ALS8
MCID: AMY090
MIFTS: 42

Amyotrophic Lateral Sclerosis 8 (ALS8)

Categories: Genetic diseases, Mental 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 58 12 54 76 13 74
Amyotrophic Lateral Sclerosis Type 8 12 54 30 6 15
Als8 58 12 54 76
Sclerosis, Lateral, Amyotrophic, Type Type 8 41

Characteristics:

OMIM:

58
Inheritance:
autosomal dominant

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


HPO:

33
amyotrophic lateral sclerosis 8:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Amyotrophic Lateral Sclerosis 8

UniProtKB/Swiss-Prot : 76 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 amyotrophic lateral sclerosis 1 and lateral sclerosis, and has symptoms including weakness, muscular fasciculation 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 are Sphingolipid metabolism and Statin Pathway. The drugs Sevoflurane and Dexamethasone acetate have been mentioned in the context of this disorder. 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.

Description from OMIM: 608627

Related Diseases for Amyotrophic Lateral Sclerosis 8

Symptoms & Phenotypes for Amyotrophic Lateral Sclerosis 8

Human phenotypes related to Amyotrophic Lateral Sclerosis 8:

33 (show all 13)
# Description HPO Frequency HPO Source Accession
1 dysphagia 33 very rare (1%) HP:0002015
2 fasciculations 33 very rare (1%) HP:0002380
3 proximal muscle weakness 33 very rare (1%) HP:0003701
4 distal muscle weakness 33 very rare (1%) HP:0002460
5 muscle spasm 33 very rare (1%) HP:0003394
6 dysarthria 33 HP:0001260
7 skeletal muscle atrophy 33 HP:0003202
8 amyotrophic lateral sclerosis 33 HP:0007354
9 areflexia 33 HP:0001284
10 postural tremor 33 HP:0002174
11 progressive muscle weakness 33 HP:0003323
12 neuronal loss in central nervous system 33 HP:0002529
13 morphological abnormality of the pyramidal tract 33 HP:0002062

Symptoms via clinical synopsis from OMIM:

58
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:


weakness, muscular fasciculation, static tremor

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

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-2 9.36 EPHA6
2 Decreased viability GR00221-A-2 9.36 EPHA6
3 Decreased viability GR00221-A-3 9.36 COL4A3BP
4 Decreased viability GR00221-A-4 9.36 EPHA6
5 Decreased viability GR00301-A 9.36 ACP4 COL4A3BP EPHA6
6 Decreased viability GR00342-S-1 9.36 EPHA6
7 Decreased viability GR00381-A-1 9.36 EPHA6
8 Decreased viability GR00402-S-2 9.36 ACP4 COL4A3BP
9 Condensed cis-Golgi GR00365-A 9.13 ACP4 COL4A3BP PTPRF

Drugs & Therapeutics for Amyotrophic Lateral Sclerosis 8

Drugs for Amyotrophic Lateral Sclerosis 8 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 33)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Sevoflurane Approved, Vet_approved Phase 4 28523-86-6 5206
2
Dexamethasone acetate Approved, Investigational, Vet_approved Phase 4 1177-87-3
3
Dexamethasone Approved, Investigational, Vet_approved Phase 4 50-02-2 5743
4
Ondansetron Approved Phase 4 99614-02-5 4595
5 Central Nervous System Depressants Phase 4,Phase 1
6 Anesthetics, Inhalation Phase 4,Phase 1
7 Anesthetics Phase 4,Phase 1
8 Xenon Phase 4,Phase 1
9 Platelet Aggregation Inhibitors Phase 4
10 Anesthetics, General Phase 4,Phase 1
11 Dermatologic Agents Phase 4
12 Antipruritics Phase 4
13 Gastrointestinal Agents Phase 4
14 glucocorticoids Phase 4
15 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 4
16 Tranquilizing Agents Phase 4
17 Antiemetics Phase 4
18 Anti-Anxiety Agents Phase 4
19 Antineoplastic Agents, Hormonal Phase 4
20 Hormone Antagonists Phase 4
21 Antipsychotic Agents Phase 4
22 Serotonin Agents Phase 4
23 Serotonin Antagonists Phase 4
24 Neurotransmitter Agents Phase 4
25 Hormones Phase 4
26
protease inhibitors Phase 4
27 Autonomic Agents Phase 4
28 BB 1101 Phase 4
29 Psychotropic Drugs Phase 4
30 Peripheral Nervous System Agents Phase 4
31 Anti-Inflammatory Agents Phase 4
32 HIV Protease Inhibitors Phase 4
33
Serotonin Investigational, Nutraceutical Phase 4 50-67-9 5202

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Hemodynamic Stability During Carotid Endarterectomy.Comparison of LENOXe™ (Xenon 100% v/v) Versus Sevoflurane Completed NCT00937807 Phase 4 xenon;sévoflurane
2 Depth of Hypnosis and Postoperative Nausea and Vomiting During Xenon Anaesthesia Completed NCT00793663 Phase 4 Xenon;Sevoflurane;Dexamethasone;NaCl;Ondansetron;NaCl
3 Sympathetic Neural Outflow During Xenon Anesthesia in Humans Completed NCT01043419 Phase 1 xenon

Search 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 30 VAPB

Anatomical Context for Amyotrophic Lateral Sclerosis 8

MalaCards organs/tissues related to Amyotrophic Lateral Sclerosis 8:

42
Brain, Spinal Cord, Skeletal Muscle

Publications for Amyotrophic Lateral Sclerosis 8

Articles related to Amyotrophic Lateral Sclerosis 8:

# Title Authors Year
1
Vapb/Amyotrophic lateral sclerosis 8 knock-in mice display slowly progressive motor behavior defects accompanying ER stress and autophagic response. ( 26362257 )
2015
2
The amyotrophic lateral sclerosis 8 protein, VAP, is required for ER protein quality control. ( 24271015 )
2013
3
The amyotrophic lateral sclerosis 8 protein VAPB is cleaved, secreted, and acts as a ligand for Eph receptors. ( 18555774 )
2008

Variations for Amyotrophic Lateral Sclerosis 8

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

76
# Symbol AA change Variation ID SNP ID
1 VAPB p.Pro56Ser VAR_026743 rs74315431
2 VAPB p.Thr46Ile VAR_067964 rs281875284

ClinVar genetic disease variations for Amyotrophic Lateral Sclerosis 8:

6 (show all 46)
# Gene Variation Type Significance SNP ID Assembly Location
1 VAPB NM_004738.4(VAPB): c.656G> T (p.Gly219Val) single nucleotide variant Uncertain significance rs786205553 GRCh37 Chromosome 20, 57019215: 57019215
2 VAPB NM_004738.4(VAPB): c.656G> T (p.Gly219Val) single nucleotide variant Uncertain significance rs786205553 GRCh38 Chromosome 20, 58444159: 58444159
3 VAPB NM_004738.4(VAPB): c.166C> T (p.Pro56Ser) single nucleotide variant Pathogenic rs74315431 GRCh37 Chromosome 20, 56993374: 56993374
4 VAPB NM_004738.4(VAPB): c.166C> T (p.Pro56Ser) single nucleotide variant Pathogenic rs74315431 GRCh38 Chromosome 20, 58418318: 58418318
5 VAPB NM_004738.4(VAPB): c.137C> T (p.Thr46Ile) single nucleotide variant Pathogenic rs281875284 GRCh37 Chromosome 20, 56993345: 56993345
6 VAPB NM_004738.4(VAPB): c.137C> T (p.Thr46Ile) single nucleotide variant Pathogenic rs281875284 GRCh38 Chromosome 20, 58418289: 58418289
7 VAPB NM_004738.4(VAPB): c.390T> G (p.Asp130Glu) single nucleotide variant Likely benign rs146459055 GRCh37 Chromosome 20, 57014075: 57014075
8 VAPB NM_004738.4(VAPB): c.390T> G (p.Asp130Glu) single nucleotide variant Likely benign rs146459055 GRCh38 Chromosome 20, 58439019: 58439019
9 VAPB NM_004738.4(VAPB): c.479_481delCTT (p.Ser160del) deletion Likely benign rs566283411 GRCh37 Chromosome 20, 57016045: 57016047
10 VAPB NM_004738.4(VAPB): c.479_481delCTT (p.Ser160del) deletion Likely benign rs566283411 GRCh38 Chromosome 20, 58440989: 58440991
11 VAPB NM_004738.4(VAPB): c.574-4G> A single nucleotide variant Conflicting interpretations of pathogenicity rs201798741 GRCh37 Chromosome 20, 57019129: 57019129
12 VAPB NM_004738.4(VAPB): c.574-4G> A single nucleotide variant Conflicting interpretations of pathogenicity rs201798741 GRCh38 Chromosome 20, 58444073: 58444073
13 VAPB NM_004738.4(VAPB): c.667C> T (p.Arg223Trp) single nucleotide variant Uncertain significance rs144718603 GRCh37 Chromosome 20, 57019226: 57019226
14 VAPB NM_004738.4(VAPB): c.667C> T (p.Arg223Trp) single nucleotide variant Uncertain significance rs144718603 GRCh38 Chromosome 20, 58444170: 58444170
15 VAPB NM_004738.4(VAPB): c.59-4A> G single nucleotide variant Benign rs193136039 GRCh38 Chromosome 20, 58418207: 58418207
16 VAPB NM_004738.4(VAPB): c.59-4A> G single nucleotide variant Benign rs193136039 GRCh37 Chromosome 20, 56993263: 56993263
17 VAPB NM_004738.4(VAPB): c.348T> C (p.Asp116=) single nucleotide variant Likely benign rs751762415 GRCh38 Chromosome 20, 58438977: 58438977
18 VAPB NM_004738.4(VAPB): c.348T> C (p.Asp116=) single nucleotide variant Likely benign rs751762415 GRCh37 Chromosome 20, 57014033: 57014033
19 VAPB NM_004738.4(VAPB): c.492C> T (p.Thr164=) single nucleotide variant Benign/Likely benign rs139884809 GRCh37 Chromosome 20, 57016058: 57016058
20 VAPB NM_004738.4(VAPB): c.492C> T (p.Thr164=) single nucleotide variant Benign/Likely benign rs139884809 GRCh38 Chromosome 20, 58441002: 58441002
21 VAPB NM_004738.4(VAPB): c.510G> A (p.Met170Ile) single nucleotide variant Likely benign rs143144050 GRCh38 Chromosome 20, 58441020: 58441020
22 VAPB NM_004738.4(VAPB): c.510G> A (p.Met170Ile) single nucleotide variant Likely benign rs143144050 GRCh37 Chromosome 20, 57016076: 57016076
23 VAPB NM_004738.4(VAPB): c.195C> A (p.Ala65=) single nucleotide variant Likely benign rs1555813003 GRCh37 Chromosome 20, 56993403: 56993403
24 VAPB NM_004738.4(VAPB): c.195C> A (p.Ala65=) single nucleotide variant Likely benign rs1555813003 GRCh38 Chromosome 20, 58418347: 58418347
25 VAPB NM_004738.4(VAPB): c.709A> G (p.Ile237Val) single nucleotide variant Uncertain significance rs1555816248 GRCh37 Chromosome 20, 57019268: 57019268
26 VAPB NM_004738.4(VAPB): c.709A> G (p.Ile237Val) single nucleotide variant Uncertain significance rs1555816248 GRCh38 Chromosome 20, 58444212: 58444212
27 VAPB NM_004738.4(VAPB): c.104C> T (p.Pro35Leu) single nucleotide variant Uncertain significance rs1456089445 GRCh37 Chromosome 20, 56993312: 56993312
28 VAPB NM_004738.4(VAPB): c.104C> T (p.Pro35Leu) single nucleotide variant Uncertain significance rs1456089445 GRCh38 Chromosome 20, 58418256: 58418256
29 VAPB NM_004738.4(VAPB): c.289A> G (p.Thr97Ala) single nucleotide variant Uncertain significance rs752091117 GRCh37 Chromosome 20, 57009735: 57009735
30 VAPB NM_004738.4(VAPB): c.289A> G (p.Thr97Ala) single nucleotide variant Uncertain significance rs752091117 GRCh38 Chromosome 20, 58434679: 58434679
31 VAPB NM_004738.4(VAPB): c.174C> T (p.Ser58=) single nucleotide variant Likely benign rs139149560 GRCh37 Chromosome 20, 56993382: 56993382
32 VAPB NM_004738.4(VAPB): c.174C> T (p.Ser58=) single nucleotide variant Likely benign rs139149560 GRCh38 Chromosome 20, 58418326: 58418326
33 VAPB NM_004738.4(VAPB): c.194C> T (p.Ala65Val) single nucleotide variant Uncertain significance rs1555813002 GRCh37 Chromosome 20, 56993402: 56993402
34 VAPB NM_004738.4(VAPB): c.194C> T (p.Ala65Val) single nucleotide variant Uncertain significance rs1555813002 GRCh38 Chromosome 20, 58418346: 58418346
35 VAPB NM_004738.4(VAPB): c.496G> A (p.Val166Ile) single nucleotide variant Uncertain significance rs538630783 GRCh37 Chromosome 20, 57016062: 57016062
36 VAPB NM_004738.4(VAPB): c.496G> A (p.Val166Ile) single nucleotide variant Uncertain significance rs538630783 GRCh38 Chromosome 20, 58441006: 58441006
37 VAPB NM_004738.4(VAPB): c.482T> C (p.Leu161Ser) single nucleotide variant Uncertain significance rs1555815825 GRCh37 Chromosome 20, 57016048: 57016048
38 VAPB NM_004738.4(VAPB): c.482T> C (p.Leu161Ser) single nucleotide variant Uncertain significance rs1555815825 GRCh38 Chromosome 20, 58440992: 58440992
39 VAPB NM_004738.4(VAPB): c.545G> A (p.Arg182Lys) single nucleotide variant Uncertain significance GRCh38 Chromosome 20, 58441055: 58441055
40 VAPB NM_004738.4(VAPB): c.545G> A (p.Arg182Lys) single nucleotide variant Uncertain significance GRCh37 Chromosome 20, 57016111: 57016111
41 VAPB NM_004738.4(VAPB): c.58+5G> A single nucleotide variant Uncertain significance GRCh38 Chromosome 20, 58389522: 58389522
42 VAPB NM_004738.4(VAPB): c.58+5G> A single nucleotide variant Uncertain significance GRCh37 Chromosome 20, 56964578: 56964578
43 VAPB NM_004738.4(VAPB): c.111C> A (p.Asp37Glu) single nucleotide variant Uncertain significance GRCh38 Chromosome 20, 58418263: 58418263
44 VAPB NM_004738.4(VAPB): c.111C> A (p.Asp37Glu) single nucleotide variant Uncertain significance GRCh37 Chromosome 20, 56993319: 56993319
45 VAPB NM_004738.4(VAPB): c.493G> A (p.Glu165Lys) single nucleotide variant Uncertain significance GRCh37 Chromosome 20, 57016059: 57016059
46 VAPB NM_004738.4(VAPB): c.493G> A (p.Glu165Lys) single nucleotide variant Uncertain significance GRCh38 Chromosome 20, 58441003: 58441003

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
Show member pathways
11.33 COL4A3BP OSBP VAPA VAPB
2
Show member pathways
11.03 VAPA VAPB

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 membrane GO:0016020 9.76 ACP4 COL4A3BP EPHA6 FAF1 OSBP PTPRF
2 endoplasmic reticulum GO:0005783 9.62 COL4A3BP OSBP VAPA VAPB
3 endoplasmic reticulum membrane GO:0005789 9.56 COL4A3BP OSBP VAPA VAPB
4 perinuclear region of cytoplasm GO:0048471 9.26 COL4A3BP FAF1 OSBP VAPA
5 endoplasmic reticulum exit site GO:0070971 8.62 VAPA VAPB

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

# Name GO ID Score Top Affiliating Genes
1 cell death GO:0008219 9.26 FAF1 VAPA
2 COPII-coated vesicle budding GO:0090114 9.16 VAPA VAPB
3 sphingolipid biosynthetic process GO:0030148 9.13 COL4A3BP VAPA VAPB
4 endoplasmic reticulum organization GO:0007029 8.8 COL4A3BP VAPA VAPB

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

# Name GO ID Score Top Affiliating Genes
1 protein domain specific binding GO:0019904 9.33 FAF1 OSBP VAPA
2 protein tyrosine phosphatase activity GO:0004725 9.26 ACP4 PTPRF
3 phosphatidylinositol-4-phosphate binding GO:0070273 8.96 COL4A3BP OSBP
4 FFAT motif binding GO:0033149 8.62 VAPA VAPB

Sources for Amyotrophic Lateral Sclerosis 8

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
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
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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