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LGSS
MCID: LGS001
MIFTS: 58

Legius Syndrome (LGSS)

Categories: Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases, Skin diseases
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Genes Variations Tissues Related diseases Publications Symptoms & Phenotypes
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Aliases & Classifications for Legius Syndrome

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MalaCards integrated aliases for Legius Syndrome:

Name: Legius Syndrome 57 24 19 42 58 73 28 12 5 38 75
Neurofibromatosis Type 1-Like Syndrome 57 24 42
Nfls 57 42 73
Neurofibromatosis 1-Like Syndrome 58 73
Lgss 57 73
Neurofibromatosis, Type 1-Like Syndrome 71
Neurofibromatosis Type 1 Like Syndrome 19
Nonmosaic Legius Syndrome 58
Nf1-Like Syndrome 58
Nonmosaic Lgss 58

Characteristics:


Inheritance:

Autosomal dominant 58 57

Prevelance:

1-9/100000 (Worldwide) 58

Age Of Onset:

Childhood,Infancy,Neonatal 58

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
some patients do not have dysmorphic features
phenotypic overlap with neurofibromatosis 1 (nf1, )


GeneReviews:

24
Penetrance The vast majority of individuals with spred1 pathogenic variants have café au lait macules and/or freckling; however, the age of pigment penetrance is not established. only two individuals (a male age 60 years and a child age 2 years), each with a presumed spred1 pathogenic variant, were reported not to have café au lait macules or freckling [brems et al 2007, messiaen et al 2009]....

Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Fetal diseases
Anatomical: Skin diseases Neuronal diseases
See all MalaCards categories (disease lists)
ICD10: 32
Orphanet: 58  
Rare skin diseases
Developmental anomalies during embryogenesis


Sources

Summaries for Legius Syndrome

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MedlinePlus Genetics: 42 Legius syndrome is a condition characterized by changes in skin coloring (pigmentation). Almost all affected individuals have multiple café-au-lait spots, which are flat patches on the skin that are darker than the surrounding area. Another pigmentation change, freckles in the armpits and groin, may occur in some affected individuals.Other signs and symptoms of Legius syndrome may include an abnormally large head (macrocephaly) and unusual facial characteristics. Although most people with Legius syndrome have normal intelligence, some affected individuals have been diagnosed with learning disabilities, attention-deficit disorder (ADD), or attention-deficit/hyperactivity disorder (ADHD).Many of the signs and symptoms of Legius syndrome also occur in a similar disorder called neurofibromatosis type 1. It can be difficult to tell the two disorders apart in early childhood. However, the features of the two disorders differ later in life.

MalaCards based summary: Legius Syndrome, also known as neurofibromatosis type 1-like syndrome, is related to neurofibromatosis, type i and noonan syndrome with multiple lentigines. An important gene associated with Legius Syndrome is SPRED1 (Sprouty Related EVH1 Domain Containing 1), and among its related pathways/superpathways are Signal Transduction and RAF/MAP kinase cascade. Affiliated tissues include skin, lung and brain, and related phenotypes are multiple cafe-au-lait spots and specific learning disability

OMIM®: 57 Legius syndrome is an autosomal dominant disorder that shows some similarities to neurofibromatosis type I (NF1; 162200), which is caused by mutation in the neurofibromin gene (613113); however, Legius syndrome is less severe. Individuals with Legius syndrome typically have multiple cafe-au-lait spots, sometimes associated with skin fold freckling, variable dysmorphic features such as hypertelorism or macrocephaly, lipomas, and mild learning disabilities or attention problems. Legius syndrome is not associated with neurofibromas, optic gliomas, Lisch nodules, or tumor predisposition. The SPRED1 gene encodes a negative regulator of the RAS-MAPK pathway, similar to neurofibromin, and thus may be considered a RASopathy (review by Brems et al., 2012). (611431) (Updated 08-Dec-2022)

UniProtKB/Swiss-Prot: 73 An autosomal dominant syndrome characterized mainly by cafe-au-lait macules without neurofibromas or other tumor manifestations of neurofibromatosis type 1, axillary freckling, and macrocephaly. Additional clinical manifestations include Noonan-like facial dysmorphism, lipomas, learning disabilities, and features of attention-deficit hyperactivity disorder.

GARD: 19 Legius syndrome, also known as NF1-like syndrome, is a rare, genetic skin pigmentation disorder characterized by multiple café-au-lait macules with or without axillary or inguinal freckling.

Orphanet: 58 Legius syndrome, also known as NF1-like syndrome, is a rare, genetic skin pigmentation disorder characterized by multiple café-au-lait macules with or without axillary or inguinal freckling.

Wikipedia: 75 Legius syndrome (LS) is an autosomal dominant condition characterized by cafe au lait spots. It was... more...

GeneReviews: NBK47312
Sources

Related Diseases for Legius Syndrome

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

(show top 50) (show all 76)
# Related Disease Score Top Affiliating Genes
1 neurofibromatosis, type i 31.8 SPRED1 NF1 HRAS
2 noonan syndrome with multiple lentigines 31.3 SPRY1 SPRED1 NF1 HRAS
3 noonan syndrome 1 31.1 SPRY1 SPRED2 SPRED1 NF1 HRAS
4 neurofibromatosis 31.0 SPRED1 NF1 HRAS
5 neurofibromatosis-noonan syndrome 30.9 SPRED1 NF1 HRAS
6 lipomatosis, multiple 30.5 SPRED1 NF1
7 learning disability 30.4 SPRED1 NF1
8 moyamoya disease 1 30.1 SPRED1 NF1
9 plexiform neurofibroma 30.0 SPRED1 NF1 HRAS
10 rasopathy 29.2 SPRY1 SPRED2 SPRED1 NF1 HRAS
11 mosaic legius syndrome 11.1
12 neurofibroma 10.4
13 contractures, pterygia, and spondylocarpotarsal fusion syndrome 1a 10.3
14 skin granular cell tumor 10.2 SPRED1 NF1
15 optic nerve neoplasm 10.2 SPRED1 NF1
16 cafe-au-lait spots, multiple 10.2
17 bap1 tumor predisposition syndrome 10.2
18 optic nerve glioma 10.2 SPRED1 NF1
19 conjunctival nevus 10.2 NF1 HRAS
20 acral lentiginous melanoma 10.2 NF1 HRAS
21 non-langerhans-cell histiocytosis 10.2 NF1 HRAS
22 adult malignant schwannoma 10.1 NF1 HRAS
23 neurilemmomatosis 10.1 SPRED1 NF1
24 pulmonic stenosis 10.1 NF1 HRAS
25 noonan syndrome and noonan-related syndrome 10.1 SPRED1 HRAS
26 malignant spindle cell melanoma 10.1 NF1 HRAS
27 malignant conjunctival melanoma 10.1 NF1 HRAS
28 conjunctival cancer 10.1 NF1 HRAS
29 nodular malignant melanoma 10.1 NF1 HRAS
30 duodenum cancer 10.1 NF1 HRAS
31 myelodysplastic/myeloproliferative neoplasm 10.1 NF1 HRAS
32 proteus syndrome 10.1 NF1 HRAS
33 schimmelpenning-feuerstein-mims syndrome 10.1 NF1 HRAS
34 pleomorphic rhabdomyosarcoma 10.1 NF1 HRAS
35 ocular melanoma 10.1 NF1 HRAS
36 pseudo-turner syndrome 10.1 SPRED2 HRAS
37 attention deficit-hyperactivity disorder 10.1
38 inherited cancer-predisposing syndrome 10.1
39 nevus, epidermal 10.1 NF1 HRAS
40 serous cystadenocarcinoma 10.1 NF1 HRAS
41 small intestine cancer 10.1 NF1 HRAS
42 skin benign neoplasm 10.1 NF1 HRAS
43 skeletal muscle cancer 10.1 NF1 HRAS
44 muscle cancer 10.1 NF1 HRAS
45 cardiovascular organ benign neoplasm 10.0 NF1 HRAS
46 neurofibromatosis, type ii 10.0
47 acoustic neuroma 10.0
48 malignant dermis tumor 10.0 SPRED1 NF1 HRAS
49 vulvar melanoma 10.0 SPRED1 NF1 HRAS
50 malignant skin fibrous histiocytoma 10.0 SPRED1 NF1 HRAS

Graphical network of the top 20 diseases related to Legius Syndrome:



Diseases related to Legius Syndrome
Sources

Symptoms & Phenotypes for Legius Syndrome

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Human phenotypes related to Legius Syndrome:

58 30 (show top 50) (show all 56)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 multiple cafe-au-lait spots 58 30 Hallmark (90%) Very frequent (99-80%)
 HP:0007565
2 specific learning disability 58 30 Frequent (33%) Frequent (79-30%)
 HP:0001328
3 axillary freckling 58 30 Frequent (33%) Frequent (79-30%)
 HP:0000997
4 inguinal freckling 58 30 Frequent (33%) Frequent (79-30%)
 HP:0030052
5 macrocephaly 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0000256
6 short stature 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0004322
7 multiple lipomas 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0001012
8 abnormal sternum morphology 30 Occasional (7.5%) HP:0000766
9 seizure 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0001250
10 scoliosis 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0002650
11 hypotonia 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0001252
12 hearing impairment 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0000365
13 cataract 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0000518
14 delayed speech and language development 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0000750
15 cognitive impairment 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0100543
16 attention deficit hyperactivity disorder 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0007018
17 nephrolithiasis 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0000787
18 motor delay 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0001270
19 mitral valve prolapse 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0001634
20 clinodactyly of the 5th finger 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0004209
21 pulmonic stenosis 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0001642
22 dystonia 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0001332
23 nephroblastoma 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0002667
24 ovarian neoplasm 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0100615
25 brain imaging abnormality 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0410263
26 paroxysmal atrial tachycardia 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0006671
27 desmoid tumors 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0100245
28 xanthelasma 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0001114
29 polydactyly 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0010442
30 chiari type i malformation 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0007099
31 vestibular schwannoma 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0009588
32 acute monocytic leukemia 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0004845
33 male urethral meatus stenosis 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0032077
34 non-small cell lung carcinoma 58 30 Very rare (1%) Very rare (<4-1%)
 HP:0030358
35 neurofibromas 58 30 Excluded (0%)
 HP:0001067
36 ptosis 30 HP:0000508
37 high palate 30 HP:0000218
38 short neck 30 HP:0000470
39 hypertelorism 30 HP:0000316
40 behavioral abnormality 58 Frequent (79-30%)
41 micrognathia 30 HP:0000347
42 low posterior hairline 30 HP:0002162
43 high, narrow palate 30 HP:0002705
44 epicanthus 30 HP:0000286
45 downslanted palpebral fissures 30 HP:0000494
46 low-set, posteriorly rotated ears 30 HP:0000368
47 lisch nodules 58 Excluded (0%)
48 triangular face 30 HP:0000325
49 neoplasm of the central nervous system 58 Excluded (0%)
50 abnormality of the sternum 58 Occasional (29-5%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Head And Neck Eyes:
ptosis
hypertelorism
downslanting palpebral fissures
epicanthal folds

Muscle Soft Tissue:
hypotonia
lipomas

Skin Nails Hair Skin:
axillary freckling
cafe-au-lait spots

Head And Neck Ears:
low-set posteriorly rotated ears

Chest Ribs Sternum Clavicles And Scapulae:
pectus deformities (in some patients)

Head And Neck Face:
noonan-like facies in a minority of patients
triangular face with age

Head And Neck Mouth:
short neck
micrognathia
high arched palate
deeply grooved philtrum
high peaks of upper lip vermilion border

Skin Nails Hair Hair:
low posterior hairline

Neurologic Central Nervous System:
no neurofibromas
learning difficulties

Neurologic Behavioral Psychiatric Manifestations:
attention deficit-hyperactivity

Head And Neck Head:
macrocephaly (less common)

Clinical features from OMIM®:

611431 (Updated 08-Dec-2022)

GenomeRNAi Phenotypes related to Legius Syndrome according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased cell migration GR00055-A-1 9.23 NF1 SPRED2
2 Increased cell migration GR00055-A-3 9.23 NF1 SPRED2

MGI Mouse Phenotypes related to Legius Syndrome:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 10 HRAS NF1 SPRED1 SPRED2 SPRED3 SPRY2
2 neoplasm MP:0002006 9.88 HRAS NF1 SPRY1 SPRY2 SPRY4
3 endocrine/exocrine gland MP:0005379 9.85 HRAS NF1 SPRED1 SPRED3 SPRY1 SPRY2
4 renal/urinary system MP:0005367 9.83 HRAS NF1 SPRED2 SPRED3 SPRY1
5 limbs/digits/tail MP:0005371 9.8 NF1 SPRED1 SPRED2 SPRY2 SPRY4
6 craniofacial MP:0005382 9.72 HRAS NF1 SPRED1 SPRY2 SPRY4
7 respiratory system MP:0005388 9.65 HRAS NF1 SPRED1 SPRY2 SPRY4
8 reproductive system MP:0005389 9.63 NF1 SPRED1 SPRED2 SPRED3 SPRY1 SPRY2
9 skeleton MP:0005390 9.43 HRAS NF1 SPRED1 SPRED2 SPRY2 SPRY4
10 vision/eye MP:0005391 9.1 NF1 SPRED1 SPRED2 SPRED3 SPRY2 SPRY4
Sources

Drugs & Therapeutics for Legius Syndrome

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Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Prevalence of Constitutional Mismatch-repair Deficiency Among Suspected Neurofibromatosis Type 1/Legius Syndrome Children Without a Malignancy and Without a NF1 or SPRED1 Mutation Unknown status NCT03757247
2 Variation in Gene Expression in Neurofibromatosis Type 1 Completed NCT00111384
3 Investigation Into the Natural History and Metabolic and Molecular Basis of RASopathies. Recruiting NCT04395495
4 Clinical, Genetic, and Epidemiologic Study of Children and Adults With RASopathies Recruiting NCT04888936
5 Acceptance and Commitment Therapy for Caregivers of Children With a RASopathy: An Internal Pilot Feasibility Study and Follow-up Phase III Randomized Controlled Trial Recruiting NCT05361811

Search NIH Clinical Center for Legius Syndrome

Sources

Genetic Tests for Legius Syndrome

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Genetic tests related to Legius Syndrome:

# Genetic test Affiliating Genes
1 Legius Syndrome 28 SPRED1
Sources

Anatomical Context for Legius Syndrome

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Organs/tissues related to Legius Syndrome:

MalaCards : Skin, Lung, Brain, Smooth Muscle, Eye, Liver
Sources

Publications for Legius Syndrome

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Articles related to Legius Syndrome:

(show top 50) (show all 193)
# Title Authors PMID Year
1
Review and update of SPRED1 mutations causing Legius syndrome. 62 24 57 5
22753041 2012
2
Identification of five novel SPRED1 germline mutations in Legius syndrome. 62 24 57 5
21649642 2011
3
Identification of SPRED1 deletions using RT-PCR, multiplex ligation-dependent probe amplification and quantitative PCR. 62 24 57 5
21548021 2011
4
SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype. 62 24 57 5
19443465 2009
5
Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. 24 57 5
17704776 2007
6
SPRED1 germline mutations caused a neurofibromatosis type 1 overlapping phenotype. 62 57 5
19366998 2009
7
The first Slovak Legius syndrome patient carrying the SPRED1 gene mutation. 62 24 5
28150585 2017
8
Interaction between a Domain of the Negative Regulator of the Ras-ERK Pathway, SPRED1 Protein, and the GTPase-activating Protein-related Domain of Neurofibromin Is Implicated in Legius Syndrome and Neurofibromatosis Type 1. 62 24 5
26635368 2016
9
A shared molecular mechanism underlies the human rasopathies Legius syndrome and Neurofibromatosis-1. 62 24 5
22751498 2012
10
Legius syndrome in fourteen families. 62 24 5
21089071 2011
11
Clinical and mutational spectrum of neurofibromatosis type 1-like syndrome. 62 24 5
19920235 2009
12
Neurofibromatosis type 1 molecular diagnosis: what can NGS do for you when you have a large gene with loss of function mutations? 24 5
25074460 2015
13
Pathogenic Mutations Associated with Legius Syndrome Modify the Spred1 Surface and Are Involved in Direct Binding to the Ras Inactivator Neurofibromin. 62 5
31401120 2019
14
The absence that makes the difference: choroidal abnormalities in Legius syndrome. 62 5
28747691 2017
15
Expanding the Noonan spectrum/RASopathy NGS panel: Benefits of adding NF1 and SPRED1. 62 24
32107864 2020
16
Clinical and Genetic Findings in Children with Neurofibromatosis Type 1, Legius Syndrome, and Other Related Neurocutaneous Disorders. 62 24
31370276 2019
17
The neurofibromin recruitment factor Spred1 binds to the GAP related domain without affecting Ras inactivation. 62 24
27313208 2016
18
Comprehensive RNA Analysis of the NF1 Gene in Classically Affected NF1 Affected Individuals Meeting NIH Criteria has High Sensitivity and Mutation Negative Testing is Reassuring in Isolated Cases With Pigmentary Features Only. 62 24
27322474 2016
19
Family with Legius syndrome (neurofibromatosis type 1-like syndrome). 62 24
25981987 2015
20
Legius syndrome: case report and review of literature. 62 24
25883013 2015
21
SPRED1, a RAS MAPK pathway inhibitor that causes Legius syndrome, is a tumour suppressor downregulated in paediatric acute myeloblastic leukaemia. 62 24
24469042 2015
22
Observations on intelligence and behavior in 15 patients with Legius syndrome. 62 24
21495177 2011
23
SPRED 1 mutations in a neurofibromatosis clinic. 62 24
20179001 2010
24
Pigmentary findings in neurofibromatosis type 1-like syndrome (Legius syndrome): potential diagnostic dilemmas. 62 24
19920242 2009
25
Splicing in action: assessing disease causing sequence changes. 5
16199547 2005
26
Mutational spectrum by phenotype: panel-based NGS testing of patients with clinical suspicion of RASopathy and children with multiple café-au-lait macules. 24
31573083 2020
27
Targeted Genomic Profiling of Acral Melanoma. 24
30657954 2019
28
Whole-genome landscape of mucosal melanoma reveals diverse drivers and therapeutic targets. 24
31320640 2019
29
Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype-phenotype correlation. 24
30190611 2019
30
Human tumor genomics and zebrafish modeling identify SPRED1 loss as a driver of mucosal melanoma. 24
30385465 2018
31
Mosaicism for a SPRED1 deletion revealed in a patient with clinically suspected mosaic neurofibromatosis. 24
27423141 2017
32
Timing, rates and spectra of human germline mutation. 24
26656846 2016
33
High Incidence of Noonan Syndrome Features Including Short Stature and Pulmonic Stenosis in Patients carrying NF1 Missense Mutations Affecting p.Arg1809: Genotype-Phenotype Correlation. 24
26178382 2015
34
SPRED1 disorder and predisposition to leukemia in children. 24
19643996 2009
35
The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation. 24
19467855 2009
36
A severe form of Noonan syndrome and autosomal dominant café-au-lait spots - evidence for different genetic origins. 24
19120036 2009
37
Spred is a Sprouty-related suppressor of Ras signalling. 24
11493923 2001
38
The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. 24
9207339 1997
39
National Institutes of Health Consensus Development Conference Statement: neurofibromatosis. Bethesda, Md., USA, July 13-15, 1987. 24
3152465 1988
40
Neurofibromatosis type 1: A comparison of the 1997 NIH and the 2021 revised diagnostic criteria in 75 children and adolescents. 62
35713653 2022
41
Awareness, use and understanding of nutrition labels among adults from five countries: Findings from the 2018-2020 International Food Policy Study. 62
36122623 2022
42
Serum neurofilament light chain levels are correlated with the infarct volume in patients with acute ischemic stroke. 62
36181119 2022
43
Advantages of graphical nutrition facts label: faster attention capture and improved healthiness judgement. 62
35894181 2022
44
Plasma neurofilament light chain as a biomarker of Alzheimer's disease in Subjective Cognitive Decline and Mild Cognitive Impairment. 62
35288777 2022
45
Ballistic Properties and Izod Impact Resistance of Novel Epoxy Composites Reinforced with Caranan Fiber (Mauritiella armata). 62
36015605 2022
46
System resilience and neighbourhood action on social determinants of health inequalities: an English Case Study. 62
35801904 2022
47
The Elastic Modulus and Damage Stress-Strain Model of Polypropylene Fiber and Nano Clay Modified Lime Treated Soil under Axial Load. 62
35808649 2022
48
RASopathies: Dermatologists' viewpoints. 62
35138057 2022
49
Neurofilament proteins as a potential biomarker in chemotherapy-induced polyneuropathy. 62
35133982 2022
50
Challenges in the diagnosis of neurofibromatosis type 1 (NF1) in young children facilitated by means of revised diagnostic criteria including genetic testing for pathogenic NF1 gene variants. 62
34928431 2022
Sources

Variations for Legius Syndrome

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ClinVar genetic disease variations for Legius Syndrome:

5 (show top 50) (show all 456)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SPRED1 NM_152594.3(SPRED1):c.423+1G>A SNV Pathogenic
 1811 rs1566868058 GRCh37: 15:38617011-38617011
GRCh38: 15:38324810-38324810
2 SPRED1 NM_152594.3(SPRED1):c.643C>T (p.Gln215Ter) SNV Pathogenic
 1812 rs121434314 GRCh37: 15:38641683-38641683
GRCh38: 15:38349482-38349482
3 SPRED1 NM_152594.3(SPRED1):c.784A>T (p.Arg262Ter) SNV Pathogenic
 1815 rs121434317 GRCh37: 15:38643314-38643314
GRCh38: 15:38351113-38351113
4 SPRED1 NM_152594.3(SPRED1):c.131T>A (p.Val44Asp) SNV Pathogenic
 1816 rs121434318 GRCh37: 15:38591672-38591672
GRCh38: 15:38299471-38299471
5 SPRED1 NC_000015.10:g.(?_38299373)_(38357249_?)del DEL Pathogenic
 417474 GRCh37: 15:38591574-38649450
GRCh38: 15:38299373-38357249
6 SPRED1 NM_152594.3(SPRED1):c.423+2T>C SNV Pathogenic
 505193 rs1555391161 GRCh37: 15:38617012-38617012
GRCh38: 15:38324811-38324811
7 SPRED1 NM_152594.3(SPRED1):c.7_20del (p.Glu3fs) DEL Pathogenic
 547789 rs1555386651 GRCh37: 15:38545392-38545405
GRCh38: 15:38253191-38253204
8 SPRED1 NM_152594.3(SPRED1):c.1044_1046delinsC (p.Arg349fs) INDEL Pathogenic
 565472 rs1566876929 GRCh37: 15:38643574-38643576
GRCh38: 15:38351373-38351375
9 overlap with 4 genes NC_000015.10:g.(?_38253166)_(39021201_?)del DEL Pathogenic
 583432 GRCh37: 15:38545367-39313402
GRCh38: 15:38253166-39021201
10 SPRED1 NC_000015.10:g.(?_38253180)_(38351670_?)del DEL Pathogenic
 584323 GRCh37: 15:38545381-38643871
GRCh38: 15:38253180-38351670
11 SPRED1 NM_152594.3(SPRED1):c.306_307dup (p.Phe103fs) DUP Pathogenic
 650362 rs1595746834 GRCh37: 15:38614539-38614540
GRCh38: 15:38322338-38322339
12 SPRED1 NC_000015.10:g.(?_38253186)_(38253227_?)del DEL Pathogenic
 832303 GRCh37: 15:38545387-38545428
GRCh38:
13 SPRED1 NM_152594.3(SPRED1):c.103G>T (p.Gly35Ter) SNV Pathogenic
 547791 rs1555389690 GRCh37: 15:38591644-38591644
GRCh38: 15:38299443-38299443
14 SPRED1 NM_152594.3(SPRED1):c.1A>G (p.Met1Val) SNV Pathogenic
 930640 rs1894017295 GRCh37: 15:38545387-38545387
GRCh38: 15:38253186-38253186
15 SPRED1 NC_000015.9:g.(?_38545367)_(38545438_?)del DEL Pathogenic
 1073447 GRCh37: 15:38545367-38545438
GRCh38:
16 SPRED1 NM_152594.3(SPRED1):c.1015C>T (p.Gln339Ter) SNV Pathogenic
 592540 rs1566876895 GRCh37: 15:38643545-38643545
GRCh38: 15:38351344-38351344
17 SPRED1 NM_152594.3(SPRED1):c.1011C>A (p.Tyr337Ter) SNV Pathogenic
 1391856 GRCh37: 15:38643541-38643541
GRCh38: 15:38351340-38351340
18 SPRED1 NM_152594.3(SPRED1):c.305del (p.Thr102fs) DEL Pathogenic
 1420112 GRCh37: 15:38614539-38614539
GRCh38: 15:38322338-38322338
19 SPRED1 NM_152594.3(SPRED1):c.692del (p.Pro230_Leu231insTer) DEL Pathogenic
 1415230 GRCh37: 15:38643220-38643220
GRCh38: 15:38351019-38351019
20 SPRED1 NM_152594.3(SPRED1):c.40del (p.Tyr14fs) DEL Pathogenic
 1386579 GRCh37: 15:38591580-38591580
GRCh38: 15:38299379-38299379
21 SPRED1 NM_152594.3(SPRED1):c.421C>T (p.Gln141Ter) SNV Pathogenic
 409627 rs1060502505 GRCh37: 15:38617008-38617008
GRCh38: 15:38324807-38324807
22 SPRED1 NM_152594.3(SPRED1):c.355dup (p.Ala119fs) DUP Pathogenic
 943158 rs1895621783 GRCh37: 15:38614588-38614589
GRCh38: 15:38322387-38322388
23 SPRED1 NM_152594.3(SPRED1):c.619A>T (p.Arg207Ter) SNV Pathogenic
 960145 rs368660900 GRCh37: 15:38641659-38641659
GRCh38: 15:38349458-38349458
24 SPRED1 NM_152594.3(SPRED1):c.385G>T (p.Glu129Ter) SNV Pathogenic
 1072751 GRCh37: 15:38616972-38616972
GRCh38: 15:38324771-38324771
25 SPRED1 NM_152594.3(SPRED1):c.190C>T (p.Arg64Ter) SNV Pathogenic
 1813 rs121434315 GRCh37: 15:38591731-38591731
GRCh38: 15:38299530-38299530
26 SPRED1 NM_152594.3(SPRED1):c.1151_1152del (p.Glu384fs) MICROSAT Pathogenic
 241989 rs878855228 GRCh37: 15:38643679-38643680
GRCh38: 15:38351478-38351479
27 SPRED1 NM_152594.3(SPRED1):c.342_343del (p.Gly115fs) MICROSAT Pathogenic
 536687 rs1555391061 GRCh37: 15:38614574-38614575
GRCh38: 15:38322373-38322374
28 SPRED1 NM_152594.3(SPRED1):c.384dup (p.Glu129fs) DUP Pathogenic
 568389 rs1566868022 GRCh37: 15:38616967-38616968
GRCh38: 15:38324766-38324767
29 SPRED1 NM_152594.3(SPRED1):c.234dup (p.Asp79fs) DUP Pathogenic
 573472 rs1566867209 GRCh37: 15:38614462-38614463
GRCh38: 15:38322261-38322262
30 SPRED1 NM_152594.3(SPRED1):c.301_307del (p.Leu101fs) DEL Pathogenic
 578285 rs1566867246 GRCh37: 15:38614533-38614539
GRCh38: 15:38322332-38322338
31 SPRED1 NM_152594.3(SPRED1):c.613C>T (p.Gln205Ter) SNV Pathogenic
 1451597 GRCh37: 15:38641653-38641653
GRCh38: 15:38349452-38349452
32 SPRED1 NC_000015.10:g.(?_38299363)_(38324819_?)del DEL Pathogenic
 831554 GRCh37: 15:38591564-38617020
GRCh38:
33 SPRED1 NM_152594.3(SPRED1):c.1273del (p.Met425fs) DEL Pathogenic
 1693579 GRCh37: 15:38643802-38643802
GRCh38: 15:38351601-38351601
34 SPRED1 NM_152594.3(SPRED1):c.637C>T (p.Gln213Ter) SNV Pathogenic
 1814 rs121434316 GRCh37: 15:38641677-38641677
GRCh38: 15:38349476-38349476
35 SPRED1 NM_152594.3(SPRED1):c.1099_1102del (p.Ser367fs) MICROSAT Pathogenic
 468788 rs1555392783 GRCh37: 15:38643625-38643628
GRCh38: 15:38351424-38351427
36 SPRED1 NM_152594.3(SPRED1):c.676C>T (p.Gln226Ter) SNV Pathogenic
 536686 rs1555392609 GRCh37: 15:38641716-38641716
GRCh38: 15:38349515-38349515
37 SPRED1 NM_152594.3(SPRED1):c.923_924del (p.Ser308fs) MICROSAT Pathogenic
 468800 rs1555392759 GRCh37: 15:38643451-38643452
GRCh38: 15:38351250-38351251
38 SPRED1 NM_152594.3(SPRED1):c.305C>G (p.Thr102Arg) SNV Pathogenic
 520837 rs754706111 GRCh37: 15:38614539-38614539
GRCh38: 15:38322338-38322338
39 SPRED1 NM_152594.3(SPRED1):c.1053del (p.Lys351fs) DEL Pathogenic
 581681 rs1566876954 GRCh37: 15:38643580-38643580
GRCh38: 15:38351379-38351379
40 SPRED1 NM_152594.3(SPRED1):c.900dup (p.Lys301Ter) DUP Pathogenic
 640306 rs1595763656 GRCh37: 15:38643429-38643430
GRCh38: 15:38351228-38351229
41 SPRED1 NM_152594.3(SPRED1):c.1151del (p.Glu384fs) DEL Pathogenic
 642469 rs1595763928 GRCh37: 15:38643681-38643681
GRCh38: 15:38351480-38351480
42 SPRED1 NM_152594.3(SPRED1):c.903_906del (p.Leu302fs) DEL Pathogenic
 817884 rs1595763662 GRCh37: 15:38643432-38643435
GRCh38: 15:38351231-38351234
43 SPRED1 NM_152594.3(SPRED1):c.800G>A (p.Trp267Ter) SNV Pathogenic
 641432 rs1595763557 GRCh37: 15:38643330-38643330
GRCh38: 15:38351129-38351129
44 SPRED1 NM_152594.3(SPRED1):c.326_329dup (p.Arg110delinsSerTer) DUP Pathogenic
 636663 rs1595746858 GRCh37: 15:38614558-38614559
GRCh38: 15:38322357-38322358
45 SPRED1 NM_152594.3(SPRED1):c.177dup (p.Ile60fs) DUP Pathogenic
 955012 rs1895110802 GRCh37: 15:38591712-38591713
GRCh38: 15:38299511-38299512
46 SPRED1 NM_152594.3(SPRED1):c.906_910del (p.Leu302fs) MICROSAT Pathogenic
 636493 rs1595763659 GRCh37: 15:38643430-38643434
GRCh38: 15:38351229-38351233
47 SPRED1 NM_152594.3(SPRED1):c.1232_1241del (p.Ser411fs) DEL Pathogenic
 1068652 GRCh37: 15:38643758-38643767
GRCh38: 15:38351557-38351566
48 SPRED1 NM_152594.3(SPRED1):c.794dup (p.Asp265fs) DUP Pathogenic
 1068945 GRCh37: 15:38643323-38643324
GRCh38: 15:38351122-38351123
49 SPRED1 NC_000015.9:g.(?_38591554)_(38591768_?)del DEL Pathogenic
 1073310 GRCh37: 15:38591554-38591768
GRCh38:
50 SPRED1 NC_000015.9:g.(?_38591568)_(38643870_?)del DEL Pathogenic
 1073448 GRCh37: 15:38591568-38643870
GRCh38:

UniProtKB/Swiss-Prot genetic disease variations for Legius Syndrome:

73
# Symbol AA change Variation ID SNP ID
1 SPRED1 p.Trp31Cys VAR_064827
2 SPRED1 p.Val44Asp VAR_064828 rs121434318

Copy number variations for Legius Syndrome from CNVD:

6
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 91538 15 31400000 37900000 Copy number SPRED1 Legius syndrome
Sources

Expression for Legius Syndrome

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Search GEO for disease gene expression data for Legius Syndrome.
Sources

Pathways for Legius Syndrome

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Pathways related to Legius Syndrome according to GeneCards Suite gene sharing:

(show all 13)
# Super pathways Score Top Affiliating Genes
1
Signal Transduction 66
13.28 HRAS NF1 SPRED1 SPRED2 SPRED3 SPRY1
2
RAF/MAP kinase cascade 66
Show member pathways
 13 SPRED3 SPRED2 SPRED1 NF1 HRAS
3
Signaling by Receptor Tyrosine Kinases 66
12.27 SPRY2 SPRY1 SPRED2 SPRED1 HRAS
4
Negative regulation of FGFR1 signaling 66
Show member pathways
 12.2 SPRY2 SPRED2 SPRED1 HRAS
5
Signaling by FGFR2 66
Show member pathways
 11.84 SPRY2 SPRED2 SPRED1 HRAS
6
Tyrosine Kinases / Adaptors 3
11.8 SPRY2 SPRY1 SPRED1
7
Development EPO-induced Jak-STAT pathway 22
Show member pathways
 11.68 SPRED2 SPRED1 HRAS
8
Signaling by EGFR 66
Show member pathways
 11.57 SPRY2 SPRY1 HRAS
9
MAP Kinase Signaling 3
11.31 SPRY2 SPRY1 NF1 HRAS
10
BDNF-TrkB signaling 74
Show member pathways
 11.3 NF1 HRAS
11
Oncogenic MAPK signaling 66
Show member pathways
 11.2 SPRED3 SPRED2 SPRED1 NF1 HRAS
12
Syndecan-2-mediated signaling events 61
11.04 NF1 HRAS
13
Regulation of Ras family activation 61
Show member pathways
 11 NF1 HRAS
Sources

GO Terms for Legius Syndrome

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Biological processes related to Legius Syndrome according to GeneCards Suite gene sharing:

(show all 24)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of transforming growth factor beta receptor signaling pathway GO:0030512 10.18 SPRY2 SPRY1 SPRED3 SPRED2 SPRED1
2 negative regulation of cell population proliferation GO:0008285 10.14 HRAS NF1 SPRY1 SPRY2
3 negative regulation of MAP kinase activity GO:0043407 10.13 SPRY4 SPRY3 SPRY2 SPRY1 NF1
4 animal organ development GO:0048513 10.1 SPRY4 SPRY3 SPRY2 SPRY1
5 negative regulation of MAPK cascade GO:0043409 10.1 SPRY3 SPRED3 SPRED2 SPRED1 NF1
6 negative regulation of ERK1 and ERK2 cascade GO:0070373 10.1 SPRY4 SPRY3 SPRY2 SPRY1 SPRED3 SPRED2
7 negative regulation of epithelial to mesenchymal transition GO:0010719 10.07 SPRY2 SPRY1 SPRED3 SPRED2 SPRED1
8 negative regulation of fibroblast growth factor receptor signaling pathway GO:0040037 10.06 SPRY1 SPRY2 SPRY3 SPRY4
9 negative regulation of angiogenesis GO:0016525 10.05 SPRY2 SPRED1 NF1
10 negative regulation of GTPase activity GO:0034260 10 SPRY2 SPRY1 HRAS
11 negative regulation of peptidyl-threonine phosphorylation GO:0010801 9.99 SPRY2 SPRED2 SPRED1
12 negative regulation of Ras protein signal transduction GO:0046580 9.97 NF1 SPRY1 SPRY2 SPRY3 SPRY4
13 fibroblast proliferation GO:0048144 9.92 NF1 HRAS
14 establishment of mitotic spindle orientation GO:0000132 9.91 SPRY2 SPRY1
15 metanephros development GO:0001656 9.91 SPRY1 NF1
16 regulation of cell population proliferation GO:0042127 9.9 SPRY2 NF1 HRAS
17 regulation of long-term neuronal synaptic plasticity GO:0048169 9.88 NF1 HRAS
18 positive regulation of DNA damage response, signal transduction by p53 class mediator GO:0043517 9.87 SPRED2 SPRED1
19 bud elongation involved in lung branching GO:0060449 9.86 SPRY2 SPRY1
20 negative regulation of neurotrophin TRK receptor signaling pathway GO:0051387 9.85 SPRY1 SPRY2
21 regulation of protein deacetylation GO:0090311 9.84 SPRED2 SPRED1
22 multicellular organism development GO:0007275 9.7 SPRED1 SPRED2 SPRED3 SPRY1 SPRY2 SPRY3
23 negative regulation of lens fiber cell differentiation GO:1902747 9.65 SPRY2 SPRY1 SPRED3 SPRED2 SPRED1
24 regulation of signal transduction GO:0009966 9.23 SPRY4 SPRY3 SPRY2 SPRY1 SPRED3 SPRED2

Molecular functions related to Legius Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein kinase binding GO:0019901 9.76 SPRED1 SPRED2 SPRED3 SPRY2
2 stem cell factor receptor binding GO:0005173 9.26 SPRED2 SPRED1
3 protein serine/threonine kinase inhibitor activity GO:0030291 9.1 SPRED1 SPRED2 SPRY2
Sources

Sources for Legius Syndrome

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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
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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