MCID: MYP087
MIFTS: 48

Myopathy, Tubular Aggregate, 1

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

Aliases & Classifications for Myopathy, Tubular Aggregate, 1

MalaCards integrated aliases for Myopathy, Tubular Aggregate, 1:

Name: Myopathy, Tubular Aggregate, 1 53 71 69
Tubular Aggregate Myopathy 53 12 49 24 55 71 14 69
Myopathy, Tubular Aggregate 53 49 13
Tam 53 24 71
Myopathy with Tubular Aggregates 24 28
Tam1 53 71
Myopathy, Tubular Aggregate; Tam 53

Characteristics:

Orphanet epidemiological data:

55
tubular aggregate myopathy
Inheritance: Autosomal dominant;

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
slowly progressive
some patients may be asymptomatic
childhood or young adult onset
mild phenotype


HPO:

31
myopathy, tubular aggregate, 1:
Onset and clinical course adult onset slow progression
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 55  
Rare neurological diseases


Summaries for Myopathy, Tubular Aggregate, 1

NIH Rare Diseases : 49 Tubular aggregate myopathy is a disorder that affects the skeletal muscles. Signs and symptoms typically begin in childhood and worsen over time. The leg muscles are most often affected, but the arm muscles may also be involved. Symptoms include muscle pain, cramping, weakness or stiffness; and exercise-induced muscle fatigue. Affected individuals may have an unusual walking style (gait) or difficulty running, climbing stairs, or getting up from a squatting position. Some individuals develop contractures. This condition may be caused by mutations in the STIM1 orĀ ORAI1 genes. It is usually inherited in an autosomal dominant manner, but autosomal recessive inheritance has also been reported. Last updated: 12/27/2016

MalaCards based summary : Myopathy, Tubular Aggregate, 1, also known as tubular aggregate myopathy, is related to stormorken syndrome and myopathy, and has symptoms including myalgia, muscle cramps and fatiguable weakness of proximal limb muscles. An important gene associated with Myopathy, Tubular Aggregate, 1 is STIM1 (Stromal Interaction Molecule 1), and among its related pathways/superpathways are Cardiac conduction and Myometrial Relaxation and Contraction Pathways. Affiliated tissues include skeletal muscle, and related phenotypes are growth/size/body region and homeostasis/metabolism

OMIM : 53 Tubular aggregates in muscle, first described by Engel (1964), are structures of variable appearance consisting of an outer tubule containing either one or more microtubule-like structures or amorphous material. They are a nonspecific pathologic finding that may occur in a variety of circumstances, including alcohol- and drug-induced myopathies, exercise-induced cramps or muscle weakness, and inherited myopathies. Tubular aggregates are derived from the sarcoplasmic reticulum (Salviati et al., 1985) and are believed to represent an adaptive mechanism aimed at regulating an increased intracellular level of calcium in order to prevent the muscle fibers from hypercontraction and necrosis (Martin et al., 1997; Muller et al., 2001). (160565)

UniProtKB/Swiss-Prot : 71 Myopathy, tubular aggregate, 1: A rare congenital myopathy characterized by regular arrays of membrane tubules on muscle biopsies without additional histopathological hallmarks. Tubular aggregates in muscle are structures of variable appearance consisting of an outer tubule containing either one or more microtubule-like structures or amorphous material. They may occur in a variety of circumstances, including inherited myopathies, alcohol- and drug-induced myopathies, exercise-induced cramps or muscle weakness.

Genetics Home Reference : 24 Tubular aggregate myopathy is a disorder that primarily affects the skeletal muscles, which are muscles the body uses for movement. This disorder causes muscle pain, cramping, or weakness that begins in childhood and worsens over time. The muscles of the lower limbs are most often affected, although the upper limbs can also be involved. Affected individuals can have difficulty running, climbing stairs, or getting up from a squatting position. The weakness may also lead to an unusual walking style (gait). Some people with this condition develop joint deformities (contractures) in the arms and legs.

Related Diseases for Myopathy, Tubular Aggregate, 1

Diseases in the Myopathy, Tubular Aggregate, 1 family:

Myopathy, Tubular Aggregate, 2

Diseases related to Myopathy, Tubular Aggregate, 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 48)
# Related Disease Score Top Affiliating Genes
1 stormorken syndrome 32.0 ORAI1 STIM1 STIM2
2 myopathy 28.7 ACTA1 ATP2A1 CASQ1 EMD FLNC ORAI1
3 myopathy, tubular aggregate, 2 12.5
4 myeloproliferative syndrome, transient 11.8
5 congenital myasthenic syndromes with glycosylation defect 10.4 DPAGT1 GFPT1
6 sclerosteosis 2 10.4 DOK7 DPAGT1
7 brody myopathy 10.4 ATP2A1 RYR1
8 native american myopathy 10.3 QDPR RYR1
9 familial periodic paralysis 10.3 QDPR RYR1
10 malignant hyperthermia susceptibility 10.3 CASQ1 RYR1
11 central core myopathy 10.3 QDPR RYR1
12 myopathy, proximal, and ophthalmoplegia 10.3 EMD RYR1
13 congenital structural myopathy 10.2 ACTA1 RYR1
14 myotonic disease 10.2 ATP2A1 RYR1
15 myopathy, congenital, with fiber-type disproportion 10.2 ACTA1 RYR1
16 cenani-lenz syndactyly syndrome 10.1 DOK7 DPAGT1
17 distal arthrogryposis 10.1 ACTA1 DOK7 RYR1
18 congenital myasthenic syndrome 10.1 DOK7 DPAGT1 GFPT1
19 myopathy, myofibrillar, 2 10.1 ACTA1 FLNC
20 congenital fiber-type disproportion 10.1 ACTA1 EMD RYR1
21 autosomal dominant limb-girdle muscular dystrophy 10.0 EMD FLNC
22 gastric cancer 10.0
23 breast cancer 9.9
24 systemic lupus erythematosus 9.9
25 lupus erythematosus 9.9
26 glioma 9.9
27 hypoxia 9.9
28 catecholaminergic polymorphic ventricular tachycardia 9.9 CALR CASQ1 RYR1 TRDN
29 ovarian cancer 9.7
30 down syndrome 9.7
31 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 9.7
32 microvascular complications of diabetes 3 9.7
33 microvascular complications of diabetes 4 9.7
34 microvascular complications of diabetes 6 9.7
35 microvascular complications of diabetes 7 9.7
36 dengue virus 9.7
37 leukemia 9.7
38 lymphocytic choriomeningitis 9.7
39 dysentery 9.7
40 shigellosis 9.7
41 squamous cell carcinoma 9.7
42 endometriosis 9.7
43 astrocytoma 9.7
44 pustulosis of palm and sole 9.7
45 myeloid leukemia 9.7
46 psoriasis 9.7
47 pneumocystosis 9.7 FLNC GYPA
48 malignant hyperthermia 9.4 CALR CASQ1 QDPR RYR1 SRL

Graphical network of the top 20 diseases related to Myopathy, Tubular Aggregate, 1:



Diseases related to Myopathy, Tubular Aggregate, 1

Symptoms & Phenotypes for Myopathy, Tubular Aggregate, 1

Symptoms via clinical synopsis from OMIM:

53
Muscle Soft Tissue:
exercise-induced myalgia
proximal muscle weakness
muscle stiffness
easy fatigability
frequent falls
more
Head And Neck Eyes:
external ophthalmoplegia (in some patients)
pupillary abnormalities (reported in 1 family)
difficulties with night vision (reported in 1 family)

Skeletal:
contractures (in some patients)

Laboratory Abnormalities:
increased serum creatine kinase

Respiratory:
respiratory insufficiency (in some patients)


Clinical features from OMIM:

160565

Human phenotypes related to Myopathy, Tubular Aggregate, 1:

55 31 (show all 27)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 myalgia 55 31 hallmark (90%) Very frequent (99-80%) HP:0003326
2 muscle cramps 55 31 hallmark (90%) Very frequent (99-80%) HP:0003394
3 fatiguable weakness of proximal limb muscles 55 31 hallmark (90%) Very frequent (99-80%) HP:0030200
4 increased variability in muscle fiber diameter 55 31 frequent (33%) Frequent (79-30%) HP:0003557
5 muscle fiber tubular inclusions 55 31 hallmark (90%) Very frequent (99-80%) HP:0100301
6 centrally nucleated skeletal muscle fibers 55 31 frequent (33%) Frequent (79-30%) HP:0003687
7 type 2 muscle fiber atrophy 55 31 occasional (7.5%) Occasional (29-5%) HP:0003554
8 exercise-induced myalgia 31 HP:0003738
9 respiratory insufficiency 31 occasional (7.5%) HP:0002093
10 flexion contracture 31 occasional (7.5%) HP:0001371
11 myopathy 31 HP:0003198
12 elevated serum creatine phosphokinase 31 HP:0003236
13 areflexia of lower limbs 31 HP:0002522
14 nyctalopia 31 occasional (7.5%) HP:0000662
15 fatigable weakness 55 Very frequent (99-80%)
16 external ophthalmoplegia 31 occasional (7.5%) HP:0000544
17 proximal amyotrophy 31 HP:0007126
18 proximal muscle weakness 31 HP:0003701
19 emg: myopathic abnormalities 55 Very frequent (99-80%)
20 muscle stiffness 31 HP:0003552
21 easy fatigability 31 HP:0003388
22 frequent falls 31 HP:0002359
23 hyporeflexia of lower limbs 31 HP:0002600
24 difficulty running 31 HP:0009046
25 weakness of the intrinsic hand muscles 31 HP:0009005
26 emg 31 hallmark (90%) HP:0003458
27 abnormal pupil morphology 31 occasional (7.5%) HP:0000615

UMLS symptoms related to Myopathy, Tubular Aggregate, 1:


muscular stiffness, exercise-induced myalgia

MGI Mouse Phenotypes related to Myopathy, Tubular Aggregate, 1:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10 ACTA1 CALR CASQ1 CHD7 DOK7 FLNC
2 homeostasis/metabolism MP:0005376 9.93 STIM1 STIM2 ACTA1 ATP2A1 CALR CASQ1
3 mortality/aging MP:0010768 9.77 ACTA1 ATP2A1 CALR CHD7 DOK7 DPAGT1
4 muscle MP:0005369 9.36 EMD FLNC RYR1 SRL TRDN ACTA1

Drugs & Therapeutics for Myopathy, Tubular Aggregate, 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Congenital Muscle Disease Study of Patient and Family Reported Medical Information Recruiting NCT01403402

Search NIH Clinical Center for Myopathy, Tubular Aggregate, 1

Genetic Tests for Myopathy, Tubular Aggregate, 1

Genetic tests related to Myopathy, Tubular Aggregate, 1:

# Genetic test Affiliating Genes
1 Myopathy with Tubular Aggregates 28 STIM1

Anatomical Context for Myopathy, Tubular Aggregate, 1

MalaCards organs/tissues related to Myopathy, Tubular Aggregate, 1:

38
Skeletal Muscle

Publications for Myopathy, Tubular Aggregate, 1

Articles related to Myopathy, Tubular Aggregate, 1:

(show all 19)
# Title Authors Year
1
ORAI1 Mutations with Distinct Channel Gating Defects in Tubular Aggregate Myopathy. ( 28058752 )
2017
2
A novel gain-of-function mutation in ORAI1 causes late-onset tubular aggregate myopathy and congenital miosis. ( 27882542 )
2017
3
Identification and characterization of three novel mutations in the CASQ1 gene in four patients with tubular aggregate myopathy. ( 28895244 )
2017
4
Calcium Dyshomeostasis in Tubular Aggregate Myopathy. ( 27879676 )
2016
5
50 years to diagnosis: Autosomal dominant tubular aggregate myopathy caused by a novel STIM1 mutation. ( 25953320 )
2015
6
Muscle MR imaging in tubular aggregate myopathy. ( 24722334 )
2014
7
Dominant mutations in ORAI1 cause tubular aggregate myopathy with hypocalcemia via constitutive activation of store-operated Ca2+ channels. ( 25227914 )
2014
8
Childhood onset tubular aggregate myopathy associated with de novo STIM1 mutations. ( 24570283 )
2014
9
Clinical, histological and genetic characterisation of patients with tubular aggregate myopathy caused by mutations in STIM1. ( 25326555 )
2014
10
Constitutive activation of the calcium sensor STIM1 causes tubular-aggregate myopathy. ( 23332920 )
2013
11
Tubular aggregate myopathy: a phenotypic spectrum and morphological study. ( 21045502 )
2010
12
Autosomal recessive tubular aggregate myopathy in an Indian family. ( 18684652 )
2009
13
Tubular aggregate myopathy associated with retinal degeneration. ( 18443606 )
2008
14
Tubular aggregate myopathy: a rare form of myopathy. ( 18824361 )
2008
15
Tubular aggregate myopathy presenting with acute type II respiratory failure and severe orthopnoea. ( 16396955 )
2006
16
Tubular aggregate myopathy: a case report. ( 12589105 )
2003
17
Tubular aggregate myopathy with abnormal pupils and skeletal deformities. ( 12185172 )
2002
18
Dominantly inherited tubular aggregate myopathy. ( 1484321 )
1992
19
Steroid-responsive tubular aggregate myopathy. ( 2041544 )
1991

Variations for Myopathy, Tubular Aggregate, 1

UniProtKB/Swiss-Prot genetic disease variations for Myopathy, Tubular Aggregate, 1:

71 (show all 13)
# Symbol AA change Variation ID SNP ID
1 CASQ1 p.Asp44Asn VAR_079704 rs140253806
2 CASQ1 p.Gly103Asp VAR_079705
3 CASQ1 p.Ile385Thr VAR_079706 rs371278891
4 STIM1 p.His72Gln VAR_069892 rs397515436
5 STIM1 p.Asp84Gly VAR_069893 rs397514675
6 STIM1 p.His109Asn VAR_069894 rs397514676
7 STIM1 p.His109Arg VAR_069895 rs397514677
8 STIM1 p.Ile115Phe VAR_074037 rs527236030
9 STIM1 p.Asn80Thr VAR_075619 rs748277951
10 STIM1 p.Gly81Asp VAR_075620
11 STIM1 p.Leu96Val VAR_075621
12 STIM1 p.Phe108Ile VAR_075622
13 STIM1 p.Phe108Leu VAR_075623

ClinVar genetic disease variations for Myopathy, Tubular Aggregate, 1:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 STIM1 NM_003156.3(STIM1): c.251A> G (p.Asp84Gly) single nucleotide variant Pathogenic rs397514675 GRCh37 Chromosome 11, 3988893: 3988893
2 STIM1 NM_003156.3(STIM1): c.325C> A (p.His109Asn) single nucleotide variant Pathogenic rs397514676 GRCh37 Chromosome 11, 4045157: 4045157
3 STIM1 NM_003156.3(STIM1): c.326A> G (p.His109Arg) single nucleotide variant Pathogenic rs397514677 GRCh37 Chromosome 11, 4045158: 4045158
4 STIM1 NM_003156.3(STIM1): c.216C> A (p.His72Gln) single nucleotide variant Pathogenic rs397515436 GRCh37 Chromosome 11, 3988858: 3988858
5 STIM1 NM_003156.3(STIM1): c.910C> T (p.Arg304Trp) single nucleotide variant Pathogenic rs483352867 GRCh38 Chromosome 11, 4074620: 4074620
6 STIM1 NM_003156.3(STIM1): c.343A> T (p.Ile115Phe) single nucleotide variant Pathogenic rs527236030 GRCh38 Chromosome 11, 4023945: 4023945
7 STIM1 NM_003156.3(STIM1): c.239A> C (p.Asn80Thr) single nucleotide variant Pathogenic rs748277951 GRCh38 Chromosome 11, 3967651: 3967651

Expression for Myopathy, Tubular Aggregate, 1

Search GEO for disease gene expression data for Myopathy, Tubular Aggregate, 1.

Pathways for Myopathy, Tubular Aggregate, 1

GO Terms for Myopathy, Tubular Aggregate, 1

Cellular components related to Myopathy, Tubular Aggregate, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum GO:0005783 9.97 ATP2A1 CALR CASQ1 DPAGT1 EMD STIM1
2 sarcoplasmic reticulum membrane GO:0033017 9.55 ATP2A1 CASQ1 RYR1 STIM1 TRDN
3 I band GO:0031674 9.48 CASQ1 RYR1
4 junctional sarcoplasmic reticulum membrane GO:0014701 9.46 RYR1 TRDN
5 junctional membrane complex GO:0030314 9.43 RYR1 TRDN
6 smooth endoplasmic reticulum GO:0005790 9.43 CALR CASQ1 RYR1
7 cortical endoplasmic reticulum GO:0032541 9.4 EMD STIM1
8 terminal cisterna GO:0014802 9.32 CASQ1 RYR1
9 sarcoplasmic reticulum lumen GO:0033018 9.26 CALR CASQ1 SRL TRDN
10 sarcoplasmic reticulum GO:0016529 9.17 ATP2A1 CALR CASQ1 RYR1 SRL STIM1

Biological processes related to Myopathy, Tubular Aggregate, 1 according to GeneCards Suite gene sharing:

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 ion transmembrane transport GO:0034220 9.81 ATP2A1 CASQ1 RYR1 TRDN
2 calcium ion transport GO:0006816 9.71 ATP2A1 RYR1 STIM1 STIM2
3 muscle contraction GO:0006936 9.67 ACTA1 EMD RYR1 TRDN
4 calcium ion transmembrane transport GO:0070588 9.65 ATP2A1 ORAI1 RYR1 STIM1 STIM2
5 skeletal muscle fiber development GO:0048741 9.56 ACTA1 RYR1
6 regulation of calcium ion transport GO:0051924 9.55 ORAI1 STIM1
7 positive regulation of calcium ion transport GO:0051928 9.54 ORAI1 STIM2
8 calcium ion import GO:0070509 9.52 ATP2A1 ORAI1
9 regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum GO:0010880 9.5 CASQ1 CHD7 TRDN
10 regulation of store-operated calcium entry GO:2001256 9.49 CASQ1 STIM1
11 UDP-N-acetylglucosamine metabolic process GO:0006047 9.48 DPAGT1 GFPT1
12 release of sequestered calcium ion into cytosol by sarcoplasmic reticulum GO:0014808 9.46 RYR1 TRDN
13 activation of store-operated calcium channel activity GO:0032237 9.43 STIM1 STIM2
14 cellular calcium ion homeostasis GO:0006874 9.35 CALR RYR1 STIM1 STIM2 TRDN
15 store-operated calcium entry GO:0002115 9.33 ORAI1 STIM1 STIM2
16 regulation of cardiac conduction GO:1903779 9.02 ATP2A1 CASQ1 RYR1 STIM1 TRDN

Molecular functions related to Myopathy, Tubular Aggregate, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 calcium ion binding GO:0005509 9.5 ATP2A1 CALR CASQ1 RYR1 SDF4 STIM1
2 calcium channel regulator activity GO:0005246 9.16 STIM1 STIM2
3 store-operated calcium channel activity GO:0015279 8.8 ORAI1 STIM1 STIM2

Sources for Myopathy, Tubular Aggregate, 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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