MCID: AMY045
MIFTS: 34

Amyotrophic Lateral Sclerosis 4, Juvenile

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Mental 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 amyotrophic lateral sclerosis 1, 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 and spinal cord, and related phenotypes are peripheral axonal degeneration and hyperreflexia

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 12)
# Related Disease Score Top Affiliating Genes
1 juvenile amyotrophic lateral sclerosis 31.5 ALS2 SETX UPF1
2 amyotrophic lateral sclerosis 1 28.4 ALS2 SETX SUGCT TPK1
3 frontotemporal dementia and/or amyotrophic lateral sclerosis 4 11.3
4 amyotrophic lateral sclerosis type 6 10.2 ALS2 SETX
5 amyotrophic lateral sclerosis 11 10.2 ALS2 SETX
6 amyotrophic lateral sclerosis 7 10.1 ALS2 SETX
7 amyotrophic lateral sclerosis 3 10.1 ALS2 SUGCT
8 amyotrophic lateral sclerosis 9 10.1 ALS2 SETX
9 amyotrophic lateral sclerosis 10 with or without frontotemporal dementia 10.0 ALS2 SETX
10 lateral sclerosis 9.9
11 spinocerebellar ataxia, autosomal recessive 1 9.9 ALS2 SETX
12 motor neuron disease 9.7 ALS2 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:

32 (show all 14)
# Description HPO Frequency HPO Source Accession
1 peripheral axonal degeneration 32 HP:0000764
2 hyperreflexia 32 HP:0001347
3 pes cavus 32 HP:0001761
4 abnormal upper motor neuron morphology 32 HP:0002127
5 clonus 32 occasional (7.5%) HP:0002169
6 difficulty walking 32 HP:0002355
7 abnormal lower motor neuron morphology 32 HP:0002366
8 degeneration of anterior horn cells 32 HP:0002398
9 distal muscle weakness 32 HP:0002460
10 diffuse axonal swelling 32 HP:0003405
11 babinski sign 32 HP:0003487
12 pallor of dorsal columns of the spinal cord 32 HP:0006825
13 amyotrophic lateral sclerosis 32 HP:0007354
14 axonal degeneration 32 HP:0040078

UMLS symptoms related to Amyotrophic Lateral Sclerosis 4, Juvenile:


upper motor neuron signs

GenomeRNAi Phenotypes related to Amyotrophic Lateral Sclerosis 4, Juvenile according to GeneCards Suite gene sharing:

26 (show all 16)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-105 9.6 TPK1
2 Increased shRNA abundance (Z-score > 2) GR00366-A-107 9.6 XRN2
3 Increased shRNA abundance (Z-score > 2) GR00366-A-130 9.6 TPK1
4 Increased shRNA abundance (Z-score > 2) GR00366-A-137 9.6 TPK1
5 Increased shRNA abundance (Z-score > 2) GR00366-A-146 9.6 UPF1
6 Increased shRNA abundance (Z-score > 2) GR00366-A-151 9.6 TPK1
7 Increased shRNA abundance (Z-score > 2) GR00366-A-157 9.6 TPK1
8 Increased shRNA abundance (Z-score > 2) GR00366-A-159 9.6 UPF1 XRN2
9 Increased shRNA abundance (Z-score > 2) GR00366-A-16 9.6 TPK1
10 Increased shRNA abundance (Z-score > 2) GR00366-A-161 9.6 UPF1
11 Increased shRNA abundance (Z-score > 2) GR00366-A-189 9.6 UPF1
12 Increased shRNA abundance (Z-score > 2) GR00366-A-194 9.6 TPK1
13 Increased shRNA abundance (Z-score > 2) GR00366-A-42 9.6 TPK1
14 Increased shRNA abundance (Z-score > 2) GR00366-A-57 9.6 TPK1
15 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.6 UPF1 XRN2 TPK1
16 Increased shRNA abundance (Z-score > 2) GR00366-A-92 9.6 XRN2

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

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 228)
# 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.6848_6851delCAGA (p.Thr2283Lysfs) deletion Pathogenic rs398124286 GRCh37 Chromosome 9, 135152531: 135152534
8 SETX NM_015046.5(SETX): c.6848_6851delCAGA (p.Thr2283Lysfs) deletion Pathogenic rs398124286 GRCh38 Chromosome 9, 132277144: 132277147
9 SETX NM_015046.6(SETX): c.1504C> T (p.Arg502Trp) single nucleotide variant Likely pathogenic rs534723946 GRCh37 Chromosome 9, 135205481: 135205481
10 SETX NM_015046.6(SETX): c.1504C> T (p.Arg502Trp) single nucleotide variant Likely pathogenic rs534723946 GRCh38 Chromosome 9, 132330094: 132330094
11 SETX NM_015046.5(SETX): c.7640T> C (p.Ile2547Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs151117904 GRCh37 Chromosome 9, 135140020: 135140020
12 SETX NM_015046.5(SETX): c.7640T> C (p.Ile2547Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs151117904 GRCh38 Chromosome 9, 132264633: 132264633
13 SETX NM_015046.5(SETX): c.59G> A (p.Arg20His) single nucleotide variant Benign/Likely benign rs79740039 GRCh38 Chromosome 9, 132349370: 132349370
14 SETX NM_015046.5(SETX): c.59G> A (p.Arg20His) single nucleotide variant Benign/Likely benign rs79740039 GRCh37 Chromosome 9, 135224757: 135224757
15 SETX NM_015046.5(SETX): c.3809C> T (p.Pro1270Leu) single nucleotide variant Likely benign rs144334281 GRCh38 Chromosome 9, 132327789: 132327789
16 SETX NM_015046.5(SETX): c.3809C> T (p.Pro1270Leu) single nucleotide variant Likely benign rs144334281 GRCh37 Chromosome 9, 135203176: 135203176
17 SETX NM_015046.5(SETX): c.7114G> A (p.Asp2372Asn) single nucleotide variant Benign/Likely benign rs150673589 GRCh38 Chromosome 9, 132271795: 132271795
18 SETX NM_015046.5(SETX): c.7114G> A (p.Asp2372Asn) single nucleotide variant Benign/Likely benign rs150673589 GRCh37 Chromosome 9, 135147182: 135147182
19 SETX NM_015046.5(SETX): c.6935+8T> C single nucleotide variant Benign/Likely benign rs17148873 GRCh37 Chromosome 9, 135152439: 135152439
20 SETX NM_015046.5(SETX): c.6935+8T> C single nucleotide variant Benign/Likely benign rs17148873 GRCh38 Chromosome 9, 132277052: 132277052
21 SETX NM_015046.5(SETX): c.6507G> A (p.Gly2169=) single nucleotide variant Benign/Likely benign rs34073320 GRCh37 Chromosome 9, 135158690: 135158690
22 SETX NM_015046.5(SETX): c.6507G> A (p.Gly2169=) single nucleotide variant Benign/Likely benign rs34073320 GRCh38 Chromosome 9, 132283303: 132283303
23 SETX NM_015046.5(SETX): c.4755T> G (p.Pro1585=) single nucleotide variant Benign/Likely benign rs151237267 GRCh37 Chromosome 9, 135202230: 135202230
24 SETX NM_015046.5(SETX): c.4755T> G (p.Pro1585=) single nucleotide variant Benign/Likely benign rs151237267 GRCh38 Chromosome 9, 132326843: 132326843
25 SETX NM_015046.5(SETX): c.4660T> G (p.Cys1554Gly) single nucleotide variant Benign/Likely benign rs112089123 GRCh38 Chromosome 9, 132326938: 132326938
26 SETX NM_015046.5(SETX): c.4660T> G (p.Cys1554Gly) single nucleotide variant Benign/Likely benign rs112089123 GRCh37 Chromosome 9, 135202325: 135202325
27 SETX NM_015046.5(SETX): c.2975A> G (p.Lys992Arg) single nucleotide variant Benign/Likely benign rs61742937 GRCh37 Chromosome 9, 135204010: 135204010
28 SETX NM_015046.5(SETX): c.2975A> G (p.Lys992Arg) single nucleotide variant Benign/Likely benign rs61742937 GRCh38 Chromosome 9, 132328623: 132328623
29 SETX NM_015046.5(SETX): c.5283A> G (p.Gln1761=) single nucleotide variant Conflicting interpretations of pathogenicity rs139063885 GRCh37 Chromosome 9, 135187235: 135187235
30 SETX NM_015046.5(SETX): c.5283A> G (p.Gln1761=) single nucleotide variant Conflicting interpretations of pathogenicity rs139063885 GRCh38 Chromosome 9, 132311848: 132311848
31 SETX NM_015046.5(SETX): c.7724C> T (p.Pro2575Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs34000644 GRCh37 Chromosome 9, 135139936: 135139936
32 SETX NM_015046.5(SETX): c.7724C> T (p.Pro2575Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs34000644 GRCh38 Chromosome 9, 132264549: 132264549
33 SETX NM_015046.5(SETX): c.2672T> C (p.Val891Ala) single nucleotide variant Benign/Likely benign rs148181729 GRCh37 Chromosome 9, 135204313: 135204313
34 SETX NM_015046.5(SETX): c.2672T> C (p.Val891Ala) single nucleotide variant Benign/Likely benign rs148181729 GRCh38 Chromosome 9, 132328926: 132328926
35 SETX NM_015046.5(SETX): c.2216G> A (p.Gly739Glu) single nucleotide variant Benign/Likely benign rs36024203 GRCh37 Chromosome 9, 135204769: 135204769
36 SETX NM_015046.5(SETX): c.2216G> A (p.Gly739Glu) single nucleotide variant Benign/Likely benign rs36024203 GRCh38 Chromosome 9, 132329382: 132329382
37 SETX NM_015046.5(SETX): c.472T> G (p.Leu158Val) single nucleotide variant Conflicting interpretations of pathogenicity rs145438764 GRCh37 Chromosome 9, 135218103: 135218103
38 SETX NM_015046.5(SETX): c.472T> G (p.Leu158Val) single nucleotide variant Conflicting interpretations of pathogenicity rs145438764 GRCh38 Chromosome 9, 132342716: 132342716
39 SETX NM_015046.5(SETX): c.7371T> C (p.His2457=) single nucleotide variant Benign/Likely benign rs113071480 GRCh37 Chromosome 9, 135140289: 135140289
40 SETX NM_015046.5(SETX): c.7371T> C (p.His2457=) single nucleotide variant Benign/Likely benign rs113071480 GRCh38 Chromosome 9, 132264902: 132264902
41 SETX NM_015046.5(SETX): c.4612C> T (p.Arg1538Trp) single nucleotide variant Uncertain significance rs147018359 GRCh38 Chromosome 9, 132326986: 132326986
42 SETX NM_015046.5(SETX): c.4612C> T (p.Arg1538Trp) single nucleotide variant Uncertain significance rs147018359 GRCh37 Chromosome 9, 135202373: 135202373
43 SETX NM_015046.5(SETX): c.3826C> G (p.Gln1276Glu) single nucleotide variant Uncertain significance rs148604312 GRCh38 Chromosome 9, 132327772: 132327772
44 SETX NM_015046.5(SETX): c.3826C> G (p.Gln1276Glu) single nucleotide variant Uncertain significance rs148604312 GRCh37 Chromosome 9, 135203159: 135203159
45 SETX NM_015046.5(SETX): c.3229G> A (p.Asp1077Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs145097270 GRCh37 Chromosome 9, 135203756: 135203756
46 SETX NM_015046.5(SETX): c.3229G> A (p.Asp1077Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs145097270 GRCh38 Chromosome 9, 132328369: 132328369
47 SETX NM_015046.6(SETX): c.7200-11_7200-10delTT deletion Benign rs531485265 GRCh38 Chromosome 9, 132269712: 132269713
48 SETX NM_015046.6(SETX): c.7200-11_7200-10delTT deletion Benign rs531485265 GRCh37 Chromosome 9, 135145099: 135145100
49 SETX NM_015046.6(SETX): c.7101A> G (p.Gly2367=) single nucleotide variant Benign rs79233884 GRCh37 Chromosome 9, 135147195: 135147195
50 SETX NM_015046.6(SETX): c.7101A> G (p.Gly2367=) single nucleotide variant Benign rs79233884 GRCh38 Chromosome 9, 132271808: 132271808

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 RNA processing GO:0006396 8.96 SETX XRN2
2 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 helicase activity GO:0004386 8.96 SETX UPF1
2 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
Content
Loading form....