ALS8
MCID: AMY090
MIFTS: 42

Amyotrophic Lateral Sclerosis 8 (ALS8)

Categories: Genetic diseases, Mental diseases, Metabolic diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Amyotrophic Lateral Sclerosis 8

MalaCards integrated aliases for Amyotrophic Lateral Sclerosis 8:

Name: Amyotrophic Lateral Sclerosis 8 56 12 52 73 13 71
Amyotrophic Lateral Sclerosis Type 8 12 52 29 6 15
Als8 56 12 52 73
Sclerosis, Lateral, Amyotrophic, Type Type 8 39

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
age of onset from third to sixth decade of life


HPO:

31
amyotrophic lateral sclerosis 8:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0050752
OMIM 56 608627
OMIM Phenotypic Series 56 PS105400
MeSH 43 D000690
MedGen 41 C1837728
UMLS 71 C1837728

Summaries for Amyotrophic Lateral Sclerosis 8

UniProtKB/Swiss-Prot : 73 Amyotrophic lateral sclerosis 8: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.

MalaCards based summary : Amyotrophic Lateral Sclerosis 8, also known as amyotrophic lateral sclerosis type 8, is related to motor neuron disease and lateral sclerosis, and has symptoms including muscular fasciculation, weakness and static tremor. An important gene associated with Amyotrophic Lateral Sclerosis 8 is VAPB (VAMP Associated Protein B And C), and among its related pathways/superpathways is Neuroscience. Affiliated tissues include brain, spinal cord and skeletal muscle, and related phenotypes are dysphagia and fasciculations

Disease Ontology : 12 An amyotrophic lateral sclerosis that has material basis in mutation in the VAPB gene on chromosome 20.

More information from OMIM: 608627 PS105400

Related Diseases for Amyotrophic Lateral Sclerosis 8

Diseases in the Juvenile Amyotrophic Lateral Sclerosis family:

Amyotrophic Lateral Sclerosis 1 Amyotrophic Lateral Sclerosis 2, Juvenile
Amyotrophic Lateral Sclerosis 5, Juvenile Amyotrophic Lateral Sclerosis 4, Juvenile
Amyotrophic Lateral Sclerosis 21 Amyotrophic Lateral Sclerosis 3
Amyotrophic Lateral Sclerosis 7 Amyotrophic Lateral Sclerosis 8
Amyotrophic Lateral Sclerosis 9 Amyotrophic Lateral Sclerosis 11
Amyotrophic Lateral Sclerosis 12 Amyotrophic Lateral Sclerosis 16, Juvenile
Amyotrophic Lateral Sclerosis 17 Amyotrophic Lateral Sclerosis 18
Amyotrophic Lateral Sclerosis 20 Amyotrophic Lateral Sclerosis 19
Amyotrophic Lateral Sclerosis 23 Amyotrophic Lateral Sclerosis 24
Amyotrophic Lateral Sclerosis 25 Amyotrophic Lateral Sclerosis Type 5
Amyotrophic Lateral Sclerosis Type 6 Amyotrophic Lateral Sclerosis Type 14
Amyotrophic Lateral Sclerosis Type 15 Amyotrophic Lateral Sclerosis Type 22
Tardbp-Related Amyotrophic Lateral Sclerosis

Diseases related to Amyotrophic Lateral Sclerosis 8 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 68)
# Related Disease Score Top Affiliating Genes
1 motor neuron disease 28.7 VAPB TARDBP SOD1 SIGMAR1 SETX OPTN
2 lateral sclerosis 27.0 VAPB UBQLN2 TARDBP SPG11 SOD1 SIGMAR1
3 amyotrophic lateral sclerosis 1 26.0 VPS54 VAPB VAPA UBQLN2 TARDBP SPG11
4 primary lateral sclerosis, adult, 1 10.4 SOD1 ALS2
5 agraphia 10.2 TARDBP C9orf72
6 alzheimer disease 7 10.2 TARDBP SIGMAR1 RMDN3
7 spinal muscular atrophy, late-onset, finkel type 10.1
8 amyotrophic lateral sclerosis 3 10.1
9 oral candidiasis 10.1
10 candidiasis 10.1
11 neuromuscular disease 10.1
12 mood disorder 10.1
13 progressive non-fluent aphasia 10.1 CHMP2B C9orf72
14 movement disease 10.0 TARDBP FUS C9orf72
15 charcot-marie-tooth disease, axonal, type 2cc 10.0 SOD1 C9orf72
16 spinal and bulbar muscular atrophy, x-linked 1 10.0 TARDBP SOD1 FUS C9orf72
17 associative agnosia 10.0 TARDBP CHMP2B C9orf72
18 semantic dementia 10.0 TARDBP CHMP2B C9orf72
19 dysgraphia 10.0 TARDBP CHMP2B C9orf72
20 prosopagnosia 10.0 TARDBP CHMP2B C9orf72
21 writing disorder 10.0 TARDBP CHMP2B C9orf72
22 spinal muscular atrophy, type iv 10.0 VAPB RMDN3
23 dyscalculia 10.0 TARDBP CHMP2B
24 mutism 10.0 TARDBP CHMP2B C9orf72
25 spastic paraplegia 57, autosomal recessive 9.9 SPG11 ALS2
26 pseudobulbar palsy 9.9 TARDBP CHMP2B C9orf72 ALS2
27 nominal aphasia 9.9 TARDBP FUS CHMP2B C9orf72
28 autosomal dominant cerebellar ataxia 9.8 TARDBP SOD1 SETX FUS C9orf72
29 perry syndrome 9.8 TARDBP FUS CHMP2B C9orf72
30 progressive bulbar palsy 9.8 VAPB TARDBP SOD1 FUS C9orf72 ALS2
31 speech and communication disorders 9.8 TARDBP FUS CHMP2B C9orf72
32 amyotrophic lateral sclerosis type 5 9.7 VAPB SPG11 SOD1 SETX ALS2
33 amyotrophic lateral sclerosis 19 9.7 UBQLN2 TARDBP SOD1 C9orf72 ALS2
34 muscular atrophy 9.7 VAPB TARDBP SIGMAR1 SETX FUS C9orf72
35 amyotrophic lateral sclerosis 20 9.7 SPG11 SIGMAR1 C9orf72 ALS2
36 amyotrophic lateral sclerosis 7 9.7 SPG11 SETX CHMP2B ALS2
37 supranuclear palsy, progressive, 1 9.7 TARDBP SOD1 FUS CHMP2B C9orf72
38 dementia, lewy body 9.7 TARDBP SOD1 FUS CHMP2B C9orf72
39 pontocerebellar hypoplasia, type 2e 9.6 VPS54 SOD1 KCNIP1 CHMP2B ALS2
40 dystonia 9.6 SETX FUS CHMP2B C9orf72 ALS2
41 juvenile amyotrophic lateral sclerosis 9.6 SPG11 SIGMAR1 SETX FUS ALS2
42 aphasia 9.6 TARDBP OPTN FUS CHMP2B C9orf72
43 aceruloplasminemia 9.6 SPG11 SOD1 SETX C9orf72
44 charcot-marie-tooth disease, axonal, type 2e 9.6 SPG11 SOD1 RMDN3 FIG4 ALS2
45 spinal muscular atrophy 9.5 VAPB TARDBP SOD1 SIGMAR1 SETX FUS
46 amyotrophic lateral sclerosis 21 9.5 VAPB SPG11 SIGMAR1 SETX FUS ALS2
47 frontotemporal dementia 9.3 UBQLN2 TARDBP SOD1 FUS CHMP2B C9orf72
48 dementia 9.3 UBQLN2 TARDBP SOD1 FUS CHMP2B C9orf72
49 hereditary spastic paraplegia 9.3 UBQLN2 SPG11 SETX C9orf72 ALS2
50 spastic paraplegia 64, autosomal recessive 9.2 UBQLN2 SPG11 SIGMAR1 SETX FUS ALS2

Graphical network of the top 20 diseases related to Amyotrophic Lateral Sclerosis 8:



Diseases related to Amyotrophic Lateral Sclerosis 8

Symptoms & Phenotypes for Amyotrophic Lateral Sclerosis 8

Human phenotypes related to Amyotrophic Lateral Sclerosis 8:

31 (show all 13)
# Description HPO Frequency HPO Source Accession
1 dysphagia 31 very rare (1%) HP:0002015
2 fasciculations 31 very rare (1%) HP:0002380
3 proximal muscle weakness 31 very rare (1%) HP:0003701
4 distal muscle weakness 31 very rare (1%) HP:0002460
5 muscle spasm 31 very rare (1%) HP:0003394
6 dysarthria 31 HP:0001260
7 skeletal muscle atrophy 31 HP:0003202
8 areflexia 31 HP:0001284
9 amyotrophic lateral sclerosis 31 HP:0007354
10 postural tremor 31 HP:0002174
11 progressive muscle weakness 31 HP:0003323
12 neuronal loss in central nervous system 31 HP:0002529
13 morphological abnormality of the pyramidal tract 31 HP:0002062

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
dysarthria
dysphagia
postural tremor
no cognitive impairment
lower motor neuron signs in lower limbs or all limbs
more
Muscle Soft Tissue:
fasciculations
weakness
atrophy

Clinical features from OMIM:

608627

UMLS symptoms related to Amyotrophic Lateral Sclerosis 8:


muscular fasciculation, weakness, static tremor

GenomeRNAi Phenotypes related to Amyotrophic Lateral Sclerosis 8 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00221-A-2 10.09 SOD1
2 Decreased viability GR00221-A-3 10.09 SOD1
3 Decreased viability GR00221-A-4 10.09 FUS SOD1
4 Decreased viability GR00381-A-1 10.09 FIG4 SIGMAR1
5 Decreased viability GR00381-A-3 10.09 SIGMAR1
6 Decreased viability GR00402-S-2 10.09 ALS2 C9orf72 CHMP2B FIG4 FUS KCNIP1
7 no effect GR00402-S-1 9.62 ALS2 C9orf72 CHMP2B FIG4 FUS KCNIP1

Drugs & Therapeutics for Amyotrophic Lateral Sclerosis 8

Search Clinical Trials , NIH Clinical Center for Amyotrophic Lateral Sclerosis 8

Genetic Tests for Amyotrophic Lateral Sclerosis 8

Genetic tests related to Amyotrophic Lateral Sclerosis 8:

# Genetic test Affiliating Genes
1 Amyotrophic Lateral Sclerosis Type 8 29 VAPB

Anatomical Context for Amyotrophic Lateral Sclerosis 8

MalaCards organs/tissues related to Amyotrophic Lateral Sclerosis 8:

40
Brain, Spinal Cord, Skeletal Muscle, Bone

Publications for Amyotrophic Lateral Sclerosis 8

Articles related to Amyotrophic Lateral Sclerosis 8:

(show all 23)
# Title Authors PMID Year
1
Characterization of the properties of a novel mutation in VAPB in familial amyotrophic lateral sclerosis. 56 6
20940299 2010
2
SOD1, ANG, VAPB, TARDBP, and FUS mutations in familial amyotrophic lateral sclerosis: genotype-phenotype correlations. 56 6
20577002 2010
3
New VAPB deletion variant and exclusion of VAPB mutations in familial ALS. 56 6
18322265 2008
4
A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. 56 6
15372378 2004
5
Amyotrophic lateral sclerosis-related VAPB P56S mutation differentially affects the function and survival of corticospinal and spinal motor neurons. 61 56
23771029 2013
6
A common founder for amyotrophic lateral sclerosis type 8 (ALS8) in the Brazilian population. 61 6
16187141 2005
7
Amyotrophic lateral sclerosis-associated mutant VAPBP56S perturbs calcium homeostasis to disrupt axonal transport of mitochondria. 6
22258555 2012
8
EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS)--revised report of an EFNS task force. 6
21914052 2012
9
VAPB interacts with the mitochondrial protein PTPIP51 to regulate calcium homeostasis. 6
22131369 2012
10
Motor neuron disease-associated mutant vesicle-associated membrane protein-associated protein (VAP) B recruits wild-type VAPs into endoplasmic reticulum-derived tubular aggregates. 6
17804640 2007
11
A novel locus for late onset amyotrophic lateral sclerosis/motor neurone disease variant at 20q13. 56
15060112 2004
12
Amyotrophic Lateral Sclerosis Overview 6
20301623 2001
13
Amyotrophic lateral sclerosis type 8 is not a pure motor disease: evidence from a neuropsychological and behavioural study. 61
31089860 2019
14
The VAMP-associated protein VAPB is required for cardiac and neuronal pacemaker channel function. 61
29879376 2018
15
Nucleocytoplasmic transport defect in a North American patient with ALS8. 61
29560381 2018
16
Vapb/Amyotrophic lateral sclerosis 8 knock-in mice display slowly progressive motor behavior defects accompanying ER stress and autophagic response. 61
26362257 2015
17
The amyotrophic lateral sclerosis 8 protein, VAP, is required for ER protein quality control. 61
24271015 2014
18
Increased levels of phosphoinositides cause neurodegeneration in a Drosophila model of amyotrophic lateral sclerosis. 61
23492670 2013
19
The ALS8 protein VAPB interacts with the ER-Golgi recycling protein YIF1A and regulates membrane delivery into dendrites. 61
23736259 2013
20
The ALS8-associated mutant VAPB(P56S) is resistant to proteolysis in neurons. 61
21275991 2011
21
The amyotrophic lateral sclerosis 8 protein VAPB is cleaved, secreted, and acts as a ligand for Eph receptors. 61
18555774 2008
22
Proportionate mortality of Italian soccer players: is amyotrophic lateral sclerosis an occupational disease? 61
15921041 2005
23
[Prognostic factors in the survival of patients with neuromuscular diseases after an episode of acute respiratory insufficiency]. 61
8041989 1994

Variations for Amyotrophic Lateral Sclerosis 8

ClinVar genetic disease variations for Amyotrophic Lateral Sclerosis 8:

6 (show all 21) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 VAPB NM_004738.4(VAPB):c.166C>T (p.Pro56Ser)SNV Pathogenic 4806 rs74315431 20:56993374-56993374 20:58418318-58418318
2 VAPB NM_004738.4(VAPB):c.137C>T (p.Thr46Ile)SNV Pathogenic 30510 rs281875284 20:56993345-56993345 20:58418289-58418289
3 VAPB NM_004738.4(VAPB):c.667C>T (p.Arg223Trp)SNV Uncertain significance 448853 rs144718603 20:57019226-57019226 20:58444170-58444170
4 VAPB NM_004738.4(VAPB):c.656G>T (p.Gly219Val)SNV Uncertain significance 191163 rs786205553 20:57019215-57019215 20:58444159-58444159
5 VAPB NM_004738.4(VAPB):c.709A>G (p.Ile237Val)SNV Uncertain significance 534267 rs1555816248 20:57019268-57019268 20:58444212-58444212
6 VAPB NM_004738.4(VAPB):c.104C>T (p.Pro35Leu)SNV Uncertain significance 534272 rs1456089445 20:56993312-56993312 20:58418256-58418256
7 VAPB NM_004738.4(VAPB):c.289A>G (p.Thr97Ala)SNV Uncertain significance 534270 rs752091117 20:57009735-57009735 20:58434679-58434679
8 VAPB NM_004738.4(VAPB):c.194C>T (p.Ala65Val)SNV Uncertain significance 534269 rs1555813002 20:56993402-56993402 20:58418346-58418346
9 VAPB NM_004738.4(VAPB):c.482T>C (p.Leu161Ser)SNV Uncertain significance 534271 rs1555815825 20:57016048-57016048 20:58440992-58440992
10 VAPB NM_004738.4(VAPB):c.545G>A (p.Arg182Lys)SNV Uncertain significance 574815 rs1568720020 20:57016111-57016111 20:58441055-58441055
11 VAPB NM_004738.4(VAPB):c.58+5G>ASNV Uncertain significance 574276 rs753611165 20:56964578-56964578 20:58389522-58389522
12 VAPB NM_004738.4(VAPB):c.111C>A (p.Asp37Glu)SNV Uncertain significance 579701 rs781691837 20:56993319-56993319 20:58418263-58418263
13 VAPB NM_004738.4(VAPB):c.493G>A (p.Glu165Lys)SNV Uncertain significance 570108 rs772254840 20:57016059-57016059 20:58441003-58441003
14 VAPB NM_004738.4(VAPB):c.199A>G (p.Ile67Val)SNV Uncertain significance 656346 20:56993407-56993407 20:58418351-58418351
15 VAPB NM_004738.4(VAPB):c.668G>C (p.Arg223Pro)SNV Uncertain significance 639834 20:57019227-57019227 20:58444171-58444171
16 VAPB NM_004738.4(VAPB):c.674T>C (p.Leu225Ser)SNV Uncertain significance 647542 20:57019233-57019233 20:58444177-58444177
17 VAPB NM_004738.4(VAPB):c.688T>G (p.Leu230Val)SNV Uncertain significance 650970 20:57019247-57019247 20:58444191-58444191
18 subset of 16 genes: GNAS NC_000020.10:g.(?_56993257)_(57967907_?)dupduplication Uncertain significance 663415 20:56993257-57967907
19 VAPB NM_004738.4(VAPB):c.348T>C (p.Asp116=)SNV Likely benign 465873 rs751762415 20:57014033-57014033 20:58438977-58438977
20 VAPB NM_004738.4(VAPB):c.510G>A (p.Met170Ile)SNV Likely benign 465875 rs143144050 20:57016076-57016076 20:58441020-58441020
21 VAPB NM_004738.4(VAPB):c.195C>A (p.Ala65=)SNV Likely benign 534273 rs1555813003 20:56993403-56993403 20:58418347-58418347

UniProtKB/Swiss-Prot genetic disease variations for Amyotrophic Lateral Sclerosis 8:

73
# Symbol AA change Variation ID SNP ID
1 VAPB p.Pro56Ser VAR_026743 rs74315431
2 VAPB p.Thr46Ile VAR_067964 rs281875284

Expression for Amyotrophic Lateral Sclerosis 8

Search GEO for disease gene expression data for Amyotrophic Lateral Sclerosis 8.

Pathways for Amyotrophic Lateral Sclerosis 8

Pathways related to Amyotrophic Lateral Sclerosis 8 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.46 TARDBP SOD1 SIGMAR1 OPTN

GO Terms for Amyotrophic Lateral Sclerosis 8

Cellular components related to Amyotrophic Lateral Sclerosis 8 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 10.17 VAPB UBQLN2 TARDBP SPG11 SOD1 SETX
2 endoplasmic reticulum GO:0005783 9.95 YIF1A VAPB VAPA SIGMAR1 P3H3 OSBP
3 perinuclear region of cytoplasm GO:0048471 9.83 VPS54 VAPA OSBP OPTN FUS
4 Golgi membrane GO:0000139 9.77 VAPB VAPA OSBP OPTN FIG4
5 dendrite GO:0030425 9.65 SPG11 KCNIP1 FUS C9orf72 ALS2
6 cytoplasmic vesicle GO:0031410 9.43 UBQLN2 SPG11 SOD1 SIGMAR1 OPTN C9orf72
7 autophagosome GO:0005776 9.33 UBQLN2 OPTN C9orf72
8 growth cone GO:0030426 8.92 SIGMAR1 SETX C9orf72 ALS2

Biological processes related to Amyotrophic Lateral Sclerosis 8 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 locomotory behavior GO:0007626 9.54 SOD1 FIG4 ALS2
2 axon extension GO:0048675 9.43 SPG11 C9orf72
3 gene expression GO:0010467 9.4 TARDBP FUS
4 regulation of autophagosome assembly GO:2000785 9.32 UBQLN2 C9orf72
5 neurofilament cytoskeleton organization GO:0060052 9.26 VPS54 SOD1
6 autophagy GO:0006914 9.26 UBQLN2 OPTN CHMP2B C9orf72
7 COPII-coated vesicle budding GO:0090114 9.16 VAPB VAPA
8 cell death GO:0008219 8.8 VAPA OPTN ALS2

Molecular functions related to Amyotrophic Lateral Sclerosis 8 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.6 YIF1A VPS54 VAPB VAPA UBQLN2 TARDBP
2 FFAT motif binding GO:0033149 8.96 VAPB VAPA

Sources for Amyotrophic Lateral Sclerosis 8

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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