VL
MCID: MGL002
MIFTS: 51

Megalencephalic Leukoencephalopathy with Subcortical Cysts (VL) malady

Genetic diseases, Rare diseases, Neuronal diseases categories
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Summaries for Megalencephalic Leukoencephalopathy with Subcortical Cysts

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NIH Rare Diseases:42 Megalencephalic leukoencephalopathy with subcortical cysts is a condition that affects brain development and function. children with this condition have an enlarged brain (megalencephaly) that is evident at birth or within the first year of life. they also have an abnormality of the brain's white matter (leukoencephalopathy). the leukoencephalopathy may ultimately result in abnormal muscle tensing (spasticity), difficulty coordinating movements (ataxia), cysts in the brain (subcortical cysts), abnormal muscle tone (dystonia), swallowing difficulties, speech difficulties, and seizures. despite the brain abnormalities people with this condition tend to have only mild to moderate learning impairment. this condition may affect a child’s ability to walk, however some children are able to walk well into adulthood. it is important to protect people with mlc from even mild head trauma, because head trauma can cause further impairments and may lead to coma. this condition is genetic and is passed through families in an autosomal recessive pattern. it is most often caused by changes in the mlc1 gene. last updated: 6/4/2009

MalaCards based summary: Megalencephalic Leukoencephalopathy with Subcortical Cysts, also known as vacuolating megalencephalic leukoencephalopathy with subcortical cysts, is related to megalencephalic leukoencephalopathy with subcortical cysts 2a and megalencephalic leukoencephalopathy with subcortical cysts 2b, remitting, with or without mental retardation, and has symptoms including An important gene associated with Megalencephalic Leukoencephalopathy with Subcortical Cysts is MLC1 (megalencephalic leukoencephalopathy with subcortical cysts 1), and among its related pathways are Hepatic ABC Transporters and Mineral absorption. The compounds chlorambucil and sodium have been mentioned in the context of this disorder. Affiliated tissues include brain, cortex and monocytes, and related mouse phenotypes are hearing/vestibular/ear and cardiovascular system.

Genetics Home Reference:21 Megalencephalic leukoencephalopathy with subcortical cysts is a progressive condition that affects brain development and function. Individuals with this condition typically have an enlarged brain (megalencephaly) that is evident at birth or within the first year of life. Megalencephaly progressively increases the size of the head. Affected people also have leukoencephalopathy, an abnormality of the brain's white matter. White matter consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses. In megalencephalic leukoencephalopathy with subcortical cysts, the myelin is swollen and stippled with fluid-filled pockets (vacuoles). Over time, the swelling decreases and the myelin begins to waste away (atrophy). Individuals affected with this condition may develop subcortical cysts below an area of the brain called the cerebral cortex. These cysts can grow in size and number.

Wikipedia:65 Megalencephalic leukoencephalopathy with subcortical cysts (MLC, or Van der Knaap disease) is a form of... more...

Descriptions from OMIM:46 604004,613925,613926

GeneReviews summary for mlc

Aliases & Classifications for Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Sources:
19GeneReviews, 42NIH Rare Diseases, 20GeneTests, 21Genetics Home Reference, 46OMIM, 48Orphanet, 62UMLS, 26ICD10 via Orphanet, 63UMLS via Orphanet
See all sources

Megalencephalic Leukoencephalopathy with Subcortical Cysts, Aliases & Descriptions:

Name: Megalencephalic Leukoencephalopathy with Subcortical Cysts 19 42 20 21 46 48 62
Vacuolating Megalencephalic Leukoencephalopathy with Subcortical Cysts 19 42 21 48
Mlc 42 21 48
Leukoencephalopathy with Swelling and Cysts 42 21
Vacuolating Leukoencephalopathy 21 62
Lvm 42 21
Leukoencephalopathy with Swelling and a Discrepantly Mild Course 21
Infantile Leukoencephalopathy and Megalencephaly 21
 
Megalencephaly - Cystic Leukodystrophy 48
Megalencephaly-Cystic Leukodystrophy 42
Megalencephalic Leukodystrophy 48
Van Der Knaap Syndrome 48
Van Der Knapp Disease 21
Van Der Knaap Disease 19
Derivative Chromosome 62
Vl 21


Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Genetic diseases, Rare diseases
Anatomical: Neuronal diseases


Characteristics (Orphanet epidemiological data):

48
megalencephalic leukoencephalopathy with subcortical cysts:
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: <1/1000000; Age of onset: Neonatal/infancy


External Ids:

ICD10 via Orphanet26 E75.2
UMLS via Orphanet63 C1858854

Related Diseases for Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Diseases in the Megalencephalic Leukoencephalopathy with Subcortical Cysts family:

Mlc1-Related Megalencephalic Leukoencephalopathy with Subcortical Cysts Hepacam-Related Megalencephalic Leukoencephalopathy with Subcortical Cysts
Megalencephalic Leukoencephalopathy with Subcortical Cysts 2a Megalencephalic Leukoencephalopathy with Subcortical Cysts 1

Diseases related to Megalencephalic Leukoencephalopathy with Subcortical Cysts via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show all 29)
idRelated DiseaseScoreTop Affiliating Genes
1megalencephalic leukoencephalopathy with subcortical cysts 2a10.8
2megalencephalic leukoencephalopathy with subcortical cysts 2b, remitting, with or without mental retardation10.8
3megalencephalic leukoencephalopathy with subcortical cysts 110.8
4mlc1-related megalencephalic leukoencephalopathy with subcortical cysts10.6
5hepacam-related megalencephalic leukoencephalopathy with subcortical cysts10.6
6alexander disease10.5
7leukodystrophy10.5
8endotheliitis10.2
9visceral leishmaniasis10.2
10myeloma10.2
11hepatocellular carcinoma10.0
12leukemia10.0
13digeorge syndrome10.0
14influenza10.0
15intestinal disease10.0
16ischemia10.0
17liver cancer10.0
18lung cancer10.0
19alzheimer's disease10.0
20arthritis10.0
21chronic lymphocytic leukemia10.0
22myasthenia gravis10.0
23myocardial infarction10.0
24rheumatoid arthritis10.0
25inferior myocardial infarction10.0
26neuropathy10.0
27peripheral neuropathy10.0
28haemophilus influenzae10.0
29malignant glioma9.8AQP4, CLCN2, MCL1

Graphical network of the top 20 diseases related to Megalencephalic Leukoencephalopathy with Subcortical Cysts:



Diseases related to megalencephalic leukoencephalopathy with subcortical cysts

Symptoms for Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Symptoms by clinical synopsis from OMIM:

604004

Clinical features from OMIM:

604004,613925,613926

HPO human phenotypes related to Megalencephalic Leukoencephalopathy with Subcortical Cysts:

(show all 11)
id Description Frequency HPO Source Accession
1 autosomal recessive inheritance HP:0000007
2 macrocephaly HP:0000256
3 seizures HP:0001250
4 ataxia HP:0001251
5 intellectual disability, mild HP:0001256
6 spasticity HP:0001257
7 motor delay HP:0001270
8 megalencephaly HP:0001355
9 infantile onset HP:0003593
10 diffuse spongiform leukoencephalopathy HP:0006943
11 diffuse swelling of cerebral white matter HP:0007341

Drugs & Therapeutics for Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Drug clinical trials:

Search ClinicalTrials for Megalencephalic Leukoencephalopathy with Subcortical Cysts

Search NIH Clinical Center for Megalencephalic Leukoencephalopathy with Subcortical Cysts

Genetic Tests for Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Genetic tests related to Megalencephalic Leukoencephalopathy with Subcortical Cysts:

id Genetic test Affiliating Genes
1 Megalencephalic Leukoencephalopathy with Subcortical Cysts20 MLC1

Anatomical Context for Megalencephalic Leukoencephalopathy with Subcortical Cysts

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MalaCards organs/tissues related to Megalencephalic Leukoencephalopathy with Subcortical Cysts:

32
Brain, Cortex, Monocytes

Animal Models for Megalencephalic Leukoencephalopathy with Subcortical Cysts or affiliated genes

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MGI Mouse Phenotypes related to Megalencephalic Leukoencephalopathy with Subcortical Cysts:

36
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053778.7FBLN1, AQP4, TRPV4
2MP:00053858.2TRPV4, AQP4, CLCN2, FBLN1, ATP1B1
3MP:00107718.1TRPV4, BAMBI, MCL1, FBLN1

Publications for Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Articles related to Megalencephalic Leukoencephalopathy with Subcortical Cysts:

(show top 50)    (show all 53)
idTitleAuthorsYear
1
Teaching neuroimages: Resolution of MRI abnormalities in megalencephalic leukoencephalopathy with subcortical cysts. (24821940)
2014
2
Twelve-year monitoring of a patient with megalencephalic leukoencephalopathy with subcortical cysts. (24584635)
2014
3
Megalencephalic leukoencephalopathy with subcortical cysts protein 1 regulates glial surface localization of GLIALCAM from fish to humans. (24824219)
2014
4
Megalencephalic leukoencephalopathy with subcortical cysts protein-1 modulates endosomal pH and protein trafficking in astrocytes: relevance to MLC disease pathogenesis. (24561067)
2014
5
Clinical, Neuroimaging, and Genetic Characteristics of Megalencephalic Leukoencephalopathy With Subcortical Cysts inA Egyptian Patients. (24315536)
2014
6
Expanding the spectrum of megalencephalic leukoencephalopathy with subcortical cysts in two patients with GLIALCAM mutations. (24202401)
2013
7
Megalencephalic leukoencephalopathy with subcortical cysts. (24273671)
2013
8
Monocytes and macrophages as biomarkers for the diagnosis of megalencephalic leukoencephalopathy with subcortical cysts. (23851226)
2013
9
An unusually mild presentation of megalencephalic leukoencephalopathy with subcortical cysts. (23485252)
2013
10
Megalencephalic leukoencephalopathy with subcortical cysts in all three siblings of a non-Aggarwal Indian family. (22919198)
2012
11
Megalencephalic leukoencephalopathy with subcortical cysts protein 1 functionally cooperates with the TRPV4 cation channel to activate the response of astrocytes to osmotic stress: dysregulation by pathological mutations. (22328087)
2012
12
Megalencephalic leukoencephalopathy with subcortical cysts: chronic white matter oedema due to a defect in brain ion and water homoeostasis. (23079554)
2012
13
Functional studies of MLC1 mutations in Chinese patients with megalencephalic leukoencephalopathy with subcortical cysts. (22416245)
2012
14
A Japanese adult case of megalencephalic leukoencephalopathy with subcortical cysts with a good long-term prognosis. (22382567)
2012
15
Megalencephalic leukoencephalopathy with subcortical cysts: A report of four cases. (21977097)
2011
16
Molecular mechanisms of MLC1 and GLIALCAM mutations in megalencephalic leukoencephalopathy with subcortical cysts. (21624973)
2011
17
Identification of novel MLC1 mutations in Chinese patients with megalencephalic leukoencephalopathy with subcortical cysts (MLC). (21160490)
2011
18
Mutant GlialCAM causes megalencephalic leukoencephalopathy with subcortical cysts, benign familial macrocephaly, and macrocephaly with retardation and autism. (21419380)
2011
19
A commentary on Identification of novel MLC1 mutations in Chinese patients with megalencephalic leukoencephalopathy with subcortical cysts (MLC). (21307857)
2011
20
A child with macrocephaly: case report of a patient with megalencephalic leukoencephalopathy with subcortical cysts and a compound heterozygosity for two mutations in the MLC1 gene. (21487377)
2011
21
Two cases with megalencephalic leukoencephalopathy with subcortical cysts and MLC1 mutations in the Turkish population. (20560255)
2010
22
Analysis of CLCN2 as candidate gene for megalencephalic leukoencephalopathy with subcortical cysts. (20187760)
2010
23
Megalencephalic leukoencephalopathy with subcortical cysts: a third confirmed case with literature review. (18821826)
2009
24
Megalencephalic leukoencephalopathy with subcortical cysts in a Tunisian boy. (19168821)
2009
25
Megalencephalic leukoencephalopathy with subcortical cysts in an adult. (19402576)
2009
26
Molecular pathogenesis of megalencephalic leukoencephalopathy with subcortical cysts: mutations in MLC1 cause folding defects. (18757878)
2008
27
Megalencephalic leukoencephalopathy with subcortical cysts: report of 4 new cases]. (18772751)
2008
28
SPECT revealed cortical dysfunction in a patient who had genetically definite megalencephalic leukoencephalopathy with subcortical cysts. (17507156)
2007
29
Late-onset neuropsychological symptoms in a Japanese patient with megalencephalic leukoencephalopathy with subcortical cysts. (17236107)
2006
30
Vacuolating megalencephalic leukoencephalopathy with subcortical cysts: functional studies of novel variants in MLC1. (16470554)
2006
31
An adult case of megalencephalic leukoencephalopathy with subcortical cysts with S93L mutation in MLC1 gene: a case report and diffusion MRI. (17077634)
2006
32
Megalencephalic leukoencephalopathy with subcortical cysts: an update and extended mutation analysis of MLC1. (16652334)
2006
33
Megalencephalic leukoencephalopathy with subcortical cysts. (15695862)
2005
34
Megalencephalic leukoencephalopathy with subcortical cysts. (15758546)
2005
35
Megalencephalic leukoencephalopathy with subcortical cysts in two siblings owing to two novel mutations: case reports and review of the literature. (15832614)
2005
36
Localization and functional analyses of the MLC1 protein involved in megalencephalic leukoencephalopathy with subcortical cysts. (15367490)
2004
37
Megalencephalic leukoencephalopathy with subcortical cysts. (15163886)
2004
38
A case of megalencephalic leukoencephalopathy with subcortical cysts (van der Knaap disease): molecular genetic study. (12850517)
2003
39
Megalencephalic leukoencephalopathy with subcortical cysts: MRI and proton spectroscopic features. (14742938)
2003
40
Megalencephalic leukoencephalopathy with subcortical cysts. (14572144)
2003
41
Megalencephalic leukoencephalopathy with subcortical cysts in an adult: quantitative proton MR spectroscopy and diffusion tensor MRI. (12684714)
2003
42
Clinical and genetic heterogeneity in megalencephalic leukoencephalopathy with subcortical cysts (MLC). (12973664)
2003
43
The brain-specific protein MLC1 implicated in megalencephalic leukoencephalopathy with subcortical cysts is expressed in glial cells in the murine brain. (14603469)
2003
44
Consciousness disturbances in megalencephalic leukoencephalopathy with subcortical cysts. (12973663)
2003
45
Identification of novel mutations in MLC1 responsible for megalencephalic leukoencephalopathy with subcortical cysts. (11935341)
2002
46
Reduced amplification efficiency of KIAA0027/MLC1 alleles: implications for the molecular diagnosis of megalencephalic leukoencephalopathy with subcortical cysts. (12477442)
2002
47
Megalencephalic leukoencephalopathy with subcortical cysts; a founder effect in Israeli patients and a higher than expected carrier rate among Libyan Jews. (12189496)
2002
48
Mutations of MLC1 (KIAA0027), encoding a putative membrane protein, cause megalencephalic leukoencephalopathy with subcortical cysts. (11254442)
2001
49
Vacuoliting megalencephalic leukoencephalopathy with subcortical cysts, mapped to chromosome 22qtel. (10677334)
2000
50
Megalencephalic Leukoencephalopathy with Subcortical Cysts (20301707)
1993

Variations for Megalencephalic Leukoencephalopathy with Subcortical Cysts

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UniProtKB/Swiss-Prot genetic disease variations for Megalencephalic Leukoencephalopathy with Subcortical Cysts:

64 (show all 15)
id Symbol AA change Variation ID SNP ID
1MLC1p.Ser93LeuVAR_011699rs80358245
2MLC1p.Thr118ArgVAR_011700rs281875316
3MLC1p.Gly212ArgVAR_011701rs281875317
4MLC1p.Ser280LeuVAR_011702rs121908341
5MLC1p.Gly59GluVAR_017438rs80358242
6MLC1p.Pro92SerVAR_017439rs121908345
7MLC1p.Asn141LysVAR_017440rs121908343
8MLC1p.Asn141SerVAR_017441rs121908344
9MLC1p.Ser69LeuVAR_067762rs281875309
10MLC1p.Met80IleVAR_067763rs281875310
11MLC1p.Arg84CysVAR_067764rs281875311
12MLC1p.Cys125ArgVAR_067765rs281875314
13MLC1p.Ala245ProVAR_067766rs281875312
14MLC1p.Ser246ArgVAR_067767rs281875315
15MLC1p.Thr320LysVAR_067768rs281875313

Clinvar genetic disease variations for Megalencephalic Leukoencephalopathy with Subcortical Cysts:

6 (show all 21)
id Gene Name Type Significance SNP ID Assembly Location
1MLC1NM_015166.3(MLC1): c.178-10T> Asingle nucleotide variantPathogenicrs80358243GRCh37Chr 22, 50521612: 50521612
2MLC1NM_015166.3: c.298_423+108deldeletionPathogenicGRCh37Chr 22, 50518239: 50518796
3HEPACAMNM_152722.4(HEPACAM): c.587C> A (p.Ser196Tyr)single nucleotide variantPathogenicrs387907049GRCh37Chr 11, 124793747: 124793747
4HEPACAMHEPACAM, TRP263TERundetermined variantPathogenic
5HEPACAMNM_152722.4(HEPACAM): c.275G> A (p.Arg92Gln)single nucleotide variantPathogenicrs387907050GRCh37Chr 11, 124794776: 124794776
6HEPACAMNM_152722.4(HEPACAM): c.631G> A (p.Asp211Asn)single nucleotide variantPathogenicrs387907051GRCh37Chr 11, 124793703: 124793703
7HEPACAMNM_152722.4(HEPACAM): c.292C> T (p.Arg98Cys)single nucleotide variantPathogenicrs387907052GRCh37Chr 11, 124794759: 124794759
8HEPACAMNM_152722.4(HEPACAM): c.265G> A (p.Gly89Ser)single nucleotide variantPathogenicrs387907053GRCh37Chr 11, 124794786: 124794786
9HEPACAMNM_152722.4(HEPACAM): c.274C> T (p.Arg92Trp)single nucleotide variantPathogenicrs387907055GRCh37Chr 11, 124794777: 124794777
10MLC1NM_015166.3(MLC1): c.206C> T (p.Ser69Leu)single nucleotide variantPathogenicrs281875309GRCh37Chr 22, 50521574: 50521574
11MLC1NM_015166.3(MLC1): c.839C> T (p.Ser280Leu)single nucleotide variantPathogenicrs121908341GRCh37Chr 22, 50506917: 50506917
12MLC1NM_015166.3(MLC1): c.278C> T (p.Ser93Leu)single nucleotide variantPathogenicrs80358245GRCh37Chr 22, 50518816: 50518816
13MLC1MLC1, 7-BP DEL, NT564deletionPathogenic
14MLC1MLC1, IVS10AS, A-G, -2single nucleotide variantPathogenic
15MLC1NM_015166.3(MLC1): c.423C> A (p.Asn141Lys)single nucleotide variantPathogenicrs121908343GRCh37Chr 22, 50518347: 50518347
16MLC1NM_015166.3(MLC1): c.422A> G (p.Asn141Ser)single nucleotide variantPathogenicrs121908344GRCh37Chr 22, 50518348: 50518348
17MLC1NM_015166.3(MLC1): c.274C> T (p.Pro92Ser)single nucleotide variantPathogenicrs121908345GRCh37Chr 22, 50518820: 50518820
18MLC1NM_015166.3(MLC1): c.594_597delCTCA (p.Tyr198Terfs)deletionPathogenicrs267607236GRCh37Chr 22, 50515270: 50515273
19MLC1NM_015166.3(MLC1): c.176G> A (p.Gly59Glu)single nucleotide variantPathogenicrs80358242GRCh37Chr 22, 50523156: 50523156
20MLC1NM_015166.3(MLC1): c.135dupC (p.Cys46Leufs)duplicationPathogenicrs80358241GRCh37Chr 22, 50523196: 50523197
21MLC1MLC1, 17-BP DEL, G INSindelPathogenic

Expression for genes affiliated with Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Expression patterns in normal tissues for genes affiliated with Megalencephalic Leukoencephalopathy with Subcortical Cysts

Search GEO for disease gene expression data for Megalencephalic Leukoencephalopathy with Subcortical Cysts.

Pathways for genes affiliated with Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Pathways related to Megalencephalic Leukoencephalopathy with Subcortical Cysts according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
9.7CLCN2, ATP1B1
29.7CLCN2, ATP1B1
39.7AQP4, ATP1B1
4
Show member pathways
9.3ATP1B1, CLCN2, TRPV4
5
Show member pathways
8.9TRPV4, AQP4, CLCN2, ATP1B1

Compounds for genes affiliated with Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Sources:
44Novoseek, 11DrugBank, 24HMDB
See all sources

Compounds related to Megalencephalic Leukoencephalopathy with Subcortical Cysts according to GeneCards/GeneDecks:

idCompoundScoreTop Affiliating Genes
1chlorambucil44 1110.4MCL1, MGST1
2sodium44 249.6TRPV4, AQP4, CLCN2, ATP1B1

GO Terms for genes affiliated with Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Cellular components related to Megalencephalic Leukoencephalopathy with Subcortical Cysts according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1cytoplasmic vesicleGO:0314109.7TRPV4, MLC1
2cell-cell junctionGO:0059119.6HEPACAM, AQP4, MLC1
3caveolaGO:0059019.5ATP1B1, MLC1
4basolateral plasma membraneGO:0163239.5AQP4, ATP1B1, MLC1
5plasma membraneGO:0058867.8MLC1, ATP1B1, CLCN2, AQP4, BAMBI, TRPV4
6integral component of membraneGO:0160217.4MGST1, MLC1, MCL1, HEPACAM, BAMBI, TRPV4

Biological processes related to Megalencephalic Leukoencephalopathy with Subcortical Cysts according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1regulation of response to osmotic stressGO:0474849.8TRPV4, MLC1
2hyperosmotic salinity responseGO:0425389.5AQP4, TRPV4
3ion transmembrane transportGO:0342209.3TRPV4, CLCN2, ATP1B1
4transportGO:0068109.0AQP4, CLCN2, ATP1B1, MLC1
5transmembrane transportGO:0550858.6TRPV4, AQP4, CLCN2, ATP1B1

Products for genes affiliated with Megalencephalic Leukoencephalopathy with Subcortical Cysts

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Sources for Megalencephalic Leukoencephalopathy with Subcortical Cysts

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet