ALXDRD
MCID: ALX003
MIFTS: 62

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 56 12 74 24 52 25 53 58 73 36 29 13 6 43 15 71
Alexander's Disease 12 25 73 39
Alexanders Leukodystrophy 52 71
Alxdrd 56 73
Axd 25 58
Megalencephaly in Infancy Accompanied by Progressive Spasticity and Dementia 52
Fibrinoid Degeneration of Astrocytes 25
Leukodystrophy with Rosenthal Fibers 25
Dysmyelinogenic Leukodystrophy 25
Demyelinogenic Leukodystrophy 25
Alexander Disease Type Ii 58
Alexander Disease Type I 58
Alexanders Disease 54
Axd Type Ii 58
Axd Type I 58
Alx 25

Characteristics:

Orphanet epidemiological data:

58
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:

56
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:

31
alexander disease:
Inheritance autosomal dominant inheritance
Onset and clinical course infantile onset


GeneReviews:

24
Penetrance Penetrance appears to be nearly 100% in individuals with the infantile and juvenile forms [li et al 2002, messing & brenner 2003a]....

Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases


Summaries for Alexander Disease

Genetics Home Reference : 25 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. Most cases of Alexander disease begin before age 2 and are described as the infantile form. Signs and symptoms of the infantile form typically include an enlarged brain and head size (megalencephaly), seizures, stiffness in the arms and/or legs (spasticity), intellectual disability, and developmental delay. Less frequently, onset occurs later in childhood (the juvenile form) or in adulthood. Common problems in juvenile and adult forms of Alexander disease include speech abnormalities, swallowing difficulties, seizures, and poor coordination (ataxia). Rarely, a neonatal form of Alexander disease occurs within the first month of life and is associated with severe intellectual disability and developmental delay, a buildup of fluid in the brain (hydrocephalus), and seizures. Alexander disease is also characterized by abnormal protein deposits known as Rosenthal fibers. These deposits are found in specialized cells called astroglial cells, which support and nourish other cells in the brain and spinal cord (central nervous system).

MalaCards based summary : Alexander Disease, also known as alexander's disease, is related to leukodystrophy and status epilepticus, 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 Proteoglycans in cancer and Regulation of degradation of deltaF508 CFTR in CF. The drugs Metronidazole and Anti-Bacterial Agents have been mentioned in the context of this disorder. Affiliated tissues include brain, spinal cord and eye, 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.

NIH Rare Diseases : 52 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 : 56 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)

NINDS : 53 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.

KEGG : 36 Alexander disease is a rare, but often fatal neurological disorder that has been divided into three subtypes based on the age of onset: the infantile, juvenile and adult forms. The characteristic neuropathological feature of all forms of Alexander's disease is the presence of Rosenthal fibers which include protein aggregates that contain glial fibrillary acidic protein (GFAP) and small stress proteins in astrocytes.

UniProtKB/Swiss-Prot : 73 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 : 74 Alexander disease is a very rare autosomal dominant leukodystrophy, which are neurological conditions... more...

GeneReviews: NBK1172

Related Diseases for Alexander Disease

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

(show top 50) (show all 154)
# Related Disease Score Top Affiliating Genes
1 leukodystrophy 32.1 PLP1 NDUFV1 HEPACAM GFAP CRYAB
2 status epilepticus 30.1 SLC1A2 GFAP CASP3
3 traumatic brain injury 30.1 GFAP CASP3
4 leukoencephalopathy, hereditary diffuse, with spheroids 30.0 SLC1A2 GFAP CRYAB
5 central nervous system disease 29.7 PLP1 HTT GFAP CRYAB CRYAA
6 amyotrophic lateral sclerosis 1 28.7 SLC1A2 HTT HSPB2 HSPB1 GFAP CRYAB
7 ataxia and polyneuropathy, adult-onset 10.5
8 primitive neuroectodermal tumor of the cervix uteri 10.4 VIM GFAP
9 macrocephaly/megalencephaly syndrome, autosomal recessive 10.4
10 megalencephaly 10.4
11 angiocentric glioma 10.4 VIM GFAP
12 middle cranial fossa meningioma 10.4 MAPK14 HTT
13 parachordoma 10.4 VIM GFAP
14 early-onset lamellar cataract 10.4 CRYAB CRYAA
15 spasticity 10.4
16 distal hereditary motor neuronopathy type 2 10.4 HSPB3 HSPB1
17 myopathy, myofibrillar, 1 10.4 SYNM PLEC CRYAB
18 anaplastic ependymoma 10.3 VIM GFAP
19 chordoid meningioma 10.3 VIM GFAP
20 rhabdoid meningioma 10.3 VIM GFAP
21 dysphagia 10.3
22 benign ependymoma 10.3 VIM MTOR GFAP
23 myopathy, myofibrillar, 2 10.3 PLEC CRYAB
24 asthma 10.2
25 pulmonary edema 10.2
26 astrocytoma 10.2
27 pathologic nystagmus 10.2
28 myoclonus 10.2
29 tremor 10.2
30 corticobasal degeneration 10.2 MTOR HSPB2 CRYAB
31 inflammatory myofibroblastic tumor 10.2 VIM SYNM CASP3
32 retinal ischemia 10.2 HSPB1 CRYAA CASP3
33 pick disease of brain 10.2 HTT GFAP CRYAB CASP3
34 binswanger's disease 10.2 PLP1 GFAP
35 encephalomalacia 10.2 SLC1A2 GFAP CASP3
36 glioma 10.2
37 autonomic dysfunction 10.2
38 hypotonia 10.2
39 glial tumor 10.2
40 chordoma 10.2 VIM MTOR GFAP
41 spinal and bulbar muscular atrophy, x-linked 1 10.2 HTT HDAC6 CRYAA
42 subependymal giant cell astrocytoma 10.2 VIM MTOR GFAP CRYAB
43 machado-joseph disease 10.2 HTT HSPB2 HSPB1
44 scoliosis 10.1
45 hydrocephalus 10.1
46 visual epilepsy 10.1
47 paraplegia 10.1
48 seizure disorder 10.1
49 charcot-marie-tooth disease, axonal, type 2f 10.1 HSPB3 HSPB2 HSPB1
50 myofibrillar myopathy 10.1 SYNM PLEC CRYAB CRYAA

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:

58 31 (show top 50) (show all 66)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000256
2 agenesis of corpus callosum 58 31 hallmark (90%) Very frequent (99-80%) HP:0001274
3 frontal bossing 58 31 hallmark (90%) Very frequent (99-80%) HP:0002007
4 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
5 seizures 58 31 hallmark (90%) Very frequent (99-80%) HP:0001250
6 spasticity 58 31 hallmark (90%) Very frequent (99-80%) HP:0001257
7 megalencephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001355
8 failure to thrive 58 31 hallmark (90%) Very frequent (99-80%) HP:0001508
9 nausea and vomiting 58 31 hallmark (90%) Very frequent (99-80%) HP:0002017
10 clonus 58 31 hallmark (90%) Very frequent (99-80%) HP:0002169
11 eeg abnormality 58 31 hallmark (90%) Very frequent (99-80%) HP:0002353
12 scoliosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0002650
13 abnormal pyramidal sign 58 31 hallmark (90%) Very frequent (99-80%) HP:0007256
14 large face 58 31 hallmark (90%) Very frequent (99-80%) HP:0100729
15 ptosis 58 31 frequent (33%) Frequent (79-30%) HP:0000508
16 nystagmus 58 31 frequent (33%) Frequent (79-30%) HP:0000639
17 diplopia 58 31 frequent (33%) Frequent (79-30%) HP:0000651
18 emotional lability 58 31 frequent (33%) Frequent (79-30%) HP:0000712
19 depressivity 58 31 frequent (33%) Frequent (79-30%) HP:0000716
20 hyperhidrosis 58 31 frequent (33%) Frequent (79-30%) HP:0000975
21 ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0001251
22 dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0001260
23 gait disturbance 58 31 frequent (33%) Frequent (79-30%) HP:0001288
24 tremor 58 31 frequent (33%) Frequent (79-30%) HP:0001337
25 dysphonia 58 31 frequent (33%) Frequent (79-30%) HP:0001618
26 dysphagia 58 31 frequent (33%) Frequent (79-30%) HP:0002015
27 constipation 58 31 frequent (33%) Frequent (79-30%) HP:0002019
28 hypothermia 58 31 frequent (33%) Frequent (79-30%) HP:0002045
29 dysphasia 58 31 frequent (33%) Frequent (79-30%) HP:0002357
30 tetraplegia 58 31 frequent (33%) Frequent (79-30%) HP:0002445
31 cerebral calcification 58 31 frequent (33%) Frequent (79-30%) HP:0002514
32 hypotension 58 31 frequent (33%) Frequent (79-30%) HP:0002615
33 kyphosis 58 31 frequent (33%) Frequent (79-30%) HP:0002808
34 sleep apnea 58 31 frequent (33%) Frequent (79-30%) HP:0010535
35 facial palsy 58 31 frequent (33%) Frequent (79-30%) HP:0010628
36 recurrent singultus 58 31 frequent (33%) Frequent (79-30%) HP:0100247
37 short neck 58 31 occasional (7.5%) Occasional (29-5%) HP:0000470
38 high palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000218
39 hydrocephalus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000238
40 diabetes mellitus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000819
41 hypothyroidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000821
42 hypertension 58 31 occasional (7.5%) Occasional (29-5%) HP:0000822
43 precocious puberty 58 31 occasional (7.5%) Occasional (29-5%) HP:0000826
44 osteopenia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000938
45 muscular hypotonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001252
46 sudden cardiac death 58 31 occasional (7.5%) Occasional (29-5%) HP:0001645
47 chorea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002072
48 respiratory insufficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0002093
49 developmental regression 58 31 occasional (7.5%) Occasional (29-5%) HP:0002376
50 encephalitis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002383

Symptoms via clinical synopsis from OMIM:

56
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:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.21 CASP3 CRYAB GFAP HDAC6 HSPB2 HTT
2 cellular MP:0005384 10.07 CASP3 CRYAB GFAP HDAC6 HSPB1 HSPB2
3 cardiovascular system MP:0005385 10.02 CASP3 GFAP HSPB1 HSPB2 HTT MAPK14
4 homeostasis/metabolism MP:0005376 10 CASP3 CRYAB GFAP HDAC6 HEPACAM HSPB1
5 muscle MP:0005369 9.61 CASP3 CRYAB GFAP MAPK14 MTOR PLEC
6 nervous system MP:0003631 9.36 CASP3 GFAP HDAC6 HEPACAM HTT MAPK14

Drugs & Therapeutics for Alexander Disease

Drugs for Alexander Disease (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Metronidazole Approved 443-48-1 4173
2 Anti-Bacterial Agents
3 Anti-Infective Agents
4 Antiprotozoal Agents
5 Antiparasitic Agents

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Evaluation of Outcome Metrics 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 29 GFAP

Anatomical Context for Alexander Disease

MalaCards organs/tissues related to Alexander Disease:

40
Brain, Spinal Cord, Eye, Testes, Pituitary, Cortex, Medulla Oblongata

Publications for Alexander Disease

Articles related to Alexander Disease:

(show top 50) (show all 489)
# Title Authors PMID Year
1
The Alexander disease-causing glial fibrillary acidic protein mutant, R416W, accumulates into Rosenthal fibers by a pathway that involves filament aggregation and the association of alpha B-crystallin and HSP27. 24 56 6 54 61
16826512 2006
2
Adult Alexander disease with autosomal dominant transmission: a distinct entity caused by mutation in the glial fibrillary acid protein gene. 54 61 56 6 24
12975300 2003
3
Identification of GFAP gene mutation in hereditary adult-onset Alexander's disease. 54 6 56 24 61
12447932 2002
4
Infantile Alexander disease: spectrum of GFAP mutations and genotype-phenotype correlation. 61 56 6 54 24
11567214 2001
5
Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. 61 24 6 54 56
11138011 2001
6
Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms of Alexander disease. 24 56 6 61
15732097 2005
7
GFAP mutations and polymorphisms in 13 unrelated Italian patients affected by Alexander disease. 6 54 61 56
17894839 2007
8
Propensity for paternal inheritance of de novo mutations in Alexander disease. 56 24 54 61
16365765 2006
9
Alexander disease: ventricular garlands and abnormalities of the medulla and spinal cord. 56 61 24 54
16505300 2006
10
Alexander disease with serial MRS and a new mutation in the glial fibrillary acidic protein gene. 61 6 56
14557587 2003
11
Juvenile Alexander disease with a novel mutation in glial fibrillary acidic protein gene. 61 56 6
12034796 2002
12
Adult-onset Alexander disease, associated with a mutation in an alternative GFAP transcript, may be phenotypically modulated by a non-neutral HDAC6 variant. 24 61 56
23634874 2013
13
Nationwide survey of Alexander disease in Japan and proposed new guidelines for diagnosis. 61 6 24
21533827 2011
14
Alexander disease with hypothermia, microcoria, and psychiatric and endocrine disturbances. 56 24 61
17438228 2007
15
Unusual variants of Alexander's disease. 61 56 24
15732098 2005
16
Molecular findings in symptomatic and pre-symptomatic Alexander disease patients. 61 24 56
12034785 2002
17
Alexander disease: diagnosis with MR imaging. 61 24 56
11237983 2001
18
Diagnosis of Alexander disease in a Japanese patient by molecular genetic analysis. 61 54 6
11587071 2001
19
c.1289G>A (p.Arg430His) variant in the epsilon isoform of the GFAP gene in a patient with adult onset Alexander disease. 61 56
30048824 2019
20
Oligomers of mutant glial fibrillary acidic protein (GFAP) Inhibit the proteasome system in alexander disease astrocytes, and the small heat shock protein alphaB-crystallin reverses the inhibition. 61 54 24
20110364 2010
21
Suppression of GFAP toxicity by alphaB-crystallin in mouse models of Alexander disease. 56 61
19129171 2009
22
An infantile case of Alexander disease unusual for its MRI features and a GFAP allele carrying both the p.Arg79His mutation and the p.Glu223Gln coding variant. 24 54 61
19444543 2009
23
Novel deletion mutation in GFAP gene in an infantile form of Alexander disease. 24 54 61
18054694 2008
24
Adult-onset Alexander disease : report on a family. 61 54 24
18004641 2008
25
Alexander disease with occipital predominance and a novel c.799G>C mutation in the GFAP gene. 24 61 54
17805552 2007
26
Increased levels of GFAP in the cerebrospinal fluid in three subtypes of genetically confirmed Alexander disease. 24 54 61
16217707 2005
27
Alexander-disease mutation of GFAP causes filament disorganization and decreased solubility of GFAP. 54 24 61
15840648 2005
28
Asymptomatic hereditary Alexander's disease caused by a novel mutation in GFAP. 24 61 54
15465095 2004
29
Dominantly-inherited adult-onset leukodystrophy with palatal tremor caused by a mutation in the glial fibrillary acidic protein gene. 61 24 54
15390001 2004
30
A case of adult-onset Alexander disease with Arg416Trp human glial fibrillary acidic protein gene mutation. 61 54 24
14550921 2003
31
Alexander disease: GFAP mutations unify young and old. 24 61 54
12849260 2003
32
A novel GFAP mutation and disseminated white matter lesions: adult Alexander disease? 61 54 24
12944715 2003
33
Alexander Disease 61 6
20301351 2002
34
GFAP mutations in Alexander disease. 61 54 24
12175861 2002
35
Autosomal dominant palatal myoclonus and spinal cord atrophy. 61 24 54
11867077 2002
36
Alexander disease: new insights from genetics. 61 24 54
11398833 2001
37
Hereditary adult-onset Alexander's disease with palatal myoclonus, spastic paraparesis, and cerebellar ataxia. 56 61
8848205 1995
38
Alpha B-crystallin is expressed in non-lenticular tissues and accumulates in Alexander's disease brain. 56 61
2539261 1989
39
Light and electron microscopic observations on Rosenthal fibers in Alexander's disease and in multiple sclerosis. 61 56
5471920 1970
40
Identification of a novel nonsense mutation in the rod domain of GFAP that is associated with Alexander disease. 61 24
24755947 2015
41
Neuroimaging and clinical features in type II (late-onset) Alexander disease. 61 24
24306001 2014
42
Acute onset of adult Alexander disease. 24 61
23706596 2013
43
Familial adult-onset Alexander disease with a novel mutation (D78N) in the glial fibrillary acidic protein gene with unusual bilateral basal ganglia involvement. 61 24
23743246 2013
44
Splice site, frameshift, and chimeric GFAP mutations in Alexander disease. 61 24
22488673 2012
45
Archetypal and new families with Alexander disease and novel mutations in GFAP. 61 24
21987397 2012
46
A case of sporadic adult Alexander disease presenting with acute onset, remission and relapse. 24 61
20562394 2010
47
Alexander disease causing hereditary late-onset ataxia with only minimal white matter changes: A report of two sibs. 24 61
18581469 2008
48
Alexander disease and megalencephalic leukoencephalopathy with subcortical cysts: leukodystrophies arising from astrocyte dysfunction. 61 24
16807904 2006
49
Adult Alexander's disease without leukoencephalopathy. 24 61
16240361 2005
50
GFAP: functional implications gleaned from studies of genetically engineered mice. 24 61
12761871 2003

Variations for Alexander Disease

ClinVar genetic disease variations for Alexander Disease:

6 (show top 50) (show all 165) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GFAP NM_002055.5(GFAP):c.187A>C (p.Lys63Gln)SNV Pathogenic 66459 rs60095124 17:42992668-42992668 17:44915300-44915300
2 GFAP NM_002055.5(GFAP):c.208C>T (p.Arg70Trp)SNV Pathogenic 66460 rs60343255 17:42992647-42992647 17:44915279-44915279
3 GFAP NM_002055.5(GFAP):c.209G>A (p.Arg70Gln)SNV Pathogenic 66461 rs267607510 17:42992646-42992646 17:44915278-44915278
4 GFAP NM_002055.5(GFAP):c.214G>A (p.Glu72Lys)SNV Pathogenic 66463 rs267607523 17:42992641-42992641 17:44915273-44915273
5 GFAP NM_002055.5(GFAP):c.218T>A (p.Met73Lys)SNV Pathogenic 66464 rs61060395 17:42992637-42992637 17:44915269-44915269
6 GFAP NM_002055.5(GFAP):c.218T>G (p.Met73Arg)SNV Pathogenic 66465 rs61060395 17:42992637-42992637 17:44915269-44915269
7 GFAP NM_002055.5(GFAP):c.221T>C (p.Met74Thr)SNV Pathogenic 66466 rs267607504 17:42992634-42992634 17:44915266-44915266
8 GFAP NM_002055.5(GFAP):c.226C>G (p.Leu76Val)SNV Pathogenic 66467 rs57120761 17:42992629-42992629 17:44915261-44915261
9 GFAP NM_002055.5(GFAP):c.234C>A (p.Asp78Glu)SNV Pathogenic 16179 rs121909720 17:42992621-42992621 17:44915253-44915253
10 GFAP NM_002055.5(GFAP):c.1055T>C (p.Leu352Pro)SNV Pathogenic 16178 rs28932769 17:42988676-42988676 17:44911308-44911308
11 GFAP NM_002055.5(GFAP):c.827G>T (p.Arg276Leu)SNV Pathogenic 16177 rs121909719 17:42989119-42989119 17:44911751-44911751
12 GFAP NM_001131019.3(GFAP):c.1086G>C (p.Glu362Asp)SNV Pathogenic 16176 rs121909718 17:42988645-42988645 17:44911277-44911277
13 GFAP NM_002055.5(GFAP):c.229A>T (p.Asn77Tyr)SNV Pathogenic 16175 rs58732244 17:42992626-42992626 17:44915258-44915258
14 GFAP NM_002055.5(GFAP):c.226C>T (p.Leu76Phe)SNV Pathogenic 16174 rs57120761 17:42992629-42992629 17:44915261-44915261
15 GFAP NM_002055.5(GFAP):c.262C>A (p.Arg88Ser)SNV Pathogenic 16173 rs61622935 17:42992593-42992593 17:44915225-44915225
16 GFAP NM_002055.5(GFAP):c.262C>T (p.Arg88Cys)SNV Pathogenic 16172 rs61622935 17:42992593-42992593 17:44915225-44915225
17 GFAP NM_002055.5(GFAP):c.235C>T (p.Arg79Cys)SNV Pathogenic 16171 rs59793293 17:42992620-42992620 17:44915252-44915252
18 GFAP NM_002055.5(GFAP):c.236G>A (p.Arg79His)SNV Pathogenic 16170 rs59285727 17:42992619-42992619 17:44915251-44915251
19 GFAP NM_002055.5(GFAP):c.1246C>T (p.Arg416Trp)SNV Pathogenic 16169 rs121909717 17:42985443-42985443 17:44908075-44908075
20 GFAP NM_002055.5(GFAP):c.716G>A (p.Arg239His)SNV Pathogenic 16168 rs59565950 17:42990701-42990701 17:44913333-44913333
21 GFAP NM_002055.5(GFAP):c.715C>T (p.Arg239Cys)SNV Pathogenic 16167 rs58064122 17:42990702-42990702 17:44913334-44913334
22 GFAP NM_002055.5(GFAP):c.230A>G (p.Asn77Ser)SNV Pathogenic 66468 rs57590980 17:42992625-42992625 17:44915257-44915257
23 GFAP NM_002055.5(GFAP):c.235C>G (p.Arg79Gly)SNV Pathogenic 66470 rs59793293 17:42992620-42992620 17:44915252-44915252
24 GFAP NM_002055.5(GFAP):c.236G>C (p.Arg79Pro)SNV Pathogenic 66471 rs59285727 17:42992619-42992619 17:44915251-44915251
25 GFAP NM_002055.5(GFAP):c.236G>T (p.Arg79Leu)SNV Pathogenic 66472 rs59285727 17:42992619-42992619 17:44915251-44915251
26 GFAP NM_002055.5(GFAP):c.247T>C (p.Tyr83His)SNV Pathogenic 66473 rs267607506 17:42992608-42992608 17:44915240-44915240
27 GFAP NM_002055.5(GFAP):c.256_259delinsGAGT (p.Lys86_Val87delinsGluPhe)indel Pathogenic 66475 rs267607501 17:42992596-42992599 17:44915228-44915231
28 GFAP NM_002055.5(GFAP):c.259G>C (p.Val87Leu)SNV Pathogenic 66477 rs267607518 17:42992596-42992596 17:44915228-44915228
29 GFAP NM_002055.5(GFAP):c.260T>G (p.Val87Gly)SNV Pathogenic 66478 rs60449251 17:42992595-42992595 17:44915227-44915227
30 GFAP NM_002055.5(GFAP):c.269T>C (p.Leu90Pro)SNV Pathogenic 66479 rs59661476 17:42992586-42992586 17:44915218-44915218
31 GFAP NM_002055.5(GFAP):c.290T>C (p.Leu97Pro)SNV Pathogenic 66480 rs59568967 17:42992565-42992565 17:44915197-44915197
32 GFAP NM_002055.5(GFAP):c.302T>C (p.Leu101Pro)SNV Pathogenic 66481 rs267607516 17:42992553-42992553 17:44915185-44915185
33 GFAP NM_002055.5(GFAP):c.382G>A (p.Asp128Asn)SNV Pathogenic 66484 rs267607509 17:42992473-42992473 17:44915105-44915105
34 GFAP NM_002055.5(GFAP):c.1070T>C (p.Leu357Pro)SNV Pathogenic 66428 rs267607515 17:42988661-42988661 17:44911293-44911293
35 GFAP NM_002055.5(GFAP):c.1075C>G (p.Leu359Val)SNV Pathogenic 66429 rs60825166 17:42988656-42988656 17:44911288-44911288
36 GFAP NM_002055.5(GFAP):c.1076T>C (p.Leu359Pro)SNV Pathogenic 66430 rs267607511 17:42988655-42988655 17:44911287-44911287
37 GFAP NM_002055.5(GFAP):c.1079A>T (p.Asp360Val)SNV Pathogenic 66431 rs62636501 17:42988652-42988652 17:44911284-44911284
38 GFAP NM_002055.5(GFAP):c.1090G>C (p.Ala364Pro)SNV Pathogenic 66432 rs58645997 17:42988641-42988641 17:44911273-44911273
39 GFAP NM_002055.5(GFAP):c.1091C>T (p.Ala364Val)SNV Pathogenic 66433 rs267607503 17:42988640-42988640 17:44911272-44911272
40 GFAP NM_002055.5(GFAP):c.1096T>C (p.Tyr366His)SNV Pathogenic 66434 rs58008462 17:42988635-42988635 17:44911267-44911267
41 GFAP NM_002055.5(GFAP):c.1097A>G (p.Tyr366Cys)SNV Pathogenic 66435 rs267607502 17:42988634-42988634 17:44911266-44911266
42 GFAP NM_002055.5(GFAP):c.1111G>C (p.Glu371Gln)SNV Pathogenic 66436 rs267607526 17:42988620-42988620 17:44911252-44911252
43 GFAP NM_002055.5(GFAP):c.1112A>G (p.Glu371Gly)SNV Pathogenic 66437 rs57815192 17:42988619-42988619 17:44911251-44911251
44 GFAP NM_002055.5(GFAP):c.1112A>T (p.Glu371Val)SNV Pathogenic 66438 rs57815192 17:42988619-42988619 17:44911251-44911251
45 GFAP NM_002055.5(GFAP):c.1117G>A (p.Glu373Lys)SNV Pathogenic 66439 rs58075601 17:42988614-42988614 17:44911246-44911246
46 GFAP NM_002055.5(GFAP):c.1117G>C (p.Glu373Gln)SNV Pathogenic 66440 rs58075601 17:42988614-42988614 17:44911246-44911246
47 GFAP NM_002055.5(GFAP):c.1121A>G (p.Glu374Gly)SNV Pathogenic 66441 rs59628143 17:42988610-42988610 17:44911242-44911242
48 GFAP NM_002055.5(GFAP):c.1126C>T (p.Arg376Trp)SNV Pathogenic 66443 rs267607512 17:42988605-42988605 17:44911237-44911237
49 GFAP NM_002055.5(GFAP):c.1148C>T (p.Thr383Ile)SNV Pathogenic 66447 rs267607517 17:42988006-42988006 17:44910638-44910638
50 GFAP NM_002055.5(GFAP):c.1157A>T (p.Asn386Ile)SNV Pathogenic 66448 rs61726471 17:42987997-42987997 17:44910629-44910629

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

73 (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

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 11.57 MTOR MAPK14 HSPB2 CASP3
2
Show member pathways
11.33 HSPB1 HDAC6 CRYAA
3
Show member pathways
10.96 VIM SYNM PLEC GFAP

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 cytosol GO:0005829 10.18 VIM PLEC NDUFV1 MTOR MAPK14 HTT
2 axon GO:0030424 9.65 SLC1A2 HTT HEPACAM HDAC6 CRYAB
3 intermediate filament GO:0005882 9.62 VIM SYNM PLEC GFAP
4 cytoplasm GO:0005737 9.55 VIM SYNM PLEC MTOR MAPK14 HTT
5 contractile fiber GO:0043292 9.33 PLEC HSPB1 CRYAB
6 intermediate filament cytoskeleton GO:0045111 9.26 VIM SYNM PLEC GFAP

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

# Name GO ID Score Top Affiliating Genes
1 wound healing GO:0042060 9.63 PLEC MTOR CASP3
2 response to wounding GO:0009611 9.61 SLC1A2 GFAP CASP3
3 response to unfolded protein GO:0006986 9.58 HSPB3 HSPB2 HSPB1
4 regulation of macroautophagy GO:0016241 9.54 MTOR HDAC6 CASP3
5 positive regulation of myotube differentiation GO:0010831 9.48 MTOR MAPK14
6 response to amino acid GO:0043200 9.43 SLC1A2 MTOR CASP3
7 Bergmann glial cell differentiation GO:0060020 9.32 VIM GFAP
8 intermediate filament-based process GO:0045103 9.16 VIM GFAP
9 negative regulation of intracellular transport GO:0032387 8.96 CRYAB CRYAA
10 astrocyte development GO:0014002 8.8 VIM PLP1 GFAP

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

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 10.11 VIM SYNM SLC1A2 PLP1 PLEC NDUFV1
2 identical protein binding GO:0042802 9.8 VIM MTOR HTT HSPB1 GFAP CRYAB
3 structural constituent of cytoskeleton GO:0005200 9.26 VIM SYNM PLEC GFAP
4 structural constituent of eye lens GO:0005212 8.8 VIM CRYAB CRYAA

Sources for Alexander Disease

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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