MCID: AMY090
MIFTS: 42

Amyotrophic Lateral Sclerosis 8

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

Aliases & Classifications for Amyotrophic Lateral Sclerosis 8

MalaCards integrated aliases for Amyotrophic Lateral Sclerosis 8:

Name: Amyotrophic Lateral Sclerosis 8 57 12 53 75 13 73
Amyotrophic Lateral Sclerosis Type 8 12 53 29 6 15
Als8 57 12 53 75
Sclerosis, Lateral, Amyotrophic, Type Type 8 40

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

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


HPO:

32
amyotrophic lateral sclerosis 8:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Amyotrophic Lateral Sclerosis 8

UniProtKB/Swiss-Prot : 75 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 muscular fasciculation, static tremor and weakness. An important gene associated with Amyotrophic Lateral Sclerosis 8 is VAPB (VAMP Associated Protein B And C), and among its related pathways/superpathways are Apoptosis and Autophagy and Sphingolipid metabolism. The drugs Sevoflurane and Dexamethasone have been mentioned in the context of this disorder. Affiliated tissues include brain, spinal cord and skeletal muscle, and related phenotypes are dysarthria and dysphagia

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

Symptoms via clinical synopsis from OMIM:

57
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

Human phenotypes related to Amyotrophic Lateral Sclerosis 8:

32 (show all 13)
# Description HPO Frequency HPO Source Accession
1 dysarthria 32 HP:0001260
2 dysphagia 32 very rare (1%) HP:0002015
3 skeletal muscle atrophy 32 HP:0003202
4 amyotrophic lateral sclerosis 32 HP:0007354
5 muscle cramps 32 very rare (1%) HP:0003394
6 areflexia 32 HP:0001284
7 fasciculations 32 very rare (1%) HP:0002380
8 postural tremor 32 HP:0002174
9 distal muscle weakness 32 very rare (1%) HP:0002460
10 proximal muscle weakness 32 very rare (1%) HP:0003701
11 neuronal loss in central nervous system 32 HP:0002529
12 progressive muscle weakness 32 HP:0003323
13 morphological abnormality of the pyramidal tract 32 HP:0002062

UMLS symptoms related to Amyotrophic Lateral Sclerosis 8:


muscular fasciculation, static tremor, weakness

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

26 (show all 20)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-150 9.91 PTPRF VAPA
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-165 9.91 VAPA
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-17 9.91 VAPA
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-180 9.91 VAPA
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-184 9.91 VAPA
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-22 9.91 FAF1
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-53 9.91 PTPRF
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-68 9.91 FAF1
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-71 9.91 VAPA FAF1
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-72 9.91 PTPRF
11 Increased shRNA abundance (Z-score > 2) GR00366-A-105 9.36 PTPRF
12 Increased shRNA abundance (Z-score > 2) GR00366-A-121 9.36 VAPA
13 Increased shRNA abundance (Z-score > 2) GR00366-A-146 9.36 PTPRF
14 Increased shRNA abundance (Z-score > 2) GR00366-A-149 9.36 PTPRF
15 Increased shRNA abundance (Z-score > 2) GR00366-A-185 9.36 PTPRF
16 Increased shRNA abundance (Z-score > 2) GR00366-A-186 9.36 PTPRF VAPA
17 Increased shRNA abundance (Z-score > 2) GR00366-A-214 9.36 PTPRF
18 Increased shRNA abundance (Z-score > 2) GR00366-A-23 9.36 PTPRF
19 Increased shRNA abundance (Z-score > 2) GR00366-A-76 9.36 VAPA
20 Increased shRNA abundance (Z-score > 2) GR00366-A-90 9.36 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 Approved, Investigational, Vet_approved Phase 4 50-02-2 5743
3
Ondansetron Approved Phase 4 99614-02-5 4595
4 Xenon Phase 4,Phase 1
5 Dexamethasone acetate Phase 4 1177-87-3
6 glucocorticoids Phase 4
7
protease inhibitors Phase 4
8 Central Nervous System Depressants Phase 4,Phase 1
9 Serotonin Agents Phase 4
10 Serotonin Antagonists Phase 4
11 Gastrointestinal Agents Phase 4
12 Neurotransmitter Agents Phase 4
13 HIV Protease Inhibitors Phase 4
14 Anesthetics Phase 4,Phase 1
15 Hormone Antagonists Phase 4
16 Anesthetics, General Phase 4,Phase 1
17 Dermatologic Agents Phase 4
18 Anesthetics, Inhalation Phase 4,Phase 1
19 Tranquilizing Agents Phase 4
20 Hormones Phase 4
21 Anti-Anxiety Agents Phase 4
22 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 4
23 Peripheral Nervous System Agents Phase 4
24 Platelet Aggregation Inhibitors Phase 4
25 Antiemetics Phase 4
26 Anti-Inflammatory Agents Phase 4
27 Antipruritics Phase 4
28 Antipsychotic Agents Phase 4
29 Psychotropic Drugs Phase 4
30 BB 1101 Phase 4
31 Autonomic Agents Phase 4
32 Antineoplastic Agents, Hormonal 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 29 VAPB

Anatomical Context for Amyotrophic Lateral Sclerosis 8

MalaCards organs/tissues related to Amyotrophic Lateral Sclerosis 8:

41
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:

75
# 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 38)
# Gene Variation Type Significance SNP ID Assembly Location
1 VAPB NM_004738.4(VAPB): c.166C> T (p.Pro56Ser) single nucleotide variant Pathogenic rs74315431 GRCh37 Chromosome 20, 56993374: 56993374
2 VAPB NM_004738.4(VAPB): c.166C> T (p.Pro56Ser) single nucleotide variant Pathogenic rs74315431 GRCh38 Chromosome 20, 58418318: 58418318
3 VAPB NM_004738.4(VAPB): c.137C> T (p.Thr46Ile) single nucleotide variant Pathogenic rs281875284 GRCh37 Chromosome 20, 56993345: 56993345
4 VAPB NM_004738.4(VAPB): c.137C> T (p.Thr46Ile) single nucleotide variant Pathogenic rs281875284 GRCh38 Chromosome 20, 58418289: 58418289
5 VAPB NM_004738.4(VAPB): c.656G> T (p.Gly219Val) single nucleotide variant Uncertain significance rs786205553 GRCh37 Chromosome 20, 57019215: 57019215
6 VAPB NM_004738.4(VAPB): c.656G> T (p.Gly219Val) single nucleotide variant Uncertain significance rs786205553 GRCh38 Chromosome 20, 58444159: 58444159
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 rs886056812 GRCh38 Chromosome 20, 58440989: 58440991
10 VAPB NM_004738.4(VAPB): c.479_481delCTT (p.Ser160del) deletion Likely benign rs886056812 GRCh37 Chromosome 20, 57016045: 57016047
11 VAPB NM_004738.4(VAPB): c.574-4G> A single nucleotide variant Conflicting interpretations of pathogenicity rs201798741 GRCh38 Chromosome 20, 58444073: 58444073
12 VAPB NM_004738.4(VAPB): c.574-4G> A single nucleotide variant Conflicting interpretations of pathogenicity rs201798741 GRCh37 Chromosome 20, 57019129: 57019129
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 Likely benign rs139884809 GRCh37 Chromosome 20, 57016058: 57016058
20 VAPB NM_004738.4(VAPB): c.492C> T (p.Thr164=) single nucleotide variant 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 GRCh37 Chromosome 20, 56993403: 56993403
24 VAPB NM_004738.4(VAPB): c.195C> A (p.Ala65=) single nucleotide variant Likely benign GRCh38 Chromosome 20, 58418347: 58418347
25 VAPB NM_004738.4(VAPB): c.709A> G (p.Ile237Val) single nucleotide variant Uncertain significance GRCh37 Chromosome 20, 57019268: 57019268
26 VAPB NM_004738.4(VAPB): c.709A> G (p.Ile237Val) single nucleotide variant Uncertain significance GRCh38 Chromosome 20, 58444212: 58444212
27 VAPB NM_004738.4(VAPB): c.104C> T (p.Pro35Leu) single nucleotide variant Uncertain significance GRCh37 Chromosome 20, 56993312: 56993312
28 VAPB NM_004738.4(VAPB): c.104C> T (p.Pro35Leu) single nucleotide variant Uncertain significance 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 GRCh38 Chromosome 20, 58418346: 58418346
34 VAPB NM_004738.4(VAPB): c.194C> T (p.Ala65Val) single nucleotide variant Uncertain significance GRCh37 Chromosome 20, 56993402: 56993402
35 VAPB NM_004738.4(VAPB): c.496G> A (p.Val166Ile) single nucleotide variant Uncertain significance rs538630783 GRCh38 Chromosome 20, 58441006: 58441006
36 VAPB NM_004738.4(VAPB): c.496G> A (p.Val166Ile) single nucleotide variant Uncertain significance rs538630783 GRCh37 Chromosome 20, 57016062: 57016062
37 VAPB NM_004738.4(VAPB): c.482T> C (p.Leu161Ser) single nucleotide variant Uncertain significance GRCh37 Chromosome 20, 57016048: 57016048
38 VAPB NM_004738.4(VAPB): c.482T> C (p.Leu161Ser) single nucleotide variant Uncertain significance GRCh38 Chromosome 20, 58440992: 58440992

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 11.42 BCAP31 FAF1
2
Show member pathways
11.2 OSBP VAPA VAPB
3
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 perinuclear region of cytoplasm GO:0048471 9.5 FAF1 OSBP VAPA
2 endoplasmic reticulum GO:0005783 9.46 BCAP31 OSBP VAPA VAPB
3 Golgi membrane GO:0000139 9.43 OSBP VAPA VAPB
4 endoplasmic reticulum membrane GO:0005789 9.26 BCAP31 OSBP VAPA VAPB
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 sphingolipid biosynthetic process GO:0030148 9.32 VAPA VAPB
2 cell death GO:0008219 9.26 FAF1 VAPA
3 endoplasmic reticulum organization GO:0007029 9.16 VAPA VAPB
4 ER to Golgi vesicle-mediated transport GO:0006888 9.13 BCAP31 VAPA VAPB
5 COPII-coated vesicle budding GO:0090114 8.62 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-containing complex binding GO:0044877 9.16 BCAP31 PTPRF
2 protein domain specific binding GO:0019904 9.13 FAF1 OSBP VAPA
3 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 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....