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MCID: MGL013
MIFTS: 45

Megalencephaly

Categories: Fetal diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes
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Aliases & Classifications for Megalencephaly

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MalaCards integrated aliases for Megalencephaly:

Name: Megalencephaly 54 59 29 6 33
Macroencephaly 59

Classifications:

MalaCards categories:
Global: Fetal diseases Rare diseases
Anatomical: Neuronal diseases
See all MalaCards categories (disease lists)
ICD10: 33 34
Orphanet: 59  
Rare neurological diseases
Developmental anomalies during embryogenesis


External Ids:

ICD10 33 Q04.5
ICD10 via Orphanet 34 Q04.5
UMLS via Orphanet 73 C0221355 C2720434
Orphanet 59 ORPHA2477
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Summaries for Megalencephaly

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NINDS : 54 Megalencephaly, also called macrencephaly, is a condition in which an infant or child has an abnormally large, heavy, and usually malfunctioning brain. By definition, the brain weight is greater than average for the age and gender of the child. Head enlargement may be evident at birth or the head may become abnormally large in the early years of life. Megalencephaly is thought to be related to a disturbance in the regulation of cell production in the brain. In normal development, neuron proliferation - the process in which nerve cells divide to form new generations of cells - is regulated so that the correct number of cells is produced in the proper place at the appropriate time. In a megalencephalic brain, too many cells are produced either during development or progressively as part of another disorder, such as one of the neurofibromatoses or leukodystrophies. Symptoms of megalencephaly include delayed development, seizures, and corticospinal (brain cortex and spinal cord) dysfunction. Megalencephaly affects males more often than females. Unilateral megalencephaly or hemimegalencephaly is a rare condition that is characterized by the enlargement of one side of the brain. Children with this disorder may have a large, asymmetrical head accompanied by seizures, partial paralysis, and impaired cognitive development. Megalencephaly is different from macrocephaly (also called megacephaly or megalocephaly), which describes a big head, and which doesn’t necessarily indicate abnormality. Large head size is passed down through the generations in some families.

MalaCards based summary : Megalencephaly, also known as macroencephaly, is related to megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 and megalencephaly-capillary malformation-polymicrogyria syndrome. An important gene associated with Megalencephaly is SCN1A (Sodium Voltage-Gated Channel Alpha Subunit 1), and among its related pathways/superpathways are Pathways in cancer and Glioma. Affiliated tissues include brain, cortex and spinal cord, and related phenotypes are macrocephaly and short neck

Wikipedia : 75 Megalencephaly (or macrencephaly; abbreviated MEG) is a growth development disorder in which the brain... more...

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Related Diseases for Megalencephaly

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Diseases in the Megalencephaly family:

Megalencephaly, Autosomal Dominant

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

(show top 50) (show all 166)
# Related Disease Score Top Affiliating Genes
1 megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 34.3 PIK3R2 CCND2
2 megalencephaly-capillary malformation-polymicrogyria syndrome 34.0 PIK3R2 PIK3CA
3 polymicrogyria 30.9 PIK3R2 CCND2
4 cutis marmorata telangiectatica congenita 29.6 PIK3R2 PIK3CA
5 macrocephaly/megalencephaly syndrome, autosomal recessive 12.7
6 polyhydramnios, megalencephaly, and symptomatic epilepsy 12.7
7 megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 12.7
8 megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 12.7
9 leukoencephalopathy, cystic, without megalencephaly 12.7
10 megalencephaly, autosomal dominant 12.5
11 hemimegalencephaly 12.4
12 megalencephaly with dysmyelination 12.3
13 isolated megalencephaly 12.3
14 megalencephalic leukoencephalopathy with subcortical cysts 1 12.2
15 focal alopecia congenital megalencephaly 12.1
16 alexander disease 12.0
17 cowden syndrome 1 11.9
18 rnase t2-deficient leukoencephalopathy 11.9
19 smith-kingsmore syndrome 11.7
20 macrocephaly, benign familial 11.5
21 macrocephaly, dysmorphic facies, and psychomotor retardation 11.5
22 mental retardation, autosomal recessive 34, with variant lissencephaly 11.5
23 pik3ca-related overgrowth spectrum 11.3
24 neurofaciodigitorenal syndrome 11.1
25 mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations 11.1
26 early-onset parkinsonism-intellectual disability syndrome 11.1
27 hydrocephalus 10.6
28 congenital hydrocephalus 10.6
29 polymicrogyria with or without vascular-type ehlers-danlos syndrome 10.6
30 polydactyly 10.6
31 overgrowth syndrome 10.5
32 pik3ca-related segmental overgrowth 10.5
33 hypotonia 10.4
34 alacrima, achalasia, and mental retardation syndrome 10.4
35 polydactyly, postaxial, type a1 10.4
36 chromosome 2q35 duplication syndrome 10.4
37 hydrocephalus, congenital, 1 10.3
38 ataxia and polyneuropathy, adult-onset 10.3
39 leukodystrophy 10.3
40 autism 10.2
41 tuberous sclerosis 10.2
42 cerebral malformation 10.2
43 thymoma, familial 10.2
44 autism spectrum disorder 10.2
45 thymoma 10.2
46 seizure disorder 10.2
47 sotos syndrome 1 10.1
48 tuberous sclerosis 1 10.1
49 congenital heart defects, hamartomas of tongue, and polysyndactyly 10.1
50 cortical dysplasia, complex, with other brain malformations 7 10.1

Graphical network of the top 20 diseases related to Megalencephaly:



Diseases related to Megalencephaly
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Symptoms & Phenotypes for Megalencephaly

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Human phenotypes related to Megalencephaly:

59 32 (show all 16)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0000256
2 short neck 59 32 hallmark (90%) Very frequent (99-80%) HP:0000470
3 frontal bossing 59 32 hallmark (90%) Very frequent (99-80%) HP:0002007
4 intellectual disability 59 32 hallmark (90%) Very frequent (99-80%) HP:0001249
5 delayed skeletal maturation 59 32 hallmark (90%) Very frequent (99-80%) HP:0002750
6 wide nasal bridge 59 32 hallmark (90%) Very frequent (99-80%) HP:0000431
7 dolichocephaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0000268
8 prominent occiput 59 32 hallmark (90%) Very frequent (99-80%) HP:0000269
9 deeply set eye 59 32 hallmark (90%) Very frequent (99-80%) HP:0000490
10 abnormality of the fontanelles or cranial sutures 59 32 hallmark (90%) Very frequent (99-80%) HP:0000235
11 pointed chin 59 32 hallmark (90%) Very frequent (99-80%) HP:0000307
12 truncal obesity 59 32 hallmark (90%) Very frequent (99-80%) HP:0001956
13 genu valgum 59 32 frequent (33%) Frequent (79-30%) HP:0002857
14 macroorchidism 59 32 frequent (33%) Frequent (79-30%) HP:0000053
15 atrial septal defect 59 32 frequent (33%) Frequent (79-30%) HP:0001631
16 long penis 59 32 frequent (33%) Frequent (79-30%) HP:0000040

GenomeRNAi Phenotypes related to Megalencephaly according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-2 10 PIK3CA
2 Decreased viability GR00173-A 10 PIK3R2
3 Decreased viability GR00221-A-1 10 PIK3CA PIK3R2 STRADA
4 Decreased viability GR00221-A-2 10 PIK3CA PIK3R2 STRADA
5 Decreased viability GR00221-A-3 10 STRADA
6 Decreased viability GR00221-A-4 10 PIK3CA PIK3R2 STRADA
7 Decreased viability GR00301-A 10 PIK3R2
8 Decreased viability GR00402-S-2 10 PIK3CA PIK3R2 STRADA
9 Decreased cell migration GR00055-A-1 9.13 PIK3CA PIK3R2 STRADA
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Drugs & Therapeutics for Megalencephaly

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Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2 Recruiting NCT03548779
2 Natural History Study of Individuals With Autism and Germline Heterozygous PTEN Mutations Active, not recruiting NCT02461446

Search NIH Clinical Center for Megalencephaly

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Genetic Tests for Megalencephaly

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Genetic tests related to Megalencephaly:

# Genetic test Affiliating Genes
1 Megalencephaly 29
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Anatomical Context for Megalencephaly

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MalaCards organs/tissues related to Megalencephaly:

41
Brain, Cortex, Spinal Cord, Eye, Skin, Liver, Cerebellum
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Publications for Megalencephaly

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Articles related to Megalencephaly:

(show top 50) (show all 393)
# Title Authors PMID Year
1
Differential Altered Auditory Event-Related Potential Responses in Young Boys on the Autism Spectrum With and Without Disproportionate Megalencephaly. 38
31157516 2019
2
Phenotypic spectrum associated with a CRADD founder variant underlying frontotemporal predominant pachygyria in the Finnish population. 38
30914828 2019
3
RNASET2-deficient leukoencephalopathy mimicking congenital CMV infection and Aicardi-Goutieres syndrome: a case report with a novel pathogenic variant. 38
31349848 2019
4
[Syndromes with vascular skin anomalies]. 38
31111168 2019
5
MYCN de novo gain-of-function mutation in a patient with a novel megalencephaly syndrome. 38
30573562 2019
6
A Longitudinal Study of Local Gyrification Index in Young Boys With Autism Spectrum Disorder. 38
29850803 2019
7
Severe presentation and complex brain malformations in an individual carrying a CCND2 variant. 38
31056854 2019
8
Recurrent mosaic MTOR c.5930C > T (p.Thr1977Ile) variant causing megalencephaly, asymmetric polymicrogyria, and cutaneous pigmentary mosaicism: Case report and review of the literature. 38
30569621 2019
9
Heterozygosity for Nuclear Factor One X in mice models features of Malan syndrome. 38
30503862 2019
10
Polymicrogyria in association with hypoglycemia points to mutation in the mTOR pathway. 38
29883676 2018
11
Novel Homozygous Deletion in STRADA Gene Associated With Polyhydramnios, Megalencephaly, and Epilepsy in 2 Siblings: Implications for Diagnosis and Treatment. 38
30311510 2018
12
From microcephaly to megalencephaly: determinants of brain size. 38
30936767 2018
13
Mutations in MAST1 Cause Mega-Corpus-Callosum Syndrome with Cerebellar Hypoplasia and Cortical Malformations. 38
30449657 2018
14
PUF60-SCRIB fusion transcript in a patient with 8q24.3 microdeletion and atypical Verheij syndrome. 38
30472487 2018
15
Co-occurrence of mutations in FOXP1 and PTCH1 in a girl with extreme megalencephaly, callosal dysgenesis and profound intellectual disability. 38
30181650 2018
16
Clinical pitfalls in the diagnosis of segmental overgrowth syndromes: a child with the c.2740G > A mutation in PIK3CA gene. 38
30231930 2018
17
Dysplastic megalencephaly phenotype presenting with prenatal high-output cardiac failure. 38
29594439 2018
18
Macrocephaly: Solving the Diagnostic Dilemma. 38
30086108 2018
19
PARD3 dysfunction in conjunction with dynamic HIPPO signaling drives cortical enlargement with massive heterotopia. 38
29899142 2018
20
A Novel CCND2 Mutation in a Previously Reported Case of Megalencephaly and Perisylvian Polymicrogyria with Postaxial Polydactyly and Hydrocephalus. 38
29642246 2018
21
In vitro efficacy of ARQ 092, an allosteric AKT inhibitor, on primary fibroblast cells derived from patients with PIK3CA-related overgrowth spectrum (PROS). 38
29549527 2018
22
Novel de novo ZBTB20 mutations in three cases with Primrose syndrome and constant corpus callosum anomalies. 38
29681083 2018
23
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-related overgrowth spectrum: A brief report. 38
29493003 2018
24
Increased cerebral blood flow on arterial spin labeling magnetic resonance imaging can localize to seizure focus in newborns: A report of 3 cases. 38
29600511 2018
25
Dendrite growth and the effect of ectopic Rheb expression on cortical neurons. 38
29447953 2018
26
mTOR mutations in Smith-Kingsmore syndrome: Four additional patients and a review. 38
28892148 2018
27
Hypoglycaemia represents a clinically significant manifestation of PIK3CA- and CCND2-associated segmental overgrowth. 38
28941273 2018
28
Dysplasia and overgrowth: magnetic resonance imaging of pediatric brain abnormalities secondary to alterations in the mechanistic target of rapamycin pathway. 38
29279945 2018
29
Novel RNASET2 Pathogenic Variants in an East Asian Child with Delayed Psychomotor Development. 38
29336640 2018
30
Repositioning of Somatic Golgi Apparatus Is Essential for the Dendritic Establishment of Adult-Born Hippocampal Neurons. 38
29217690 2018
31
Contribution of Altered Endocannabinoid System to Overactive mTORC1 Signaling in Focal Cortical Dysplasia. 38
30687088 2018
32
Commentary on "Megalencephaly-capillary malformation-polymicrogyria syndrome: the first case report in Korea". 38
29441111 2018
33
Megalencephaly-capillary malformation polymicrogyria: A review and complex pediatric case report. 38
27216985 2017
34
Mutations of AKT3 are associated with a wide spectrum of developmental disorders including extreme megalencephaly. 38
28969385 2017
35
Olfactory nerve hypertrophy: a clue to the presence of ipsilateral megalencephaly. 38
29066644 2017
36
Spindle Misorientation of Cerebral and Cerebellar Progenitors Is a Mechanistic Cause of Megalencephaly. 38
28943256 2017
37
Variation in a range of mTOR-related genes associates with intracranial volume and intellectual disability. 38
29051493 2017
38
Prenatal and postnatal evaluation of polymicrogyria with band heterotopia. 38
28828134 2017
39
Impact of clinical exomes in neurodevelopmental and neurometabolic disorders. 38
28688840 2017
40
Hypoinsulinaemic, hypoketotic hypoglycaemia due to mosaic genetic activation of PI3-kinase. 38
28566443 2017
41
Update on classification and diagnosis of vascular malformations. 38
28654575 2017
42
Molecular Diagnosis of Mosaic Overgrowth Syndromes Using a Custom-Designed Next-Generation Sequencing Panel. 38
28502725 2017
43
Megalencephalic leukoencephalopathy with cysts: the Glialcam-null mouse model. 38
28695146 2017
44
A clinical review on megalencephaly: A large brain as a possible sign of cerebral impairment. 38
28658095 2017
45
DEPDC5 as a potential therapeutic target for epilepsy. 38
28406046 2017
46
Differential roles for Akt and mTORC1 in the hypertrophy of Pten mutant neurons, a cellular model of brain overgrowth disorders. 38
28457820 2017
47
In pursuit of neurophenotypes: The consequences of having autism and a big brain. 38
28239961 2017
48
A novel de novo germline mutation Glu40Lys in AKT3 causes megalencephaly with growth hormone deficiency. 38
28190287 2017
49
[PIK3CA-related overgrowth syndrome (PROS)]. 38
28577738 2017
50
Brain Development and Akt Signaling: the Crossroads of Signaling Pathway and Neurodevelopmental Diseases. 38
28025777 2017
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Variations for Megalencephaly

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ClinVar genetic disease variations for Megalencephaly:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 SCN1A NM_006920.6(SCN1A): c.3294dup (p.Ser1099fs) duplication Pathogenic 2:166892659-166892660 2:166036150-166036150
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Expression for Megalencephaly

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Search GEO for disease gene expression data for Megalencephaly.
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Pathways for Megalencephaly

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Pathways related to Megalencephaly according to GeneCards Suite gene sharing:

(show all 41)
# Super pathways Score Top Affiliating Genes
1
Pathways in cancer 37
12.57 PIK3R2 PIK3CA CCND2
2
Glioma 37
Show member pathways
 12.42 PIK3R2 PIK3CA CCND2
3
MicroRNAs in cancer 37
12.26 PIK3R2 PIK3CA CCND2
4
Prolactin Signaling Pathway 1 37
Show member pathways
 12.2 PIK3R2 PIK3CA CCND2
5
JAK-STAT signaling pathway (KEGG) 37
Show member pathways
 12.13 PIK3R2 PIK3CA CCND2
6
AMP-activated Protein Kinase (AMPK) Signaling 1
Show member pathways
 12.13 STRADA PIK3R2 PIK3CA
7
mTOR signalling 66
Show member pathways
 12.08 STRADA PIK3R2 PIK3CA
8
Development IGF-1 receptor signaling 22
Show member pathways
 12.05 PIK3R2 PIK3CA CCND2
9
Human T-cell leukemia virus 1 infection 37
12.04 PIK3R2 PIK3CA CCND2
10
MAPK Signaling: Mitogen Stimulation Pathway 65
Show member pathways
 11.91 PIK3R2 PIK3CA CCND2
11
Viral carcinogenesis 37
11.91 PIK3R2 PIK3CA CCND2
12
Cellular senescence (KEGG) 37
11.75 PIK3R2 PIK3CA CCND2
13
Amoebiasis 37
11.69 PIK3R2 PIK3CA
14
Type II diabetes mellitus 1 37
Show member pathways
 11.67 PIK3R2 PIK3CA
15
Small cell lung cancer 37
11.64 PIK3R2 PIK3CA
16
Fc gamma R-mediated phagocytosis 37
11.64 PIK3R2 PIK3CA
17
FoxO signaling pathway 37
Show member pathways
 11.63 PIK3R2 PIK3CA CCND2
18
IL-6 signaling pathway 1
Show member pathways
 11.6 PIK3R2 PIK3CA
19
VEGF Pathway (Tocris) 61
Show member pathways
 11.58 PIK3R2 PIK3CA
20
IL-2 Signaling Pathway 1
Show member pathways
 11.56 PIK3R2 PIK3CA CCND2
21
Bacterial invasion of epithelial cells 37
11.52 PIK3R2 PIK3CA
22
Platinum drug resistance 37
11.52 PIK3R2 PIK3CA
23
Human Thyroid Stimulating Hormone (TSH) signaling pathway 1
11.48 PIK3R2 PIK3CA
24
Central carbon metabolism in cancer 37
11.48 PIK3R2 PIK3CA
25
IL2 signaling events mediated by PI3K 1
Show member pathways
 11.47 PIK3CA CCND2
26
Role of phospholipids in phagocytosis 66
Show member pathways
 11.39 PIK3R2 PIK3CA
27
DNA Damage Response (only ATM dependent) 1
11.39 PIK3R2 PIK3CA CCND2
28
mTOR signaling pathway (KEGG) 37
Show member pathways
 11.39 TBC1D7 STRADA PIK3R2 PIK3CA
29
Regulation of lipolysis in adipocytes 37
11.37 PIK3R2 PIK3CA
30
Development_Leptin signaling via PI3K-dependent pathway 22
11.34 PIK3R2 PIK3CA
31
Cell adhesion_Plasmin signaling 22
11.31 PIK3R2 PIK3CA
32
Carbohydrate digestion and absorption 37
11.25 PIK3R2 PIK3CA
33
G13 Signaling Pathway 1
11.22 PIK3R2 PIK3CA
34
Aldosterone-regulated sodium reabsorption 37
11.17 PIK3R2 PIK3CA
35
IL-10 Pathway 64
11.12 PIK3R2 CCND2
36
PI3K / Akt Signaling 4
11.1 TBC1D7 PIK3R2 PIK3CA
37
PI3K-AKT-mTOR signaling pathway and therapeutic opportunities 1
11.03 PIK3R2 PIK3CA
38
Telomere Extension by Telomerase 64
Show member pathways
 10.99 PIK3R2 PIK3CA
39
Cytoskeleton remodeling_Role of PDGFs in cell migration 22
10.84 PIK3R2 PIK3CA
40
Nephrin interactions 66
10.8 PIK3R2 PIK3CA
41
Regulation of signaling by CBL 66
10.66 PIK3R2 PIK3CA
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GO Terms for Megalencephaly

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Cellular components related to Megalencephaly according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 phosphatidylinositol 3-kinase complex GO:0005942 8.62 PIK3R2 PIK3CA

Biological processes related to Megalencephaly according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 activation of protein kinase activity GO:0032147 9.32 STRADA PIK3CA
2 vascular endothelial growth factor receptor signaling pathway GO:0048010 9.26 PIK3R2 PIK3CA
3 phosphatidylinositol-mediated signaling GO:0048015 8.96 PIK3R2 PIK3CA
4 phosphatidylinositol-3-phosphate biosynthetic process GO:0036092 8.85 PIK3CA
5 phosphatidylinositol 3-kinase signaling GO:0014065 8.62 PIK3R2 PIK3CA

Molecular functions related to Megalencephaly according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 phosphatidylinositol-4,5-bisphosphate 3-kinase activity GO:0046934 8.85 PIK3CA
2 1-phosphatidylinositol-3-kinase activity GO:0016303 8.65 PIK3CA
3 protein kinase activator activity GO:0030295 8.62 STRADA PIK3CA
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Sources for Megalencephaly

About this section
3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 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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