ALS21
MCID: AMY069
MIFTS: 39

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 56 73 29 6 71
Als21 56 12 73
Distal Myopathy with Vocal Cord Weakness 58 73
Amyotrophic Lateral Sclerosis Type 21 12 15
Myopathy, Distal 2 13 71
Vcpdm 58 73
Vocal Cord and Pharyngeal Dysfunction with Distal Myopathy, Formerly; Vcpdm, Formerly 56
Vocal Cord and Pharyngeal Dysfunction with Distal Myopathy, Formerly 56
Vocal Cord and Pharyngeal Dysfunction with Distal Myopathy 73
Myopathy, Distal, 2, Formerly; Mpd2, Formerly 56
Vocal Cord and Pharyngeal Distal Myopathy 58
Sclerosis, Lateral, Amyotrophic, Type 21 39
Myopathy, Distal, 2, Formerly 56
Matr3-Related Distal Myopathy 58
Distal Myopathy 2 73
Vcpdm, Formerly 56
Mpd2, Formerly 56
Mpd2 73

Characteristics:

Orphanet epidemiological data:

58
vocal cord and pharyngeal distal myopathy
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

56
Miscellaneous:
adult onset
variable severity
can be slowly or rapidly progressive

Inheritance:
autosomal dominant


HPO:

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


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Amyotrophic Lateral Sclerosis 21

OMIM : 56 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 muscular atrophy and spinal muscular atrophy, and has symptoms including upper motor neuron signs An important gene associated with Amyotrophic Lateral Sclerosis 21 is MATR3 (Matrin 3). Affiliated tissues include bone, and related phenotypes are hyperreflexia and dysarthria

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

UniProtKB/Swiss-Prot : 73 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
Tardbp-Related Amyotrophic Lateral Sclerosis

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

(show all 47)
# Related Disease Score Top Affiliating Genes
1 muscular atrophy 28.7 VAPB SIGMAR1 SETX FUS
2 spinal muscular atrophy 28.7 VAPB SIGMAR1 SETX FUS
3 distal myopathy with vocal cord weakness 12.8
4 miyoshi muscular dystrophy 10.2
5 myopathy 10.2
6 distal hereditary motor neuronopathy type 7 10.2
7 charcot-marie-tooth hereditary neuropathy 10.2
8 distal hereditary motor neuropathy type 7 10.2
9 spastic paraplegia 57, autosomal recessive 10.0 SPG11 ALS2
10 spastic paraplegia 4, autosomal dominant 9.9 SPG11 ALS2
11 amyotrophic lateral sclerosis 19 9.9 PRPH MATR3 ALS2
12 cataract 9.8
13 spinal and bulbar muscular atrophy, x-linked 1 9.8 FUS ATXN2
14 progressive bulbar palsy 9.8 VAPB FUS ALS2
15 spinocerebellar ataxia 29 9.8 SETX ATXN2
16 tremor 9.7 FUS ATXN2
17 progressive muscular atrophy 9.7 VAPB FUS ATXN2
18 inclusion body myopathy with paget disease of bone and frontotemporal dementia 9.7 MATR3 FUS ATXN2
19 motor peripheral neuropathy 9.5 SPG11 SETX
20 cerebellar disease 9.4 SETX ATXN2
21 autosomal dominant cerebellar ataxia 9.4 SETX FUS ATXN2
22 amyotrophic lateral sclerosis type 5 9.4 VAPB SPG11 SETX ALS2
23 aceruloplasminemia 9.3 SPG11 SETX ATXN2
24 amyotrophic lateral sclerosis 7 9.3 SPG11 SETX PRPH ALS2
25 hereditary spastic paraplegia 9.2 SPG11 SETX ATXN2 ALS2
26 charcot-marie-tooth disease 9.0 VAPB SPG11 SETX PRPH ALS2
27 amyotrophic lateral sclerosis 12 9.0 VAPB SPG11 SETX FUS ALS2
28 amyotrophic lateral sclerosis 20 8.9 SPG11 SIGMAR1 PRPH MATR3 ALS2
29 motor neuron disease 8.7 VAPB SIGMAR1 SETX FUS ALS2
30 amyotrophic lateral sclerosis 4, juvenile 8.6 VAPB SPG11 SETX FUS ATXN2 ALS2
31 hemochromatosis, type 1 8.6 VAPB SPG11 SETX FUS ATXN2 ALS2
32 spastic paraplegia 64, autosomal recessive 8.6 SPG11 SIGMAR1 SETX FUS ALS2
33 juvenile amyotrophic lateral sclerosis 8.6 SPG11 SIGMAR1 SETX FUS ALS2
34 amyotrophic lateral sclerosis type 15 8.5 VAPB SPG11 SIGMAR1 SETX PRPH ALS2
35 amyotrophic lateral sclerosis type 14 8.5 VAPB SIGMAR1 SETX PRPH FUS ALS2
36 amyotrophic lateral sclerosis 18 8.5 VAPB SIGMAR1 SETX PRPH FUS ALS2
37 amyotrophic lateral sclerosis 17 8.5 VAPB SPG11 SIGMAR1 SETX PRPH ALS2
38 spinocerebellar ataxia 2 8.4 VAPB SPG11 SETX MATR3 FUS ATXN2
39 amyotrophic lateral sclerosis 16, juvenile 8.4 VAPB SPG11 SIGMAR1 SETX FUS ALS2
40 amyotrophic lateral sclerosis type 6 8.4 VAPB SPG11 SIGMAR1 SETX FUS ALS2
41 amyotrophic lateral sclerosis 11 8.4 VAPB SPG11 SIGMAR1 SETX FUS ALS2
42 amyotrophic lateral sclerosis 9 8.4 VAPB SPG11 SIGMAR1 SETX FUS ALS2
43 amyotrophic lateral sclerosis 8 8.4 VAPB SPG11 SIGMAR1 SETX FUS ALS2
44 amyotrophic lateral sclerosis 10 with or without frontotemporal dementia 7.8 VAPB SPG11 SIGMAR1 SETX MATR3 FUS
45 frontotemporal dementia and/or amyotrophic lateral sclerosis 1 7.8 VAPB SPG11 SIGMAR1 SETX MATR3 FUS
46 lateral sclerosis 7.5 VAPB SPG11 SIGMAR1 SETX PRPH MATR3
47 amyotrophic lateral sclerosis 1 7.2 VAPB SPG11 SIGMAR1 SETX PRPH 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:

58 31 (show all 37)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hyperreflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001347
2 dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0001260
3 dysphagia 58 31 frequent (33%) Frequent (79-30%) HP:0002015
4 respiratory insufficiency due to muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0002747
5 emg abnormality 58 31 frequent (33%) Frequent (79-30%) HP:0003457
6 rimmed vacuoles 58 31 frequent (33%) Frequent (79-30%) HP:0003805
7 amyotrophic lateral sclerosis 58 31 frequent (33%) Frequent (79-30%) HP:0007354
8 nasal speech 58 31 frequent (33%) Frequent (79-30%) HP:0001611
9 hoarse voice 58 31 frequent (33%) Frequent (79-30%) HP:0001609
10 difficulty walking 58 31 frequent (33%) Frequent (79-30%) HP:0002355
11 weak voice 58 31 frequent (33%) Frequent (79-30%) HP:0001621
12 aspiration 58 31 frequent (33%) Frequent (79-30%) HP:0002835
13 exercise-induced myalgia 58 31 frequent (33%) Frequent (79-30%) HP:0003738
14 distal muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0002460
15 vocal cord paresis 58 31 frequent (33%) Frequent (79-30%) HP:0001604
16 bulbar palsy 58 31 frequent (33%) Frequent (79-30%) HP:0001283
17 unsteady gait 58 31 frequent (33%) Frequent (79-30%) HP:0002317
18 abnormality of the calf musculature 58 31 frequent (33%) Frequent (79-30%) HP:0001430
19 imperfect vocal cord adduction 58 31 frequent (33%) Frequent (79-30%) HP:0005934
20 bowing of the vocal cords 58 31 frequent (33%) Frequent (79-30%) HP:0008756
21 ankle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0031374
22 mildly elevated creatine kinase 31 frequent (33%) HP:0008180
23 abnormal morphology of musculature of pharynx 31 frequent (33%) HP:0430015
24 dementia 58 31 occasional (7.5%) Very rare (<4-1%) HP:0000726
25 distal sensory impairment 58 31 occasional (7.5%) Very rare (<4-1%) HP:0002936
26 shoulder girdle muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0003547
27 abnormality of the extraocular muscles 58 31 occasional (7.5%) Occasional (29-5%) HP:0008049
28 distal upper limb amyotrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0007149
29 decreased nerve conduction velocity 58 31 very rare (1%) Very rare (<4-1%) HP:0000762
30 bulbar signs 31 HP:0002483
31 mildly elevated creatine phosphokinase 58 Frequent (79-30%)
32 inflammatory myopathy 58 Excluded (0%)
33 abnormal upper motor neuron morphology 31 HP:0002127
34 abnormal lower motor neuron morphology 31 HP:0002366
35 abnormality of musculature of pharynx 58 Frequent (79-30%)
36 elevated serum creatine kinase 31 HP:0003236
37 abnormality of the nasopharynx 31 HP:0001739

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
hyperreflexia
dysarthria
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

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

MalaCards organs/tissues related to Amyotrophic Lateral Sclerosis 21:

40
Bone

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. 61 56 6
19344878 2009
2
Vocal cord and pharyngeal weakness with autosomal dominant distal myopathy: clinical description and gene localization to 5q31. 61 56 6
9837826 1998
3
Phenotype of matrin-3-related distal myopathy in 16 German patients. 56 6
25154462 2014
4
Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis. 56 6
24686783 2014
5
EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS)--revised report of an EFNS task force. 6
21914052 2012
6
Amyotrophic Lateral Sclerosis Overview 6
20301623 2001
7
Autosomal dominant distal myopathy: linkage to chromosome 14. 56
7847377 1995
8
A mutant MATR3 mouse model to explain multisystem proteinopathy. 61
31056746 2019
9
Analysis of spinal and muscle pathology in transgenic mice overexpressing wild-type and ALS-linked mutant MATR3. 61
30563574 2018
10
Myotilin is not the causative gene for vocal cord and pharyngeal weakness with distal myopathy (VCPDM). 61
16674563 2006

Variations for Amyotrophic Lateral Sclerosis 21

ClinVar genetic disease variations for Amyotrophic Lateral Sclerosis 21:

6 (show all 30) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MATR3 NM_018834.6(MATR3):c.254C>G (p.Ser85Cys)SNV Pathogenic 14002 rs121434591 5:138643358-138643358 5:139307669-139307669
2 MATR3 NM_018834.6(MATR3):c.344T>G (p.Phe115Cys)SNV Pathogenic 126561 rs587777300 5:138643448-138643448 5:139307759-139307759
3 MATR3 NM_018834.6(MATR3):c.1864A>G (p.Thr622Ala)SNV Pathogenic 126562 rs587777301 5:138658372-138658372 5:139322683-139322683
4 MATR3 NM_018834.6(MATR3):c.460C>T (p.Pro154Ser)SNV Pathogenic 126563 rs587777302 5:138643564-138643564 5:139307875-139307875
5 MATR3 NM_018834.6(MATR3):c.1912G>C (p.Asp638His)SNV Uncertain significance 474080 rs1554148872 5:138658420-138658420 5:139322731-139322731
6 MATR3 NM_018834.6(MATR3):c.793C>A (p.Leu265Ile)SNV Uncertain significance 474084 rs1554146560 5:138643897-138643897 5:139308208-139308208
7 MATR3 NM_018834.6(MATR3):c.2038G>A (p.Asp680Asn)SNV Uncertain significance 474081 rs752161415 5:138658546-138658546 5:139322857-139322857
8 MATR3 NM_018834.6(MATR3):c.322G>T (p.Ala108Ser)SNV Uncertain significance 541136 rs745440760 5:138643426-138643426 5:139307737-139307737
9 MATR3 NM_018834.6(MATR3):c.2161G>A (p.Glu721Lys)SNV Uncertain significance 541137 rs764645698 5:138661141-138661141 5:139325452-139325452
10 MATR3 NM_018834.6(MATR3):c.2504A>G (p.Asn835Ser)SNV Uncertain significance 351142 rs201165929 5:138665044-138665044 5:139329355-139329355
11 MATR3 NM_018834.6(MATR3):c.2521C>T (p.Arg841Cys)SNV Uncertain significance 351143 rs781050726 5:138665061-138665061 5:139329372-139329372
12 MATR3 NM_018834.6(MATR3):c.2180A>G (p.Asn727Ser)SNV Uncertain significance 571163 rs1468138513 5:138661160-138661160 5:139325471-139325471
13 MATR3 NM_018834.6(MATR3):c.2213A>G (p.Glu738Gly)SNV Uncertain significance 569504 rs538917496 5:138661193-138661193 5:139325504-139325504
14 MATR3 NM_018834.6(MATR3):c.2234C>T (p.Ala745Val)SNV Uncertain significance 574594 rs199797401 5:138661214-138661214 5:139325525-139325525
15 MATR3 NM_018834.6(MATR3):c.1598G>A (p.Ser533Asn)SNV Uncertain significance 578420 rs1033118784 5:138655186-138655186 5:139319497-139319497
16 MATR3 NM_018834.6(MATR3):c.2282A>G (p.Asn761Ser)SNV Uncertain significance 581337 rs758675030 5:138661262-138661262 5:139325573-139325573
17 MATR3 NM_018834.6(MATR3):c.1435-10T>CSNV Uncertain significance 566721 rs772340385 5:138655013-138655013 5:139319324-139319324
18 MATR3 NM_018834.6(MATR3):c.1948A>C (p.Met650Leu)SNV Uncertain significance 578787 rs749026971 5:138658456-138658456 5:139322767-139322767
19 MATR3 NM_018834.6(MATR3):c.2372-3dupduplication Uncertain significance 580361 rs1561945483 5:138661848-138661849 5:139326159-139326160
20 MATR3 NM_018834.6(MATR3):c.304C>T (p.Arg102Cys)SNV Uncertain significance 657091 5:138643408-138643408 5:139307719-139307719
21 MATR3 NM_018834.6(MATR3):c.561T>G (p.Asp187Glu)SNV Uncertain significance 658267 5:138643665-138643665 5:139307976-139307976
22 MATR3 NM_018834.6(MATR3):c.1132G>A (p.Ala378Thr)SNV Uncertain significance 651450 5:138652744-138652744 5:139317055-139317055
23 MATR3 NM_018834.6(MATR3):c.1363A>G (p.Thr455Ala)SNV Uncertain significance 663874 5:138654651-138654651 5:139318962-139318962
24 MATR3 NM_018834.6(MATR3):c.1572G>T (p.Lys524Asn)SNV Uncertain significance 664538 5:138655160-138655160 5:139319471-139319471
25 MATR3 NM_018834.6(MATR3):c.1874A>C (p.Lys625Thr)SNV Uncertain significance 644662 5:138658382-138658382 5:139322693-139322693
26 MATR3 NM_018834.6(MATR3):c.2273C>A (p.Thr758Lys)SNV Uncertain significance 640602 5:138661253-138661253 5:139325564-139325564
27 MATR3 NM_018834.6(MATR3):c.2525G>C (p.Arg842Thr)SNV Uncertain significance 652772 5:138665065-138665065 5:139329376-139329376
28 MATR3 NM_018834.6(MATR3):c.190T>C (p.Leu64=)SNV Likely benign 474079 rs775134951 5:138643294-138643294 5:139307605-139307605
29 MATR3 NM_018834.6(MATR3):c.1896T>C (p.Gly632=)SNV Likely benign 541139 rs202208841 5:138658404-138658404 5:139322715-139322715
30 MATR3 NM_018834.6(MATR3):c.1602+6A>GSNV Benign/Likely benign 263208 rs80036770 5:138655196-138655196 5:139319507-139319507

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

73
# 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 axon GO:0030424 9.43 SPG11 SETX ALS2
2 nuclear inner membrane GO:0005637 9.16 SIGMAR1 MATR3
3 polysome GO:0005844 8.96 FUS ATXN2
4 growth cone GO:0030426 8.8 SIGMAR1 SETX ALS2

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 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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