FTDALS3
MCID: FRN043
MIFTS: 40

Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3 (FTDALS3)

Categories: Bone diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3

MalaCards integrated aliases for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3:

Name: Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3 57 12 72 29 6
Ftdals3 57 12 72
Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis-3 12 15
Dementia, Frontotemporal, and/or Amyotrophic Lateral Sclerosis, Type 3 39

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Miscellaneous:
phenotypic variability
progressive disorder
onset in late adulthood
patients may have either dementia or motor neuron disease or both

Inheritance:
autosomal dominant


HPO:

31
frontotemporal dementia and/or amyotrophic lateral sclerosis 3:
Inheritance autosomal dominant inheritance
Onset and clinical course progressive


Classifications:



Summaries for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3

UniProtKB/Swiss-Prot : 72 Frontotemporal dementia and/or amyotrophic lateral sclerosis 3: A neurodegenerative disorder characterized by frontotemporal dementia and/or amyotrophic lateral sclerosis in affected individuals. There is high intrafamilial variation. Frontotemporal dementia is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. Some FTDALS3 patients may also develop Paget disease of bone.

MalaCards based summary : Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3, also known as ftdals3, is related to amyotrophic lateral sclerosis 3 and neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset. An important gene associated with Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3 is SQSTM1 (Sequestosome 1), and among its related pathways/superpathways is 3-phosphoinositide degradation. Affiliated tissues include spinal cord, temporal lobe and bone, and related phenotypes are hyperreflexia and dysarthria

Disease Ontology : 12 An amyotrophic lateral sclerosis that has material basis in mutation in the SQSTM1 gene on chromosome 5q35.

OMIM® : 57 Frontotemporal dementia and/or amyotrophic lateral sclerosis-3 is an autosomal dominant neurodegenerative disorder characterized by adult or late adult onset of cognitive impairment, behavioral abnormalities, and speech apraxia and/or upper and lower motor neuron signs. Some patients may also develop Paget disease of bone. The phenotype is highly variable, even within families (summary by Rea et al., 2014). For a discussion of genetic heterogeneity of FTDALS, see FTDALS1 (105550). (616437) (Updated 05-Apr-2021)

Related Diseases for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3

Diseases in the Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 1 family:

Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 7 Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6
Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 2 Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3
Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4 Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 8
Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 5

Diseases related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 66)
# Related Disease Score Top Affiliating Genes
1 amyotrophic lateral sclerosis 3 10.3 SQSTM1 MRNIP
2 neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset 10.3 SQSTM1 MRNIP
3 paget disease of bone 3 10.3 SQSTM1 MRNIP
4 amyotrophic lateral sclerosis 19 10.2 TARDBP PRPH
5 amyotrophic lateral sclerosis type 15 10.1 PRPH C9orf72
6 nonaka myopathy 10.1 TARDBP SQSTM1
7 gerstmann-straussler disease 10.1 PRPH MGRN1
8 agraphia 10.1 TARDBP C9orf72
9 semantic dementia 10.1 TARDBP C9orf72
10 prosopagnosia 10.1 TARDBP C9orf72
11 amyotrophic lateral sclerosis 18 10.1 PRPH FUS
12 amyotrophic lateral sclerosis 21 10.0 PRPH FUS
13 epilepsy, idiopathic generalized 2 10.0 TARDBP C9orf72
14 amyotrophic lateral sclerosis 16, juvenile 10.0 PRPH FUS
15 locked-in syndrome 10.0 TARDBP FUS
16 mutism 10.0 TARDBP C9orf72
17 frontotemporal dementia and/or amyotrophic lateral sclerosis 7 10.0 TARDBP FUS
18 perry syndrome 10.0 TARDBP C9orf72
19 giant axonal neuropathy 2 10.0 TARDBP FUS
20 amyotrophic lateral sclerosis-parkinsonism/dementia complex 1 10.0 TARDBP C9orf72
21 extraosseous chondrosarcoma 10.0 TAF15 FUS
22 amyotrophic lateral sclerosis type 12 9.9 TARDBP FUS
23 progressive bulbar palsy 9.9 FUS C9orf72
24 associative agnosia 9.8 TARDBP FUS C9orf72
25 ideomotor apraxia 9.8 TARDBP FUS C9orf72
26 nominal aphasia 9.8 TARDBP FUS C9orf72
27 liposarcoma 9.8 TARDBP TAF15 FUS
28 aphasia 9.8 TARDBP FUS C9orf72
29 charcot-marie-tooth disease, type 4j 9.8 SYNJ2 INPP5B
30 pica disease 9.8 TARDBP FUS C9orf72
31 dysgraphia 9.8 TARDBP FUS C9orf72
32 writing disorder 9.8 TARDBP FUS C9orf72
33 alzheimer disease 7 9.8 TARDBP FUS C9orf72
34 amyotrophic lateral sclerosis 10 with or without frontotemporal dementia 9.8 TARDBP FUS C9orf72
35 progressive muscular atrophy 9.8 TARDBP FUS C9orf72
36 amyotrophic lateral sclerosis 8 9.8 TARDBP FUS C9orf72
37 amyotrophic lateral sclerosis 4, juvenile 9.7 TARDBP FUS C9orf72
38 amyotrophic lateral sclerosis type 6 9.7 TARDBP FUS C9orf72
39 dermatopathia pigmentosa reticularis 9.7 TARDBP FUS C9orf72
40 spinocerebellar ataxia 2 9.7 TARDBP FUS C9orf72
41 fragile x-associated tremor/ataxia syndrome 9.7 FUS C9orf72
42 spinal and bulbar muscular atrophy, x-linked 1 9.7 TARDBP FUS C9orf72
43 supranuclear palsy, progressive, 1 9.7 TARDBP FUS C9orf72
44 speech and communication disorders 9.7 TARDBP FUS C9orf72
45 movement disease 9.7 TARDBP FUS C9orf72
46 lowe oculocerebrorenal syndrome 9.7 SYNJ2 INPP5B
47 autosomal dominant cerebellar ataxia 9.6 TARDBP FUS C9orf72
48 frontotemporal dementia 9.6 TARDBP SQSTM1 FUS C9orf72
49 dementia 9.6 TARDBP SQSTM1 FUS C9orf72
50 spinal muscular atrophy, distal, autosomal recessive, 4 9.6 TARDBP SQSTM1 FUS C9orf72

Graphical network of the top 20 diseases related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3:



Diseases related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3

Symptoms & Phenotypes for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3

Human phenotypes related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3:

31 (show all 16)
# Description HPO Frequency HPO Source Accession
1 hyperreflexia 31 HP:0001347
2 dysarthria 31 HP:0001260
3 dysphagia 31 HP:0002015
4 skeletal muscle atrophy 31 HP:0003202
5 cerebral cortical atrophy 31 HP:0002120
6 fasciculations 31 HP:0002380
7 hyporeflexia 31 HP:0001265
8 disinhibition 31 HP:0000734
9 apathy 31 HP:0000741
10 personality changes 31 HP:0000751
11 mutism 31 HP:0002300
12 language impairment 31 HP:0002463
13 bulbar palsy 31 HP:0001283
14 frontotemporal dementia 31 HP:0002145
15 abnormal lower motor neuron morphology 31 HP:0002366
16 amyotrophic lateral sclerosis 31 HP:0007354

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
hyperreflexia
dysarthria
hyporeflexia
mutism
language impairment
more
Muscle Soft Tissue:
muscle weakness
fasciculations
amyotrophy
fibrillations

Respiratory:
bulbar weakness

Skeletal:
paget disease of bone (in some patients)

Abdomen Gastrointestinal:
dysphagia
swallowing difficulties

Neurologic Behavioral Psychiatric Manifestations:
disinhibition
apathy
personality changes
abnormal behavior
executive dysfunction

Head And Neck Face:
orofacial apraxia

Clinical features from OMIM®:

616437 (Updated 05-Apr-2021)

Drugs & Therapeutics for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3

Search Clinical Trials , NIH Clinical Center for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3

Genetic Tests for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3

Genetic tests related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3:

# Genetic test Affiliating Genes
1 Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3 29 SQSTM1

Anatomical Context for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3

MalaCards organs/tissues related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3:

40
Spinal Cord, Temporal Lobe, Bone, Skeletal Muscle

Publications for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3

Articles related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3:

(show all 18)
# Title Authors PMID Year
1
A phenotype of atypical apraxia of speech in a family carrying SQSTM1 mutation. 57 6
25114083 2015
2
SQSTM1 mutations in French patients with frontotemporal dementia or frontotemporal dementia with amyotrophic lateral sclerosis. 57 6
24042580 2013
3
SQSTM1 mutations in familial and sporadic amyotrophic lateral sclerosis. 57 6
22084127 2011
4
Detection of SQSTM1/P392L post-zygotic mutations in Paget's disease of bone. 6
25241215 2015
5
Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration. 6
24899140 2014
6
SQSTM1 mutations--bridging Paget disease of bone and ALS/FTLD. 57
24486447 2014
7
Sequestosome-1 (SQSTM1) sequence variants in ALS cases in the UK: prevalence and coexistence of SQSTM1 mutations in ALS kindred with PDB. 6
23942205 2014
8
Mutations in SQSTM1 encoding p62 in amyotrophic lateral sclerosis: genetics and neuropathology. 6
23417734 2013
9
Mutations in the gene encoding p62 in Japanese patients with amyotrophic lateral sclerosis. 57
23303844 2013
10
SQSTM1 mutations in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. 57
22972638 2012
11
A point mutation in the ubiquitin-associated domain of SQSMT1 is sufficient to cause a Paget's disease-like disorder in mice. 6
21515589 2011
12
Contributions of the measles virus nucleocapsid gene and the SQSTM1/p62(P392L) mutation to Paget's disease. 6
21195346 2011
13
The p62 P392L mutation linked to Paget's disease induces activation of human osteoclasts. 6
19589897 2009
14
A SQSTM1/p62 mutation linked to Paget's disease increases the osteoclastogenic potential of the bone microenvironment. 6
18765443 2008
15
A novel mutation (K378X) in the sequestosome 1 gene associated with increased NF-kappaB signaling and Paget's disease of bone with a severe phenotype. 6
16813535 2006
16
Loss of ubiquitin-binding associated with Paget's disease of bone p62 (SQSTM1) mutations. 6
15765181 2005
17
Structural and functional studies of mutations affecting the UBA domain of SQSTM1 (p62) which cause Paget's disease of bone. 6
15493999 2004
18
Recurrent mutation of the gene encoding sequestosome 1 (SQSTM1/p62) in Paget disease of bone. 6
11992264 2002

Variations for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3

ClinVar genetic disease variations for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SQSTM1 NM_003900.5(SQSTM1):c.98C>T (p.Ala33Val) SNV Pathogenic 253029 rs200396166 GRCh37: 5:179248034-179248034
GRCh38: 5:179821034-179821034
2 SQSTM1 NM_003900.5(SQSTM1):c.1175C>T (p.Pro392Leu) SNV Pathogenic 8108 rs104893941 GRCh37: 5:179263445-179263445
GRCh38: 5:179836445-179836445
3 SQSTM1 NM_003900.5(SQSTM1):c.1160C>T (p.Pro387Leu) SNV Pathogenic 202211 rs776749939 GRCh37: 5:179260777-179260777
GRCh38: 5:179833777-179833777
4 MRNIP , SQSTM1 NM_003900.5(SQSTM1):c.*1022G>A SNV Pathogenic 1031365 GRCh37: 5:179264615-179264615
GRCh38: 5:179837615-179837615
5 MRNIP , SQSTM1 NM_003900.5(SQSTM1):c.*1033dup Duplication Pathogenic 1031366 GRCh37: 5:179264621-179264622
GRCh38: 5:179837621-179837622
6 SQSTM1 NM_003900.5(SQSTM1):c.1175C>T (p.Pro392Leu) SNV Likely pathogenic 8108 rs104893941 GRCh37: 5:179263445-179263445
GRCh38: 5:179836445-179836445
7 SQSTM1 NM_003900.5(SQSTM1):c.1128del (p.Gly376_Leu377insTer) Deletion Likely pathogenic 976342 GRCh37: 5:179260743-179260743
GRCh38: 5:179833743-179833743
8 SQSTM1 NM_003900.5(SQSTM1):c.711_713GAA[1] (p.Lys238del) Microsatellite Uncertain significance 202213 rs796052214 GRCh37: 5:179252183-179252185
GRCh38: 5:179825183-179825185
9 SQSTM1 NM_003900.5(SQSTM1):c.-27C>T SNV Uncertain significance 975908 GRCh37: 5:179247910-179247910
GRCh38: 5:179820910-179820910

UniProtKB/Swiss-Prot genetic disease variations for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3:

72 (show all 23)
# Symbol AA change Variation ID SNP ID
1 SQSTM1 p.Pro387Leu VAR_023592 rs776749939
2 SQSTM1 p.Pro392Leu VAR_023593 rs104893941
3 SQSTM1 p.Gly411Ser VAR_023597 rs143511494
4 SQSTM1 p.Gly425Arg VAR_023598 rs757212984
5 SQSTM1 p.Ala16Val VAR_073899 rs155416229
6 SQSTM1 p.Ala33Val VAR_073901 rs200396166
7 SQSTM1 p.Asp80Glu VAR_073902 rs148366738
8 SQSTM1 p.Val90Met VAR_073903 rs181263868
9 SQSTM1 p.Arg107Trp VAR_073906 rs771903158
10 SQSTM1 p.Asp129Asn VAR_073912 rs753212399
11 SQSTM1 p.Val153Ile VAR_073914 rs145056421
12 SQSTM1 p.Arg212Cys VAR_073916 rs201263163
13 SQSTM1 p.Gly219Val VAR_073918
14 SQSTM1 p.Ser226Pro VAR_073919 rs765200636
15 SQSTM1 p.Pro228Leu VAR_073920 rs151191977
16 SQSTM1 p.Pro232Thr VAR_073921 rs122574651
17 SQSTM1 p.Asp258Asn VAR_073923 rs774986849
18 SQSTM1 p.Ser318Pro VAR_073927
19 SQSTM1 p.Asp329Gly VAR_073930 rs148294622
20 SQSTM1 p.Pro348Leu VAR_073932 rs772889843
21 SQSTM1 p.Ser370Pro VAR_073934 rs143956614
22 SQSTM1 p.Ala381Val VAR_073935 rs772122047
23 SQSTM1 p.Thr430Pro VAR_073936 rs770118706

Expression for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3

Search GEO for disease gene expression data for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3.

Pathways for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3

Pathways related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 9.92 SYNJ2 INPP5B

GO Terms for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3

Cellular components related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.65 TARDBP TAF15 SYNJ2 SQSTM1 PRPH MGRN1
2 endosome GO:0005768 9.46 SQSTM1 MGRN1 INPP5B C9orf72
3 perikaryon GO:0043204 8.8 PRPH FUS C9orf72

Biological processes related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 gene expression GO:0010467 9.32 TARDBP FUS
2 phosphatidylinositol dephosphorylation GO:0046856 9.26 SYNJ2 INPP5B
3 mRNA stabilization GO:0048255 9.16 TAF15 FUS
4 inositol phosphate dephosphorylation GO:0046855 8.96 SYNJ2 INPP5B
5 positive regulation of double-strand break repair via homologous recombination GO:1905168 8.62 MRNIP FUS

Molecular functions related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ionotropic glutamate receptor binding GO:0035255 8.96 SQSTM1 FUS
2 phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity GO:0004439 8.62 SYNJ2 INPP5B

Sources for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3

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 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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