FTDALS4
MCID: FRN045
MIFTS: 36

Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4 (FTDALS4)

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

Aliases & Classifications for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4

MalaCards integrated aliases for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4:

Name: Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4 57 12 72 29 6
Ftdals4 57 12 72
Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis-4 12 15
Dementia, Frontotemporal, and/or Amyotrophic Lateral Sclerosis, Type 4 39

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Miscellaneous:
adult onset
phenotypic variability
progressive disorder

Inheritance:
autosomal dominant


HPO:

31
frontotemporal dementia and/or amyotrophic lateral sclerosis 4:
Inheritance autosomal dominant inheritance
Onset and clinical course progressive adult onset


Classifications:



Summaries for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4

UniProtKB/Swiss-Prot : 72 Frontotemporal dementia and/or amyotrophic lateral sclerosis 4: 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.

MalaCards based summary : Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4, also known as ftdals4, is related to gerstmann-straussler disease and neuronopathy, distal hereditary motor, type viib. An important gene associated with Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4 is TBK1 (TANK Binding Kinase 1), and among its related pathways/superpathways are Pathways of neurodegeneration - multiple diseases and Golgi-to-ER retrograde transport. Affiliated tissues include spinal cord, temporal lobe and skeletal muscle, and related phenotypes are hyperreflexia and dysarthria

Disease Ontology : 12 An amyotrophic lateral sclerosis that has material basis in mutation in the TBK1 gene on chromosome 12q14.

OMIM® : 57 Frontotemporal dementia and/or amyotrophic lateral sclerosis-4 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. The phenotype is highly variable (summary by Freischmidt et al., 2015). For a discussion of genetic heterogeneity of FTDALS, see FTDALS1 (105550). (616439) (Updated 05-Apr-2021)

Related Diseases for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4

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 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 14)
# Related Disease Score Top Affiliating Genes
1 gerstmann-straussler disease 9.9 PRPH MGRN1
2 neuronopathy, distal hereditary motor, type viib 9.8 TARDBP KIF5A
3 alzheimer disease 7 9.8 TBK1 TARDBP
4 amyotrophic lateral sclerosis 19 9.8 TARDBP PRPH
5 frontotemporal dementia 9.7 TBK1 TARDBP KIF5A
6 aphasia 9.7 TBK1 TARDBP
7 multisystem proteinopathy 9.7 TARDBP TAF15
8 frontotemporal dementia and/or amyotrophic lateral sclerosis 1 9.6 TBK1 TARDBP KIF5A
9 liposarcoma 9.5 TARDBP TAF15
10 lateral sclerosis 9.4 TBK1 TARDBP PRPH KIF5A
11 frontotemporal dementia and/or amyotrophic lateral sclerosis 2 9.4 VPS54 PRPH MGRN1 BNIP1
12 amyotrophic lateral sclerosis type 22 9.3 VPS54 TARDBP PRPH MGRN1
13 amyotrophic lateral sclerosis 1 8.8 VPS54 TBK1 TARDBP TAF15 PRPH MGRN1
14 frontotemporal dementia and/or amyotrophic lateral sclerosis 3 8.7 VPS54 TARDBP TAF15 PRPH MGRN1 BNIP1

Graphical network of the top 20 diseases related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4:



Diseases related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4

Symptoms & Phenotypes for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4

Human phenotypes related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4:

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

Abdomen Gastrointestinal:
dysphagia
swallowing difficulties

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

Clinical features from OMIM®:

616439 (Updated 05-Apr-2021)

Drugs & Therapeutics for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4

Search Clinical Trials , NIH Clinical Center for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4

Genetic Tests for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4

Genetic tests related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4:

# Genetic test Affiliating Genes
1 Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4 29 TBK1

Anatomical Context for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4

MalaCards organs/tissues related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4:

40
Spinal Cord, Temporal Lobe, Skeletal Muscle

Publications for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4

Articles related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4:

# Title Authors PMID Year
1
Whole-genome sequencing reveals important role for TBK1 and OPTN mutations in frontotemporal lobar degeneration without motor neuron disease. 6 57
25943890 2015
2
Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia. 57 6
25803835 2015
3
Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. 57 6
25700176 2015
4
Loss of TBK1 is a frequent cause of frontotemporal dementia in a Belgian cohort. 6
26581300 2015
5
TBK1 mutation frequencies in French frontotemporal dementia and amyotrophic lateral sclerosis cohorts. 6
26476236 2015

Variations for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4

ClinVar genetic disease variations for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4:

6 (show top 50) (show all 71)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TBK1 NM_013254.4(TBK1):c.2138+2T>C SNV Pathogenic 203437 rs876657406 GRCh37: 12:64891821-64891821
GRCh38: 12:64498041-64498041
2 TBK1 NM_013254.4(TBK1):c.958del (p.Thr320fs) Deletion Pathogenic 203438 rs755950225 GRCh37: 12:64875767-64875767
GRCh38: 12:64481987-64481987
3 TBK1 NM_013254.4(TBK1):c.1340+1G>A SNV Pathogenic 203439 rs767898276 GRCh37: 12:64879798-64879798
GRCh38: 12:64486018-64486018
4 TBK1 NM_013254.4(TBK1):c.2086G>A (p.Glu696Lys) SNV Pathogenic 203440 rs748112833 GRCh37: 12:64891767-64891767
GRCh38: 12:64497987-64497987
5 TBK1 NM_013254.4(TBK1):c.1201A>G (p.Lys401Glu) SNV Pathogenic 203441 rs756751089 GRCh37: 12:64879246-64879246
GRCh38: 12:64485466-64485466
6 TBK1 NM_013254.4(TBK1):c.1345_1348TTAA[1] (p.Ile450fs) Microsatellite Pathogenic 203435 rs876657404 GRCh37: 12:64882269-64882272
GRCh38: 12:64488489-64488492
7 TBK1 NM_013254.4(TBK1):c.1387_1388del (p.Glu463fs) Deletion Pathogenic 542552 rs1555204731 GRCh37: 12:64882312-64882313
GRCh38: 12:64488532-64488533
8 TBK1 NM_013254.4(TBK1):c.421dup (p.Ile141fs) Duplication Pathogenic 580261 rs1565814492 GRCh37: 12:64860742-64860743
GRCh38: 12:64466962-64466963
9 TBK1 NM_013254.4(TBK1):c.922C>T (p.Arg308Ter) SNV Pathogenic 873222 GRCh37: 12:64875731-64875731
GRCh38: 12:64481951-64481951
10 TBK1 NM_013254.4(TBK1):c.86dup (p.Lys30fs) Duplication Pathogenic 807704 rs1592350883 GRCh37: 12:64849734-64849735
GRCh38: 12:64455954-64455955
11 TBK1 NM_013254.4(TBK1):c.87G>A (p.Lys29=) SNV Pathogenic 807705 rs1592350887 GRCh37: 12:64849737-64849737
GRCh38: 12:64455957-64455957
12 TBK1 NM_013254.4(TBK1):c.427C>T (p.Arg143Cys) SNV Pathogenic 807706 rs1027249002 GRCh37: 12:64860749-64860749
GRCh38: 12:64466969-64466969
13 TBK1 NM_013254.4(TBK1):c.992+1G>A SNV Pathogenic 807707 rs1341055534 GRCh37: 12:64875802-64875802
GRCh38: 12:64482022-64482022
14 TBK1 GRCh37/hg19 12q14.2(chr12:64868010-64895161) copy number loss Pathogenic 813327 GRCh37: 12:64868010-64895161
GRCh38:
15 TBK1 NM_013254.4(TBK1):c.1318C>T (p.Arg440Ter) SNV Pathogenic 997032 rs142030898 GRCh37: 12:64879775-64879775
GRCh38: 12:64485995-64485995
16 TBK1 NM_013254.4(TBK1):c.1922_1924AAG[2] (p.Glu643del) Microsatellite Pathogenic 807508 rs1402092579 GRCh37: 12:64891001-64891003
GRCh38: 12:64497221-64497223
17 TBK1 NM_013254.4(TBK1):c.1153G>T (p.Glu385Ter) SNV Likely pathogenic 1027795 GRCh37: 12:64878243-64878243
GRCh38: 12:64484463-64484463
18 KIF5A NM_004984.4(KIF5A):c.3005A>G (p.Asp1002Gly) SNV Likely pathogenic 873195 GRCh37: 12:57976397-57976397
GRCh38: 12:57582614-57582614
19 TBK1 NM_013254.4(TBK1):c.701+1G>A SNV Likely pathogenic 643946 rs1592362719 GRCh37: 12:64868171-64868171
GRCh38: 12:64474391-64474391
20 TBK1 NM_013254.4(TBK1):c.1434_1435TG[1] (p.Val479fs) Microsatellite Likely pathogenic 203436 rs876657405 GRCh37: 12:64882360-64882361
GRCh38: 12:64488580-64488581
21 TBK1 NM_013254.4(TBK1):c.40A>G (p.Ile14Val) SNV Uncertain significance 475939 rs781325780 GRCh37: 12:64849690-64849690
GRCh38: 12:64455910-64455910
22 TBK1 NM_013254.4(TBK1):c.992C>T (p.Thr331Ile) SNV Uncertain significance 475942 rs200758840 GRCh37: 12:64875801-64875801
GRCh38: 12:64482021-64482021
23 TBK1 NM_013254.4(TBK1):c.1412G>C (p.Cys471Ser) SNV Uncertain significance 542551 rs369875862 GRCh37: 12:64882338-64882338
GRCh38: 12:64488558-64488558
24 TBK1 NM_013254.4(TBK1):c.1148G>T (p.Ser383Ile) SNV Uncertain significance 645888 rs1592369002 GRCh37: 12:64878238-64878238
GRCh38: 12:64484458-64484458
25 TBK1 NM_013254.4(TBK1):c.1072C>T (p.Arg358Cys) SNV Uncertain significance 654729 rs780192375 GRCh37: 12:64878162-64878162
GRCh38: 12:64484382-64484382
26 TBK1 NM_013254.4(TBK1):c.1505A>G (p.His502Arg) SNV Uncertain significance 655436 rs1206925876 GRCh37: 12:64883883-64883883
GRCh38: 12:64490103-64490103
27 TBK1 NM_013254.4(TBK1):c.802A>G (p.Ser268Gly) SNV Uncertain significance 664607 rs746971642 GRCh37: 12:64873892-64873892
GRCh38: 12:64480112-64480112
28 TBK1 NM_013254.4(TBK1):c.230_232CAA[2] (p.Thr79del) Microsatellite Uncertain significance 565435 rs748007618 GRCh37: 12:64858114-64858116
GRCh38: 12:64464334-64464336
29 TBK1 NM_013254.4(TBK1):c.1359T>G (p.Asp453Glu) SNV Uncertain significance 568127 rs1565821771 GRCh37: 12:64882285-64882285
GRCh38: 12:64488505-64488505
30 TBK1 NM_013254.4(TBK1):c.1116A>G (p.Lys372=) SNV Uncertain significance 571522 rs775134475 GRCh37: 12:64878206-64878206
GRCh38: 12:64484426-64484426
31 TBK1 NM_013254.4(TBK1):c.2177T>C (p.Val726Ala) SNV Uncertain significance 573808 rs765585935 GRCh37: 12:64895148-64895148
GRCh38: 12:64501368-64501368
32 TBK1 NM_013254.4(TBK1):c.1603G>A (p.Ala535Thr) SNV Uncertain significance 575829 rs199905735 GRCh37: 12:64889344-64889344
GRCh38: 12:64495564-64495564
33 TBK1 NM_013254.4(TBK1):c.1792A>G (p.Met598Val) SNV Uncertain significance 516884 rs899858451 GRCh37: 12:64890760-64890760
GRCh38: 12:64496980-64496980
34 TBK1 NM_013254.4(TBK1):c.1957G>C (p.Glu653Gln) SNV Uncertain significance 580527 rs144370662 GRCh37: 12:64891037-64891037
GRCh38: 12:64497257-64497257
35 TBK1 NM_013254.4(TBK1):c.2080_2082del (p.Lys694del) Deletion Uncertain significance 935520 GRCh37: 12:64891761-64891763
GRCh38: 12:64497981-64497983
36 TBK1 NM_013254.4(TBK1):c.1619A>T (p.Glu540Val) SNV Uncertain significance 937635 GRCh37: 12:64889360-64889360
GRCh38: 12:64495580-64495580
37 TBK1 NM_013254.4(TBK1):c.813-3T>C SNV Uncertain significance 961128 GRCh37: 12:64875619-64875619
GRCh38: 12:64481839-64481839
38 TBK1 NM_013254.4(TBK1):c.1179A>G (p.Ile393Met) SNV Uncertain significance 964860 GRCh37: 12:64878269-64878269
GRCh38: 12:64484489-64484489
39 TBK1 NM_013254.4(TBK1):c.1739A>G (p.Glu580Gly) SNV Uncertain significance 976241 GRCh37: 12:64890165-64890165
GRCh38: 12:64496385-64496385
40 TBK1 NM_013254.4(TBK1):c.683G>A (p.Arg228His) SNV Uncertain significance 848091 GRCh37: 12:64868152-64868152
GRCh38: 12:64474372-64474372
41 TBK1 NM_013254.4(TBK1):c.1622G>A (p.Gly541Asp) SNV Uncertain significance 852130 GRCh37: 12:64889363-64889363
GRCh38: 12:64495583-64495583
42 TBK1 NM_013254.4(TBK1):c.1073G>A (p.Arg358His) SNV Uncertain significance 853808 GRCh37: 12:64878163-64878163
GRCh38: 12:64484383-64484383
43 TBK1 NM_013254.4(TBK1):c.1659A>C (p.Gln553His) SNV Uncertain significance 855734 GRCh37: 12:64889494-64889494
GRCh38: 12:64495714-64495714
44 TBK1 NM_013254.4(TBK1):c.1588G>A (p.Gly530Arg) SNV Uncertain significance 1027796 GRCh37: 12:64889329-64889329
GRCh38: 12:64495549-64495549
45 TBK1 NM_013254.4(TBK1):c.1180T>G (p.Tyr394Asp) SNV Uncertain significance 1043369 GRCh37: 12:64878270-64878270
GRCh38: 12:64484490-64484490
46 TBK1 NM_013254.4(TBK1):c.1261G>A (p.Val421Ile) SNV Uncertain significance 1004314 GRCh37: 12:64879718-64879718
GRCh38: 12:64485938-64485938
47 TBK1 NM_013254.4(TBK1):c.1718G>A (p.Arg573His) SNV Uncertain significance 475936 rs186475789 GRCh37: 12:64889553-64889553
GRCh38: 12:64495773-64495773
48 TBK1 NM_013254.4(TBK1):c.871A>G (p.Lys291Glu) SNV Uncertain significance 425012 rs34774243 GRCh37: 12:64875680-64875680
GRCh38: 12:64481900-64481900
49 TBK1 NM_013254.4(TBK1):c.1952C>A (p.Thr651Asn) SNV Uncertain significance 647255 rs1592376939 GRCh37: 12:64891032-64891032
GRCh38: 12:64497252-64497252
50 TBK1 NM_013254.4(TBK1):c.1887G>C (p.Gln629His) SNV Uncertain significance 968673 GRCh37: 12:64890967-64890967
GRCh38: 12:64497187-64497187

UniProtKB/Swiss-Prot genetic disease variations for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4:

72
# Symbol AA change Variation ID SNP ID
1 TBK1 p.Arg47His VAR_073938
2 TBK1 p.Tyr105Cys VAR_073939 rs136666878
3 TBK1 p.Ile305Thr VAR_073940 rs770942184
4 TBK1 p.Arg308Gln VAR_073941
5 TBK1 p.Arg357Gln VAR_073942 rs758357594
6 TBK1 p.Lys401Glu VAR_073943 rs756751089
7 TBK1 p.Met559Arg VAR_073944
8 TBK1 p.Ala571Val VAR_073945 rs765035140
9 TBK1 p.Met598Val VAR_073946 rs899858451
10 TBK1 p.Glu696Lys VAR_073948 rs748112833

Expression for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4

Search GEO for disease gene expression data for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4.

Pathways for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4

Pathways related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.64 TBK1 TARDBP PRPH KIF5A
2
Show member pathways
11.42 VPS54 KIF5A BNIP1
3
Show member pathways
10.99 PRPH KIF5A

GO Terms for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4

Cellular components related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.17 TBK1 TARDBP TAF15 PRPH MGRN1 KIF5A

Biological processes related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 retrograde vesicle-mediated transport, Golgi to ER GO:0006890 8.62 KIF5A BNIP1

Sources for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4

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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