ALXDRD
MCID: ALX003
MIFTS: 58

Alexander Disease (ALXDRD)

Categories: Eye diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Alexander Disease

MalaCards integrated aliases for Alexander Disease:

Name: Alexander Disease 58 12 77 25 54 26 55 60 76 38 30 13 6 45 15 74
Alexander's Disease 12 26 76 41
Alexanders Leukodystrophy 54 74
Alxdrd 58 76
Axd 26 60
Megalencephaly in Infancy Accompanied by Progressive Spasticity and Dementia 54
Fibrinoid Degeneration of Astrocytes 26
Leukodystrophy with Rosenthal Fibers 26
Dysmyelinogenic Leukodystrophy 26
Demyelinogenic Leukodystrophy 26
Alexander Disease Type Ii 60
Alexander Disease Type I 60
Alexanders Disease 56
Axd Type Ii 60
Axd Type I 60
Alx 26

Characteristics:

Orphanet epidemiological data:

60
alexander disease
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Japan); Age of onset: All ages; Age of death: any age;
alexander disease type ii
Inheritance: Autosomal dominant; Age of onset: Adolescent,Adult,Childhood; Age of death: adult;
alexander disease type i
Inheritance: Not applicable; Age of onset: Infancy,Neonatal;

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
average age of onset 6 months (range birth - 2 years)
death by age 5 (infantile form)
three variants distinguished by age of onset - infantile ( onset before age 2), juvenile (onset in childhood), and adult
juvenile patients have slower clinical course with preserved intellect, bulbar signs, ataxia, and spasticity
adult patients have heterogeneous symptoms including some with relapsing-remitting symptoms similar to multiple sclerosis


HPO:

33
alexander disease:
Onset and clinical course infantile onset
Inheritance autosomal dominant inheritance


GeneReviews:

25
Penetrance Penetrance appears to be nearly 100% in individuals with the infantile and juvenile forms [li et al 2002, messing & brenner 2003a]...

Classifications:



Summaries for Alexander Disease

NINDS : 55 Alexander disease is one of a group of neurological conditions known as the leukodystrophies.  Leukodystrophies are disorders that result from abnormalities in myelin, the “white matter” that protects nerve fibers in the brain. In Alexander disease, the destruction of white matter is accompanied by the formation of Rosenthal fibers--abnormal clumps of protein that accumulate in non-nerve cells (astrocytes) in the brain.  The most common type of Alexander disease is the infantile form that usually begins during the first two years of life.  Symptoms include mental and physical developmental delays, followed by the loss of developmental milestones, an abnormal increase in head size, and seizures. The juvenile form of Alexander disease has an onset between the ages of two and thirteen years.  These children may have excessive vomiting, difficulty swallowing and speaking, poor coordination, and loss of motor control.  Adult-onset forms of Alexander disease are less common.  The symptoms sometimes mimic those of Parkinson’s disease or multiple sclerosis, or may present primarily as a psychiatric disorder. The disease occurs in both males and females, and there are no ethnic, racial, geographic, or cultural/economic differences in its distribution.  Alexander disease is a progressive and often fatal disease. 

MalaCards based summary : Alexander Disease, also known as alexander's disease, is related to leukodystrophy and aceruloplasminemia, and has symptoms including seizures and muscle spasticity. An important gene associated with Alexander Disease is GFAP (Glial Fibrillary Acidic Protein), and among its related pathways/superpathways are Cytoskeleton remodeling Neurofilaments and ATM Signaling Network in Development and Disease. Affiliated tissues include brain, eye and bone, and related phenotypes are macrocephaly and agenesis of corpus callosum

Disease Ontology : 12 A leukodystrophy that is characterized by the destruction of white matter and the formation of Rosenthal fibers consisting of abnormal clumps of protein that accumulate in astrocytes.

Genetics Home Reference : 26 Alexander disease is a rare disorder of the nervous system. It is one of a group of disorders, called leukodystrophies, that involve the destruction of myelin. Myelin is the fatty covering that insulates nerve fibers and promotes the rapid transmission of nerve impulses. If myelin is not properly maintained, the transmission of nerve impulses could be disrupted. As myelin deteriorates in leukodystrophies such as Alexander disease, nervous system functions are impaired.

NIH Rare Diseases : 54 Alexander disease is a type of leukodystrophy characterized by the destruction of  the myelin sheath (the fatty covering that acts as an insulator around nerve fiber) and abnormal protein deposits known as Rosenthal fibers. Most cases of Alexander disease begin before age 2 years (the infantile form). Symptoms of the infantile form include an enlarged brain and head, seizures, stiffness in the arms and/or legs, mental retardation, and delayed physical development. Less frequently, onset occurs later in childhood (the juvenile form) or adulthood. Common problems in juvenile and adult forms of Alexander disease include speech abnormalities, swallowing difficulties, and poor coordination. Alexander disease is caused by mutations in the GFAP gene. While this condition is inherited in an autosomal dominant fashion, most cases result from new mutations in the gene.

OMIM : 58 In decreasing order of frequency, 3 forms of Alexander disease are recognized, based on age of onset: infantile, juvenile, and adult. Younger patients typically present with seizures, megalencephaly, developmental delay, and spasticity. In older patients, bulbar or pseudobulbar symptoms predominate, frequently accompanied by spasticity. The disease is progressive, with most patients dying within 10 years of onset. Imaging studies of the brain typically show cerebral white matter abnormalities, preferentially affecting the frontal region (Gorospe et al., 2002). All 3 forms have been shown to be caused by mutations in the GFAP gene. (203450)

UniProtKB/Swiss-Prot : 76 Alexander disease: A rare disorder of the central nervous system. The most common form affects infants and young children, and is characterized by progressive failure of central myelination, usually leading to death within the first decade. Infants with Alexander disease develop a leukodystrophy with macrocephaly, seizures, and psychomotor retardation. Patients with juvenile or adult forms typically experience ataxia, bulbar signs and spasticity, and a more slowly progressive course. Histologically, Alexander disease is characterized by Rosenthal fibers, homogeneous eosinophilic inclusions in astrocytes.

Wikipedia : 77 Alexander disease is one of a group of neurological conditions known as the leukodystrophies, which are... more...

GeneReviews: NBK1172

Related Diseases for Alexander Disease

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

(show all 47)
# Related Disease Score Top Affiliating Genes
1 leukodystrophy 11.6
2 aceruloplasminemia 10.2
3 neural tube defects 10.1
4 neural tube defects, folate-sensitive 10.1
5 paraplegia 10.1
6 glioma 10.1
7 tremor 10.1
8 frontonasal dysplasia 1 10.0
9 schizophrenia 10.0
10 frontonasal dysplasia 3 10.0
11 microphthalmia 10.0
12 pulmonary edema 10.0
13 endometriosis 10.0
14 acute respiratory distress syndrome 10.0
15 epidermolysis bullosa simplex with muscular dystrophy 10.0 PLEC SYNM
16 subependymal glioma 10.0 GFAP MTOR
17 benign ependymoma 10.0 GFAP MTOR
18 hemimegalencephaly 10.0 GFAP MTOR
19 ataxia and polyneuropathy, adult-onset 10.0
20 west syndrome 10.0
21 scoliosis 10.0
22 encephalopathy 10.0
23 subependymal giant cell astrocytoma 10.0 GFAP MTOR
24 multiple sclerosis 10.0
25 hydrocephalus 10.0
26 thrombotic thrombocytopenic purpura 10.0
27 obstructive hydrocephalus 10.0
28 status epilepticus 10.0
29 purpura 10.0
30 spastic paraparesis 10.0
31 central nervous system benign neoplasm 9.9 GFAP MTOR
32 leukoencephalopathy, hereditary diffuse, with spheroids 9.9 CRYAB GFAP
33 corticobasal degeneration 9.9 CRYAB MTOR
34 alzheimer disease 9.8
35 seizures, benign familial neonatal, 1 9.8
36 megalencephalic leukoencephalopathy with subcortical cysts 1 9.8
37 brain injury 9.8
38 traumatic brain injury 9.8
39 sleep apnea 9.8
40 spastic ataxia 9.8
41 astrocytoma 9.8
42 dystonia 9.8
43 microcephaly 9.8
44 myoclonus 9.8
45 central nervous system disease 9.7 CRYAB GFAP HTT
46 machado-joseph disease 9.7 HSPB1 HTT
47 amyotrophic lateral sclerosis 1 9.5 CRYAB GFAP HSPB1 HTT

Graphical network of the top 20 diseases related to Alexander Disease:



Diseases related to Alexander Disease

Symptoms & Phenotypes for Alexander Disease

Human phenotypes related to Alexander Disease:

60 33 (show top 50) (show all 66)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 60 33 hallmark (90%) Very frequent (99-80%) HP:0000256
2 agenesis of corpus callosum 60 33 hallmark (90%) Very frequent (99-80%) HP:0001274
3 frontal bossing 60 33 hallmark (90%) Very frequent (99-80%) HP:0002007
4 intellectual disability 60 33 hallmark (90%) Very frequent (99-80%) HP:0001249
5 seizures 60 33 hallmark (90%) Very frequent (99-80%) HP:0001250
6 spasticity 60 33 hallmark (90%) Very frequent (99-80%) HP:0001257
7 megalencephaly 60 33 hallmark (90%) Very frequent (99-80%) HP:0001355
8 failure to thrive 60 33 hallmark (90%) Very frequent (99-80%) HP:0001508
9 nausea and vomiting 60 33 hallmark (90%) Very frequent (99-80%) HP:0002017
10 clonus 60 33 hallmark (90%) Very frequent (99-80%) HP:0002169
11 eeg abnormality 60 33 hallmark (90%) Very frequent (99-80%) HP:0002353
12 scoliosis 60 33 hallmark (90%) Very frequent (99-80%) HP:0002650
13 abnormal pyramidal sign 60 33 hallmark (90%) Very frequent (99-80%) HP:0007256
14 large face 60 33 hallmark (90%) Very frequent (99-80%) HP:0100729
15 ptosis 60 33 frequent (33%) Frequent (79-30%) HP:0000508
16 nystagmus 60 33 frequent (33%) Frequent (79-30%) HP:0000639
17 diplopia 60 33 frequent (33%) Frequent (79-30%) HP:0000651
18 emotional lability 60 33 frequent (33%) Frequent (79-30%) HP:0000712
19 depressivity 60 33 frequent (33%) Frequent (79-30%) HP:0000716
20 hyperhidrosis 60 33 frequent (33%) Frequent (79-30%) HP:0000975
21 ataxia 60 33 frequent (33%) Frequent (79-30%) HP:0001251
22 dysarthria 60 33 frequent (33%) Frequent (79-30%) HP:0001260
23 gait disturbance 60 33 frequent (33%) Frequent (79-30%) HP:0001288
24 tremor 60 33 frequent (33%) Frequent (79-30%) HP:0001337
25 dysphonia 60 33 frequent (33%) Frequent (79-30%) HP:0001618
26 dysphagia 60 33 frequent (33%) Frequent (79-30%) HP:0002015
27 constipation 60 33 frequent (33%) Frequent (79-30%) HP:0002019
28 hypothermia 60 33 frequent (33%) Frequent (79-30%) HP:0002045
29 dysphasia 60 33 frequent (33%) Frequent (79-30%) HP:0002357
30 tetraplegia 60 33 frequent (33%) Frequent (79-30%) HP:0002445
31 cerebral calcification 60 33 frequent (33%) Frequent (79-30%) HP:0002514
32 hypotension 60 33 frequent (33%) Frequent (79-30%) HP:0002615
33 kyphosis 60 33 frequent (33%) Frequent (79-30%) HP:0002808
34 sleep apnea 60 33 frequent (33%) Frequent (79-30%) HP:0010535
35 facial palsy 60 33 frequent (33%) Frequent (79-30%) HP:0010628
36 recurrent singultus 60 33 frequent (33%) Frequent (79-30%) HP:0100247
37 short neck 60 33 occasional (7.5%) Occasional (29-5%) HP:0000470
38 high palate 60 33 occasional (7.5%) Occasional (29-5%) HP:0000218
39 hydrocephalus 60 33 occasional (7.5%) Occasional (29-5%) HP:0000238
40 diabetes mellitus 60 33 occasional (7.5%) Occasional (29-5%) HP:0000819
41 hypothyroidism 60 33 occasional (7.5%) Occasional (29-5%) HP:0000821
42 hypertension 60 33 occasional (7.5%) Occasional (29-5%) HP:0000822
43 precocious puberty 60 33 occasional (7.5%) Occasional (29-5%) HP:0000826
44 osteopenia 60 33 occasional (7.5%) Occasional (29-5%) HP:0000938
45 muscular hypotonia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001252
46 sudden cardiac death 60 33 occasional (7.5%) Occasional (29-5%) HP:0001645
47 chorea 60 33 occasional (7.5%) Occasional (29-5%) HP:0002072
48 respiratory insufficiency 60 33 occasional (7.5%) Occasional (29-5%) HP:0002093
49 developmental regression 60 33 occasional (7.5%) Occasional (29-5%) HP:0002376
50 encephalitis 60 33 occasional (7.5%) Occasional (29-5%) HP:0002383

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
hydrocephalus
seizures
spasticity
psychomotor regression
diffuse demyelination (increased signal intensity in t2-weighted images, especially frontal lobes)
more
Laboratory Abnormalities:
presence of rosenthal fibers (cytoplasmic inclusions) in astrocytes
presence of glial fibrillary acidic proteins (gfap) in astrocytes
elevated csf protein

Head And Neck Head:
progressive macrocephaly

Clinical features from OMIM:

203450

UMLS symptoms related to Alexander Disease:


seizures, muscle spasticity

MGI Mouse Phenotypes related to Alexander Disease:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.95 CRYAB GFAP HDAC6 HTT MTOR PLEC
2 cellular MP:0005384 9.87 CRYAB GFAP HDAC6 HSPB1 HTT MTOR
3 cardiovascular system MP:0005385 9.85 GFAP HSPB1 HTT MTOR PLEC SYNM
4 growth/size/body region MP:0005378 9.8 GFAP HDAC6 HSPB1 HTT MTOR PLEC
5 immune system MP:0005387 9.63 GFAP HDAC6 HSPB1 HTT MTOR PLEC
6 muscle MP:0005369 9.35 CRYAB GFAP MTOR PLEC SYNM
7 normal MP:0002873 9.1 GFAP HDAC6 HSPB1 HTT MTOR PLEC

Drugs & Therapeutics for Alexander Disease

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Natural History and Outcome Measures in Alexander Disease Recruiting NCT02714764

Search NIH Clinical Center for Alexander Disease

Cochrane evidence based reviews: alexander disease

Genetic Tests for Alexander Disease

Genetic tests related to Alexander Disease:

# Genetic test Affiliating Genes
1 Alexander Disease 30 GFAP

Anatomical Context for Alexander Disease

MalaCards organs/tissues related to Alexander Disease:

42
Brain, Eye, Bone, Cortex, Medulla Oblongata, Spinal Cord, Bone Marrow

Publications for Alexander Disease

Articles related to Alexander Disease:

(show top 50) (show all 325)
# Title Authors Year
1
c.1289G>A (p.Arg430His) variant in the epsilon isoform of the GFAP gene in a patient with adult onset Alexander disease. ( 30048824 )
2019
2
Aggregate formation analysis of GFAPR416W found in one case of Alexander disease. ( 30213442 )
2019
3
A Case of Juvenile Alexander Disease Presenting as Microcephaly. ( 30628038 )
2019
4
Adult-onset Alexander disease with a heterozygous D128N GFAP mutation: a pathological study. ( 30942895 )
2019
5
A novel mutation in the GFAP gene expands the phenotype of Alexander disease. ( 31004048 )
2019
6
Neuropsychological features of adult form of Alexander disease. ( 31039531 )
2019
7
An unusual presentation of late-onset Alexander's disease with slow orthostatic tremor and a novel GFAP variant. ( 30755139 )
2019
8
A Novel Mutation in the Adult-Onset Alexander's Disease GFAP Gene. ( 30755773 )
2019
9
A case of severe Alexander disease with de novo c. 239 T > C, p.(F80S), in GFAP. ( 29573842 )
2018
10
Alexander disease: an astrocytopathy that produces a leukodystrophy. ( 29740945 )
2018
11
Tissue and cellular rigidity and mechanosensitive signaling activation in Alexander disease. ( 29765022 )
2018
12
Neonatal Alexander Disease: Novel GFAP Mutation and Comparison to Previously Published Cases. ( 29801191 )
2018
13
Neuroimaging in Juvenile Alexander Disease: Tumour-like Brainstem Lesions. ( 29911736 )
2018
14
Botox Injection for Laryngeal Dysfunction in Alexander Disease. ( 30017431 )
2018
15
Teaching NeuroImages: Alexander disease with features of both frontal and bulbospinal involvement. ( 30037922 )
2018
16
Atypical Alexander disease with dystonia, retinopathy, and a brain mass mimicking astrocytoma. ( 30046660 )
2018
17
GFAP Mutations in Astrocytes Impair Oligodendrocyte Progenitor Proliferation and Myelination in an hiPSC Model of Alexander Disease. ( 30075130 )
2018
18
GFAP canonical transcript may not be suitable for the diagnosis of adult-onset Alexander disease. ( 30355306 )
2018
19
Myelin changes in Alexander disease. ( 28342553 )
2018
20
Antisense suppression of glial fibrillary acidic protein as a treatment for Alexander disease. ( 29226998 )
2018
21
Whole Exon Deletion in the GFAP Gene Is a Novel Molecular Mechanism Causing Alexander Disease. ( 29253910 )
2018
22
An unusual GFAP mutation in a Taiwanese child with infantile Alexander disease. ( 29339051 )
2018
23
Aberrant astrocyte Ca2+ signals "AxCa signals" exacerbate pathological alterations in an Alexander disease model. ( 29383757 )
2018
24
Alexander disease. ( 29478608 )
2018
25
Alexander's disease and the story of Louise. ( 27580295 )
2018
26
Reduced cerebrospinal fluid monoamines in Alexander's disease: a clue to a symptomatic therapy. ( 30134051 )
2018
27
Neurobehavioral characterization of adult-onset Alexander disease: A family study. ( 29620072 )
2017
28
Alexander Disease. ( 28112050 )
2017
29
Disorders of Astrocytes: Alexander Disease as a Model. ( 28135564 )
2017
30
Glial fibrillary acidic protein exhibits altered turnover kinetics in a mouse model of Alexander disease. ( 28223355 )
2017
31
The origin of Rosenthal fibers and their contributions to astrocyte pathology in Alexander disease. ( 28359321 )
2017
32
Central hypothermia associated with Alexander disease. A case report. ( 28384596 )
2017
33
Quantitative Evaluation of Brain Stem Atrophy Using Magnetic Resonance Imaging in Adult Patients with Alexander Disease. ( 28448978 )
2017
34
Considering Spastic Paraplegia Type 7 and Adult-Onset Alexander Disease. ( 28459923 )
2017
35
Considering Spastic Paraplegia Type 7 and Adult-Onset Alexander Disease-Reply. ( 28459933 )
2017
36
Alexander Disease Mutations Produce Cells with Coexpression of Glial Fibrillary Acidic Protein and NG2 in Neurosphere Cultures and Inhibit Differentiation into Mature Oligodendrocytes. ( 28634469 )
2017
37
Long-term follow-up of a case of adult-onset Alexander disease presenting with cognitive impairment as the initial symptom. ( 28681773 )
2017
38
A novel three-base duplication, E243dup, of GFAP identified in a patient with Alexander disease. ( 28690862 )
2017
39
Infantile Alexander Disease: Case Report and Review of Literature. ( 28764307 )
2017
40
Aggregation-prone GFAP mutation in Alexander disease validated using a zebrafish model. ( 28882119 )
2017
41
A Novel GFAP Mutation in Late-Onset Alexander Disease Showing Diffusion Restriction. ( 29057636 )
2017
42
Novel GFAP Variant in Adult-onset Alexander Disease With Progressive Ataxia and Palatal Tremor. ( 29095329 )
2017
43
Ataxia and autonomic dysfunction as presenting symptoms in late-onset Alexander disease. ( 29431177 )
2017
44
Respiratory difficulty with palatal, laryngeal and respiratory muscle tremor in adult-onset Alexander's disease. ( 28438749 )
2017
45
Adult Alexander disease with de novo c.1193C>T heterozygous variant in GFAP gene. ( 26396075 )
2016
46
A canine orthologue of the human GFAP c.716G>A (p.Arg239His) variant causes Alexander disease in a Labrador retriever. ( 26486469 )
2016
47
Alexander Disease: A Novel Mutation in GFAP Leading to Epilepsia Partialis Continua. ( 26719496 )
2016
48
Unusual presentations and intrafamilial phenotypic variability in infantile onset Alexander disease. ( 26743065 )
2016
49
A novel GFAP mutation in a type II (late-onset) Alexander disease patient. ( 26914930 )
2016
50
Composition of Rosenthal Fibers, the Protein Aggregate Hallmark of Alexander Disease. ( 27193225 )
2016

Variations for Alexander Disease

UniProtKB/Swiss-Prot genetic disease variations for Alexander Disease:

76 (show top 50) (show all 62)
# Symbol AA change Variation ID SNP ID
1 GFAP p.Leu76Phe VAR_017465 rs57120761
2 GFAP p.Asn77Tyr VAR_017466 rs58732244
3 GFAP p.Arg79Cys VAR_017467 rs59793293
4 GFAP p.Arg79His VAR_017468 rs59285727
5 GFAP p.Arg88Cys VAR_017469 rs61622935
6 GFAP p.Arg88Ser VAR_017470 rs61622935
7 GFAP p.Arg239Cys VAR_017471 rs58064122
8 GFAP p.Arg239His VAR_017472 rs59565950
9 GFAP p.Arg258Pro VAR_017474 rs61726468
10 GFAP p.Glu362Asp VAR_017475 rs121909718
11 GFAP p.Arg416Trp VAR_017476 rs121909717
12 GFAP p.Asp78Glu VAR_017477 rs121909720
13 GFAP p.Lys63Gln VAR_071517 rs60095124
14 GFAP p.Arg66Gln VAR_071518 rs797044569
15 GFAP p.Arg70Gln VAR_071519 rs267607510
16 GFAP p.Arg70Trp VAR_071520 rs60343255
17 GFAP p.Glu72Lys VAR_071521 rs267607523
18 GFAP p.Met73Lys VAR_071522 rs61060395
19 GFAP p.Met73Arg VAR_071523 rs61060395
20 GFAP p.Met73Thr VAR_071524 rs61060395
21 GFAP p.Met74Thr VAR_071525 rs267607504
22 GFAP p.Leu76Val VAR_071526 rs57120761
23 GFAP p.Asn77Lys VAR_071527
24 GFAP p.Asn77Ser VAR_071528 rs57590980
25 GFAP p.Asp78Asn VAR_071529 rs797044571
26 GFAP p.Arg79Gly VAR_071530 rs59793293
27 GFAP p.Arg79Leu VAR_071531 rs59285727
28 GFAP p.Arg79Pro VAR_071532 rs59285727
29 GFAP p.Tyr83His VAR_071533 rs267607506
30 GFAP p.Lys86Glu VAR_071534 rs797044573
31 GFAP p.Leu90Pro VAR_071535 rs59661476
32 GFAP p.Leu97Pro VAR_071536 rs59568967
33 GFAP p.Leu101Pro VAR_071537 rs267607516
34 GFAP p.Glu207Lys VAR_071540 rs267607500
35 GFAP p.Glu207Gln VAR_071541 rs267607500
36 GFAP p.Glu210Lys VAR_071542 rs57661783
37 GFAP p.Leu235Pro VAR_071543 rs60269890
38 GFAP p.Lys236Thr VAR_071544 rs267607525
39 GFAP p.Arg239Leu VAR_071545 rs59565950
40 GFAP p.Arg239Pro VAR_071546 rs59565950
41 GFAP p.Tyr242Asp VAR_071547 rs60551555
42 GFAP p.Ala253Gly VAR_071548 rs61726470
43 GFAP p.Tyr257Cys VAR_071549 rs267607505
44 GFAP p.Ala267Pro VAR_071550 rs797044581
45 GFAP p.Arg276Leu VAR_071551 rs121909719
46 GFAP p.Lys279Glu VAR_071552 rs58536923
47 GFAP p.Arg330Gly VAR_071553 rs267607513
48 GFAP p.Glu332Lys VAR_071554 rs267607514
49 GFAP p.Leu352Pro VAR_071555 rs28932769
50 GFAP p.Leu359Pro VAR_071556 rs267607511

ClinVar genetic disease variations for Alexander Disease:

6 (show top 50) (show all 325)
# Gene Variation Type Significance SNP ID Assembly Location
1 GFAP NM_002055.4(GFAP): c.715C> T (p.Arg239Cys) single nucleotide variant Pathogenic rs58064122 GRCh37 Chromosome 17, 42990702: 42990702
2 GFAP NM_002055.4(GFAP): c.715C> T (p.Arg239Cys) single nucleotide variant Pathogenic rs58064122 GRCh38 Chromosome 17, 44913334: 44913334
3 GFAP NM_002055.4(GFAP): c.716G> A (p.Arg239His) single nucleotide variant Pathogenic rs59565950 GRCh37 Chromosome 17, 42990701: 42990701
4 GFAP NM_002055.4(GFAP): c.716G> A (p.Arg239His) single nucleotide variant Pathogenic rs59565950 GRCh38 Chromosome 17, 44913333: 44913333
5 GFAP NM_002055.4(GFAP): c.1246C> T (p.Arg416Trp) single nucleotide variant Pathogenic rs121909717 GRCh37 Chromosome 17, 42985443: 42985443
6 GFAP NM_002055.4(GFAP): c.1246C> T (p.Arg416Trp) single nucleotide variant Pathogenic rs121909717 GRCh38 Chromosome 17, 44908075: 44908075
7 GFAP NM_002055.4(GFAP): c.236G> A (p.Arg79His) single nucleotide variant Pathogenic rs59285727 GRCh37 Chromosome 17, 42992619: 42992619
8 GFAP NM_002055.4(GFAP): c.236G> A (p.Arg79His) single nucleotide variant Pathogenic rs59285727 GRCh38 Chromosome 17, 44915251: 44915251
9 GFAP NM_002055.4(GFAP): c.235C> T (p.Arg79Cys) single nucleotide variant Pathogenic rs59793293 GRCh37 Chromosome 17, 42992620: 42992620
10 GFAP NM_002055.4(GFAP): c.235C> T (p.Arg79Cys) single nucleotide variant Pathogenic rs59793293 GRCh38 Chromosome 17, 44915252: 44915252
11 GFAP NM_002055.4(GFAP): c.262C> T (p.Arg88Cys) single nucleotide variant Pathogenic rs61622935 GRCh37 Chromosome 17, 42992593: 42992593
12 GFAP NM_002055.4(GFAP): c.262C> T (p.Arg88Cys) single nucleotide variant Pathogenic rs61622935 GRCh38 Chromosome 17, 44915225: 44915225
13 GFAP NM_002055.4(GFAP): c.262C> A (p.Arg88Ser) single nucleotide variant Pathogenic rs61622935 GRCh37 Chromosome 17, 42992593: 42992593
14 GFAP NM_002055.4(GFAP): c.262C> A (p.Arg88Ser) single nucleotide variant Pathogenic rs61622935 GRCh38 Chromosome 17, 44915225: 44915225
15 GFAP NM_002055.4(GFAP): c.226C> T (p.Leu76Phe) single nucleotide variant Pathogenic rs57120761 GRCh37 Chromosome 17, 42992629: 42992629
16 GFAP NM_002055.4(GFAP): c.226C> T (p.Leu76Phe) single nucleotide variant Pathogenic rs57120761 GRCh38 Chromosome 17, 44915261: 44915261
17 GFAP NM_002055.4(GFAP): c.229A> T (p.Asn77Tyr) single nucleotide variant Pathogenic rs58732244 GRCh37 Chromosome 17, 42992626: 42992626
18 GFAP NM_002055.4(GFAP): c.229A> T (p.Asn77Tyr) single nucleotide variant Pathogenic rs58732244 GRCh38 Chromosome 17, 44915258: 44915258
19 GFAP NM_002055.4(GFAP): c.1086G> C (p.Glu362Asp) single nucleotide variant Pathogenic rs121909718 GRCh37 Chromosome 17, 42988645: 42988645
20 GFAP NM_002055.4(GFAP): c.1086G> C (p.Glu362Asp) single nucleotide variant Pathogenic rs121909718 GRCh38 Chromosome 17, 44911277: 44911277
21 GFAP NM_002055.4(GFAP): c.827G> T (p.Arg276Leu) single nucleotide variant Pathogenic rs121909719 GRCh37 Chromosome 17, 42989119: 42989119
22 GFAP NM_002055.4(GFAP): c.827G> T (p.Arg276Leu) single nucleotide variant Pathogenic rs121909719 GRCh38 Chromosome 17, 44911751: 44911751
23 GFAP NM_002055.4(GFAP): c.1055T> C (p.Leu352Pro) single nucleotide variant Pathogenic rs28932769 GRCh37 Chromosome 17, 42988676: 42988676
24 GFAP NM_002055.4(GFAP): c.1055T> C (p.Leu352Pro) single nucleotide variant Pathogenic rs28932769 GRCh38 Chromosome 17, 44911308: 44911308
25 GFAP NM_002055.4(GFAP): c.234C> A (p.Asp78Glu) single nucleotide variant Pathogenic rs121909720 GRCh37 Chromosome 17, 42992621: 42992621
26 GFAP NM_002055.4(GFAP): c.234C> A (p.Asp78Glu) single nucleotide variant Pathogenic rs121909720 GRCh38 Chromosome 17, 44915253: 44915253
27 CCDC103; GFAP NM_002055.4(GFAP): c.*28C> G single nucleotide variant Benign/Likely benign rs11558961 GRCh37 Chromosome 17, 42984687: 42984687
28 CCDC103; GFAP NM_002055.4(GFAP): c.*28C> G single nucleotide variant Benign/Likely benign rs11558961 GRCh38 Chromosome 17, 44907319: 44907319
29 GFAP NM_002055.4(GFAP): c.1070T> C (p.Leu357Pro) single nucleotide variant Pathogenic rs267607515 GRCh37 Chromosome 17, 42988661: 42988661
30 GFAP NM_002055.4(GFAP): c.1070T> C (p.Leu357Pro) single nucleotide variant Pathogenic rs267607515 GRCh38 Chromosome 17, 44911293: 44911293
31 GFAP NM_002055.4(GFAP): c.1075C> G (p.Leu359Val) single nucleotide variant Pathogenic rs60825166 GRCh37 Chromosome 17, 42988656: 42988656
32 GFAP NM_002055.4(GFAP): c.1075C> G (p.Leu359Val) single nucleotide variant Pathogenic rs60825166 GRCh38 Chromosome 17, 44911288: 44911288
33 GFAP NM_002055.4(GFAP): c.1076T> C (p.Leu359Pro) single nucleotide variant Pathogenic rs267607511 GRCh37 Chromosome 17, 42988655: 42988655
34 GFAP NM_002055.4(GFAP): c.1076T> C (p.Leu359Pro) single nucleotide variant Pathogenic rs267607511 GRCh38 Chromosome 17, 44911287: 44911287
35 GFAP NM_002055.4(GFAP): c.1079A> T (p.Asp360Val) single nucleotide variant Pathogenic rs62636501 GRCh37 Chromosome 17, 42988652: 42988652
36 GFAP NM_002055.4(GFAP): c.1079A> T (p.Asp360Val) single nucleotide variant Pathogenic rs62636501 GRCh38 Chromosome 17, 44911284: 44911284
37 GFAP NM_002055.4(GFAP): c.1090G> C (p.Ala364Pro) single nucleotide variant Pathogenic rs58645997 GRCh37 Chromosome 17, 42988641: 42988641
38 GFAP NM_002055.4(GFAP): c.1090G> C (p.Ala364Pro) single nucleotide variant Pathogenic rs58645997 GRCh38 Chromosome 17, 44911273: 44911273
39 GFAP NM_002055.4(GFAP): c.1091C> T (p.Ala364Val) single nucleotide variant Pathogenic rs267607503 GRCh37 Chromosome 17, 42988640: 42988640
40 GFAP NM_002055.4(GFAP): c.1091C> T (p.Ala364Val) single nucleotide variant Pathogenic rs267607503 GRCh38 Chromosome 17, 44911272: 44911272
41 GFAP NM_002055.4(GFAP): c.1096T> C (p.Tyr366His) single nucleotide variant Pathogenic rs58008462 GRCh37 Chromosome 17, 42988635: 42988635
42 GFAP NM_002055.4(GFAP): c.1096T> C (p.Tyr366His) single nucleotide variant Pathogenic rs58008462 GRCh38 Chromosome 17, 44911267: 44911267
43 GFAP NM_002055.4(GFAP): c.1097A> G (p.Tyr366Cys) single nucleotide variant Pathogenic rs267607502 GRCh37 Chromosome 17, 42988634: 42988634
44 GFAP NM_002055.4(GFAP): c.1097A> G (p.Tyr366Cys) single nucleotide variant Pathogenic rs267607502 GRCh38 Chromosome 17, 44911266: 44911266
45 GFAP NM_002055.4(GFAP): c.1111G> C (p.Glu371Gln) single nucleotide variant Pathogenic rs267607526 GRCh37 Chromosome 17, 42988620: 42988620
46 GFAP NM_002055.4(GFAP): c.1111G> C (p.Glu371Gln) single nucleotide variant Pathogenic rs267607526 GRCh38 Chromosome 17, 44911252: 44911252
47 GFAP NM_002055.4(GFAP): c.1112A> G (p.Glu371Gly) single nucleotide variant Pathogenic rs57815192 GRCh37 Chromosome 17, 42988619: 42988619
48 GFAP NM_002055.4(GFAP): c.1112A> G (p.Glu371Gly) single nucleotide variant Pathogenic rs57815192 GRCh38 Chromosome 17, 44911251: 44911251
49 GFAP NM_002055.4(GFAP): c.1112A> T (p.Glu371Val) single nucleotide variant Pathogenic rs57815192 GRCh37 Chromosome 17, 42988619: 42988619
50 GFAP NM_002055.4(GFAP): c.1112A> T (p.Glu371Val) single nucleotide variant Pathogenic rs57815192 GRCh38 Chromosome 17, 44911251: 44911251

Expression for Alexander Disease

Search GEO for disease gene expression data for Alexander Disease.

Pathways for Alexander Disease

Pathways related to Alexander Disease according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.83 GFAP PLEC SYNM
2 10.82 HSPB1 MTOR
3 10.51 MTOR NDUFV1

GO Terms for Alexander Disease

Cellular components related to Alexander Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 axon GO:0030424 9.63 CRYAB HDAC6 HTT
2 cytosol GO:0005829 9.56 CRYAB GFAP HDAC6 HSPB1 HTT MTOR
3 intermediate filament GO:0005882 9.54 GFAP PLEC SYNM
4 intermediate filament cytoskeleton GO:0045111 9.43 GFAP PLEC
5 inclusion body GO:0016234 9.32 HDAC6 HTT
6 costamere GO:0043034 9.26 PLEC SYNM
7 postsynaptic cytosol GO:0099524 9.16 HTT MTOR
8 contractile fiber GO:0043292 8.8 CRYAB HSPB1 PLEC
9 cytoplasm GO:0005737 10.01 CRYAB GFAP HDAC6 HSPB1 HTT MTOR

Biological processes related to Alexander Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 regulation of autophagy GO:0010506 9.37 HDAC6 HSPB1
2 regulation of macroautophagy GO:0016241 9.32 HDAC6 MTOR
3 regulation of protein phosphorylation GO:0001932 9.26 HSPB1 MTOR
4 regulation of cellular response to heat GO:1900034 9.16 CRYAB MTOR
5 intermediate filament cytoskeleton organization GO:0045104 8.96 PLEC SYNM
6 positive regulation of glial cell proliferation GO:0060252 8.62 GFAP MTOR

Molecular functions related to Alexander Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 identical protein binding GO:0042802 9.35 CRYAB GFAP HSPB1 HTT MTOR
2 ubiquitin binding GO:0043130 9.32 HDAC6 HSPB1
3 structural constituent of muscle GO:0008307 9.26 PLEC SYNM
4 beta-tubulin binding GO:0048487 9.16 HDAC6 HTT
5 structural constituent of cytoskeleton GO:0005200 8.8 GFAP PLEC SYNM

Sources for Alexander Disease

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
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38 KEGG
39 LifeMap
41 LOVD
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45 MeSH
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55 NINDS
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58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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