ALS21
MCID: AMY069
MIFTS: 40

Amyotrophic Lateral Sclerosis 21 (ALS21)

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

Aliases & Classifications for Amyotrophic Lateral Sclerosis 21

MalaCards integrated aliases for Amyotrophic Lateral Sclerosis 21:

Name: Amyotrophic Lateral Sclerosis 21 57 74 29 6 72
Als21 57 12 74
Distal Myopathy with Vocal Cord Weakness 59 74
Amyotrophic Lateral Sclerosis Type 21 12 15
Myopathy, Distal 2 13 72
Vcpdm 59 74
Vocal Cord and Pharyngeal Dysfunction with Distal Myopathy, Formerly; Vcpdm, Formerly 57
Vocal Cord and Pharyngeal Dysfunction with Distal Myopathy, Formerly 57
Vocal Cord and Pharyngeal Dysfunction with Distal Myopathy 74
Myopathy, Distal, 2, Formerly; Mpd2, Formerly 57
Vocal Cord and Pharyngeal Distal Myopathy 59
Sclerosis, Lateral, Amyotrophic, Type 21 40
Myopathy, Distal, 2, Formerly 57
Matr3-Related Distal Myopathy 59
Distal Myopathy 2 74
Vcpdm, Formerly 57
Mpd2, Formerly 57
Mpd2 74

Characteristics:

Orphanet epidemiological data:

59
vocal cord and pharyngeal distal myopathy
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

57
Miscellaneous:
adult onset
variable severity
can be slowly or rapidly progressive

Inheritance:
autosomal dominant


HPO:

32
amyotrophic lateral sclerosis 21:
Inheritance autosomal dominant inheritance
Onset and clinical course variable expressivity adult onset


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0060212
MeSH 44 D000690
ICD10 via Orphanet 34 G71.0
Orphanet 59 ORPHA600
UMLS 72 C1853723 C3807521

Summaries for Amyotrophic Lateral Sclerosis 21

OMIM : 57 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 miyoshi muscular dystrophy, and has symptoms including upper motor neuron signs An important gene associated with Amyotrophic Lateral Sclerosis 21 is MATR3 (Matrin 3). Related phenotypes are dysarthria and hyperreflexia

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

UniProtKB/Swiss-Prot : 74 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.

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 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

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

(show all 30)
# Related Disease Score Top Affiliating Genes
1 distal myopathy with vocal cord weakness 12.8
2 miyoshi muscular dystrophy 10.2
3 myopathy 10.2
4 distal hereditary motor neuronopathy type 7 10.2
5 spinal muscular atrophy 10.2
6 muscular atrophy 10.2
7 charcot-marie-tooth hereditary neuropathy 10.2
8 distal hereditary motor neuropathy type 7 10.2
9 progressive non-fluent aphasia 9.9 VCP C9orf72
10 behavioral variant of frontotemporal dementia 9.8 VCP C9orf72
11 cataract 9.8
12 brown-vialetto-van laere syndrome 9.8 SOD1 C9orf72
13 paget's disease of bone 9.7 VCP OPTN
14 amyotrophic lateral sclerosis type 6 9.7 SETX FUS
15 juvenile amyotrophic lateral sclerosis 9.6 SETX FUS
16 spinocerebellar ataxia 31 9.6 SETX FUS
17 apraxia 9.5 SETX C9orf72
18 amyotrophic lateral sclerosis 11 9.4 SETX OPTN FUS
19 amyotrophic lateral sclerosis 7 9.4 SETX OPTN FUS
20 amyotrophic lateral sclerosis 10 with or without frontotemporal dementia 9.4 SETX OPTN FUS
21 nervous system disease 9.4 SOD1 OPTN C9orf72
22 amyotrophic lateral sclerosis 9 9.4 SETX OPTN FUS
23 amyotrophic lateral sclerosis 18 9.2 SOD1 FUS C9orf72
24 dementia 9.2 VCP FUS C9orf72
25 frontotemporal dementia and/or amyotrophic lateral sclerosis 1 9.1 VCP FUS C9orf72
26 amyotrophic lateral sclerosis type 14 9.0 VCP VAPB OPTN FUS
27 frontotemporal dementia 8.7 VCP SOD1 FUS C9orf72
28 motor neuron disease 7.6 VCP VAPB SOD1 SETX OPTN FUS
29 lateral sclerosis 7.2 VCP VAPB SOD1 SETX OPTN MATR3
30 amyotrophic lateral sclerosis 1 7.2 VCP VAPB SOD1 SETX OPTN MATR3

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

Human phenotypes related to Amyotrophic Lateral Sclerosis 21:

59 32 (show all 36)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 dysarthria 59 32 frequent (33%) Frequent (79-30%) HP:0001260
2 hyperreflexia 59 32 frequent (33%) Frequent (79-30%) HP:0001347
3 dysphagia 59 32 frequent (33%) Frequent (79-30%) HP:0002015
4 respiratory insufficiency due to muscle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0002747
5 emg abnormality 59 32 frequent (33%) Frequent (79-30%) HP:0003457
6 rimmed vacuoles 59 32 frequent (33%) Frequent (79-30%) HP:0003805
7 amyotrophic lateral sclerosis 59 32 frequent (33%) Frequent (79-30%) HP:0007354
8 nasal speech 59 32 frequent (33%) Frequent (79-30%) HP:0001611
9 difficulty walking 59 32 frequent (33%) Frequent (79-30%) HP:0002355
10 hoarse voice 59 32 frequent (33%) Frequent (79-30%) HP:0001609
11 weak voice 59 32 frequent (33%) Frequent (79-30%) HP:0001621
12 aspiration 59 32 frequent (33%) Frequent (79-30%) HP:0002835
13 exercise-induced myalgia 59 32 frequent (33%) Frequent (79-30%) HP:0003738
14 distal muscle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0002460
15 vocal cord paresis 59 32 frequent (33%) Frequent (79-30%) HP:0001604
16 bulbar palsy 59 32 frequent (33%) Frequent (79-30%) HP:0001283
17 unsteady gait 59 32 frequent (33%) Frequent (79-30%) HP:0002317
18 abnormality of the calf musculature 59 32 frequent (33%) Frequent (79-30%) HP:0001430
19 imperfect vocal cord adduction 59 32 frequent (33%) Frequent (79-30%) HP:0005934
20 bowing of the vocal cords 59 32 frequent (33%) Frequent (79-30%) HP:0008756
21 ankle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0031374
22 abnormality of musculature of pharynx 59 32 frequent (33%) Frequent (79-30%) HP:0430015
23 mildly elevated creatine kinase 32 frequent (33%) HP:0008180
24 dementia 59 32 occasional (7.5%) Very rare (<4-1%) HP:0000726
25 distal sensory impairment 59 32 occasional (7.5%) Very rare (<4-1%) HP:0002936
26 shoulder girdle muscle weakness 59 32 occasional (7.5%) Occasional (29-5%) HP:0003547
27 abnormality of the extraocular muscles 59 32 occasional (7.5%) Occasional (29-5%) HP:0008049
28 distal upper limb amyotrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0007149
29 decreased nerve conduction velocity 59 32 very rare (1%) Very rare (<4-1%) HP:0000762
30 bulbar signs 32 HP:0002483
31 mildly elevated creatine phosphokinase 59 Frequent (79-30%)
32 inflammatory myopathy 59 Excluded (0%)
33 abnormal upper motor neuron morphology 32 HP:0002127
34 abnormal lower motor neuron morphology 32 HP:0002366
35 elevated serum creatine kinase 32 HP:0003236
36 abnormality of the nasopharynx 32 HP:0001739

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
dysarthria
hyperreflexia
bulbar signs
amyotrophic lateral sclerosis
upper motor neuron 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 Gastrointestinal:
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

UMLS symptoms related to Amyotrophic Lateral Sclerosis 21:


upper motor neuron signs

MGI Mouse Phenotypes related to Amyotrophic Lateral Sclerosis 21:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.1 C9orf72 MATR3 SETX SOD1 VAPB VCP

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 29 MATR3

Anatomical Context for Amyotrophic Lateral Sclerosis 21

Publications for Amyotrophic Lateral Sclerosis 21

Articles related to Amyotrophic Lateral Sclerosis 21:

# Title Authors PMID Year
1
Autosomal-dominant distal myopathy associated with a recurrent missense mutation in the gene encoding the nuclear matrix protein, matrin 3. 38 8 71
19344878 2009
2
Vocal cord and pharyngeal weakness with autosomal dominant distal myopathy: clinical description and gene localization to 5q31. 38 8 71
9837826 1998
3
Phenotype of matrin-3-related distal myopathy in 16 German patients. 8 71
25154462 2014
4
Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis. 8 71
24686783 2014
5
EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS)--revised report of an EFNS task force. 71
21914052 2012
6
Amyotrophic Lateral Sclerosis Overview 71
20301623 2001
7
Autosomal dominant distal myopathy: linkage to chromosome 14. 8
7847377 1995
8
Mutant MATR3 mouse model to explain multisystem proteinopathy. 38
31056746 2019
9
Analysis of spinal and muscle pathology in transgenic mice overexpressing wild-type and ALS-linked mutant MATR3. 38
30563574 2018
10
Myotilin is not the causative gene for vocal cord and pharyngeal weakness with distal myopathy (VCPDM). 38
16674563 2006

Variations for Amyotrophic Lateral Sclerosis 21

ClinVar genetic disease variations for Amyotrophic Lateral Sclerosis 21:

6 (show all 41)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 MATR3 NM_199189.2(MATR3): c.254C> G (p.Ser85Cys) single nucleotide variant Pathogenic rs121434591 5:138643358-138643358 5:139307669-139307669
2 MATR3 NM_199189.2(MATR3): c.344T> G (p.Phe115Cys) single nucleotide variant Pathogenic rs587777300 5:138643448-138643448 5:139307759-139307759
3 MATR3 NM_199189.2(MATR3): c.1864A> G (p.Thr622Ala) single nucleotide variant Pathogenic rs587777301 5:138658372-138658372 5:139322683-139322683
4 MATR3 NM_199189.2(MATR3): c.460C> T (p.Pro154Ser) single nucleotide variant Pathogenic rs587777302 5:138643564-138643564 5:139307875-139307875
5 MATR3 NM_199189.2(MATR3): c.2161G> A (p.Glu721Lys) single nucleotide variant Uncertain significance rs764645698 5:138661141-138661141 5:139325452-139325452
6 MATR3 NM_199189.2(MATR3): c.1912G> C (p.Asp638His) single nucleotide variant Uncertain significance rs1554148872 5:138658420-138658420 5:139322731-139322731
7 MATR3 NM_199189.2(MATR3): c.793C> A (p.Leu265Ile) single nucleotide variant Uncertain significance rs1554146560 5:138643897-138643897 5:139308208-139308208
8 MATR3 NM_199189.2(MATR3): c.2038G> A (p.Asp680Asn) single nucleotide variant Uncertain significance rs752161415 5:138658546-138658546 5:139322857-139322857
9 MATR3 NM_199189.2(MATR3): c.322G> T (p.Ala108Ser) single nucleotide variant Uncertain significance rs745440760 5:138643426-138643426 5:139307737-139307737
10 MATR3 NM_199189.2(MATR3): c.2180A> G (p.Asn727Ser) single nucleotide variant Uncertain significance 5:138661160-138661160 5:139325471-139325471
11 MATR3 NM_199189.2(MATR3): c.2213A> G (p.Glu738Gly) single nucleotide variant Uncertain significance 5:138661193-138661193 5:139325504-139325504
12 MATR3 NM_199189.2(MATR3): c.2234C> T (p.Ala745Val) single nucleotide variant Uncertain significance 5:138661214-138661214 5:139325525-139325525
13 MATR3 NM_199189.2(MATR3): c.1598G> A (p.Ser533Asn) single nucleotide variant Uncertain significance 5:138655186-138655186 5:139319497-139319497
14 MATR3 NM_199189.2(MATR3): c.2282A> G (p.Asn761Ser) single nucleotide variant Uncertain significance 5:138661262-138661262 5:139325573-139325573
15 MATR3 NM_199189.2(MATR3): c.1435-10T> C single nucleotide variant Uncertain significance 5:138655013-138655013 5:139319324-139319324
16 MATR3 NM_199189.2(MATR3): c.1948A> C (p.Met650Leu) single nucleotide variant Uncertain significance 5:138658456-138658456 5:139322767-139322767
17 MATR3 NM_199189.2(MATR3): c.2372-3dupT duplication Uncertain significance 5:138661849-138661849 5:139326160-139326160
18 MATR3 NM_199189.2(MATR3): c.304C> T (p.Arg102Cys) single nucleotide variant Uncertain significance 5:138643408-138643408 5:139307719-139307719
19 MATR3 NM_199189.2(MATR3): c.561T> G (p.Asp187Glu) single nucleotide variant Uncertain significance 5:138643665-138643665 5:139307976-139307976
20 MATR3 NM_199189.2(MATR3): c.1132G> A (p.Ala378Thr) single nucleotide variant Uncertain significance 5:138652744-138652744 5:139317055-139317055
21 MATR3 NM_199189.2(MATR3): c.1363A> G (p.Thr455Ala) single nucleotide variant Uncertain significance 5:138654651-138654651 5:139318962-139318962
22 MATR3 NM_199189.2(MATR3): c.1572G> T (p.Lys524Asn) single nucleotide variant Uncertain significance 5:138655160-138655160 5:139319471-139319471
23 MATR3 NM_199189.2(MATR3): c.1874A> C (p.Lys625Thr) single nucleotide variant Uncertain significance 5:138658382-138658382 5:139322693-139322693
24 MATR3 NM_199189.2(MATR3): c.2273C> A (p.Thr758Lys) single nucleotide variant Uncertain significance 5:138661253-138661253 5:139325564-139325564
25 MATR3 NM_199189.2(MATR3): c.2525G> C (p.Arg842Thr) single nucleotide variant Uncertain significance 5:138665065-138665065 5:139329376-139329376
26 MATR3 NM_199189.2(MATR3): c.2504A> G (p.Asn835Ser) single nucleotide variant Uncertain significance rs201165929 5:138665044-138665044 5:139329355-139329355
27 MATR3 NM_199189.2(MATR3): c.2521C> T (p.Arg841Cys) single nucleotide variant Uncertain significance rs781050726 5:138665061-138665061 5:139329372-139329372
28 MATR3 NM_199189.2(MATR3): c.15C> T (p.Phe5=) single nucleotide variant Likely benign rs184609870 5:138643119-138643119 5:139307430-139307430
29 MATR3 NM_199189.2(MATR3): c.1953T> C (p.Leu651=) single nucleotide variant Likely benign rs770765421 5:138658461-138658461 5:139322772-139322772
30 MATR3 NM_199189.2(MATR3): c.2494-6T> A single nucleotide variant Likely benign rs376395410 5:138665028-138665028 5:139329339-139329339
31 MATR3 NM_199189.2(MATR3): c.1377G> A (p.Ala459=) single nucleotide variant Likely benign rs147356202 5:138654665-138654665 5:139318976-139318976
32 MATR3 NM_199189.2(MATR3): c.1116A> G (p.Pro372=) single nucleotide variant Likely benign rs375938101 5:138651864-138651864 5:139316175-139316175
33 MATR3 NM_199189.2(MATR3): c.1896T> C (p.Gly632=) single nucleotide variant Likely benign rs202208841 5:138658404-138658404 5:139322715-139322715
34 MATR3 NM_199189.2(MATR3): c.190T> C (p.Leu64=) single nucleotide variant Likely benign rs775134951 5:138643294-138643294 5:139307605-139307605
35 MATR3 NM_199189.2(MATR3): c.2360A> G (p.Asn787Ser) single nucleotide variant Likely benign rs148402819 5:138661340-138661340 5:139325651-139325651
36 MATR3 NM_199189.2(MATR3): c.1602+6A> G single nucleotide variant Benign/Likely benign rs80036770 5:138655196-138655196 5:139319507-139319507
37 MATR3 NM_199189.2(MATR3): c.2283C> T (p.Asn761=) single nucleotide variant Benign/Likely benign rs189752689 5:138661263-138661263 5:139325574-139325574
38 MATR3 NM_199189.2(MATR3): c.1893C> T (p.Ser631=) single nucleotide variant Benign/Likely benign rs143527811 5:138658401-138658401 5:139322712-139322712
39 MATR3 NM_199189.2(MATR3): c.291A> G (p.Leu97=) single nucleotide variant Benign/Likely benign rs147239107 5:138643395-138643395 5:139307706-139307706
40 MATR3 NM_199189.2(MATR3): c.1347C> T (p.Ala449=) single nucleotide variant Benign/Likely benign rs141986556 5:138654635-138654635 5:139318946-139318946
41 MATR3 NM_199189.2(MATR3): c.2191T> C (p.Leu731=) single nucleotide variant Benign rs149714542 5:138661171-138661171 5:139325482-139325482

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

74
# 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

Expression for Amyotrophic Lateral Sclerosis 21

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

Pathways for Amyotrophic Lateral Sclerosis 21

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 cytoplasm GO:0005737 9.8 VCP VAPB SOD1 SETX OPTN FUS
2 nucleus GO:0005634 9.7 VCP SOD1 SETX OPTN MATR3 FUS
3 autophagosome GO:0005776 8.96 OPTN C9orf72
4 cytoplasmic stress granule GO:0010494 8.62 VCP C9orf72

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

# Name GO ID Score Top Affiliating Genes
1 cellular response to oxidative stress GO:0034599 9.26 SOD1 SETX
2 double-strand break repair GO:0006302 9.16 VCP SETX
3 endoplasmic reticulum unfolded protein response GO:0030968 8.96 VCP VAPB
4 autophagy GO:0006914 8.8 VCP OPTN C9orf72

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 9.76 VCP VAPB SOD1 SETX OPTN MATR3
2 identical protein binding GO:0042802 9.1 VCP SOD1 SETX OPTN MATR3 FUS
3 polyubiquitin modification-dependent protein binding GO:0031593 8.96 VCP OPTN

Sources for Amyotrophic Lateral Sclerosis 21

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 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 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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