MCID: FRN045
MIFTS: 23

Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4

Categories: Genetic diseases, Neuronal diseases, Mental 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 75 29 6
Ftdals4 57 12 75
Dementia, Frontotemporal, and/or Amyotrophic Lateral Sclerosis, Type 4 40

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
adult onset
progressive disorder
phenotypic variability


HPO:

32
frontotemporal dementia and/or amyotrophic lateral sclerosis 4:
Onset and clinical course adult onset phenotypic variability progressive
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4

UniProtKB/Swiss-Prot : 75 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, is also known as ftdals4. An important gene associated with Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4 is TBK1 (TANK Binding Kinase 1). Affiliated tissues include brain, spinal cord and temporal lobe, and related phenotypes are dysarthria and hyperreflexia

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)

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

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

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

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
dysarthria
hyperreflexia
amyotrophic lateral sclerosis
hyporeflexia
language impairment
more
Abdomen Gastrointestinal:
dysphagia
swallowing difficulties

Respiratory:
bulbar weakness

Muscle Soft Tissue:
muscle weakness
fasciculations
amyotrophy
fibrillations

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


Clinical features from OMIM:

616439

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

32 (show all 16)
# Description HPO Frequency HPO Source Accession
1 dysarthria 32 HP:0001260
2 hyperreflexia 32 HP:0001347
3 dysphagia 32 HP:0002015
4 skeletal muscle atrophy 32 HP:0003202
5 cerebral cortical atrophy 32 HP:0002120
6 amyotrophic lateral sclerosis 32 HP:0007354
7 fasciculations 32 HP:0002380
8 hyporeflexia 32 HP:0001265
9 language impairment 32 HP:0002463
10 disinhibition 32 HP:0000734
11 apathy 32 HP:0000741
12 personality changes 32 HP:0000751
13 bulbar palsy 32 HP:0001283
14 frontotemporal dementia 32 HP:0002145
15 mutism 32 HP:0002300
16 abnormal lower motor neuron morphology 32 HP:0002366

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:

41
Brain, Spinal Cord, Temporal Lobe, Skeletal Muscle

Publications for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4

Variations for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4

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

75
# Symbol AA change Variation ID SNP ID
1 TBK1 p.Arg47His VAR_073938
2 TBK1 p.Tyr105Cys VAR_073939
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

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

6
(show top 50) (show all 52)
# Gene Variation Type Significance SNP ID Assembly Location
1 TBK1 NM_013254.3(TBK1): c.1349_1352delTTAA (p.Ile450Lysfs) deletion Pathogenic rs876657404 GRCh37 Chromosome 12, 64882275: 64882278
2 TBK1 NM_013254.3(TBK1): c.1349_1352delTTAA (p.Ile450Lysfs) deletion Pathogenic rs876657404 GRCh38 Chromosome 12, 64488495: 64488498
3 TBK1 NM_013254.3(TBK1): c.1436_1437delTG (p.Val479Glufs) deletion Pathogenic rs876657405 GRCh38 Chromosome 12, 64488582: 64488583
4 TBK1 NM_013254.3(TBK1): c.1436_1437delTG (p.Val479Glufs) deletion Pathogenic rs876657405 GRCh37 Chromosome 12, 64882362: 64882363
5 TBK1 NM_013254.3(TBK1): c.2138+2T> C single nucleotide variant Pathogenic rs876657406 GRCh37 Chromosome 12, 64891821: 64891821
6 TBK1 NM_013254.3(TBK1): c.2138+2T> C single nucleotide variant Pathogenic rs876657406 GRCh38 Chromosome 12, 64498041: 64498041
7 TBK1 NM_013254.3(TBK1): c.958delA (p.Thr320Glnfs) deletion Pathogenic rs755950225 GRCh37 Chromosome 12, 64875767: 64875767
8 TBK1 NM_013254.3(TBK1): c.958delA (p.Thr320Glnfs) deletion Pathogenic rs755950225 GRCh38 Chromosome 12, 64481987: 64481987
9 TBK1 NM_013254.3(TBK1): c.1340+1G> A single nucleotide variant Pathogenic rs767898276 GRCh37 Chromosome 12, 64879798: 64879798
10 TBK1 NM_013254.3(TBK1): c.1340+1G> A single nucleotide variant Pathogenic rs767898276 GRCh38 Chromosome 12, 64486018: 64486018
11 TBK1 NM_013254.3(TBK1): c.2086G> A (p.Glu696Lys) single nucleotide variant Pathogenic rs748112833 GRCh37 Chromosome 12, 64891767: 64891767
12 TBK1 NM_013254.3(TBK1): c.2086G> A (p.Glu696Lys) single nucleotide variant Pathogenic rs748112833 GRCh38 Chromosome 12, 64497987: 64497987
13 TBK1 NM_013254.3(TBK1): c.1201A> G (p.Lys401Glu) single nucleotide variant Pathogenic rs756751089 GRCh37 Chromosome 12, 64879246: 64879246
14 TBK1 NM_013254.3(TBK1): c.1201A> G (p.Lys401Glu) single nucleotide variant Pathogenic rs756751089 GRCh38 Chromosome 12, 64485466: 64485466
15 TBK1 NM_013254.3(TBK1): c.964C> T (p.His322Tyr) single nucleotide variant Conflicting interpretations of pathogenicity rs145905497 GRCh37 Chromosome 12, 64875773: 64875773
16 TBK1 NM_013254.3(TBK1): c.964C> T (p.His322Tyr) single nucleotide variant Conflicting interpretations of pathogenicity rs145905497 GRCh38 Chromosome 12, 64481993: 64481993
17 TBK1 NM_013254.3(TBK1): c.1176A> G (p.Leu392=) single nucleotide variant Likely benign rs141806113 GRCh37 Chromosome 12, 64878266: 64878266
18 TBK1 NM_013254.3(TBK1): c.1176A> G (p.Leu392=) single nucleotide variant Likely benign rs141806113 GRCh38 Chromosome 12, 64484486: 64484486
19 TBK1 NM_013254.3(TBK1): c.1391T> C (p.Val464Ala) single nucleotide variant Benign rs35635889 GRCh37 Chromosome 12, 64882317: 64882317
20 TBK1 NM_013254.3(TBK1): c.1391T> C (p.Val464Ala) single nucleotide variant Benign rs35635889 GRCh38 Chromosome 12, 64488537: 64488537
21 TBK1 NM_013254.3(TBK1): c.519G> A (p.Leu173=) single nucleotide variant Benign rs73313869 GRCh38 Chromosome 12, 64467061: 64467061
22 TBK1 NM_013254.3(TBK1): c.519G> A (p.Leu173=) single nucleotide variant Benign rs73313869 GRCh37 Chromosome 12, 64860841: 64860841
23 TBK1 NM_013254.3(TBK1): c.1110C> T (p.Phe370=) single nucleotide variant Benign rs143590388 GRCh38 Chromosome 12, 64484420: 64484420
24 TBK1 NM_013254.3(TBK1): c.1110C> T (p.Phe370=) single nucleotide variant Benign rs143590388 GRCh37 Chromosome 12, 64878200: 64878200
25 TBK1 NM_013254.3(TBK1): c.358+9_358+12delGTTT deletion Likely benign GRCh37 Chromosome 12, 64858252: 64858255
26 TBK1 NM_013254.3(TBK1): c.358+9_358+12delGTTT deletion Likely benign GRCh38 Chromosome 12, 64464472: 64464475
27 TBK1 NM_013254.3(TBK1): c.40A> G (p.Ile14Val) single nucleotide variant Uncertain significance rs781325780 GRCh38 Chromosome 12, 64455910: 64455910
28 TBK1 NM_013254.3(TBK1): c.40A> G (p.Ile14Val) single nucleotide variant Uncertain significance rs781325780 GRCh37 Chromosome 12, 64849690: 64849690
29 TBK1 NM_013254.3(TBK1): c.66T> C (p.Asn22=) single nucleotide variant Benign rs41292019 GRCh38 Chromosome 12, 64455936: 64455936
30 TBK1 NM_013254.3(TBK1): c.66T> C (p.Asn22=) single nucleotide variant Benign rs41292019 GRCh37 Chromosome 12, 64849716: 64849716
31 TBK1 NM_013254.3(TBK1): c.992C> T (p.Thr331Ile) single nucleotide variant Uncertain significance rs200758840 GRCh38 Chromosome 12, 64482021: 64482021
32 TBK1 NM_013254.3(TBK1): c.992C> T (p.Thr331Ile) single nucleotide variant Uncertain significance rs200758840 GRCh37 Chromosome 12, 64875801: 64875801
33 TBK1 NM_013254.3(TBK1): c.1341-3delT deletion Benign GRCh38 Chromosome 12, 64488484: 64488484
34 TBK1 NM_013254.3(TBK1): c.1341-3delT deletion Benign GRCh37 Chromosome 12, 64882264: 64882264
35 TBK1 NM_013254.3(TBK1): c.1718G> A (p.Arg573His) single nucleotide variant Uncertain significance rs186475789 GRCh38 Chromosome 12, 64495773: 64495773
36 TBK1 NM_013254.3(TBK1): c.1718G> A (p.Arg573His) single nucleotide variant Uncertain significance rs186475789 GRCh37 Chromosome 12, 64889553: 64889553
37 TBK1 NM_013254.3(TBK1): c.1960-10G> T single nucleotide variant Benign/Likely benign rs371275822 GRCh38 Chromosome 12, 64497638: 64497638
38 TBK1 NM_013254.3(TBK1): c.1960-10G> T single nucleotide variant Benign/Likely benign rs371275822 GRCh37 Chromosome 12, 64891418: 64891418
39 TBK1 NM_013254.3(TBK1): c.1387_1388delGA (p.Glu463Serfs) deletion Pathogenic GRCh37 Chromosome 12, 64882313: 64882314
40 TBK1 NM_013254.3(TBK1): c.1387_1388delGA (p.Glu463Serfs) deletion Pathogenic GRCh38 Chromosome 12, 64488533: 64488534
41 TBK1 NM_013254.3(TBK1): c.1190-9A> G single nucleotide variant Likely benign rs375547018 GRCh38 Chromosome 12, 64485446: 64485446
42 TBK1 NM_013254.3(TBK1): c.1190-9A> G single nucleotide variant Likely benign rs375547018 GRCh37 Chromosome 12, 64879226: 64879226
43 TBK1 NM_013254.3(TBK1): c.812G> A (p.Arg271Gln) single nucleotide variant Likely benign rs56196591 GRCh38 Chromosome 12, 64480122: 64480122
44 TBK1 NM_013254.3(TBK1): c.812G> A (p.Arg271Gln) single nucleotide variant Likely benign rs56196591 GRCh37 Chromosome 12, 64873902: 64873902
45 TBK1 NM_013254.3(TBK1): c.1412G> C (p.Cys471Ser) single nucleotide variant Uncertain significance rs369875862 GRCh37 Chromosome 12, 64882338: 64882338
46 TBK1 NM_013254.3(TBK1): c.1412G> C (p.Cys471Ser) single nucleotide variant Uncertain significance rs369875862 GRCh38 Chromosome 12, 64488558: 64488558
47 TBK1 NM_013254.3(TBK1): c.1522C> A (p.Leu508Ile) single nucleotide variant Benign rs144424516 GRCh38 Chromosome 12, 64495483: 64495483
48 TBK1 NM_013254.3(TBK1): c.1522C> A (p.Leu508Ile) single nucleotide variant Benign rs144424516 GRCh37 Chromosome 12, 64889263: 64889263
49 TBK1 NM_013254.3(TBK1): c.1960-7G> T single nucleotide variant Likely benign rs768189768 GRCh38 Chromosome 12, 64497641: 64497641
50 TBK1 NM_013254.3(TBK1): c.1960-7G> T single nucleotide variant Likely benign rs768189768 GRCh37 Chromosome 12, 64891421: 64891421

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

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

Sources for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 4

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