MCID: AMY069
MIFTS: 39

Amyotrophic Lateral Sclerosis 21

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

Aliases & Classifications for Amyotrophic Lateral Sclerosis 21

MalaCards integrated aliases for Amyotrophic Lateral Sclerosis 21:

Name: Amyotrophic Lateral Sclerosis 21 53 71 28 69
Als21 53 12 71
Distal Myopathy with Vocal Cord Weakness 55 71
Amyotrophic Lateral Sclerosis Type 21 12 14
Vocal Cord and Pharyngeal Dysfunction with Distal Myopathy, Formerly; Vcpdm, Formerly 53
Vocal Cord and Pharyngeal Dysfunction with Distal Myopathy, Formerly 53
Vocal Cord and Pharyngeal Dysfunction with Distal Myopathy 71
Myopathy, Distal, 2, Formerly; Mpd2, Formerly 53
Myopathy, Distal, 2, Formerly 53
Myopathy, Distal 2 69
Distal Myopathy 2 71
Vcpdm, Formerly 53
Mpd2, Formerly 53
Vcpdm 71
Mpd2 71

Characteristics:

Orphanet epidemiological data:

55
distal myopathy with vocal cord weakness
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
adult onset
variable severity
can be slowly or rapidly progressive


HPO:

31
amyotrophic lateral sclerosis 21:
Onset and clinical course variable expressivity adult onset
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 55  
Rare neurological diseases


Summaries for Amyotrophic Lateral Sclerosis 21

OMIM : 53 Amyotrophic lateral sclerosis-21 is an autosomal dominant neurodegenerative disorder affecting upper and lower motor neurons, resulting in muscle weakness and respiratory failure. Some patients may develop myopathic features or dementia (summary by Johnson et al., 2014). For a discussion of genetic heterogeneity of amyotrophic lateral sclerosis, see ALS1 (105400). (606070)

MalaCards based summary : Amyotrophic Lateral Sclerosis 21, also known as als21, is related to distal myopathy with vocal cord weakness and progressive non-fluent aphasia, and has symptoms including dysarthria, hyperreflexia and dysphagia. An important gene associated with Amyotrophic Lateral Sclerosis 21 is MATR3 (Matrin 3), and among its related pathways/superpathways is Neuroscience. Related phenotypes are Increased shRNA abundance (Z-score > 2) and Increased shRNA abundance (Z-score > 2)

UniProtKB/Swiss-Prot : 71 Amyotrophic lateral sclerosis 21: A neurodegenerative disorder affecting upper and lower motor neurons, resulting in muscle weakness and respiratory failure. Some patients may develop myopathic features or dementia.

Disease Ontology : 12 An amyotrophic lateral sclerosis that has material basis in mutation in the MATR3 gene on chromosome 5.

Related Diseases for Amyotrophic Lateral Sclerosis 21

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 Type 5
Amyotrophic Lateral Sclerosis Type 6 Amyotrophic Lateral Sclerosis Type 14
Amyotrophic Lateral Sclerosis Type 15 Amyotrophic Lateral Sclerosis Type 22

Diseases related to Amyotrophic Lateral Sclerosis 21 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 35)
# Related Disease Score Top Affiliating Genes
1 distal myopathy with vocal cord weakness 12.5
2 progressive non-fluent aphasia 10.2 C9orf72 VCP
3 behavioral variant of frontotemporal dementia 10.2 C9orf72 VCP
4 juvenile amyotrophic lateral sclerosis 10.0 FUS SETX
5 apraxia 9.9 C9orf72 SETX
6 postpoliomyelitis syndrome 9.9 TARDBP VCP
7 inclusion body myopathy with paget disease of bone and frontotemporal dementia 9.9 TARDBP VCP
8 progressive muscular atrophy 9.8 C9orf72 TARDBP
9 expressive language disorder 9.7 FUS TARDBP
10 perry syndrome 9.7 C9orf72 TARDBP
11 lethal congenital contracture syndrome 1 9.7 FUS TARDBP
12 paget's disease of bone 9.7 OPTN VCP
13 anterior horn cell disease 9.7 FUS TARDBP
14 ideomotor apraxia 9.6 FUS TARDBP
15 supranuclear palsy, progressive, 1 9.6 C9orf72 TARDBP
16 pick disease of brain 9.6 FUS TARDBP
17 brown-vialetto-van laere syndrome 9.5 C9orf72 SOD1 TARDBP
18 amyotrophic lateral sclerosis type 6 9.5 FUS SETX TARDBP
19 spinocerebellar ataxia 31 9.5 FUS SETX TARDBP
20 central nervous system disease 9.4 C9orf72 SOD1 TARDBP
21 nominal aphasia 9.1 C9orf72 FUS TARDBP VCP
22 amyotrophic lateral sclerosis 11 9.1 FUS OPTN SETX TARDBP
23 basal ganglia disease 9.1 C9orf72 FUS TARDBP VCP
24 frontotemporal dementia and/or amyotrophic lateral sclerosis 1 9.1 C9orf72 FUS TARDBP VCP
25 amyotrophic lateral sclerosis 7 9.1 FUS OPTN SETX TARDBP
26 amyotrophic lateral sclerosis 9 9.1 FUS OPTN SETX TARDBP
27 amyotrophic lateral sclerosis 10 with or without frontotemporal dementia 9.1 FUS OPTN SETX TARDBP
28 dementia 9.1 C9orf72 FUS TARDBP VCP
29 amyotrophic lateral sclerosis 18 9.1 C9orf72 FUS SOD1 TARDBP
30 amyotrophic lateral sclerosis type 14 8.9 FUS OPTN TARDBP VAPB VCP
31 frontotemporal dementia 8.7 C9orf72 FUS SOD1 TARDBP VCP
32 nervous system disease 8.7 C9orf72 FUS OPTN SOD1 TARDBP
33 motor neuron disease 7.9 C9orf72 FUS OPTN SETX SOD1 TARDBP
34 lateral sclerosis 7.6 C9orf72 FUS MATR3 OPTN SETX SOD1
35 amyotrophic lateral sclerosis 1 7.6 C9orf72 FUS MATR3 OPTN SETX SOD1

Graphical network of the top 20 diseases related to Amyotrophic Lateral Sclerosis 21:



Diseases related to Amyotrophic Lateral Sclerosis 21

Symptoms & Phenotypes for Amyotrophic Lateral Sclerosis 21

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
upper motor neuron signs
dysarthria
hyperreflexia
amyotrophic lateral sclerosis
bulbar signs
more
Respiratory:
respiratory insufficiency due to muscle weakness

Muscle Soft Tissue:
distal muscle weakness
shoulder weakness
onset of weakness in hands and feet
neuropathic or myopathic changes seen on emg
noninflammatory myopathy with rimmed vacuoles and atrophic fibers seen on muscle biopsy

Respiratory Nasopharynx:
pharyngeal muscle weakness

Head And Neck Eyes:
extraocular muscle weakness (in some patients)

Voice:
hypophonic, breathy voice
wet, gurgling, hoarse voice

Abdomen Gastroin testinal:
dysphagia

Respiratory Larynx:
aspiration
bowing of the vocal cords
vocal cord weakness
incomplete closure of the glottis

Laboratory Abnormalities:
increased serum creatine kinase

Head And Neck Face:
bulbar weakness

Neurologic Peripheral Nervous System:
nerve conduction velocity (ncv) slowing (1 family)
distal sensory impairment (1 family)


Clinical features from OMIM:

606070

Human phenotypes related to Amyotrophic Lateral Sclerosis 21:

31 (show all 20)
# Description HPO Frequency HPO Source Accession
1 dysarthria 31 HP:0001260
2 hyperreflexia 31 HP:0001347
3 dysphagia 31 HP:0002015
4 respiratory insufficiency due to muscle weakness 31 HP:0002747
5 elevated serum creatine phosphokinase 31 HP:0003236
6 decreased nerve conduction velocity 31 HP:0000762
7 amyotrophic lateral sclerosis 31 HP:0007354
8 dementia 31 occasional (7.5%) HP:0000726
9 hoarse voice 31 HP:0001609
10 aspiration 31 HP:0002835
11 distal muscle weakness 31 HP:0002460
12 rimmed vacuoles 31 HP:0003805
13 bulbar palsy 31 HP:0001283
14 distal sensory impairment 31 occasional (7.5%) HP:0002936
15 abnormal upper motor neuron morphology 31 HP:0002127
16 shoulder girdle muscle weakness 31 HP:0003547
17 bulbar signs 31 HP:0002483
18 abnormal lower motor neuron morphology 31 HP:0002366
19 bowing of the vocal cords 31 HP:0008756
20 abnormality of the nasopharynx 31 HP:0001739

UMLS symptoms related to Amyotrophic Lateral Sclerosis 21:


upper motor neuron signs

GenomeRNAi Phenotypes related to Amyotrophic Lateral Sclerosis 21 according to GeneCards Suite gene sharing:

25 (show all 18)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-105 9.66 MATR3
2 Increased shRNA abundance (Z-score > 2) GR00366-A-128 9.66 SOD1
3 Increased shRNA abundance (Z-score > 2) GR00366-A-135 9.66 MATR3 SOD1
4 Increased shRNA abundance (Z-score > 2) GR00366-A-151 9.66 MATR3
5 Increased shRNA abundance (Z-score > 2) GR00366-A-159 9.66 MATR3
6 Increased shRNA abundance (Z-score > 2) GR00366-A-16 9.66 VCP
7 Increased shRNA abundance (Z-score > 2) GR00366-A-163 9.66 VCP
8 Increased shRNA abundance (Z-score > 2) GR00366-A-196 9.66 MATR3 SOD1 VCP
9 Increased shRNA abundance (Z-score > 2) GR00366-A-198 9.66 VCP
10 Increased shRNA abundance (Z-score > 2) GR00366-A-214 9.66 MATR3
11 Increased shRNA abundance (Z-score > 2) GR00366-A-215 9.66 SOD1 VCP
12 Increased shRNA abundance (Z-score > 2) GR00366-A-4 9.66 SOD1
13 Increased shRNA abundance (Z-score > 2) GR00366-A-41 9.66 SOD1
14 Increased shRNA abundance (Z-score > 2) GR00366-A-5 9.66 SOD1
15 Increased shRNA abundance (Z-score > 2) GR00366-A-54 9.66 SOD1
16 Increased shRNA abundance (Z-score > 2) GR00366-A-57 9.66 SOD1
17 Increased shRNA abundance (Z-score > 2) GR00366-A-76 9.66 VCP
18 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.66 MATR3

MGI Mouse Phenotypes related to Amyotrophic Lateral Sclerosis 21:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.17 C9orf72 MATR3 SETX SOD1 TARDBP VAPB

Drugs & Therapeutics for Amyotrophic Lateral Sclerosis 21

Search Clinical Trials , NIH Clinical Center for Amyotrophic Lateral Sclerosis 21

Genetic Tests for Amyotrophic Lateral Sclerosis 21

Genetic tests related to Amyotrophic Lateral Sclerosis 21:

# Genetic test Affiliating Genes
1 Amyotrophic Lateral Sclerosis 21 28 MATR3

Anatomical Context for Amyotrophic Lateral Sclerosis 21

Publications for Amyotrophic Lateral Sclerosis 21

Articles related to Amyotrophic Lateral Sclerosis 21:

# Title Authors Year
1
Myotilin is not the causative gene for vocal cord and pharyngeal weakness with distal myopathy (VCPDM). ( 16674563 )
2006

Variations for Amyotrophic Lateral Sclerosis 21

UniProtKB/Swiss-Prot genetic disease variations for Amyotrophic Lateral Sclerosis 21:

71
# Symbol AA change Variation ID SNP ID
1 MATR3 p.Ser85Cys VAR_063421 rs121434591
2 MATR3 p.Phe115Cys VAR_071078 rs587777300
3 MATR3 p.Thr622Ala VAR_071080 rs587777301

ClinVar genetic disease variations for Amyotrophic Lateral Sclerosis 21:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 MATR3 NM_018834.5(MATR3): c.254C> G (p.Ser85Cys) single nucleotide variant Pathogenic/Likely pathogenic rs121434591 GRCh37 Chromosome 5, 138643358: 138643358
2 MATR3 NM_199189.2(MATR3): c.344T> G (p.Phe115Cys) single nucleotide variant Pathogenic rs587777300 GRCh38 Chromosome 5, 139307759: 139307759
3 MATR3 NM_199189.2(MATR3): c.1864A> G (p.Thr622Ala) single nucleotide variant Pathogenic rs587777301 GRCh38 Chromosome 5, 139322683: 139322683
4 MATR3 NM_199189.2(MATR3): c.460C> T (p.Pro154Ser) single nucleotide variant Pathogenic rs587777302 GRCh38 Chromosome 5, 139307875: 139307875

Expression for Amyotrophic Lateral Sclerosis 21

Search GEO for disease gene expression data for Amyotrophic Lateral Sclerosis 21.

Pathways for Amyotrophic Lateral Sclerosis 21

Pathways related to Amyotrophic Lateral Sclerosis 21 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.33 OPTN SOD1 TARDBP

GO Terms for Amyotrophic Lateral Sclerosis 21

Cellular components related to Amyotrophic Lateral Sclerosis 21 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleoplasm GO:0005654 9.63 FUS OPTN SETX SOD1 TARDBP VCP
2 nucleus GO:0005634 9.23 C9orf72 FUS MATR3 OPTN SETX SOD1
3 autophagosome GO:0005776 8.96 C9orf72 OPTN

Biological processes related to Amyotrophic Lateral Sclerosis 21 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 negative regulation of protein phosphorylation GO:0001933 9.26 C9orf72 TARDBP
2 double-strand break repair GO:0006302 9.16 SETX VCP
3 endoplasmic reticulum unfolded protein response GO:0030968 8.96 VAPB VCP
4 autophagy GO:0006914 8.8 C9orf72 OPTN VCP

Molecular functions related to Amyotrophic Lateral Sclerosis 21 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.81 C9orf72 FUS MATR3 OPTN SETX SOD1
2 identical protein binding GO:0042802 9.17 FUS MATR3 OPTN SETX SOD1 TARDBP
3 polyubiquitin modification-dependent protein binding GO:0031593 8.96 OPTN VCP

Sources for Amyotrophic Lateral Sclerosis 21

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....