FTDALS6
MCID: FRN060
MIFTS: 27

Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6 (FTDALS6)

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

Aliases & Classifications for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6

MalaCards integrated aliases for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6:

Name: Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6 57
Amyotrophic Lateral Sclerosis 14, with or Without Frontotemporal Dementia 73 29 13 6
Amyotrophic Lateral Sclerosis 14 with or Without Frontotemporal Dementia, Formerly; Als14, Formerly 57
Amyotrophic Lateral Sclerosis 14 with or Without Frontotemporal Dementia, Formerly 57
Sclerosis, Lateral, Amyotrophic, Type 14, with or Without Frontotemporal Dementia 39
Als14, Formerly 57
Ftdals6 57
Als14 73

Characteristics:

HPO:

31
frontotemporal dementia and/or amyotrophic lateral sclerosis 6:
Inheritance autosomal dominant inheritance
Onset and clinical course middle age onset


Classifications:



External Ids:

OMIM® 57 613954
OMIM Phenotypic Series 57 PS105400 PS105550
MeSH 44 D000690
MedGen 41 C3151403

Summaries for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6

OMIM® : 57 Frontotemporal dementia and/or amyotrophic lateral sclerosis-6 (FTDALS6) is an autosomal dominant neurodegenerative disorder with highly variable manifestations. Some patients present in adulthood with progressive FTD, often classified as the 'behavioral variant,' which is characterized by reduced empathy, impulsive behavior, personality changes, and reduced verbal output. Other patients present with features of amyotrophic lateral sclerosis (ALS), which is a fatal neurodegenerative disease characterized by upper and lower motor neuron dysfunction resulting in rapidly progressive paralysis and death from respiratory failure. The pathologic hallmarks of this disease include pallor of the corticospinal tract due to loss of motor neurons (in ALS). In both ALS and FTD, there are ubiquitin-positive inclusions within surviving neurons as well as deposition of pathologic TDP43 (TARDBP; 605078) or p62 (SQSTM1; 601530) aggregates. Patients with a D395G mutation (601023.0014) have been shown to develop pathologic tau (MAPT; 157140) aggregates. Some patients with the disorder may have features of both diseases, and there is significant interfamilial and intrafamilial phenotypic variability (summary by Johnson et al., 2010; Wong et al., 2018; Al-Obeidi et al., 2018; Darwich et al., 2020). For a general phenotypic description and a discussion of genetic heterogeneity of FTDALS, see FTDALS1 (105550). (613954) (Updated 05-Mar-2021)

MalaCards based summary : Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6, also known as amyotrophic lateral sclerosis 14, with or without frontotemporal dementia, is related to amyotrophic lateral sclerosis type 14. An important gene associated with Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6 is VCP (Valosin Containing Protein). Affiliated tissues include spinal cord, skeletal muscle and bone, and related phenotypes are dysarthria and muscle weakness

UniProtKB/Swiss-Prot : 73 Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia: 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. Patients with ALS14 may develop frontotemporal dementia.

Related Diseases for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6

Symptoms & Phenotypes for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6

Human phenotypes related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6:

31
# Description HPO Frequency HPO Source Accession
1 dysarthria 31 HP:0001260
2 muscle weakness 31 HP:0001324
3 skeletal muscle atrophy 31 HP:0003202
4 fasciculations 31 HP:0002380
5 amyotrophic lateral sclerosis 31 HP:0007354

Clinical features from OMIM®:

613954 (Updated 05-Mar-2021)

Drugs & Therapeutics for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6

Search Clinical Trials , NIH Clinical Center for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6

Genetic Tests for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6

Genetic tests related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6:

# Genetic test Affiliating Genes
1 Amyotrophic Lateral Sclerosis 14, with or Without Frontotemporal Dementia 29 VCP

Anatomical Context for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6

MalaCards organs/tissues related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6:

40
Spinal Cord, Skeletal Muscle, Bone

Publications for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6

Articles related to Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6:

(show all 12)
# Title Authors PMID Year
1
One family, one gene and three phenotypes: A novel VCP (valosin-containing protein) mutation associated with myopathy with rimmed vacuoles, amyotrophic lateral sclerosis and frontotemporal dementia. 6 57
27538664 2016
2
Exome sequencing reveals VCP mutations as a cause of familial ALS. 6 57
21145000 2010
3
Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. 57 6
15034582 2004
4
Autosomal dominant VCP hypomorph mutation impairs disaggregation of PHF-tau. 57
33004675 2020
5
Genotype-phenotype study in patients with valosin-containing protein mutations associated with multisystem proteinopathy. 57
28692196 2018
6
Three VCP Mutations in Patients with Frontotemporal Dementia. 57
30103325 2018
7
Patients with a phenotype consistent with facioscapulohumeral muscular dystrophy display genetic and epigenetic heterogeneity. 6
21984748 2012
8
Inclusion body myopathy, Paget's disease of the bone and frontotemporal dementia: recurrence of the VCP R155H mutation in an Italian family and implications for genetic counselling. 6
18341608 2008
9
Inclusion body myopathy-associated mutations in p97/VCP impair endoplasmic reticulum-associated degradation. 6
16321991 2006
10
VAPB/ALS8 interacts with FFAT-like proteins including the p97 cofactor FAF1 and the ASNA1 ATPase. 61
24885147 2014
11
Valosin-containing protein immunoreactivity in tauopathies, synucleinopathies, polyglutamine diseases and intranuclear inclusion body disease. 61
23782134 2013
12
Heteromeric p97/p97R155C complexes induce dominant negative changes in wild-type and autophagy 9-deficient Dictyostelium strains. 61
23056506 2012

Variations for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6

ClinVar genetic disease variations for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6:

6 (show top 50) (show all 134)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 VCP NM_007126.5(VCP):c.475C>G (p.Arg159Gly) SNV Pathogenic 30152 rs387906789 9:35065349-35065349 9:35065352-35065352
2 VCP NM_007126.5(VCP):c.1774G>A (p.Asp592Asn) SNV Pathogenic 30153 rs387906790 9:35059720-35059720 9:35059723-35059723
3 VCP NM_007126.5(VCP):c.271A>T (p.Asn91Tyr) SNV Pathogenic 217877 rs863225291 9:35067919-35067919 9:35067922-35067922
4 VCP NM_007126.5(VCP):c.464G>A (p.Arg155His) SNV Pathogenic 8468 rs121909329 9:35065360-35065360 9:35065363-35065363
5 VCP NM_007126.5(VCP):c.572G>A (p.Arg191Gln) SNV Pathogenic 8473 rs121909334 9:35065252-35065252 9:35065255-35065255
6 VCP NM_007126.5(VCP):c.572G>A (p.Arg191Gln) SNV Pathogenic 8473 rs121909334 9:35065252-35065252 9:35065255-35065255
7 VCP NM_007126.5(VCP):c.475C>T (p.Arg159Cys) SNV Pathogenic 280123 rs387906789 9:35065349-35065349 9:35065352-35065352
8 VCP NM_007126.5(VCP):c.277C>T (p.Arg93Cys) SNV Pathogenic 593071 rs1554669087 9:35067913-35067913 9:35067916-35067916
9 VCP NM_007126.5(VCP):c.463C>T (p.Arg155Cys) SNV Pathogenic 8469 rs121909330 9:35065361-35065361 9:35065364-35065364
10 VCP NM_007126.5(VCP):c.476G>A (p.Arg159His) SNV Pathogenic 8474 rs121909335 9:35065348-35065348 9:35065351-35065351
11 VCP NM_007126.5(VCP):c.464G>A (p.Arg155His) SNV Pathogenic 8468 rs121909329 9:35065360-35065360 9:35065363-35065363
12 VCP NM_007126.5(VCP):c.572G>C (p.Arg191Pro) SNV Likely pathogenic 873223 9:35065252-35065252 9:35065255-35065255
13 VCP NM_007126.5(VCP):c.475C>T (p.Arg159Cys) SNV Likely pathogenic 280123 rs387906789 9:35065349-35065349 9:35065352-35065352
14 VCP NM_007126.5(VCP):c.463C>T (p.Arg155Cys) SNV Likely pathogenic 8469 rs121909330 9:35065361-35065361 9:35065364-35065364
15 VCP NM_007126.5(VCP):c.283C>T (p.Arg95Cys) SNV Likely pathogenic 280124 rs121909332 9:35067907-35067907 9:35067910-35067910
16 VCP NM_007126.5(VCP):c.*885G>A SNV Uncertain significance 913703 9:35056229-35056229 9:35056232-35056232
17 VCP NM_007126.5(VCP):c.*367G>A SNV Uncertain significance 914100 9:35056747-35056747 9:35056750-35056750
18 VCP NM_007126.5(VCP):c.697A>G (p.Ile233Val) SNV Uncertain significance 913795 9:35064162-35064162 9:35064165-35064165
19 VCP NM_007126.5(VCP):c.794T>C (p.Phe265Ser) SNV Uncertain significance 913794 9:35062992-35062992 9:35062995-35062995
20 VCP NM_007126.5(VCP):c.1864G>T (p.Ala622Ser) SNV Uncertain significance 972527 9:35059630-35059630 9:35059633-35059633
21 VCP NM_007126.5(VCP):c.2132G>A (p.Arg711Gln) SNV Uncertain significance 966733 9:35059089-35059089 9:35059092-35059092
22 VCP NM_007126.5(VCP):c.1106T>C (p.Ile369Thr) SNV Uncertain significance 963526 9:35061662-35061662 9:35061665-35061665
23 VCP NM_007126.5(VCP):c.1324A>G (p.Met442Val) SNV Uncertain significance 961078 9:35061047-35061047 9:35061050-35061050
24 VCP NM_007126.5(VCP):c.313T>C (p.Cys105Arg) SNV Uncertain significance 960799 9:35066804-35066804 9:35066807-35066807
25 VCP NM_007126.5(VCP):c.2194C>T (p.Arg732Cys) SNV Uncertain significance 952496 9:35057494-35057494 9:35057497-35057497
26 VCP NM_007126.5(VCP):c.1242G>A (p.Leu414=) SNV Uncertain significance 594371 rs375262833 9:35061129-35061129 9:35061132-35061132
27 VCP NM_007126.5(VCP):c.697A>G (p.Ile233Val) SNV Uncertain significance 913795 9:35064162-35064162 9:35064165-35064165
28 VCP NM_007126.5(VCP):c.767G>A (p.Arg256Gln) SNV Uncertain significance 946240 9:35063019-35063019 9:35063022-35063022
29 VCP NM_007126.5(VCP):c.453T>G (p.Ile151Met) SNV Uncertain significance 942825 9:35065371-35065371 9:35065374-35065374
30 VCP NM_007126.5(VCP):c.523A>G (p.Ile175Val) SNV Uncertain significance 942537 9:35065301-35065301 9:35065304-35065304
31 VCP NM_007126.5(VCP):c.377T>G (p.Ile126Ser) SNV Uncertain significance 942237 9:35066740-35066740 9:35066743-35066743
32 VCP NM_007126.5(VCP):c.2242A>T (p.Ser748Cys) SNV Uncertain significance 940463 9:35057446-35057446 9:35057449-35057449
33 VCP NM_007126.5(VCP):c.130-9T>C SNV Uncertain significance 914689 9:35068069-35068069 9:35068072-35068072
34 VCP NM_007126.5(VCP):c.1293C>T (p.Asp431=) SNV Uncertain significance 914650 9:35061078-35061078 9:35061081-35061081
35 VCP NM_007126.5(VCP):c.*216G>A SNV Uncertain significance 914611 9:35056898-35056898 9:35056901-35056901
36 VCP NM_007126.5(VCP):c.*217G>T SNV Uncertain significance 914610 9:35056897-35056897 9:35056900-35056900
37 VCP NM_007126.5(VCP):c.335A>G (p.Lys112Arg) SNV Uncertain significance 914194 9:35066782-35066782 9:35066785-35066785
38 VCP NM_007126.5(VCP):c.384T>C (p.Gly128=) SNV Uncertain significance 914193 9:35066733-35066733 9:35066736-35066736
39 VCP NM_007126.5(VCP):c.446-4G>A SNV Uncertain significance 914192 9:35065382-35065382 9:35065385-35065385
40 VCP NM_007126.5(VCP):c.591C>G (p.Ser197=) SNV Uncertain significance 914191 9:35064268-35064268 9:35064271-35064271
41 VCP NM_007126.5(VCP):c.*63G>A SNV Uncertain significance 912643 9:35057051-35057051 9:35057054-35057054
42 VCP NM_007126.5(VCP):c.954C>T (p.Gly318=) SNV Uncertain significance 287400 rs377316335 9:35062127-35062127 9:35062130-35062130
43 VCP NM_007126.5(VCP):c.1996G>A (p.Val666Ile) SNV Uncertain significance 847962 9:35059498-35059498 9:35059501-35059501
44 VCP NM_007126.5(VCP):c.995T>C (p.Met332Thr) SNV Uncertain significance 846874 9:35062086-35062086 9:35062089-35062089
45 VCP NM_007126.5(VCP):c.284G>C (p.Arg95Pro) SNV Uncertain significance 595911 rs758169026 9:35067906-35067906 9:35067909-35067909
46 VCP NM_007126.5(VCP):c.446-4_446-3delinsAT Indel Uncertain significance 842949 9:35065381-35065382 9:35065384-35065385
47 VCP NM_007126.5(VCP):c.2228C>T (p.Ala743Val) SNV Uncertain significance 837640 9:35057460-35057460 9:35057463-35057463
48 VCP NM_007126.5(VCP):c.648A>G (p.Ile216Met) SNV Uncertain significance 836876 9:35064211-35064211 9:35064214-35064214
49 VCP NM_007126.5(VCP):c.2345G>C (p.Gly782Ala) SNV Uncertain significance 835129 9:35057190-35057190 9:35057193-35057193
50 VCP NM_007126.5(VCP):c.512G>T (p.Ser171Ile) SNV Uncertain significance 640109 rs200911363 9:35065312-35065312 9:35065315-35065315

UniProtKB/Swiss-Prot genetic disease variations for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6:

73
# Symbol AA change Variation ID SNP ID
1 VCP p.Arg155His VAR_033018 rs121909329
2 VCP p.Arg191Gln VAR_033021 rs121909334
3 VCP p.Arg159Gly VAR_065910 rs387906789
4 VCP p.Asp592Asn VAR_065911 rs387906790

Expression for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6

Search GEO for disease gene expression data for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6.

Pathways for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6

GO Terms for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6

Sources for Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 6

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-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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