ALS4
MCID: AMY045
MIFTS: 40

Amyotrophic Lateral Sclerosis 4, Juvenile (ALS4)

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

Aliases & Classifications for Amyotrophic Lateral Sclerosis 4, Juvenile

MalaCards integrated aliases for Amyotrophic Lateral Sclerosis 4, Juvenile:

Name: Amyotrophic Lateral Sclerosis 4, Juvenile 57 12 13 72
Amyotrophic Lateral Sclerosis Type 4 12 53 59 29 6 15
Als4 57 53 59 74
Amyotrophic Lateral Sclerosis 4 12 53 74
Distal Hereditary Motor Neuropathy with Upper Motor Neuron Signs 12 59
Dhmn with Upper Motor Neuron Signs 12 59
Neuronopathy, Distal Hereditary Motor, with Pyramidal Features 57
Neuronopathy Distal Hereditary Motor with Pyramidal Features 74
Distal Hereditary Motor Neuropathy with Pyramidal Features 12
Sclerosis, Lateral, Amyotrophic, Type Type 4 40
Amyotrophic Lateral Sclerosis Juvenile 4 74
Als 4 12

Characteristics:

Orphanet epidemiological data:

59
amyotrophic lateral sclerosis type 4
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
slowly progressive
childhood or adolescent onset (usually less than 25 years)
has also been called 'distal hereditary motor neuronopathy' (dhmn) and 'distal spinal muscular atrophy' (dsma)


HPO:

32
amyotrophic lateral sclerosis 4, juvenile:
Inheritance autosomal dominant inheritance
Onset and clinical course slow progression


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0060196
MeSH 44 D000690
ICD10 33 G12.2
ICD10 via Orphanet 34 G12.2
UMLS via Orphanet 73 C1865409
Orphanet 59 ORPHA357043
MedGen 42 C1865409
UMLS 72 C1865409

Summaries for Amyotrophic Lateral Sclerosis 4, Juvenile

UniProtKB/Swiss-Prot : 74 Amyotrophic lateral sclerosis 4: A form of amyotrophic lateral sclerosis with childhood- or adolescent- onset, and characterized by slow disease progression and the sparing of bulbar and respiratory muscles. Amyotrophic lateral sclerosis is 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 4, Juvenile, also known as amyotrophic lateral sclerosis type 4, is related to juvenile amyotrophic lateral sclerosis and lateral sclerosis, and has symptoms including upper motor neuron signs An important gene associated with Amyotrophic Lateral Sclerosis 4, Juvenile is SETX (Senataxin). Affiliated tissues include brain, spinal cord and skeletal muscle, and related phenotypes are skeletal muscle atrophy and babinski sign

Disease Ontology : 12 An amyotrophic lateral sclerosis with juvenile onset that has material basis in mutation in the SETX gene on chromosome 9.

OMIM : 57 Childhood- and adolescent-onset forms of familial ALS (see ALS1, 105400) carry the designation 'juvenile ALS.' Several forms of autosomal recessive juvenile ALS have been identified; see ALS2 (205100) and ALS5 (602099). (602433)

Related Diseases for Amyotrophic Lateral Sclerosis 4, 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

Diseases related to Amyotrophic Lateral Sclerosis 4, Juvenile via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 25)
# Related Disease Score Top Affiliating Genes
1 juvenile amyotrophic lateral sclerosis 32.3 SETX ALS2
2 lateral sclerosis 30.9 SETX ALS2
3 amyotrophic lateral sclerosis 3 29.6 SUGCT ALS2
4 hereditary spastic paraplegia 28.9 SETX ALS2
5 amyotrophic lateral sclerosis 1 28.9 SUGCT SETX DAO ALS2
6 frontotemporal dementia and/or amyotrophic lateral sclerosis 4 11.6
7 spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 10.3
8 neuronopathy, distal hereditary motor, type i 10.1
9 apraxia 10.1
10 oral candidiasis 10.1
11 candidiasis 10.1
12 als2-related disorders 10.1
13 oculomotor apraxia 10.1
14 motor neuron disease 9.8 SETX ALS2
15 multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly 9.7
16 pulmonary alveolar microlithiasis 9.7
17 progressive muscular atrophy 9.7
18 paraplegia 9.7
19 axonal neuropathy 9.7
20 muscular atrophy 9.7
21 amyotrophic lateral sclerosis type 6 9.7 SETX DAO ALS2
22 amyotrophic lateral sclerosis 11 9.6 SETX DAO ALS2
23 amyotrophic lateral sclerosis 7 9.6 SETX DAO ALS2
24 amyotrophic lateral sclerosis 10 with or without frontotemporal dementia 9.6 SETX DAO ALS2
25 amyotrophic lateral sclerosis 9 9.5 SETX DAO ALS2

Graphical network of the top 20 diseases related to Amyotrophic Lateral Sclerosis 4, Juvenile:



Diseases related to Amyotrophic Lateral Sclerosis 4, Juvenile

Symptoms & Phenotypes for Amyotrophic Lateral Sclerosis 4, Juvenile

Human phenotypes related to Amyotrophic Lateral Sclerosis 4, Juvenile:

59 32 (show all 19)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 skeletal muscle atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0003202
2 babinski sign 59 32 frequent (33%) Frequent (79-30%) HP:0003487
3 distal muscle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0002460
4 gait disturbance 59 32 occasional (7.5%) Occasional (29-5%) HP:0001288
5 pes cavus 59 32 occasional (7.5%) Occasional (29-5%) HP:0001761
6 spastic paraplegia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001258
7 sensory impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0003474
8 clonus 32 occasional (7.5%) HP:0002169
9 hyperreflexia 32 HP:0001347
10 abnormal pyramidal sign 59 Frequent (79-30%)
11 amyotrophic lateral sclerosis 32 HP:0007354
12 difficulty walking 32 HP:0002355
13 diffuse axonal swelling 32 HP:0003405
14 abnormal upper motor neuron morphology 32 HP:0002127
15 abnormal lower motor neuron morphology 32 HP:0002366
16 degeneration of anterior horn cells 32 HP:0002398
17 axonal degeneration 32 HP:0040078
18 peripheral axonal degeneration 32 HP:0000764
19 pallor of dorsal columns of the spinal cord 32 HP:0006825

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
hyperreflexia
difficulty walking
diffuse axonal swelling
upper motor neuron signs
pallor of dorsal columns of the spinal cord
more
Skeletal Feet:
pes cavus has been reported

Neurologic Peripheral Nervous System:
diffuse axonal swelling
axonal degeneration
no sensory abnormalities

Clinical features from OMIM:

602433

UMLS symptoms related to Amyotrophic Lateral Sclerosis 4, Juvenile:


upper motor neuron signs

Drugs & Therapeutics for Amyotrophic Lateral Sclerosis 4, Juvenile

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Inflammation in Amyotrophic Lateral Sclerosis - a Study of Soluble Cluster of Differentiation 163 in the Cerebrospinal Fluid Completed NCT02325375

Search NIH Clinical Center for Amyotrophic Lateral Sclerosis 4, Juvenile

Genetic Tests for Amyotrophic Lateral Sclerosis 4, Juvenile

Genetic tests related to Amyotrophic Lateral Sclerosis 4, Juvenile:

# Genetic test Affiliating Genes
1 Amyotrophic Lateral Sclerosis Type 4 29 SETX

Anatomical Context for Amyotrophic Lateral Sclerosis 4, Juvenile

MalaCards organs/tissues related to Amyotrophic Lateral Sclerosis 4, Juvenile:

41
Brain, Spinal Cord, Skeletal Muscle

Publications for Amyotrophic Lateral Sclerosis 4, Juvenile

Articles related to Amyotrophic Lateral Sclerosis 4, Juvenile:

(show all 13)
# Title Authors PMID Year
1
DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). 8 71
15106121 2004
2
Linkage of the gene for an autosomal dominant form of juvenile amyotrophic lateral sclerosis to chromosome 9q34. 8 71
9497266 1998
3
EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS)--revised report of an EFNS task force. 71
21914052 2012
4
Autosomal dominant juvenile amyotrophic lateral sclerosis and distal hereditary motor neuronopathy with pyramidal tract signs: synonyms for the same disorder? 8
12023320 2002
5
Amyotrophic Lateral Sclerosis Overview 71
20301623 2001
6
A gene for autosomal dominant juvenile amyotrophic lateral sclerosis (ALS4) localizes to a 500-kb interval on chromosome 9q34. 8
11085590 2000
7
Autosomal dominant juvenile amyotrophic lateral sclerosis. 8
10430837 1999
8
NERVE CONDUCTION AND OTHER STUDIES IN FAMILIES WITH CHARCOT-MARIE-TOOTH DISEASE. 8
14236005 1964
9
Senataxin mutations elicit motor neuron degeneration phenotypes and yield TDP-43 mislocalization in ALS4 mice and human patients. 38
29725819 2018
10
Senataxin: Genome Guardian at the Interface of Transcription and Neurodegeneration. 38
27771483 2017
11
Human Senataxin Modulates Structural Plasticity of the Neuromuscular Junction in Drosophila through a Neuronally Conserved TGFβ Signalling Pathway. 38
27197982 2016
12
Protein interaction analysis of senataxin and the ALS4 L389S mutant yields insights into senataxin post-translational modification and uncovers mutant-specific binding with a brain cytoplasmic RNA-encoded peptide. 38
24244371 2013
13
Senataxin modulates neurite growth through fibroblast growth factor 8 signalling. 38
21576111 2011

Variations for Amyotrophic Lateral Sclerosis 4, Juvenile

ClinVar genetic disease variations for Amyotrophic Lateral Sclerosis 4, Juvenile:

6 (show top 50) (show all 170)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 SETX NM_015046.7(SETX): c.1166T> C (p.Leu389Ser) single nucleotide variant Pathogenic rs29001584 9:135205819-135205819 9:132330432-132330432
2 SETX NM_015046.5(SETX): c.6848_6851delCAGA (p.Thr2283Lysfs) deletion Pathogenic rs398124286 9:135152531-135152534 9:132277144-132277147
3 SETX NM_015046.7(SETX): c.5264del (p.Thr1755fs) deletion Pathogenic 9:135201721-135201721 9:132326334-132326334
4 SETX NM_015046.7(SETX): c.8C> T (p.Thr3Ile) single nucleotide variant Likely pathogenic rs28941475 9:135224808-135224808 9:132349421-132349421
5 SETX NM_015046.7(SETX): c.6407G> A (p.Arg2136His) single nucleotide variant Conflicting interpretations of pathogenicity rs121434378 9:135158790-135158790 9:132283403-132283403
6 SETX NM_015046.7(SETX): c.7640T> C (p.Ile2547Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs151117904 9:135140020-135140020 9:132264633-132264633
7 SETX NM_015046.7(SETX): c.5283A> G (p.Gln1761=) single nucleotide variant Conflicting interpretations of pathogenicity rs139063885 9:135187235-135187235 9:132311848-132311848
8 SETX NM_015046.7(SETX): c.7724C> T (p.Pro2575Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs34000644 9:135139936-135139936 9:132264549-132264549
9 SETX NM_015046.7(SETX): c.7490G> A (p.Ser2497Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs61735488 9:135140170-135140170 9:132264783-132264783
10 SETX NM_015046.7(SETX): c.3229G> A (p.Asp1077Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs145097270 9:135203756-135203756 9:132328369-132328369
11 SETX NM_015046.7(SETX): c.3010A> G (p.Asn1004Asp) single nucleotide variant Conflicting interpretations of pathogenicity rs77984885 9:135203975-135203975 9:132328588-132328588
12 SETX NM_015046.7(SETX): c.3057_3059TGA[7] (p.Asp1024dup) short repeat Conflicting interpretations of pathogenicity rs572772837 9:135203911-135203913 9:132328524-132328526
13 SETX NM_015046.7(SETX): c.472T> G (p.Leu158Val) single nucleotide variant Conflicting interpretations of pathogenicity rs145438764 9:135218103-135218103 9:132342716-132342716
14 SETX NM_015046.7(SETX): c.7814G> A (p.Arg2605Gln) single nucleotide variant Uncertain significance rs543247171 9:135139846-135139846 9:132264459-132264459
15 SETX NM_015046.7(SETX): c.1391C> T (p.Ser464Leu) single nucleotide variant Uncertain significance rs200614765 9:135205594-135205594 9:132330207-132330207
16 SETX NM_015046.7(SETX): c.717A> G (p.Leu239=) single nucleotide variant Uncertain significance rs147125311 9:135211684-135211684 9:132336297-132336297
17 SETX NM_015046.7(SETX): c.5949+5G> A single nucleotide variant Uncertain significance rs374656811 9:135172269-135172269 9:132296882-132296882
18 SETX NM_015046.7(SETX): c.7708C> T (p.Pro2570Ser) single nucleotide variant Uncertain significance rs1240232139 9:135139952-135139952 9:132264565-132264565
19 SETX NM_015046.7(SETX): c.71A> G (p.Asn24Ser) single nucleotide variant Uncertain significance rs981346599 9:135224745-135224745 9:132349358-132349358
20 SETX NM_015046.7(SETX): c.7870G> T (p.Asp2624Tyr) single nucleotide variant Uncertain significance rs141589525 9:135139790-135139790 9:132264403-132264403
21 SETX NM_015046.7(SETX): c.4903T> A (p.Leu1635Met) single nucleotide variant Uncertain significance rs1466879487 9:135202082-135202082 9:132326695-132326695
22 SETX NM_015046.7(SETX): c.4670C> G (p.Thr1557Ser) single nucleotide variant Uncertain significance rs1554820196 9:135202315-135202315 9:132326928-132326928
23 SETX NM_015046.7(SETX): c.5464A> G (p.Lys1822Glu) single nucleotide variant Uncertain significance rs1249423284 9:135176101-135176101 9:132300714-132300714
24 SETX NM_015046.7(SETX): c.3057_3059TGA[4] (p.Asp1023_Asp1024del) short repeat Uncertain significance rs572772837 9:135203911-135203916 9:132328524-132328529
25 SETX NM_015046.7(SETX): c.2749A> C (p.Met917Leu) single nucleotide variant Uncertain significance rs761943404 9:135204236-135204236 9:132328849-132328849
26 SETX NM_015046.7(SETX): c.1153G> A (p.Glu385Lys) single nucleotide variant Uncertain significance rs1554821963 9:135205832-135205832 9:132330445-132330445
27 SETX NM_015046.7(SETX): c.64G> T (p.Ala22Ser) single nucleotide variant Uncertain significance rs756600708 9:135224752-135224752 9:132349365-132349365
28 SETX NM_015046.7(SETX): c.5767A> G (p.Thr1923Ala) single nucleotide variant Uncertain significance rs372993859 9:135173481-135173481 9:132298094-132298094
29 SETX NM_015046.7(SETX): c.4979A> G (p.His1660Arg) single nucleotide variant Uncertain significance rs371894414 9:135202006-135202006 9:132326619-132326619
30 SETX NM_015046.7(SETX): c.4982C> G (p.Pro1661Arg) single nucleotide variant Uncertain significance rs146873848 9:135202003-135202003 9:132326616-132326616
31 SETX NM_015046.7(SETX): c.4759C> T (p.Pro1587Ser) single nucleotide variant Uncertain significance rs916634082 9:135202226-135202226 9:132326839-132326839
32 SETX NM_015046.7(SETX): c.4601A> T (p.Asp1534Val) single nucleotide variant Uncertain significance rs1554820219 9:135202384-135202384 9:132326997-132326997
33 SETX NM_015046.7(SETX): c.2282C> T (p.Ser761Leu) single nucleotide variant Uncertain significance rs200153024 9:135204703-135204703 9:132329316-132329316
34 SETX NM_015046.7(SETX): c.4051C> G (p.Gln1351Glu) single nucleotide variant Uncertain significance rs375241191 9:135202934-135202934 9:132327547-132327547
35 SETX NM_015046.7(SETX): c.3826C> G (p.Gln1276Glu) single nucleotide variant Uncertain significance rs148604312 9:135203159-135203159 9:132327772-132327772
36 SETX NM_015046.7(SETX): c.2854A> G (p.Thr952Ala) single nucleotide variant Uncertain significance rs1375463032 9:135204131-135204131 9:132328744-132328744
37 SETX NM_015046.7(SETX): c.2446A> G (p.Thr816Ala) single nucleotide variant Uncertain significance rs369470593 9:135204539-135204539 9:132329152-132329152
38 SETX NM_015046.7(SETX): c.2005A> T (p.Asn669Tyr) single nucleotide variant Uncertain significance rs143727702 9:135204980-135204980 9:132329593-132329593
39 SETX NM_015046.7(SETX): c.7708_7710CCT[1] (p.Pro2571del) short repeat Uncertain significance rs770590408 9:135139947-135139949 9:132264560-132264562
40 SETX NM_015046.7(SETX): c.1690T> G (p.Leu564Val) single nucleotide variant Uncertain significance rs761877146 9:135205295-135205295 9:132329908-132329908
41 SETX NM_015046.7(SETX): c.654G> C (p.Lys218Asn) single nucleotide variant Uncertain significance rs117861188 9:135211747-135211747 9:132336360-132336360
42 SETX NM_015046.7(SETX): c.7432A> G (p.Thr2478Ala) single nucleotide variant Uncertain significance rs142303658 9:135140228-135140228 9:132264841-132264841
43 SETX NM_015046.7(SETX): c.7139G> A (p.Arg2380Gln) single nucleotide variant Uncertain significance rs145397619 9:135147157-135147157 9:132271770-132271770
44 SETX NM_015046.7(SETX): c.5998C> G (p.Gln2000Glu) single nucleotide variant Uncertain significance rs142917412 9:135171367-135171367 9:132295980-132295980
45 SETX NM_015046.7(SETX): c.4865C> T (p.Pro1622Leu) single nucleotide variant Uncertain significance rs140781535 9:135202120-135202120 9:132326733-132326733
46 SETX NM_015046.7(SETX): c.4433C> A (p.Ala1478Glu) single nucleotide variant Uncertain significance rs143661911 9:135202552-135202552 9:132327165-132327165
47 SETX NM_015046.7(SETX): c.4045C> G (p.Gln1349Glu) single nucleotide variant Uncertain significance rs146407699 9:135202940-135202940 9:132327553-132327553
48 SETX NM_015046.7(SETX): c.3057_3059TGA[5] (p.Asp1024del) short repeat Uncertain significance rs572772837 9:135203911-135203913 9:132328524-132328526
49 SETX NM_015046.7(SETX): c.3016G> A (p.Gly1006Arg) single nucleotide variant Uncertain significance rs141266068 9:135203969-135203969 9:132328582-132328582
50 SETX NM_015046.7(SETX): c.2395C> T (p.His799Tyr) single nucleotide variant Uncertain significance rs200459144 9:135204590-135204590 9:132329203-132329203

UniProtKB/Swiss-Prot genetic disease variations for Amyotrophic Lateral Sclerosis 4, Juvenile:

74
# Symbol AA change Variation ID SNP ID
1 SETX p.Thr3Ile VAR_018776 rs28941475
2 SETX p.Leu389Ser VAR_018779 rs29001584
3 SETX p.Arg2136His VAR_018790 rs121434378
4 SETX p.Cys1554Gly VAR_071685 rs112089123
5 SETX p.Lys2029Glu VAR_071686 rs746525639
6 SETX p.Ile2547Thr VAR_071688 rs151117904

Expression for Amyotrophic Lateral Sclerosis 4, Juvenile

Search GEO for disease gene expression data for Amyotrophic Lateral Sclerosis 4, Juvenile.

Pathways for Amyotrophic Lateral Sclerosis 4, Juvenile

GO Terms for Amyotrophic Lateral Sclerosis 4, Juvenile

Cellular components related to Amyotrophic Lateral Sclerosis 4, Juvenile according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 growth cone GO:0030426 8.96 SETX ALS2
2 aggresome GO:0016235 8.62 XRN2 RANGAP1

Biological processes related to Amyotrophic Lateral Sclerosis 4, Juvenile according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA-templated transcription, termination GO:0006353 8.62 XRN2 SETX

Molecular functions related to Amyotrophic Lateral Sclerosis 4, Juvenile according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transcription termination site sequence-specific DNA binding GO:0001147 8.62 XRN2 SETX

Sources for Amyotrophic Lateral Sclerosis 4, Juvenile

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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