ETM4
MCID: TRM017
MIFTS: 35

Tremor, Hereditary Essential, 4 (ETM4)

Categories: Genetic diseases, Mental diseases, Muscle diseases, Neuronal diseases, Oral diseases, Rare diseases

Aliases & Classifications for Tremor, Hereditary Essential, 4

MalaCards integrated aliases for Tremor, Hereditary Essential, 4:

Name: Tremor, Hereditary Essential, 4 57 29 13 6 70
Etm4 57 12 72
Essential Tremor 4 12 15
Tremor, Hereditary Essential, Type 4 39
Essential Tremor, Hereditary, 4 57
Tremor, Hereditary Essential 4 72
Hereditary Essential Tremor 4 12

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant

Miscellaneous:
age at onset ranges from first to sixth decade


HPO:

31
tremor, hereditary essential, 4:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0111431
OMIM® 57 614782
OMIM Phenotypic Series 57 PS190300
MeSH 44 D020329
SNOMED-CT via HPO 68 263681008 56610005
UMLS 70 C3539195

Summaries for Tremor, Hereditary Essential, 4

UniProtKB/Swiss-Prot : 72 Tremor, hereditary essential 4: A common movement disorder mainly characterized by postural tremor of the arms. Head, legs, trunk, voice, jaw, and facial muscles also may be involved. The condition can be aggravated by emotions, hunger, fatigue and temperature extremes, and may cause a functional disability or even incapacitation. Inheritance is autosomal dominant.

MalaCards based summary : Tremor, Hereditary Essential, 4, also known as etm4, is related to tremor and tremor, hereditary essential, 2, and has symptoms including action tremor and static tremor. An important gene associated with Tremor, Hereditary Essential, 4 is FUS (FUS RNA Binding Protein), and among its related pathways/superpathways are mRNA Splicing - Major Pathway and Translational Control. Related phenotype is postural tremor.

Disease Ontology : 12 An essential tremor that has material basis in heterozygous mutation in FUS on chromosome 16p11.2.

More information from OMIM: 614782 PS190300

Related Diseases for Tremor, Hereditary Essential, 4

Graphical network of the top 20 diseases related to Tremor, Hereditary Essential, 4:



Diseases related to Tremor, Hereditary Essential, 4

Symptoms & Phenotypes for Tremor, Hereditary Essential, 4

Human phenotypes related to Tremor, Hereditary Essential, 4:

31
# Description HPO Frequency HPO Source Accession
1 postural tremor 31 HP:0002174

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
tremor, action
tremor, postural

Clinical features from OMIM®:

614782 (Updated 05-Apr-2021)

UMLS symptoms related to Tremor, Hereditary Essential, 4:


action tremor; static tremor

Drugs & Therapeutics for Tremor, Hereditary Essential, 4

Search Clinical Trials , NIH Clinical Center for Tremor, Hereditary Essential, 4

Genetic Tests for Tremor, Hereditary Essential, 4

Genetic tests related to Tremor, Hereditary Essential, 4:

# Genetic test Affiliating Genes
1 Tremor, Hereditary Essential, 4 29 FUS

Anatomical Context for Tremor, Hereditary Essential, 4

Publications for Tremor, Hereditary Essential, 4

Articles related to Tremor, Hereditary Essential, 4:

(show all 26)
# Title Authors PMID Year
1
Exome sequencing identifies FUS mutations as a cause of essential tremor. 57 6
22863194 2012
2
De novo FUS P525L mutation in Juvenile amyotrophic lateral sclerosis with dysphonia and diplopia. 6
27123482 2016
3
ALS mutations in TLS/FUS disrupt target gene expression. 6
26251528 2015
4
ALS-causative mutations in FUS/TLS confer gain and loss of function by altered association with SMN and U1-snRNP. 6
25625564 2015
5
Autosomal dominant inheritance of rapidly progressive amyotrophic lateral sclerosis due to a truncation mutation in the fused in sarcoma (FUS) gene. 6
24899262 2014
6
Activity-dependent FUS dysregulation disrupts synaptic homeostasis. 6
25324524 2014
7
Extensive molecular genetic survey of Taiwanese patients with amyotrophic lateral sclerosis. 6
24908169 2014
8
Aggregation of ALS-linked FUS mutant sequesters RNA binding proteins and impairs RNA granules formation. 6
25173930 2014
9
ALS-associated FUS mutations result in compromised FUS alternative splicing and autoregulation. 6
24204307 2013
10
Characterization of FUS mutations in amyotrophic lateral sclerosis using RNA-Seq. 6
23577159 2013
11
Familial ALS with FUS P525L mutation: two Japanese sisters with multiple systems involvement. 6
22980027 2012
12
FUS mutations in sporadic amyotrophic lateral sclerosis: clinical and genetic analysis. 6
22055719 2012
13
P525L FUS mutation is consistently associated with a severe form of juvenile amyotrophic lateral sclerosis. 6
21907581 2012
14
Pathological heterogeneity in amyotrophic lateral sclerosis with FUS mutations: two distinct patterns correlating with disease severity and mutation. 6
21604077 2011
15
Nuclear transport impairment of amyotrophic lateral sclerosis-linked mutations in FUS/TLS. 6
21280085 2011
16
Extensive FUS-immunoreactive pathology in juvenile amyotrophic lateral sclerosis with basophilic inclusions. 6
20579074 2010
17
SOD1, ANG, VAPB, TARDBP, and FUS mutations in familial amyotrophic lateral sclerosis: genotype-phenotype correlations. 6
20577002 2010
18
Frameshift and novel mutations in FUS in familial amyotrophic lateral sclerosis and ALS/dementia. 6
20668259 2010
19
ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import. 6
20606625 2010
20
Mutations of FUS gene in sporadic amyotrophic lateral sclerosis. 6
19861302 2010
21
Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. 6
19251627 2009
22
[Polygraphic validation of distraction tasks in clinical differential tremor diagnosis]. 61
9834478 1998
23
Prevalence of movement disorders in institutionalized elderly. 61
8570001 1995
24
Stress and alcohol interaction: an update of human research. 61
1898494 1991
25
[Symptomatology of the involuntary movement]. 61
2012697 1991
26
Hereditary neurodegenerative disorders in Nigerian Africans. 61
6230542 1984

Variations for Tremor, Hereditary Essential, 4

ClinVar genetic disease variations for Tremor, Hereditary Essential, 4:

6 (show top 50) (show all 67)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FUS NM_004960.3(FUS):c.1292C>T (p.Pro431Leu) SNV Pathogenic 37069 rs186547381 GRCh37: 16:31201719-31201719
GRCh38: 16:31190398-31190398
2 FUS NM_004960.3(FUS):c.646C>T (p.Arg216Cys) SNV Pathogenic 16227 rs267606832 GRCh37: 16:31196382-31196382
GRCh38: 16:31185061-31185061
3 FUS NM_004960.3(FUS):c.868C>T (p.Gln290Ter) SNV Pathogenic 37070 rs387907274 GRCh37: 16:31200479-31200479
GRCh38: 16:31189158-31189158
4 FUS NM_004960.3(FUS):c.1561C>G (p.Arg521Gly) SNV Pathogenic 16222 rs121909668 GRCh37: 16:31202739-31202739
GRCh38: 16:31191418-31191418
5 FUS NM_001170634.1(FUS):c.1504_1505AG[3] (p.Gly503fs) Microsatellite Pathogenic 665141 rs1596912983 GRCh37: 16:31202396-31202397
GRCh38: 16:31191075-31191076
6 FUS NM_004960.3(FUS):c.1574C>T (p.Pro525Leu) SNV Pathogenic 280110 rs886041390 GRCh37: 16:31202752-31202752
GRCh38: 16:31191431-31191431
7 FUS NC_000016.10:g.(?_31182388)_(31194881_?)dup Duplication Uncertain significance 831798 GRCh37: 16:31193709-31206202
GRCh38:
8 FUS NM_004960.4(FUS):c.182G>A (p.Ser61Asn) SNV Uncertain significance 834592 GRCh37: 16:31193977-31193977
GRCh38: 16:31182656-31182656
9 FUS NM_004960.4(FUS):c.291_292delinsTA (p.Pro98Thr) Indel Uncertain significance 838008 GRCh37: 16:31195279-31195280
GRCh38: 16:31183958-31183959
10 FUS NM_004960.4(FUS):c.1552A>G (p.Arg518Gly) SNV Uncertain significance 1001437 GRCh37: 16:31202730-31202730
GRCh38: 16:31191409-31191409
11 FUS NM_004960.3(FUS):c.1204_1206del (p.Ser402del) Deletion Uncertain significance 653781 rs781120756 GRCh37: 16:31201631-31201633
GRCh38: 16:31190310-31190312
12 FUS NM_004960.4(FUS):c.1541+1G>A SNV Uncertain significance 847302 GRCh37: 16:31202432-31202432
GRCh38: 16:31191111-31191111
13 FUS NM_004960.4(FUS):c.669CGG[2] (p.Gly228_Gly231del) Microsatellite Uncertain significance 969442 GRCh37: 16:31196403-31196414
GRCh38: 16:31185082-31185093
14 FUS NM_004960.4(FUS):c.1348C>T (p.Pro450Ser) SNV Uncertain significance 886474 GRCh37: 16:31202118-31202118
GRCh38: 16:31190797-31190797
15 FUS NM_004960.3(FUS):c.1555C>G (p.Gln519Glu) SNV Uncertain significance 650787 rs1567479067 GRCh37: 16:31202733-31202733
GRCh38: 16:31191412-31191412
16 FUS NM_004960.4(FUS):c.1545_1547dup (p.Glu516_His517insAsp) Duplication Uncertain significance 843607 GRCh37: 16:31202722-31202723
GRCh38: 16:31191401-31191402
17 FUS NM_004960.4(FUS):c.493_495del (p.Ser165del) Deletion Uncertain significance 850400 GRCh37: 16:31195687-31195689
GRCh38: 16:31184366-31184368
18 FUS NM_004960.4(FUS):c.571G>A (p.Gly191Ser) SNV Uncertain significance 956175 GRCh37: 16:31196307-31196307
GRCh38: 16:31184986-31184986
19 FUS NM_004960.4(FUS):c.52C>T (p.Pro18Ser) SNV Uncertain significance 887477 GRCh37: 16:31193847-31193847
GRCh38: 16:31182526-31182526
20 FUS NM_004960.4(FUS):c.493A>G (p.Ser165Gly) SNV Uncertain significance 1040027 GRCh37: 16:31195687-31195687
GRCh38: 16:31184366-31184366
21 FUS NM_004960.3(FUS):c.681_689del (p.Gly229_Gly231del) Deletion Uncertain significance 447358 rs767564995 GRCh37: 16:31196415-31196423
GRCh38: 16:31185094-31185102
22 FUS NM_004960.4(FUS):c.265T>A (p.Ser89Thr) SNV Uncertain significance 1045687 GRCh37: 16:31195253-31195253
GRCh38: 16:31183932-31183932
23 FUS NM_004960.3(FUS):c.1111C>T (p.Arg371Cys) SNV Uncertain significance 566220 rs773141319 GRCh37: 16:31201405-31201405
GRCh38: 16:31190084-31190084
24 FUS NM_004960.3(FUS):c.*108C>T SNV Uncertain significance 567482 rs780606789 GRCh37: 16:31202867-31202867
GRCh38: 16:31191546-31191546
25 FUS NM_004960.3(FUS):c.1446C>T (p.Gly482=) SNV Uncertain significance 665814 rs112061837 GRCh37: 16:31202336-31202336
GRCh38: 16:31191015-31191015
26 FUS NM_004960.3(FUS):c.673G>A (p.Gly225Ser) SNV Uncertain significance 666021 rs551577399 GRCh37: 16:31196409-31196409
GRCh38: 16:31185088-31185088
27 FUS NM_004960.3(FUS):c.743G>A (p.Arg248His) SNV Uncertain significance 581527 rs760351730 GRCh37: 16:31196479-31196479
GRCh38: 16:31185158-31185158
28 FUS NM_004960.3(FUS):c.685_687GGT[5] (p.Gly230_Gly231dup) Microsatellite Uncertain significance 582491 rs757651881 GRCh37: 16:31196420-31196421
GRCh38: 16:31185099-31185100
29 FUS NM_004960.3(FUS):c.1292C>T (p.Pro431Leu) SNV Uncertain significance 37069 rs186547381 GRCh37: 16:31201719-31201719
GRCh38: 16:31190398-31190398
30 FUS NM_004960.3(FUS):c.688G>T (p.Gly230Cys) SNV Uncertain significance 647759 rs748374535 GRCh37: 16:31196424-31196424
GRCh38: 16:31185103-31185103
31 FUS NM_001170634.1(FUS):c.666_668CGG[8] (p.Gly229_Gly230dup) Microsatellite Uncertain significance 649131 rs72550890 GRCh37: 16:31196402-31196403
GRCh38: 16:31185081-31185082
32 FUS NM_004960.3(FUS):c.1171C>G (p.Pro391Ala) SNV Uncertain significance 540278 rs560450437 GRCh37: 16:31201598-31201598
GRCh38: 16:31190277-31190277
33 FUS NM_004960.3(FUS):c.1564A>G (p.Arg522Gly) SNV Uncertain significance 540279 rs1555509693 GRCh37: 16:31202742-31202742
GRCh38: 16:31191421-31191421
34 FUS NM_004960.4(FUS):c.630G>C (p.Gln210His) SNV Uncertain significance 939159 GRCh37: 16:31196366-31196366
GRCh38: 16:31185045-31185045
35 FUS NM_004960.4(FUS):c.1544G>T (p.Gly515Val) SNV Uncertain significance 951492 GRCh37: 16:31202722-31202722
GRCh38: 16:31191401-31191401
36 FUS NM_004960.4(FUS):c.701G>A (p.Arg234His) SNV Uncertain significance 970072 GRCh37: 16:31196437-31196437
GRCh38: 16:31185116-31185116
37 FUS NM_004960.4(FUS):c.222A>G (p.Gly74=) SNV Uncertain significance 887665 GRCh37: 16:31195210-31195210
GRCh38: 16:31183889-31183889
38 FUS NM_004960.3(FUS):c.661_663del (p.Ser221del) Deletion Uncertain significance 503718 rs746633090 GRCh37: 16:31196397-31196399
GRCh38: 16:31185076-31185078
39 FUS NM_004960.4(FUS):c.685_687GGT[6] (p.Gly229_Gly231dup) Microsatellite Uncertain significance 654997 rs757651881 GRCh37: 16:31196420-31196421
GRCh38: 16:31185099-31185100
40 FUS NM_004960.3(FUS):c.1394G>A (p.Gly465Glu) SNV Uncertain significance 659572 rs141684472 GRCh37: 16:31202284-31202284
GRCh38: 16:31190963-31190963
41 FUS NM_004960.4(FUS):c.1414C>T (p.Arg472Cys) SNV Uncertain significance 834593 GRCh37: 16:31202304-31202304
GRCh38: 16:31190983-31190983
42 FUS NM_004960.4(FUS):c.238G>A (p.Gly80Ser) SNV Uncertain significance 851344 GRCh37: 16:31195226-31195226
GRCh38: 16:31183905-31183905
43 FUS NM_004960.4(FUS):c.676G>A (p.Gly226Ser) SNV Uncertain significance 804816 rs758970940 GRCh37: 16:31196412-31196412
GRCh38: 16:31185091-31185091
44 FUS NM_004960.3(FUS):c.404G>A (p.Ser135Asn) SNV Likely benign 447357 rs61732970 GRCh37: 16:31195598-31195598
GRCh38: 16:31184277-31184277
45 FUS NM_004960.4(FUS):c.744T>A (p.Arg248=) SNV Likely benign 756511 rs1596898427 GRCh37: 16:31196480-31196480
GRCh38: 16:31185159-31185159
46 FUS NC_000016.10:g.31184394_31184399dup Microsatellite Likely benign 766876 GRCh37: 16:31195692-31195693
GRCh38: 16:31184371-31184372
47 FUS NM_004960.4(FUS):c.1176G>A (p.Met392Ile) SNV Likely benign 772949 rs751937417 GRCh37: 16:31201603-31201603
GRCh38: 16:31190282-31190282
48 FUS NM_004960.3(FUS):c.1248C>T (p.Gly416=) SNV Likely benign 447354 rs368780804 GRCh37: 16:31201675-31201675
GRCh38: 16:31190354-31190354
49 FUS NM_004960.3(FUS):c.1080C>T (p.Ser360=) SNV Likely benign 444368 rs190724342 GRCh37: 16:31201374-31201374
GRCh38: 16:31190053-31190053
50 FUS NM_004960.4(FUS):c.669_671CGG[4] (p.Gly230_Gly231del) Microsatellite Likely benign 704279 rs72550890 GRCh37: 16:31196403-31196408
GRCh38: 16:31185082-31185087

UniProtKB/Swiss-Prot genetic disease variations for Tremor, Hereditary Essential, 4:

72
# Symbol AA change Variation ID SNP ID
1 FUS p.Arg216Cys VAR_068919 rs267606832
2 FUS p.Pro431Leu VAR_068923 rs186547381

Expression for Tremor, Hereditary Essential, 4

Search GEO for disease gene expression data for Tremor, Hereditary Essential, 4.

Pathways for Tremor, Hereditary Essential, 4

Pathways related to Tremor, Hereditary Essential, 4 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.42 PCBP2 PCBP1 HNRNPA1L2 FUS
2 11.08 PCBP2 PCBP1 FUS
3 10.57 PCBP2 PCBP1

GO Terms for Tremor, Hereditary Essential, 4

Cellular components related to Tremor, Hereditary Essential, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix GO:0031012 8.8 LINGO4 LINGO2 LINGO1

Biological processes related to Tremor, Hereditary Essential, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 regulation of gene expression GO:0010468 9.54 PCBP3 PCBP2 PCBP1
2 mRNA splicing, via spliceosome GO:0000398 9.43 PCBP2 PCBP1 FUS
3 RNA metabolic process GO:0016070 9.32 PCBP2 PCBP1
4 viral RNA genome replication GO:0039694 9.16 PCBP2 PCBP1
5 mRNA metabolic process GO:0016071 8.96 PCBP3 PCBP2
6 regulation of RNA metabolic process GO:0051252 8.8 PCBP3 PCBP2 PCBP1

Molecular functions related to Tremor, Hereditary Essential, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 RNA binding GO:0003723 9.65 PCBP3 PCBP2 PCBP1 HNRNPA1L2 FUS
2 nucleic acid binding GO:0003676 9.35 PCBP3 PCBP2 PCBP1 HNRNPA1L2 FUS
3 mRNA binding GO:0003729 9.33 PCBP3 PCBP2 PCBP1
4 single-stranded DNA binding GO:0003697 9.32 PCBP2 PCBP1
5 C-rich single-stranded DNA binding GO:1990829 8.62 PCBP3 PCBP2

Sources for Tremor, Hereditary Essential, 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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