ALS4
MCID: AMY045
MIFTS: 35

Amyotrophic Lateral Sclerosis 4, Juvenile (ALS4)

Categories: Genetic diseases, Mental 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 73
Amyotrophic Lateral Sclerosis Type 4 12 53 59 29 6 15
Als4 57 53 59 75
Amyotrophic Lateral Sclerosis 4 12 53 75
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 75
Distal Hereditary Motor Neuropathy with Pyramidal Features 12
Sclerosis, Lateral, Amyotrophic, Type Type 4 40
Amyotrophic Lateral Sclerosis Juvenile 4 75
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:
Onset and clinical course slow progression
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

OMIM 57 602433
Disease Ontology 12 DOID:0060196
ICD10 33 G12.2
Orphanet 59 ORPHA357043
UMLS via Orphanet 74 C1865409
ICD10 via Orphanet 34 G12.2
MedGen 42 C1865409
MeSH 44 D000690
UMLS 73 C1865409

Summaries for Amyotrophic Lateral Sclerosis 4, Juvenile

UniProtKB/Swiss-Prot : 75 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 gait disturbance and skeletal muscle atrophy

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
Tardbp-Related Amyotrophic Lateral Sclerosis

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

(show all 11)
# Related Disease Score Top Affiliating Genes
1 juvenile amyotrophic lateral sclerosis 32.2 ALS2 SETX
2 lateral sclerosis 30.5 ALS2 SETX
3 amyotrophic lateral sclerosis 1 29.6 ALS2 DAO SETX SUGCT TPK1
4 frontotemporal dementia and/or amyotrophic lateral sclerosis 4 11.4
5 amyotrophic lateral sclerosis 3 10.0 ALS2 SUGCT
6 motor neuron disease 9.9 ALS2 SETX
7 amyotrophic lateral sclerosis type 6 9.9 ALS2 DAO SETX
8 amyotrophic lateral sclerosis 11 9.9 ALS2 DAO SETX
9 amyotrophic lateral sclerosis 7 9.9 ALS2 DAO SETX
10 amyotrophic lateral sclerosis 10 with or without frontotemporal dementia 9.8 ALS2 DAO SETX
11 amyotrophic lateral sclerosis 9 9.8 ALS2 DAO SETX

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

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
hyperreflexia
difficulty walking
diffuse axonal swelling
extensor plantar responses
upper motor neuron signs
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

Human phenotypes related to Amyotrophic Lateral Sclerosis 4, Juvenile:

59 32 (show all 19)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 gait disturbance 59 32 occasional (7.5%) Occasional (29-5%) HP:0001288
2 skeletal muscle atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0003202
3 babinski sign 59 32 frequent (33%) Frequent (79-30%) HP:0003487
4 pes cavus 59 32 occasional (7.5%) Occasional (29-5%) HP:0001761
5 spastic paraplegia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001258
6 distal muscle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0002460
7 sensory impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0003474
8 hyperreflexia 32 HP:0001347
9 clonus 32 occasional (7.5%) HP:0002169
10 abnormal pyramidal signs 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 pallor of dorsal columns of the spinal cord 32 HP:0006825
19 peripheral axonal degeneration 32 HP:0000764

UMLS symptoms related to Amyotrophic Lateral Sclerosis 4, Juvenile:


upper motor neuron signs

Drugs & Therapeutics for Amyotrophic Lateral Sclerosis 4, Juvenile

Search Clinical Trials , 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

Variations for Amyotrophic Lateral Sclerosis 4, Juvenile

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

75
# 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

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

6 (show top 50) (show all 294)
# Gene Variation Type Significance SNP ID Assembly Location
1 SETX NM_015046.5(SETX): c.1166T> C (p.Leu389Ser) single nucleotide variant Pathogenic rs29001584 GRCh37 Chromosome 9, 135205819: 135205819
2 SETX NM_015046.5(SETX): c.1166T> C (p.Leu389Ser) single nucleotide variant Pathogenic rs29001584 GRCh38 Chromosome 9, 132330432: 132330432
3 SETX NM_015046.5(SETX): c.8C> T (p.Thr3Ile) single nucleotide variant Likely pathogenic rs28941475 GRCh37 Chromosome 9, 135224808: 135224808
4 SETX NM_015046.5(SETX): c.8C> T (p.Thr3Ile) single nucleotide variant Likely pathogenic rs28941475 GRCh38 Chromosome 9, 132349421: 132349421
5 SETX NM_015046.5(SETX): c.6407G> A (p.Arg2136His) single nucleotide variant Pathogenic rs121434378 GRCh37 Chromosome 9, 135158790: 135158790
6 SETX NM_015046.5(SETX): c.6407G> A (p.Arg2136His) single nucleotide variant Pathogenic rs121434378 GRCh38 Chromosome 9, 132283403: 132283403
7 SETX NM_015046.5(SETX): c.1807A> G (p.Asn603Asp) single nucleotide variant Uncertain significance rs116205032 GRCh37 Chromosome 9, 135205178: 135205178
8 SETX NM_015046.5(SETX): c.1807A> G (p.Asn603Asp) single nucleotide variant Uncertain significance rs116205032 GRCh38 Chromosome 9, 132329791: 132329791
9 SETX NM_015046.5(SETX): c.1957C> A (p.Gln653Lys) single nucleotide variant Benign rs116333061 GRCh37 Chromosome 9, 135205028: 135205028
10 SETX NM_015046.5(SETX): c.1957C> A (p.Gln653Lys) single nucleotide variant Benign rs116333061 GRCh38 Chromosome 9, 132329641: 132329641
11 SETX NM_015046.5(SETX): c.3455T> G (p.Phe1152Cys) single nucleotide variant Benign/Likely benign rs3739922 GRCh37 Chromosome 9, 135203530: 135203530
12 SETX NM_015046.5(SETX): c.3455T> G (p.Phe1152Cys) single nucleotide variant Benign/Likely benign rs3739922 GRCh38 Chromosome 9, 132328143: 132328143
13 SETX NM_015046.5(SETX): c.6848_6851delCAGA (p.Thr2283Lysfs) deletion Pathogenic rs398124286 GRCh37 Chromosome 9, 135152531: 135152534
14 SETX NM_015046.5(SETX): c.6848_6851delCAGA (p.Thr2283Lysfs) deletion Pathogenic rs398124286 GRCh38 Chromosome 9, 132277144: 132277147
15 SETX NM_015046.6(SETX): c.1504C> T (p.Arg502Trp) single nucleotide variant Likely pathogenic rs534723946 GRCh37 Chromosome 9, 135205481: 135205481
16 SETX NM_015046.6(SETX): c.1504C> T (p.Arg502Trp) single nucleotide variant Likely pathogenic rs534723946 GRCh38 Chromosome 9, 132330094: 132330094
17 SETX NM_015046.5(SETX): c.7640T> C (p.Ile2547Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs151117904 GRCh37 Chromosome 9, 135140020: 135140020
18 SETX NM_015046.5(SETX): c.7640T> C (p.Ile2547Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs151117904 GRCh38 Chromosome 9, 132264633: 132264633
19 SETX NM_015046.5(SETX): c.59G> A (p.Arg20His) single nucleotide variant Benign/Likely benign rs79740039 GRCh38 Chromosome 9, 132349370: 132349370
20 SETX NM_015046.5(SETX): c.59G> A (p.Arg20His) single nucleotide variant Benign/Likely benign rs79740039 GRCh37 Chromosome 9, 135224757: 135224757
21 SETX NM_015046.5(SETX): c.3809C> T (p.Pro1270Leu) single nucleotide variant Likely benign rs144334281 GRCh38 Chromosome 9, 132327789: 132327789
22 SETX NM_015046.5(SETX): c.3809C> T (p.Pro1270Leu) single nucleotide variant Likely benign rs144334281 GRCh37 Chromosome 9, 135203176: 135203176
23 SETX NM_015046.5(SETX): c.7114G> A (p.Asp2372Asn) single nucleotide variant Benign/Likely benign rs150673589 GRCh38 Chromosome 9, 132271795: 132271795
24 SETX NM_015046.5(SETX): c.7114G> A (p.Asp2372Asn) single nucleotide variant Benign/Likely benign rs150673589 GRCh37 Chromosome 9, 135147182: 135147182
25 SETX NM_015046.5(SETX): c.6507G> A (p.Gly2169=) single nucleotide variant Benign/Likely benign rs34073320 GRCh37 Chromosome 9, 135158690: 135158690
26 SETX NM_015046.5(SETX): c.6507G> A (p.Gly2169=) single nucleotide variant Benign/Likely benign rs34073320 GRCh38 Chromosome 9, 132283303: 132283303
27 SETX NM_015046.5(SETX): c.4755T> G (p.Pro1585=) single nucleotide variant Benign/Likely benign rs151237267 GRCh37 Chromosome 9, 135202230: 135202230
28 SETX NM_015046.5(SETX): c.4755T> G (p.Pro1585=) single nucleotide variant Benign/Likely benign rs151237267 GRCh38 Chromosome 9, 132326843: 132326843
29 SETX NM_015046.5(SETX): c.4660T> G (p.Cys1554Gly) single nucleotide variant Benign/Likely benign rs112089123 GRCh38 Chromosome 9, 132326938: 132326938
30 SETX NM_015046.5(SETX): c.4660T> G (p.Cys1554Gly) single nucleotide variant Benign/Likely benign rs112089123 GRCh37 Chromosome 9, 135202325: 135202325
31 SETX NM_015046.5(SETX): c.2975A> G (p.Lys992Arg) single nucleotide variant Benign/Likely benign rs61742937 GRCh37 Chromosome 9, 135204010: 135204010
32 SETX NM_015046.5(SETX): c.2975A> G (p.Lys992Arg) single nucleotide variant Benign/Likely benign rs61742937 GRCh38 Chromosome 9, 132328623: 132328623
33 SETX NM_015046.5(SETX): c.5283A> G (p.Gln1761=) single nucleotide variant Conflicting interpretations of pathogenicity rs139063885 GRCh37 Chromosome 9, 135187235: 135187235
34 SETX NM_015046.5(SETX): c.5283A> G (p.Gln1761=) single nucleotide variant Conflicting interpretations of pathogenicity rs139063885 GRCh38 Chromosome 9, 132311848: 132311848
35 SETX NM_015046.5(SETX): c.7724C> T (p.Pro2575Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs34000644 GRCh37 Chromosome 9, 135139936: 135139936
36 SETX NM_015046.5(SETX): c.7724C> T (p.Pro2575Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs34000644 GRCh38 Chromosome 9, 132264549: 132264549
37 SETX NM_015046.5(SETX): c.2672T> C (p.Val891Ala) single nucleotide variant Benign/Likely benign rs148181729 GRCh37 Chromosome 9, 135204313: 135204313
38 SETX NM_015046.5(SETX): c.2672T> C (p.Val891Ala) single nucleotide variant Benign/Likely benign rs148181729 GRCh38 Chromosome 9, 132328926: 132328926
39 SETX NM_015046.5(SETX): c.2216G> A (p.Gly739Glu) single nucleotide variant Benign/Likely benign rs36024203 GRCh37 Chromosome 9, 135204769: 135204769
40 SETX NM_015046.5(SETX): c.2216G> A (p.Gly739Glu) single nucleotide variant Benign/Likely benign rs36024203 GRCh38 Chromosome 9, 132329382: 132329382
41 SETX NM_015046.5(SETX): c.1391C> T (p.Ser464Leu) single nucleotide variant Uncertain significance rs200614765 GRCh37 Chromosome 9, 135205594: 135205594
42 SETX NM_015046.5(SETX): c.1391C> T (p.Ser464Leu) single nucleotide variant Uncertain significance rs200614765 GRCh38 Chromosome 9, 132330207: 132330207
43 SETX NM_015046.5(SETX): c.472T> G (p.Leu158Val) single nucleotide variant Conflicting interpretations of pathogenicity rs145438764 GRCh37 Chromosome 9, 135218103: 135218103
44 SETX NM_015046.5(SETX): c.472T> G (p.Leu158Val) single nucleotide variant Conflicting interpretations of pathogenicity rs145438764 GRCh38 Chromosome 9, 132342716: 132342716
45 SETX NM_015046.5(SETX): c.7814G> A (p.Arg2605Gln) single nucleotide variant Uncertain significance rs543247171 GRCh37 Chromosome 9, 135139846: 135139846
46 SETX NM_015046.5(SETX): c.7814G> A (p.Arg2605Gln) single nucleotide variant Uncertain significance rs543247171 GRCh38 Chromosome 9, 132264459: 132264459
47 SETX NM_015046.5(SETX): c.7371T> C (p.His2457=) single nucleotide variant Benign/Likely benign rs113071480 GRCh37 Chromosome 9, 135140289: 135140289
48 SETX NM_015046.5(SETX): c.7371T> C (p.His2457=) single nucleotide variant Benign/Likely benign rs113071480 GRCh38 Chromosome 9, 132264902: 132264902
49 SETX NM_015046.5(SETX): c.4612C> T (p.Arg1538Trp) single nucleotide variant Uncertain significance rs147018359 GRCh38 Chromosome 9, 132326986: 132326986
50 SETX NM_015046.5(SETX): c.4612C> T (p.Arg1538Trp) single nucleotide variant Uncertain significance rs147018359 GRCh37 Chromosome 9, 135202373: 135202373

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 ALS2 SETX
2 aggresome GO:0016235 8.62 RANGAP1 XRN2

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 SETX XRN2

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 SETX XRN2

Sources for Amyotrophic Lateral Sclerosis 4, Juvenile

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 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 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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