	DISEASES inferred ¹⁵
14	CNPY1	Canopy FGF Signaling Regulator 1	Protein Coding	5.16	DISEASES inferred ¹⁵
15	SPRED3	Sprouty Related EVH1 Domain Containing 3	Protein Coding	5.15	DISEASES inferred ¹⁵
16	ARPC5L	Actin Related Protein 2/3 Complex Subunit 5 Like	Protein Coding	5.14	DISEASES inferred ¹⁵
17	MAPKAPK5	MAPK Activated Protein Kinase 5	Protein Coding	5.1	DISEASES inferred ¹⁵
18	CPLX3	Complexin 3	Protein Coding	5.09	DISEASES inferred ¹⁵
19	SCAMP2	Secretory Carrier Membrane Protein 2	Protein Coding	4.99	DISEASES inferred ¹⁵
20	ACTR3B	Actin Related Protein 3B	Protein Coding	4.97	DISEASES inferred ¹⁵

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Variations for Leopard Syndrome 1

ClinVar genetic disease variations for Leopard Syndrome 1:

⁶ (show top 50) (show all 184)

#	Gene	Name	Type	Significance	ClinVarId	dbSNP ID	Position
1	RAF1	NM_001354689.3(RAF1):c.1516G>A (p.Asp506Asn)	SNV	Pathogenic	21341	rs80338798	GRCh37: 3:12627260-12627260 GRCh38: 3:12585761-12585761
2	RAF1	NM_001354689.3(RAF1):c.1897C>G (p.Leu633Val)	SNV	Pathogenic	13960	rs80338797	GRCh37: 3:12626123-12626123 GRCh38: 3:12584624-12584624
3	BRAF	NM_001374258.1(BRAF):c.721A>C (p.Thr241Pro)	SNV	Pathogenic	29807	rs387906661	GRCh37: 7:140501351-140501351 GRCh38: 7:140801551-140801551
4	BRAF	NM_001374258.1(BRAF):c.735A>T (p.Leu245Phe)	SNV	Pathogenic	40348	rs397507466	GRCh37: 7:140501337-140501337 GRCh38: 7:140801537-140801537
5	PTPN11	NM_002834.5(PTPN11):c.1529A>C (p.Gln510Pro)	SNV	Pathogenic	13344	rs121918470	GRCh37: 12:112926909-112926909 GRCh38: 12:112489105-112489105
6	PTPN11	NM_002834.5(PTPN11):c.1381G>A (p.Ala461Thr)	SNV	Pathogenic	13342	rs121918468	GRCh37: 12:112926248-112926248 GRCh38: 12:112488444-112488444
7	PTPN11	NM_002834.5(PTPN11):c.1381G>T (p.Ala461Ser)	SNV	Pathogenic	40546	rs121918468	GRCh37: 12:112926248-112926248 GRCh38: 12:112488444-112488444
8	PTPN11	NM_002834.5(PTPN11):c.1381G>A (p.Ala461Thr)	SNV	Pathogenic	13342	rs121918468	GRCh37: 12:112926248-112926248 GRCh38: 12:112488444-112488444
9	PTPN11	NM_002834.5(PTPN11):c.1493G>T (p.Arg498Leu)	SNV	Pathogenic	40554	rs397507542	GRCh37: 12:112926873-112926873 GRCh38: 12:112489069-112489069
10	PTPN11	NM_002834.5(PTPN11):c.1517A>C (p.Gln506Pro)	SNV	Pathogenic	40563	rs397507548	GRCh37: 12:112926897-112926897 GRCh38: 12:112489093-112489093
11	PTPN11	NM_002834.5(PTPN11):c.1528C>G (p.Gln510Glu)	SNV	Pathogenic	40566	rs397507549	GRCh37: 12:112926908-112926908 GRCh38: 12:112489104-112489104
12	PTPN11	NM_002834.4(PTPN11):c.836A>C (p.Tyr279Ser)	SNV	Pathogenic	65666	rs121918456	GRCh37: 12:112910827-112910827 GRCh38: 12:112473023-112473023
13	PTPN11	NM_002834.5(PTPN11):c.1517A>C (p.Gln506Pro)	SNV	Pathogenic	40563	rs397507548	GRCh37: 12:112926897-112926897 GRCh38: 12:112489093-112489093
14	RAF1	NM_001354689.3(RAF1):c.1897C>G (p.Leu633Val)	SNV	Pathogenic	13960	rs80338797	GRCh37: 3:12626123-12626123 GRCh38: 3:12584624-12584624
15	PTPN11	NM_002834.5(PTPN11):c.215C>G (p.Ala72Gly)	SNV	Pathogenic	13325	rs121918454	GRCh37: 12:112888199-112888199 GRCh38: 12:112450395-112450395
16	PTPN11	NM_002834.5(PTPN11):c.174C>G (p.Asn58Lys)	SNV	Pathogenic	40489	rs397507506	GRCh37: 12:112888158-112888158 GRCh38: 12:112450354-112450354
17	PTPN11	NM_002834.5(PTPN11):c.218C>T (p.Thr73Ile)	SNV	Pathogenic	13334	rs121918462	GRCh37: 12:112888202-112888202 GRCh38: 12:112450398-112450398
18	PTPN11	NM_002834.5(PTPN11):c.1529A>C (p.Gln510Pro)	SNV	Pathogenic	13344	rs121918470	GRCh37: 12:112926909-112926909 GRCh38: 12:112489105-112489105
19	PTPN11	NM_002834.5(PTPN11):c.181G>A (p.Asp61Asn)	SNV	Pathogenic	40495	rs397507510	GRCh37: 12:112888165-112888165 GRCh38: 12:112450361-112450361
20	PTPN11	NM_002834.5(PTPN11):c.214G>T (p.Ala72Ser)	SNV	Pathogenic	13324	rs121918453	GRCh37: 12:112888198-112888198 GRCh38: 12:112450394-112450394
21	PTPN11	NM_002834.5(PTPN11):c.1508G>A (p.Gly503Glu)	SNV	Pathogenic	40561	rs397507546	GRCh37: 12:112926888-112926888 GRCh38: 12:112489084-112489084
22	PTPN11	NM_002834.5(PTPN11):c.214G>T (p.Ala72Ser)	SNV	Pathogenic	13324	rs121918453	GRCh37: 12:112888198-112888198 GRCh38: 12:112450394-112450394
23	PTPN11	NM_002834.5(PTPN11):c.228G>T (p.Glu76Asp)	SNV	Pathogenic	40502	rs397507514	GRCh37: 12:112888212-112888212 GRCh38: 12:112450408-112450408
24	PTPN11	NM_002834.5(PTPN11):c.172A>G (p.Asn58Asp)	SNV	Pathogenic	40487	rs397507505	GRCh37: 12:112888156-112888156 GRCh38: 12:112450352-112450352
25	PTPN11	NM_002834.5(PTPN11):c.767A>G (p.Gln256Arg)	SNV	Pathogenic	40518	rs397507523	GRCh37: 12:112910758-112910758 GRCh38: 12:112472954-112472954
26	PTPN11	NM_002834.5(PTPN11):c.1493G>T (p.Arg498Leu)	SNV	Pathogenic	40554	rs397507542	GRCh37: 12:112926873-112926873 GRCh38: 12:112489069-112489069
27	PTPN11	NM_002834.5(PTPN11):c.1528C>G (p.Gln510Glu)	SNV	Pathogenic	40566	rs397507549	GRCh37: 12:112926908-112926908 GRCh38: 12:112489104-112489104
28	PTPN11	NM_002834.5(PTPN11):c.1529A>C (p.Gln510Pro)	SNV	Pathogenic	13344	rs121918470	GRCh37: 12:112926909-112926909 GRCh38: 12:112489105-112489105
29	PTPN11	NM_002834.4(PTPN11):c.1529A>G (p.Gln510Arg)	SNV	Pathogenic	13345	rs121918470	GRCh37: 12:112926909-112926909 GRCh38: 12:112489105-112489105
30	PTPN11	NM_002834.5(PTPN11):c.802G>A (p.Gly268Ser)	SNV	Pathogenic	44614	rs397507527	GRCh37: 12:112910793-112910793 GRCh38: 12:112472989-112472989
31	PTPN11	NM_002834.5(PTPN11):c.1472C>T (p.Pro491Leu)	SNV	Pathogenic	40552	rs397507540	GRCh37: 12:112926852-112926852 GRCh38: 12:112489048-112489048
32	PTPN11	NM_002834.5(PTPN11):c.184T>G (p.Tyr62Asp)	SNV	Pathogenic	13329	rs121918460	GRCh37: 12:112888168-112888168 GRCh38: 12:112450364-112450364
33	PTPN11	NM_002834.5(PTPN11):c.853T>C (p.Phe285Leu)	SNV	Pathogenic	40528	rs397507531	GRCh37: 12:112910844-112910844 GRCh38: 12:112473040-112473040
34	PTPN11	NM_002834.5(PTPN11):c.1507G>A (p.Gly503Arg)	SNV	Pathogenic	40559	rs397507545	GRCh37: 12:112926887-112926887 GRCh38: 12:112489083-112489083
35	PTPN11	NM_002834.5(PTPN11):c.1510A>G (p.Met504Val)	SNV	Pathogenic	40562	rs397507547	GRCh37: 12:112926890-112926890 GRCh38: 12:112489086-112489086
36	PTPN11	NM_002834.5(PTPN11):c.836A>G (p.Tyr279Cys)	SNV	Pathogenic	13328	rs121918456	GRCh37: 12:112910827-112910827 GRCh38: 12:112473023-112473023
37	PTPN11	NM_002834.5(PTPN11):c.836A>G (p.Tyr279Cys)	SNV	Pathogenic	13328	rs121918456	GRCh37: 12:112910827-112910827 GRCh38: 12:112473023-112473023
38	PTPN11	NM_002834.5(PTPN11):c.844A>G (p.Ile282Val)	SNV	Pathogenic	40525	rs397507529	GRCh37: 12:112910835-112910835 GRCh38: 12:112473031-112473031
39	PTPN11	NM_002834.5(PTPN11):c.1391G>C (p.Gly464Ala)	SNV	Pathogenic	13343	rs121918469	GRCh37: 12:112926258-112926258 GRCh38: 12:112488454-112488454
40	PTPN11	NM_002834.5(PTPN11):c.1492C>T (p.Arg498Trp)	SNV	Pathogenic	40553	rs397507541	GRCh37: 12:112926872-112926872 GRCh38: 12:112489068-112489068
41	RAF1	NM_001354689.3(RAF1):c.770C>T (p.Ser257Leu)	SNV	Pathogenic	13957	rs80338796	GRCh37: 3:12645699-12645699 GRCh38: 3:12604200-12604200
42	PTPN11	NM_002834.5(PTPN11):c.922A>G (p.Asn308Asp)	SNV	Pathogenic	13326	rs28933386	GRCh37: 12:112915523-112915523 GRCh38: 12:112477719-112477719
43	PTPN11	NM_002834.5(PTPN11):c.923A>G (p.Asn308Ser)	SNV	Pathogenic	13327	rs121918455	GRCh37: 12:112915524-112915524 GRCh38: 12:112477720-112477720
44	PTPN11	NM_002834.5(PTPN11):c.1510A>G (p.Met504Val)	SNV	Pathogenic	40562	rs397507547	GRCh37: 12:112926890-112926890 GRCh38: 12:112489086-112489086
45	PTPN11	NM_002834.5(PTPN11):c.1507G>C (p.Gly503Arg)	SNV	Pathogenic	40558	rs397507545	GRCh37: 12:112926887-112926887 GRCh38: 12:112489083-112489083
46	RAF1	NM_001354689.3(RAF1):c.1532C>T (p.Thr511Ile)	SNV	Pathogenic	21342	rs80338799	GRCh37: 3:12627244-12627244 GRCh38: 3:12585745-12585745
47	RAF1	NM_001354689.3(RAF1):c.770C>T (p.Ser257Leu)	SNV	Pathogenic	13957	rs80338796	GRCh37: 3:12645699-12645699 GRCh38: 3:12604200-12604200
48	PTPN11	NM_002834.5(PTPN11):c.836A>G (p.Tyr279Cys)	SNV	Pathogenic	13328	rs121918456	GRCh37: 12:112910827-112910827 GRCh38: 12:112473023-112473023
49	PTPN11	NM_002834.5(PTPN11):c.1391G>C (p.Gly464Ala)	SNV	Pathogenic	13343	rs121918469	GRCh37: 12:112926258-112926258 GRCh38: 12:112488454-112488454
50	PTPN11	NM_002834.5(PTPN11):c.1403C>T (p.Thr468Met)	SNV	Pathogenic	13331	rs121918457	GRCh37: 12:112926270-112926270 GRCh38: 12:112488466-112488466

UniProtKB/Swiss-Prot genetic disease variations for Leopard Syndrome 1:

⁷²

#	Symbol	AA change	Variation ID	SNP ID
1	PTPN11	p.Tyr279Cys	VAR_015614	rs121918456
2	PTPN11	p.Thr468Met	VAR_015621	rs121918457
3	PTPN11	p.Tyr279Ser	VAR_027188	rs121918456
4	PTPN11	p.Ala461Thr	VAR_027190	rs121918468
5	PTPN11	p.Gly464Ala	VAR_027191	rs121918469
6	PTPN11	p.Arg498Leu	VAR_027192	rs397507542
7	PTPN11	p.Arg498Trp	VAR_027193	rs397507541
8	PTPN11	p.Gln506Pro	VAR_027194	rs397509345
9	PTPN11	p.Gln510Pro	VAR_027196	rs121918470
10	PTPN11	p.Gln510Glu	VAR_076499	rs397507549

Sources

Expression for Leopard Syndrome 1

Search GEO for disease gene expression data for Leopard Syndrome 1.

Sources

Pathways for Leopard Syndrome 1

Pathways related to Leopard Syndrome 1 according to GeneCards Suite gene sharing:

#	Super pathways	Score	Top Affiliating Genes
1	Immune response Role of DAP12 receptors in NK cells ²³ Show member pathways Immune response CD16 signaling in NK cells ²³ Natural killer cell mediated cytotoxicity ³⁶	12.14	RAF1 PTPN11 BRAF ACTR3B
2	Development Slit-Robo signaling ²³ Show member pathways Cell adhesion Gap junctions ²³ Neurophysiological process Receptor-mediated axon growth repulsion ²³ Pathogenic Escherichia coli infection ¹	11.96	RAF1 BRAF ARPC5L ACTR3B
3	Development VEGF signaling via VEGFR2 - generic cascades ²³ Show member pathways Development VEGF signaling and activation ²³ VEGF - VEGF R2 Signaling Pathways ⁶⁴	11.84	RAF1 PTPN11 MAPKAPK5 BRAF
4	Oncogenic MAPK signaling ⁶⁵ Show member pathways Signaling by BRAF and RAF fusions ⁶⁵	11.71	RAF1 CLCN6 BRAF
5	Fc gamma R-mediated phagocytosis ³⁶	11.48	RAF1 ARPC5L ACTR3B
6	MAP Kinase Signaling ⁴	10.98	RAF1 PTPN11 MAPKAPK5 BRAF
7	Renal cell carcinoma ³⁶	10.97	RAF1 PTPN11 BRAF

Sources

GO Terms for Leopard Syndrome 1

Cellular components related to Leopard Syndrome 1 according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	Arp2/3 protein complex	GO:0005885	8.62	ARPC5L ACTR3B

Biological processes related to Leopard Syndrome 1 according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	Arp2/3 complex-mediated actin nucleation	GO:0034314	9.16	ARPC5L ACTR3B
2	neurotrophin TRK receptor signaling pathway	GO:0048011	8.96	RAF1 PTPN11
3	face development	GO:0060324	8.62	RAF1 BRAF

Molecular functions related to Leopard Syndrome 1 according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	MAP kinase kinase kinase activity	GO:0004709	8.96	RAF1 BRAF
2	mitogen-activated protein kinase kinase binding	GO:0031434	8.62	RAF1 BRAF

Sources

Sources for Leopard Syndrome 1

¹ BioSystems

² BitterDB

³ CDC

⁴ Cell Signaling Technology

⁵ ClinicalTrials

⁶ ClinVar

⁷ CNVD

⁸ Cochrane Library

⁹ Cosmic

¹⁰ dbSNP

¹¹ DGIdb

¹² Disease Ontology

¹³ diseasecard

¹⁴ DiseaseEnhancer

¹⁵ DISEASES

¹⁶ DrugBank

¹⁷ EFO

¹⁸ ExPASy

¹⁹ FMA

²⁰ GARD

²¹ GeneAnalytics

²² GeneCards

²³ GeneGo (Thomson Reuters)

²⁴ GeneHancer via GeneCards

²⁵ GeneReviews

²⁶ GenomeRNAi

²⁷ GEO DataSets

²⁸ GO

²⁹ GTR

³⁰ HMDB

³¹ HPO

³² ICD10

³³ ICD10 via Orphanet

³⁴ ICD9CM

³⁵ IUPHAR

³⁶ KEGG

³⁷ LifeMap

³⁸ LncRNADisease

³⁹ LOVD

⁴⁰ MalaCards

⁴¹ MedGen

⁴² MedlinePlus

⁴³ MedlinePlus Genetics

⁴⁴ MeSH

⁴⁵ MESH via Orphanet

⁴⁶ MGI

⁴⁷ miR2Disease

⁴⁸ NCBI Bookshelf

⁴⁹ NCI

⁵⁰ NCIt

⁵¹ NDF-RT

⁵² NIH Clinical Center

⁵³ NINDS

⁵⁴ Novoseek

⁵⁵ Novus Biologicals

⁵⁶ OMIM via Orphanet

⁵⁷ OMIM® (Updated 20-May-2021)

⁵⁸ Orphanet

⁵⁹ PathCards

⁶⁰ PharmGKB

⁶¹ PubMed

⁶² PubMed Health

⁶³ QIAGEN

⁶⁴ R&D Systems

⁶⁵ Reactome

⁶⁶ Sino Biological

⁶⁷ SNOMED-CT

⁶⁸ SNOMED-CT via HPO

⁶⁹ Tocris

⁷⁰ UMLS

⁷¹ UMLS via Orphanet

⁷² UniProtKB/Swiss-Prot

⁷³ Wikipedia

Leopard Syndrome 1 (LPRD1)

Aliases & Classifications for Leopard Syndrome 1

MalaCards integrated aliases for Leopard Syndrome 1:

Characteristics:

OMIM®:

HPO:

Classifications:

External Ids:

Summaries for Leopard Syndrome 1

Related Diseases for Leopard Syndrome 1

Diseases in the Leopard Syndrome 1 family:

Diseases related to Leopard Syndrome 1 via text searches within MalaCards or GeneCards Suite gene sharing:

Graphical network of the top 20 diseases related to Leopard Syndrome 1:

Symptoms & Phenotypes for Leopard Syndrome 1

Human phenotypes related to Leopard Syndrome 1:

Symptoms via clinical synopsis from OMIM®:

Clinical features from OMIM®:

UMLS symptoms related to Leopard Syndrome 1:

Drugs & Therapeutics for Leopard Syndrome 1

Interventional clinical trials:

Genetic Tests for Leopard Syndrome 1

Genetic tests related to Leopard Syndrome 1:

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MalaCards organs/tissues related to Leopard Syndrome 1:

Publications for Leopard Syndrome 1

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Genes for Leopard Syndrome 1

Genes related to Leopard Syndrome 1 (3 elite genes):

Variations for Leopard Syndrome 1

ClinVar genetic disease variations for Leopard Syndrome 1:

UniProtKB/Swiss-Prot genetic disease variations for Leopard Syndrome 1:

Expression for Leopard Syndrome 1

Pathways for Leopard Syndrome 1

Pathways related to Leopard Syndrome 1 according to GeneCards Suite gene sharing:

GO Terms for Leopard Syndrome 1

Cellular components related to Leopard Syndrome 1 according to GeneCards Suite gene sharing:

Biological processes related to Leopard Syndrome 1 according to GeneCards Suite gene sharing:

Molecular functions related to Leopard Syndrome 1 according to GeneCards Suite gene sharing:

Sources for Leopard Syndrome 1