ALS16
MCID: AMY057
MIFTS: 39

Amyotrophic Lateral Sclerosis 16, Juvenile (ALS16)

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

Aliases & Classifications for Amyotrophic Lateral Sclerosis 16, Juvenile

MalaCards integrated aliases for Amyotrophic Lateral Sclerosis 16, Juvenile:

Name: Amyotrophic Lateral Sclerosis 16, Juvenile 56 12 73 29 13 6 71
Als16 56 12 73
Amyotrophic Lateral Sclerosis Type 16 12 15
Sclerosis, Lateral, Amyotrophic, Type 16, Juvenile 39
Amyotrophic Lateral Sclerosis 16 12

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
slowly progressive
age of onset 1 to 2 years
onset in lower limbs
progresses to involve upper limbs
six patients from 1 saudi arabian family have been reported (last curated december 2011)
two of 6 patients became wheelchair-bound by age 20 years


HPO:

31
amyotrophic lateral sclerosis 16, juvenile:
Inheritance autosomal recessive inheritance
Onset and clinical course slow progression


Classifications:



External Ids:

Disease Ontology 12 DOID:0060207
OMIM 56 614373
OMIM Phenotypic Series 56 PS105400
MeSH 43 D000690
MedGen 41 C3280587
UMLS 71 C3280587

Summaries for Amyotrophic Lateral Sclerosis 16, Juvenile

UniProtKB/Swiss-Prot : 73 Amyotrophic lateral sclerosis 16, juvenile: 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 16, Juvenile, also known as als16, is related to juvenile amyotrophic lateral sclerosis and alzheimer disease 7, and has symptoms including muscle spasticity and upper motor neuron signs. An important gene associated with Amyotrophic Lateral Sclerosis 16, Juvenile is SIGMAR1 (Sigma Non-Opioid Intracellular Receptor 1). Affiliated tissues include brain, spinal cord and bone, and related phenotypes are spasticity and hyperreflexia

Disease Ontology : 12 An amyotrophic lateral sclerosis that has material basis in mutation in the SIGMAR1 gene (SETX) on chromosome 9.

More information from OMIM: 614373 PS105400

Related Diseases for Amyotrophic Lateral Sclerosis 16, Juvenile

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 16, Juvenile via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 61)
# Related Disease Score Top Affiliating Genes
1 juvenile amyotrophic lateral sclerosis 31.0 SPG11 SIGMAR1 SETX FUS ALS2
2 alzheimer disease 7 10.3 SIGMAR1 RMDN3
3 spinal muscular atrophy, type iv 10.2 VAPB RMDN3
4 spastic paraplegia 57, autosomal recessive 10.1 SPG11 ALS2
5 spinocerebellar ataxia 29 10.0 SETX ITPR3
6 pontocerebellar hypoplasia, type 2e 10.0 CHMP2B ALS2
7 spastic paraplegia 4, autosomal dominant 10.0 SPG11 ALS2
8 dyscalculia 9.9 VCP CHMP2B
9 amyotrophic lateral sclerosis type 5 9.7 VAPB SPG11 SETX ALS2
10 semantic dementia 9.7 CHMP2B C9orf72
11 dysgraphia 9.7 CHMP2B C9orf72
12 prosopagnosia 9.7 CHMP2B C9orf72
13 amyotrophic lateral sclerosis, juvenile, with dementia 9.7 VCP C9orf72
14 amyotrophic lateral sclerosis 19 9.7 UBQLN2 C9orf72 ALS2
15 amyotrophic lateral sclerosis 7 9.6 SPG11 SETX CHMP2B ALS2
16 charcot-marie-tooth disease, axonal, type 2e 9.6 VCP SPG11 RMDN3 ALS2
17 mutism 9.6 CHMP2B C9orf72
18 brown-vialetto-van laere syndrome 9.6 UBQLN2 C9orf72
19 pseudobulbar palsy 9.5 CHMP2B C9orf72 ALS2
20 amyotrophic lateral sclerosis 20 9.5 SPG11 SIGMAR1 C9orf72 ALS2
21 associative agnosia 9.4 VCP CHMP2B C9orf72
22 progressive non-fluent aphasia 9.4 VCP CHMP2B C9orf72
23 writing disorder 9.4 VCP CHMP2B C9orf72
24 progressive bulbar palsy 9.3 VAPB FUS C9orf72 ALS2
25 spinal and bulbar muscular atrophy, x-linked 1 9.2 FUS C9orf72
26 amyotrophic lateral sclerosis 21 9.2 VAPB SPG11 SIGMAR1 SETX FUS ALS2
27 spastic paraplegia 64, autosomal recessive 9.2 UBQLN2 SPG11 SIGMAR1 SETX FUS ALS2
28 muscular atrophy 9.1 VAPB SIGMAR1 SETX FUS C9orf72
29 nominal aphasia 9.0 VCP FUS CHMP2B C9orf72
30 aphasia 9.0 VCP FUS CHMP2B C9orf72
31 perry syndrome 9.0 VCP FUS CHMP2B C9orf72
32 amyotrophic lateral sclerosis 17 9.0 VAPB UBQLN2 SPG11 SIGMAR1 SETX CHMP2B
33 spinal muscular atrophy 9.0 VAPB SIGMAR1 SETX FUS C9orf72
34 autosomal dominant cerebellar ataxia 9.0 VCP SETX FUS C9orf72
35 supranuclear palsy, progressive, 1 9.0 VCP FUS CHMP2B C9orf72
36 dementia, lewy body 9.0 VCP FUS CHMP2B C9orf72
37 speech and communication disorders 9.0 VCP FUS CHMP2B C9orf72
38 amyotrophic lateral sclerosis 9 9.0 VAPB UBQLN2 SPG11 SIGMAR1 SETX FUS
39 amyotrophic lateral sclerosis 18 8.9 VAPB UBQLN2 SIGMAR1 SETX FUS CHMP2B
40 frontotemporal dementia 8.8 VCP UBQLN2 FUS CHMP2B C9orf72
41 dementia 8.8 VCP UBQLN2 FUS CHMP2B C9orf72
42 amyotrophic lateral sclerosis 12 8.8 VAPB UBQLN2 SPG11 SETX FUS CHMP2B
43 inclusion body myopathy with paget disease of bone and frontotemporal dementia 8.8 VCP UBQLN2 FUS CHMP2B C9orf72
44 dystonia 8.8 SETX FUS CHMP2B C9orf72 ALS2
45 pick disease of brain 8.8 VCP UBQLN2 FUS CHMP2B C9orf72
46 hemochromatosis, type 1 8.7 VAPB SPG11 SETX FUS C9orf72 ALS2
47 hereditary spastic paraplegia 8.7 VCP UBQLN2 SPG11 SETX C9orf72 ALS2
48 charcot-marie-tooth disease 8.7 VCP VAPB SPG11 SETX C9orf72 ALS2
49 amyotrophic lateral sclerosis 11 8.6 VAPB UBQLN2 SPG11 SIGMAR1 SETX FUS
50 progressive muscular atrophy 8.6 VCP VAPB UBQLN2 FUS CHMP2B C9orf72

Graphical network of the top 20 diseases related to Amyotrophic Lateral Sclerosis 16, Juvenile:



Diseases related to Amyotrophic Lateral Sclerosis 16, Juvenile

Symptoms & Phenotypes for Amyotrophic Lateral Sclerosis 16, Juvenile

Human phenotypes related to Amyotrophic Lateral Sclerosis 16, Juvenile:

31 (show all 6)
# Description HPO Frequency HPO Source Accession
1 spasticity 31 HP:0001257
2 hyperreflexia 31 HP:0001347
3 amyotrophic lateral sclerosis 31 HP:0007354
4 limb muscle weakness 31 HP:0003690
5 abnormal upper motor neuron morphology 31 HP:0002127
6 abnormal lower motor neuron morphology 31 HP:0002366

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
spasticity
hyperreflexia
upper motor neuron signs
lower motor neuron signs
normal cognition
more
Muscle Soft Tissue:
limb muscle weakness, upper and lower

Clinical features from OMIM:

614373

UMLS symptoms related to Amyotrophic Lateral Sclerosis 16, Juvenile:


muscle spasticity, upper motor neuron signs

MGI Mouse Phenotypes related to Amyotrophic Lateral Sclerosis 16, Juvenile:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.56 ALS2 C9orf72 ITPR3 KCNAB2 SIGMAR1 SPG11
2 nervous system MP:0003631 9.23 ALS2 C9orf72 CHMP2B ITPR3 KCNAB2 SPG11

Drugs & Therapeutics for Amyotrophic Lateral Sclerosis 16, Juvenile

Search Clinical Trials , NIH Clinical Center for Amyotrophic Lateral Sclerosis 16, Juvenile

Genetic Tests for Amyotrophic Lateral Sclerosis 16, Juvenile

Genetic tests related to Amyotrophic Lateral Sclerosis 16, Juvenile:

# Genetic test Affiliating Genes
1 Amyotrophic Lateral Sclerosis 16, Juvenile 29 SIGMAR1

Anatomical Context for Amyotrophic Lateral Sclerosis 16, Juvenile

MalaCards organs/tissues related to Amyotrophic Lateral Sclerosis 16, Juvenile:

40
Brain, Spinal Cord, Bone

Publications for Amyotrophic Lateral Sclerosis 16, Juvenile

Articles related to Amyotrophic Lateral Sclerosis 16, Juvenile:

# Title Authors PMID Year
1
A mutation in sigma-1 receptor causes juvenile amyotrophic lateral sclerosis. 56 6
21842496 2011
2
In silico analysis of SIGMAR1 variant (rs4879809) segregating in a consanguineous Pakistani family showing amyotrophic lateral sclerosis without frontotemporal lobar dementia. 6
26205306 2015
3
The role of SIGMAR1 gene mutation and mitochondrial dysfunction in amyotrophic lateral sclerosis. 6
25704016 2015
4
EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS)--revised report of an EFNS task force. 6
21914052 2012
5
Amyotrophic Lateral Sclerosis Overview 6
20301623 2001
6
El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial "Clinical limits of amyotrophic lateral sclerosis" workshop contributors. 56
7807156 1994
7
The sigma-1 receptor behaves as an atypical auxiliary subunit to modulate the functional characteristics of Kv1.2 channels expressed in HEK293 cells. 61
31222975 2019
8
Mitochondria-associated membrane collapse is a common pathomechanism in SIGMAR1- and SOD1-linked ALS. 61
27821430 2016
9
Aberrant Subcellular Dynamics of Sigma-1 Receptor Mutants Underlying Neuromuscular Diseases. 61
27418673 2016

Variations for Amyotrophic Lateral Sclerosis 16, Juvenile

ClinVar genetic disease variations for Amyotrophic Lateral Sclerosis 16, Juvenile:

6 (show all 30) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SIGMAR1 NM_005866.4(SIGMAR1):c.283dup (p.Leu95fs)duplication Pathogenic 209190 rs780136067 9:34637285-34637286 9:34637288-34637289
2 SIGMAR1 NM_005866.4(SIGMAR1):c.304G>C (p.Glu102Gln)SNV Pathogenic 30238 rs387906829 9:34637265-34637265 9:34637268-34637268
3 SIGMAR1 NM_005866.4(SIGMAR1):c.13del (p.Val5fs)deletion Pathogenic 569448 rs1564096761 9:34637682-34637682 9:34637685-34637685
4 SIGMAR1 NM_005866.4(SIGMAR1):c.19del (p.Arg7fs)deletion Pathogenic 650504 9:34637676-34637676 9:34637679-34637679
5 SIGMAR1 NM_005866.4(SIGMAR1):c.561_576del (p.Asp188fs)deletion Likely pathogenic 431075 rs1554707680 9:34635725-34635740 9:34635728-34635743
6 SIGMAR1 NM_005866.4(SIGMAR1):c.446-25_*40deldeletion Likely pathogenic 431074 rs1554707622 9:34635589-34635880 9:34635592-34635883
7 SIGMAR1 NM_005866.4(SIGMAR1):c.416G>T (p.Gly139Val)SNV Likely pathogenic 522651 rs1270528470 9:34637023-34637023 9:34637026-34637026
8 SIGMAR1 NM_005866.4(SIGMAR1):c.11C>T (p.Ala4Val)SNV Uncertain significance 534262 rs367968662 9:34637684-34637684 9:34637687-34637687
9 SIGMAR1 NM_005866.4(SIGMAR1):c.545T>C (p.Leu182Pro)SNV Uncertain significance 448379 rs781091660 9:34635756-34635756 9:34635759-34635759
10 SIGMAR1 NM_005866.4(SIGMAR1):c.463G>A (p.Gly155Arg)SNV Uncertain significance 465869 rs200076129 9:34635838-34635838 9:34635841-34635841
11 SIGMAR1 NM_005866.4(SIGMAR1):c.92G>A (p.Gly31Asp)SNV Uncertain significance 534261 rs532632647 9:34637603-34637603 9:34637606-34637606
12 SIGMAR1 NM_005866.4(SIGMAR1):c.344G>T (p.Gly115Val)SNV Uncertain significance 534263 rs1241574813 9:34637225-34637225 9:34637228-34637228
13 covers 50 genes, none of which curated to show dosage sensitivity NC_000009.11:g.(?_34458984)_(36277059_?)dupduplication Uncertain significance 584345 9:34458984-36277059
14 SIGMAR1 NM_005866.4(SIGMAR1):c.194T>A (p.Leu65Gln)SNV Uncertain significance 575556 rs140376902 9:34637375-34637375 9:34637378-34637378
15 SIGMAR1 NM_005866.4(SIGMAR1):c.79T>A (p.Trp27Arg)SNV Uncertain significance 565401 rs1564096623 9:34637616-34637616 9:34637619-34637619
16 SIGMAR1 NM_005866.4(SIGMAR1):c.632G>A (p.Arg211Gln)SNV Uncertain significance 573115 rs192644838 9:34635669-34635669 9:34635672-34635672
17 SIGMAR1 NM_005866.4(SIGMAR1):c.61G>C (p.Val21Leu)SNV Uncertain significance 567953 rs1396152845 9:34637634-34637634 9:34637637-34637637
18 SIGMAR1 NM_005866.4(SIGMAR1):c.446-5C>GSNV Uncertain significance 578578 rs1564095230 9:34635860-34635860 9:34635863-34635863
19 SIGMAR1 NM_005866.4(SIGMAR1):c.247T>C (p.Phe83Leu)SNV Uncertain significance 579502 rs773344340 9:34637322-34637322 9:34637325-34637325
20 SIGMAR1 NM_005866.4(SIGMAR1):c.*31A>GSNV Uncertain significance 208122 rs4879809 9:34635598-34635598 9:34635601-34635601
21 SIGMAR1 NM_005866.4(SIGMAR1):c.623G>A (p.Arg208Gln)SNV Uncertain significance 569077 rs541996857 9:34635678-34635678 9:34635681-34635681
22 SIGMAR1 NM_005866.4(SIGMAR1):c.298C>G (p.Leu100Val)SNV Uncertain significance 568833 rs1278952640 9:34637271-34637271 9:34637274-34637274
23 SIGMAR1 NM_005866.4(SIGMAR1):c.*51G>TSNV Uncertain significance 643550 9:34635578-34635578 9:34635581-34635581
24 SIGMAR1 NM_005866.4(SIGMAR1):c.595C>T (p.Leu199Phe)SNV Uncertain significance 655091 9:34635706-34635706 9:34635709-34635709
25 SIGMAR1 NM_005866.4(SIGMAR1):c.529G>A (p.Val177Ile)SNV Uncertain significance 659848 9:34635772-34635772 9:34635775-34635775
26 SIGMAR1 NM_005866.4(SIGMAR1):c.259G>A (p.Gly87Ser)SNV Uncertain significance 642698 9:34637310-34637310 9:34637313-34637313
27 SIGMAR1 NM_005866.4(SIGMAR1):c.140G>C (p.Arg47Pro)SNV Uncertain significance 653722 9:34637555-34637555 9:34637558-34637558
28 SIGMAR1 NM_005866.4(SIGMAR1):c.453G>A (p.Thr151=)SNV Likely benign 534264 rs751571040 9:34635848-34635848 9:34635851-34635851
29 SIGMAR1 NM_005866.4(SIGMAR1):c.339C>T (p.Ser113=)SNV Likely benign 534266 rs754738945 9:34637230-34637230 9:34637233-34637233
30 SIGMAR1 NM_005866.4(SIGMAR1):c.552C>T (p.Phe184=)SNV Benign 465870 rs61739588 9:34635749-34635749 9:34635752-34635752

UniProtKB/Swiss-Prot genetic disease variations for Amyotrophic Lateral Sclerosis 16, Juvenile:

73
# Symbol AA change Variation ID SNP ID
1 SIGMAR1 p.Glu102Gln VAR_067311 rs387906829

Expression for Amyotrophic Lateral Sclerosis 16, Juvenile

Search GEO for disease gene expression data for Amyotrophic Lateral Sclerosis 16, Juvenile.

Pathways for Amyotrophic Lateral Sclerosis 16, Juvenile

GO Terms for Amyotrophic Lateral Sclerosis 16, Juvenile

Cellular components related to Amyotrophic Lateral Sclerosis 16, Juvenile according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell GO:0005623 9.83 VAPB SPG11 RMDN3 ITPR3 CHMP2B
2 cell projection GO:0042995 9.8 SPG11 SIGMAR1 SETX KCNAB2 C9orf72
3 cytoplasm GO:0005737 9.73 VCP VAPB UBQLN2 SPG11 SETX RMDN3
4 dendrite GO:0030425 9.62 SPG11 FUS C9orf72 ALS2
5 postsynaptic density GO:0014069 9.56 SIGMAR1 KCNAB2 CHMP2B ALS2
6 axon GO:0030424 9.55 SPG11 SETX KCNAB2 C9orf72 ALS2
7 nuclear outer membrane GO:0005640 9.37 SIGMAR1 ITPR3
8 growth cone GO:0030426 8.92 SIGMAR1 SETX C9orf72 ALS2

Biological processes related to Amyotrophic Lateral Sclerosis 16, Juvenile according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endosome organization GO:0007032 9.26 CHMP2B ALS2
2 axon extension GO:0048675 9.16 SPG11 C9orf72
3 regulation of autophagosome assembly GO:2000785 8.96 UBQLN2 C9orf72
4 autophagy GO:0006914 8.92 VCP UBQLN2 CHMP2B C9orf72

Molecular functions related to Amyotrophic Lateral Sclerosis 16, Juvenile according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.93 VCP VAPB UBQLN2 SPG11 SIGMAR1 SETX
2 Rab guanyl-nucleotide exchange factor activity GO:0017112 8.96 C9orf72 ALS2
3 polyubiquitin modification-dependent protein binding GO:0031593 8.62 VCP UBQLN2

Sources for Amyotrophic Lateral Sclerosis 16, Juvenile

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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