ALS4
MCID: AMY045
MIFTS: 49

Amyotrophic Lateral Sclerosis 4, Juvenile (ALS4)

Categories: Genetic diseases, Mental diseases, Muscle diseases, Neuronal diseases, Rare 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 70
Amyotrophic Lateral Sclerosis Type 4 12 20 58 29 6 15
Als4 57 20 58 72
Amyotrophic Lateral Sclerosis 4 12 20 72
Distal Hereditary Motor Neuropathy with Upper Motor Neuron Signs 12 58
Dhmn with Upper Motor Neuron Signs 12 58
Neuronopathy, Distal Hereditary Motor, with Pyramidal Features 57
Neuronopathy Distal Hereditary Motor with Pyramidal Features 72
Distal Hereditary Motor Neuropathy with Pyramidal Features 12
Sclerosis, Lateral, Amyotrophic, Type Type 4 39
Amyotrophic Lateral Sclerosis Juvenile 4 72
Als 4 12

Characteristics:

Orphanet epidemiological data:

58
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 (Updated 20-May-2021)
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:

31
amyotrophic lateral sclerosis 4, juvenile:
Inheritance autosomal dominant inheritance
Onset and clinical course slow progression


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0060196
OMIM® 57 602433
OMIM Phenotypic Series 57 PS105400
MeSH 44 D000690
ICD10 32 G12.2
ICD10 via Orphanet 33 G12.2
UMLS via Orphanet 71 C1865409
Orphanet 58 ORPHA357043
MedGen 41 C1865409
UMLS 70 C1865409

Summaries for Amyotrophic Lateral Sclerosis 4, Juvenile

UniProtKB/Swiss-Prot : 72 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 spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2, and has symptoms including upper motor neuron signs An important gene associated with Amyotrophic Lateral Sclerosis 4, Juvenile is SETX (Senataxin), and among its related pathways/superpathways are Pathways of neurodegeneration - multiple diseases and mRNA surveillance pathway. Affiliated tissues include spinal cord, skeletal muscle and brain, 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 Juvenile amyotrophic lateral sclerosis-4 (ALS4) is an autosomal dominant disorder characterized by distal muscle weakness and atrophy, normal sensation, and pyramidal signs, with onset of symptoms before the age of 25 years, a slow rate of progression, and a normal life span (summary by Chen et al., 2004). For a phenotypic description and a discussion of genetic heterogeneity of amyotrophic lateral sclerosis, see ALS1 (105400). (602433) (Updated 20-May-2021)

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 16, Juvenile 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 12
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 top 50) (show all 91)
# Related Disease Score Top Affiliating Genes
1 juvenile amyotrophic lateral sclerosis 31.7 SPG11 SETX FUS ALS2
2 spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 30.4 XRN2 SETX RNASEH1 EXOSC9
3 amyotrophic lateral sclerosis 3 30.1 SUGCT ECE1 ALS2
4 muscular atrophy 29.7 VAPB TARDBP SETX IGHMBP2 FUS C9orf72
5 frontotemporal dementia 29.5 TARDBP SOD1 FUS C9orf72 ATXN2
6 spinal muscular atrophy 29.4 VAPB TARDBP SOD1 SETX IGHMBP2 FUS
7 hereditary spastic paraplegia 29.4 SPG11 SETX C9orf72 ATXN2 ALS2
8 progressive muscular atrophy 29.3 VAPB TARDBP SOD1 FUS C9orf72 ATXN2
9 autosomal dominant cerebellar ataxia 29.2 TARDBP SOD1 SETX H2AC18 FUS C9orf72
10 lateral sclerosis 29.0 VAPB TARDBP SPG11 SOD1 SETX FUS
11 motor neuron disease 28.9 VAPB TARDBP SOD1 SETX H2AC18 FUS
12 amyotrophic lateral sclerosis 1 27.8 VAPB TARDBP SUGCT SPG11 SOD1 SETX
13 frontotemporal dementia and/or amyotrophic lateral sclerosis 4 11.4
14 distal hereditary motor neuronopathy type 7 10.3 TARDBP ALS2
15 spinal muscular atrophy with lower extremity predominance 10.3 VAPB SETX IGHMBP2
16 autosomal recessive distal hereditary motor neuronopathy 10.3 SETX IGHMBP2
17 neuronopathy, distal hereditary motor, type viib 10.3 TARDBP ALS2
18 spastic paraplegia 57, autosomal recessive 10.2 SPG11 ALS2
19 x-linked nephrolithiasis type i 10.2 XRN2 EXOSC9
20 ophthalmomyiasis 10.2 TARDBP SOD1
21 frontotemporal dementia and/or amyotrophic lateral sclerosis 2 10.2 FUS C9orf72
22 proximal spinal muscular atrophy 10.2 VAPB SETX
23 amyotrophic lateral sclerosis 19 10.2 TARDBP SOD1 ALS2
24 agraphia 10.2 TARDBP C9orf72
25 frontotemporal dementia and/or amyotrophic lateral sclerosis 7 10.2 TARDBP FUS
26 semantic dementia 10.2 TARDBP C9orf72
27 locked-in syndrome 10.2 TARDBP SOD1 FUS
28 prosopagnosia 10.2 TARDBP C9orf72
29 amyotrophic lateral sclerosis 20 10.2 SOD1 FIG4 ALS2
30 motor peripheral neuropathy 10.2 SPG11 SETX IGHMBP2
31 associative agnosia 10.2 TARDBP FUS C9orf72
32 amyotrophic lateral sclerosis type 22 10.2 TARDBP FUS C9orf72
33 ideomotor apraxia 10.2 TARDBP FUS C9orf72
34 giant axonal neuropathy 2 10.2 TARDBP SOD1 FUS
35 nominal aphasia 10.2 TARDBP FUS C9orf72
36 aphasia 10.2 TARDBP FUS C9orf72
37 pica disease 10.2 TARDBP FUS C9orf72
38 dysgraphia 10.2 TARDBP FUS C9orf72
39 writing disorder 10.2 TARDBP FUS C9orf72
40 frontotemporal dementia and/or amyotrophic lateral sclerosis 3 10.1 TARDBP FUS C9orf72
41 epilepsy, idiopathic generalized 2 10.1 TARDBP H2AC18 C9orf72
42 spastic paraplegia 7, autosomal recessive 10.1 SPG11 SETX
43 ataxia and polyneuropathy, adult-onset 10.1
44 apraxia 10.1
45 oculomotor apraxia 10.1
46 spinocerebellar ataxia type 1 with axonal neuropathy 10.1 SETX H2AC18
47 amyotrophic lateral sclerosis 18 10.1 VAPB SETX FUS FIG4 ALS2
48 amyotrophic lateral sclerosis-parkinsonism/dementia complex 1 10.1 TARDBP SOD1 C9orf72
49 tooth disease 10.1 SPG11 IGHMBP2 H2AC18 FIG4
50 inclusion body myopathy with paget disease of bone and frontotemporal dementia 10.0 TARDBP H2AC18 FUS C9orf72

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:

58 31 (show all 19)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 skeletal muscle atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0003202
2 babinski sign 58 31 frequent (33%) Frequent (79-30%) HP:0003487
3 distal muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0002460
4 gait disturbance 58 31 occasional (7.5%) Occasional (29-5%) HP:0001288
5 pes cavus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001761
6 spastic paraplegia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001258
7 sensory impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0003474
8 clonus 31 occasional (7.5%) HP:0002169
9 hyperreflexia 31 HP:0001347
10 abnormal pyramidal sign 58 Frequent (79-30%)
11 difficulty walking 31 HP:0002355
12 degeneration of anterior horn cells 31 HP:0002398
13 abnormal upper motor neuron morphology 31 HP:0002127
14 diffuse axonal swelling 31 HP:0003405
15 abnormal lower motor neuron morphology 31 HP:0002366
16 amyotrophic lateral sclerosis 31 HP:0007354
17 axonal degeneration 31 HP:0040078
18 peripheral axonal degeneration 31 HP:0000764
19 pallor of dorsal columns of the spinal cord 31 HP:0006825

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
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 (Updated 20-May-2021)

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
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00221-A-2 9.66 SOD1
2 Decreased viability GR00221-A-3 9.66 SOD1
3 Decreased viability GR00221-A-4 9.66 FUS SOD1
4 Decreased viability GR00240-S-1 9.66 PCF11
5 Decreased viability GR00249-S 9.66 ANG ECE1 EXOSC9 P3H3 PCF11 SOD1
6 Decreased viability GR00381-A-1 9.66 ANG ECE1 FIG4 PCF11
7 Decreased viability GR00386-A-1 9.66 P3H3 PCF11 SETX
8 Decreased viability GR00402-S-2 9.66 EXOSC9 PCF11 SETX VAPB

MGI Mouse Phenotypes related to Amyotrophic Lateral Sclerosis 4, Juvenile:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 muscle MP:0005369 9.17 ALS2 ECE1 FIG4 IGHMBP2 SOD1 TARDBP

Drugs & Therapeutics for Amyotrophic Lateral Sclerosis 4, Juvenile

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 An Observational Study to Assess Clinical Manifestations and Biomarkers in Amyotrophic Lateral Sclerosis Type 4 and Other Inherited Neurological Disorders of RNA Processing Recruiting NCT04394871

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

Anatomical Context for Amyotrophic Lateral Sclerosis 4, Juvenile

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

40
Spinal Cord, Skeletal Muscle, Brain, Bone

Publications for Amyotrophic Lateral Sclerosis 4, Juvenile

Articles related to Amyotrophic Lateral Sclerosis 4, Juvenile:

(show all 24)
# Title Authors PMID Year
1
DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). 6 57
15106121 2004
2
Linkage of the gene for an autosomal dominant form of juvenile amyotrophic lateral sclerosis to chromosome 9q34. 57 6
9497266 1998
3
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. 6 61
24244371 2013
4
Senataxin modulates neurite growth through fibroblast growth factor 8 signalling. 61 6
21576111 2011
5
Ataxia with oculomotor apraxia type 2 fibroblasts exhibit increased susceptibility to oxidative DNA damage. 6
24814856 2014
6
A SUMO-dependent interaction between Senataxin and the exosome, disrupted in the neurodegenerative disease AOA2, targets the exosome to sites of transcription-induced DNA damage. 6
24105744 2013
7
SETX mutations are a frequent genetic cause of juvenile and adult onset cerebellar ataxia with neuropathy and elevated serum alpha-fetoprotein. 6
23941260 2013
8
SETX gene mutation in a family diagnosed autosomal dominant proximal spinal muscular atrophy. 6
22088787 2012
9
Mutation in the senataxin gene found in a patient affected by familial ALS with juvenile onset and slow progression. 6
21438761 2011
10
Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients. 6
19696032 2009
11
Ataxia with oculomotor apraxia type 2: a clinical and genetic study of 19 patients. 6
19141356 2009
12
Novel mutations in the senataxin DNA/RNA helicase domain in ataxia with oculomotor apraxia 2. 6
17159128 2006
13
Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2. 6
14770181 2004
14
Autosomal dominant juvenile amyotrophic lateral sclerosis and distal hereditary motor neuronopathy with pyramidal tract signs: synonyms for the same disorder? 57
12023320 2002
15
A gene for autosomal dominant juvenile amyotrophic lateral sclerosis (ALS4) localizes to a 500-kb interval on chromosome 9q34. 57
11085590 2000
16
Autosomal dominant juvenile amyotrophic lateral sclerosis. 57
10430837 1999
17
NERVE CONDUCTION AND OTHER STUDIES IN FAMILIES WITH CHARCOT-MARIE-TOOTH DISEASE. 57
14236005 1964
18
Unusual electrophysiological findings in a Chinese ALS 4 family with SETX-L389S mutation: a three-year follow-up. 61
32997296 2021
19
SETX (senataxin), the helicase mutated in AOA2 and ALS4, functions in autophagy regulation. 61
32686621 2020
20
[A case of motor and sensory polyneuropathy and respiratory failure with novel heterozygous mutation of the senataxin gene]. 61
32536663 2020
21
Tight expression regulation of senataxin, linked to motor neuron disease and ataxia, is required to avert cell-cycle block and nucleolus disassembly. 61
32577562 2020
22
Senataxin mutations elicit motor neuron degeneration phenotypes and yield TDP-43 mislocalization in ALS4 mice and human patients. 61
29725819 2018
23
Senataxin: Genome Guardian at the Interface of Transcription and Neurodegeneration. 61
27771483 2017
24
Human Senataxin Modulates Structural Plasticity of the Neuromuscular Junction in Drosophila through a Neuronally Conserved TGFβ Signalling Pathway. 61
27197982 2016

Variations for Amyotrophic Lateral Sclerosis 4, Juvenile

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

6 (show top 50) (show all 512)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SETX NM_015046.7(SETX):c.1166T>C (p.Leu389Ser) SNV Pathogenic 2289 rs29001584 GRCh37: 9:135205819-135205819
GRCh38: 9:132330432-132330432
2 SETX NM_015046.7(SETX):c.8C>T (p.Thr3Ile) SNV Pathogenic 2290 rs28941475 GRCh37: 9:135224808-135224808
GRCh38: 9:132349421-132349421
3 SETX NM_015046.7(SETX):c.6407G>A (p.Arg2136His) SNV Pathogenic 2291 rs121434378 GRCh37: 9:135158790-135158790
GRCh38: 9:132283403-132283403
4 SETX NM_015046.7(SETX):c.1166T>C (p.Leu389Ser) SNV Pathogenic 2289 rs29001584 GRCh37: 9:135205819-135205819
GRCh38: 9:132330432-132330432
5 SETX NM_015046.7(SETX):c.5264del (p.Thr1755fs) Deletion Pathogenic 572675 rs776632212 GRCh37: 9:135201721-135201721
GRCh38: 9:132326334-132326334
6 SETX NM_015046.7(SETX):c.6996_7002del (p.Asp2332fs) Deletion Pathogenic 802521 rs1362178149 GRCh37: 9:135150741-135150747
GRCh38: 9:132275354-132275360
7 SETX NM_015046.7(SETX):c.4679dup (p.Asn1560fs) Duplication Pathogenic 948110 GRCh37: 9:135202305-135202306
GRCh38: 9:132326918-132326919
8 SETX NM_015046.7(SETX):c.6268C>T (p.Gln2090Ter) SNV Pathogenic 954451 GRCh37: 9:135163679-135163679
GRCh38: 9:132288292-132288292
9 SETX NM_015046.7(SETX):c.2387_2390del (p.Lys796fs) Deletion Pathogenic 959106 GRCh37: 9:135204595-135204598
GRCh38: 9:132329208-132329211
10 SETX NM_015046.7(SETX):c.6935+1G>A SNV Pathogenic 1031858 GRCh37: 9:135152446-135152446
GRCh38: 9:132277059-132277059
11 SETX NM_015046.5(SETX):c.6848_6851delCAGA (p.Thr2283Lysfs) Microsatellite Pathogenic 95668 GRCh37: 9:135152531-135152534
GRCh38: 9:132277144-132277147
12 SETX NM_015046.5(SETX):c.6848_6851delCAGA (p.Thr2283Lysfs) Microsatellite Likely pathogenic 95668 GRCh37: 9:135152531-135152534
GRCh38: 9:132277144-132277147
13 SETX NM_015046.7(SETX):c.6017G>A (p.Cys2006Tyr) SNV Likely pathogenic 802522 rs200154603 GRCh37: 9:135171348-135171348
GRCh38: 9:132295961-132295961
14 SETX NM_015046.7(SETX):c.6843-3_6843-1del Deletion Likely pathogenic 838820 GRCh37: 9:135152540-135152542
GRCh38: 9:132277153-132277155
15 SETX NM_015046.7(SETX):c.4225A>T (p.Asn1409Tyr) SNV Conflicting interpretations of pathogenicity 155745 rs373375060 GRCh37: 9:135202760-135202760
GRCh38: 9:132327373-132327373
16 SETX NM_015046.7(SETX):c.4982C>G (p.Pro1661Arg) SNV Conflicting interpretations of pathogenicity 468516 rs146873848 GRCh37: 9:135202003-135202003
GRCh38: 9:132326616-132326616
17 SETX NM_015046.7(SETX):c.3826C>G (p.Gln1276Glu) SNV Conflicting interpretations of pathogenicity 424692 rs148604312 GRCh37: 9:135203159-135203159
GRCh38: 9:132327772-132327772
18 SETX NM_015046.7(SETX):c.1504C>T (p.Arg502Trp) SNV Uncertain significance 155742 rs534723946 GRCh37: 9:135205481-135205481
GRCh38: 9:132330094-132330094
19 SETX NM_015046.7(SETX):c.2404A>G (p.Ser802Gly) SNV Uncertain significance 536384 rs1400027699 GRCh37: 9:135204581-135204581
GRCh38: 9:132329194-132329194
20 SETX NM_015046.7(SETX):c.2123G>T (p.Ser708Ile) SNV Uncertain significance 536385 rs1554821571 GRCh37: 9:135204862-135204862
GRCh38: 9:132329475-132329475
21 SETX NM_015046.7(SETX):c.1153G>A (p.Glu385Lys) SNV Uncertain significance 536386 rs1554821963 GRCh37: 9:135205832-135205832
GRCh38: 9:132330445-132330445
22 SETX NM_015046.7(SETX):c.3462A>C (p.Glu1154Asp) SNV Uncertain significance 536387 rs1297541939 GRCh37: 9:135203523-135203523
GRCh38: 9:132328136-132328136
23 SETX NM_015046.7(SETX):c.7660T>A (p.Phe2554Ile) SNV Uncertain significance 536388 rs368269464 GRCh37: 9:135140000-135140000
GRCh38: 9:132264613-132264613
24 SETX NM_015046.7(SETX):c.93A>G (p.Gln31=) SNV Uncertain significance 468529 rs201795631 GRCh37: 9:135224723-135224723
GRCh38: 9:132349336-132349336
25 SETX NM_015046.7(SETX):c.2395C>T (p.His799Tyr) SNV Uncertain significance 448313 rs200459144 GRCh37: 9:135204590-135204590
GRCh38: 9:132329203-132329203
26 SETX NM_015046.7(SETX):c.2717C>T (p.Ser906Leu) SNV Uncertain significance 468495 rs148375192 GRCh37: 9:135204268-135204268
GRCh38: 9:132328881-132328881
27 SETX NM_015046.7(SETX):c.4759C>T (p.Pro1587Ser) SNV Uncertain significance 468513 rs916634082 GRCh37: 9:135202226-135202226
GRCh38: 9:132326839-132326839
28 SETX NM_015046.7(SETX):c.4601A>T (p.Asp1534Val) SNV Uncertain significance 468510 rs1554820219 GRCh37: 9:135202384-135202384
GRCh38: 9:132326997-132326997
29 SETX NM_015046.7(SETX):c.7413A>T (p.Arg2471Ser) SNV Uncertain significance 536389 rs1382990384 GRCh37: 9:135140247-135140247
GRCh38: 9:132264860-132264860
30 SETX NM_015046.7(SETX):c.5767A>G (p.Thr1923Ala) SNV Uncertain significance 536390 rs372993859 GRCh37: 9:135173481-135173481
GRCh38: 9:132298094-132298094
31 SETX NM_015046.7(SETX):c.5464A>G (p.Lys1822Glu) SNV Uncertain significance 536391 rs1249423284 GRCh37: 9:135176101-135176101
GRCh38: 9:132300714-132300714
32 SETX NM_015046.7(SETX):c.64G>T (p.Ala22Ser) SNV Uncertain significance 536392 rs756600708 GRCh37: 9:135224752-135224752
GRCh38: 9:132349365-132349365
33 SETX NM_015046.7(SETX):c.3016G>A (p.Gly1006Arg) SNV Uncertain significance 448317 rs141266068 GRCh37: 9:135203969-135203969
GRCh38: 9:132328582-132328582
34 SETX NM_015046.7(SETX):c.3422A>T (p.His1141Leu) SNV Uncertain significance 536393 rs1554820904 GRCh37: 9:135203563-135203563
GRCh38: 9:132328176-132328176
35 SETX NM_015046.7(SETX):c.2749A>C (p.Met917Leu) SNV Uncertain significance 536394 rs761943404 GRCh37: 9:135204236-135204236
GRCh38: 9:132328849-132328849
36 SETX NM_015046.7(SETX):c.5949+5G>A SNV Uncertain significance 488730 rs374656811 GRCh37: 9:135172269-135172269
GRCh38: 9:132296882-132296882
37 SETX NM_015046.7(SETX):c.2755G>C (p.Val919Leu) SNV Uncertain significance 536395 rs561190371 GRCh37: 9:135204230-135204230
GRCh38: 9:132328843-132328843
38 SETX NM_015046.7(SETX):c.3802A>G (p.Ile1268Val) SNV Uncertain significance 566196 rs764516725 GRCh37: 9:135203183-135203183
GRCh38: 9:132327796-132327796
39 SETX NM_015046.7(SETX):c.1391C>T (p.Ser464Leu) SNV Uncertain significance 365372 rs200614765 GRCh37: 9:135205594-135205594
GRCh38: 9:132330207-132330207
40 SETX NM_015046.7(SETX):c.3341T>C (p.Ile1114Thr) SNV Uncertain significance 568024 rs760535401 GRCh37: 9:135203644-135203644
GRCh38: 9:132328257-132328257
41 SETX NM_015046.7(SETX):c.7534C>T (p.Pro2512Ser) SNV Uncertain significance 568527 rs557347174 GRCh37: 9:135140126-135140126
GRCh38: 9:132264739-132264739
42 SETX NM_015046.7(SETX):c.4103G>T (p.Cys1368Phe) SNV Uncertain significance 568959 rs1445388214 GRCh37: 9:135202882-135202882
GRCh38: 9:132327495-132327495
43 SETX NM_015046.7(SETX):c.7660T>C (p.Phe2554Leu) SNV Uncertain significance 568960 rs368269464 GRCh37: 9:135140000-135140000
GRCh38: 9:132264613-132264613
44 SETX NM_015046.7(SETX):c.7204C>G (p.Leu2402Val) SNV Uncertain significance 569576 rs1402767850 GRCh37: 9:135145085-135145085
GRCh38: 9:132269698-132269698
45 SETX NM_015046.7(SETX):c.1204C>T (p.Arg402Cys) SNV Uncertain significance 570064 rs772044862 GRCh37: 9:135205781-135205781
GRCh38: 9:132330394-132330394
46 SETX NM_015046.7(SETX):c.6922A>G (p.Arg2308Gly) SNV Uncertain significance 571061 rs370135596 GRCh37: 9:135152460-135152460
GRCh38: 9:132277073-132277073
47 SETX NM_015046.7(SETX):c.4663C>G (p.Leu1555Val) SNV Uncertain significance 571954 rs558075773 GRCh37: 9:135202322-135202322
GRCh38: 9:132326935-132326935
48 SETX NM_015046.7(SETX):c.4757C>T (p.Pro1586Leu) SNV Uncertain significance 572586 rs1165229035 GRCh37: 9:135202228-135202228
GRCh38: 9:132326841-132326841
49 SETX NM_015046.7(SETX):c.617A>G (p.Glu206Gly) SNV Uncertain significance 365375 rs759880306 GRCh37: 9:135211784-135211784
GRCh38: 9:132336397-132336397
50 SETX NM_015046.7(SETX):c.*988G>A SNV Uncertain significance 365322 rs182693244 GRCh37: 9:135138638-135138638
GRCh38: 9:132263251-132263251

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

72
# 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.Lys2029Glu VAR_071686 rs746525639
5 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

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

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.54 VAPB TARDBP SPG11 SOD1 SETX FUS
2 11.12 TARDBP PCF11 FUS

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 axon GO:0030424 9.35 SPG11 SETX IGHMBP2 C9orf72 ALS2
2 cytoplasmic stress granule GO:0010494 9.33 TARDBP C9orf72 ATXN2
3 growth cone GO:0030426 9.02 SETX IGHMBP2 C9orf72 ANG ALS2

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

# Name GO ID Score Top Affiliating Genes
1 stress granule assembly GO:0034063 9.26 C9orf72 ATXN2
2 nuclear-transcribed mRNA catabolic process GO:0000956 9.16 XRN2 EXOSC9
3 locomotory behavior GO:0007626 9.13 SOD1 FIG4 ALS2
4 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 identical protein binding GO:0042802 9.8 XRN2 TARDBP SOD1 SETX IGHMBP2 FUS
2 nucleic acid binding GO:0003676 9.63 XRN2 TARDBP RNASEH1 IGHMBP2 FUS ANG
3 RNA binding GO:0003723 9.56 XRN2 TARDBP SETX RNASEH1 IGHMBP2 FUS
4 nuclease activity GO:0004518 9.5 XRN2 RNASEH1 ANG
5 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
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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