NEM4
MCID: NML005
MIFTS: 39

Nemaline Myopathy 4 (NEM4)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases, Respiratory diseases
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Aliases & Classifications for Nemaline Myopathy 4

MalaCards integrated aliases for Nemaline Myopathy 4:

Name: Nemaline Myopathy 4 57 11 73 28 5 43 14 71
Cap Myopathy 2 57 73 28 5 71
Nemaline Myopathy 4, Autosomal Dominant 57 11 28
Nem4 57 11 73
Tpm2-Related Nemaline Myopathy 73
Myopathy, Nemaline, Type 4 38
Nemaline Myopathy, Type 4 75
Cap Myopathy Tpm2-Related 73
Tpm2-Related Cap Myopathy 5
Cap Myopathy 71
Cap Disease 73
Capm2 73

Characteristics:


Inheritance:

Autosomal dominant 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
variable severity
genetic heterogeneity (see )
childhood onset (range birth to 12 years)


Classifications:



Summaries for Nemaline Myopathy 4

UniProtKB/Swiss-Prot 73 Nemaline myopathy 4: A form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. Nemaline myopathy type 4 presents from infancy to childhood with hypotonia and moderate-to-severe proximal weakness with minimal or no progression. Major motor milestones are delayed but independent ambulation is usually achieved, although a wheelchair may be needed in later life.

Cap myopathy 2: A rare congenital skeletal muscle disorder characterized by the presence of cap-like structures which are well demarcated and peripherally located under the sarcolemma and show abnormal accumulation of sarcomeric proteins. Clinical features are early onset of hypotonia and non-progressive or slowly progressive muscle weakness. Respiratory problems are common.

MalaCards based summary: Nemaline Myopathy 4, also known as cap myopathy 2, is related to batten-turner congenital myopathy and congenital fiber-type disproportion, and has symptoms including waddling gait An important gene associated with Nemaline Myopathy 4 is TPM2 (Tropomyosin 2). Affiliated tissues include skeletal muscle, prostate and pituitary, and related phenotypes are hypotonia and feeding difficulties in infancy

Disease Ontology: 11 A nemaline myopathy that has material basis in heterozygous mutation in the TPM2 gene on chromosome 9p13.

Wikipedia: 75 Nemaline myopathy (also called rod myopathy or nemaline rod myopathy) is a congenital, often hereditary... more...

More information from OMIM: 609285 PS161800

Related Diseases for Nemaline Myopathy 4

Diseases in the Nemaline Myopathy family:

Nemaline Myopathy 3 Nemaline Myopathy 2
Nemaline Myopathy 5 Nemaline Myopathy 6
Nemaline Myopathy 1 Nemaline Myopathy 4
Nemaline Myopathy 7 Nemaline Myopathy 8
Nemaline Myopathy 9 Nemaline Myopathy 10
Nemaline Myopathy 11, Autosomal Recessive Adult-Onset Nemaline Myopathy
Intermediate Congenital Nemaline Myopathy Severe Congenital Nemaline Myopathy
Congenital Nemaline Myopathy

Diseases related to Nemaline Myopathy 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 22)
# Related Disease Score Top Affiliating Genes
1 batten-turner congenital myopathy 30.1 TPM2 MYMK
2 congenital fiber-type disproportion 29.9 TPM2 MYMK
3 distal arthrogryposis 29.3 ZC4H2 TPM2
4 cap myopathy 11.3
5 nemaline myopathy 1 11.1
6 myopathy, congenital, with fiber-type disproportion 10.0
7 nemaline myopathy 10.0
8 myopathy 10.0
9 catastrophic antiphospholipid syndrome 10.0
10 cryopyrin-associated periodic syndrome 10.0
11 contractures, pterygia, and spondylocarpotarsal fusion syndrome 1a 9.9
12 craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 1 9.9
13 respiratory failure 9.9
14 hypotonia 9.9
15 fibrosis of extraocular muscles, congenital, 3a, with or without extraocular involvement 9.8 ZC4H2 MYMK
16 carey-fineman-ziter syndrome 1 9.8 ZC4H2 MYMK
17 multiple pterygium syndrome, escobar variant 9.8 ZC4H2 TPM2
18 cardiomyopathy, familial hypertrophic, 1 9.8 TPM2 MYMK
19 arthrogryposis, distal, type 1a 9.7
20 ptosis 9.7
21 limb-girdle muscular dystrophy 9.7
22 neuromuscular disease 9.7

Graphical network of the top 20 diseases related to Nemaline Myopathy 4:



Diseases related to Nemaline Myopathy 4

Symptoms & Phenotypes for Nemaline Myopathy 4

Human phenotypes related to Nemaline Myopathy 4:

30 (show all 20)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypotonia 30 Very rare (1%) HP:0001252
2 feeding difficulties in infancy 30 Very rare (1%) HP:0008872
3 nemaline bodies 30 Very rare (1%) HP:0003798
4 neck muscle weakness 30 Very rare (1%) HP:0000467
5 difficulty walking 30 Very rare (1%) HP:0002355
6 myopathic facies 30 Very rare (1%) HP:0002058
7 high palate 30 HP:0000218
8 flexion contracture 30 HP:0001371
9 skeletal muscle atrophy 30 HP:0003202
10 waddling gait 30 HP:0002515
11 scapular winging 30 HP:0003691
12 motor delay 30 HP:0001270
13 kyphoscoliosis 30 HP:0002751
14 type 1 muscle fiber predominance 30 HP:0003803
15 hyporeflexia 30 HP:0001265
16 gowers sign 30 HP:0003391
17 limb muscle weakness 30 HP:0003690
18 generalized hypotonia 30 HP:0001290
19 facial diplegia 30 HP:0001349
20 reduced vital capacity 30 HP:0002792

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Muscle Soft Tissue:
hypotonia
waddling gait
neck muscle weakness
difficulty walking
gowers sign
more
Neurologic Peripheral Nervous System:
hyporeflexia

Head And Neck Neck:
neck muscle weakness

Head And Neck Mouth:
high-arched palate
jaw contractures

Cardiovascular Heart:
decreased left ventricular ejection fraction (reported in 1 patient)

Skeletal:
contractures (in more severe early-onset cases)

Skeletal Spine:
kyphoscoliosis

Abdomen Gastrointestinal:
feeding difficulties

Head And Neck Face:
facial diplegia
myopathic face

Chest Ribs Sternum Clavicles And Scapulae:
winged scapulae

Respiratory:
decreased vital capacity due to muscle weakness

Neurologic Central Nervous System:
delayed motor milestones due to muscle weakness

Clinical features from OMIM®:

609285 (Updated 08-Dec-2022)

UMLS symptoms related to Nemaline Myopathy 4:


waddling gait

Drugs & Therapeutics for Nemaline Myopathy 4

Search Clinical Trials, NIH Clinical Center for Nemaline Myopathy 4

Cochrane evidence based reviews: nemaline myopathy 4

Genetic Tests for Nemaline Myopathy 4

Genetic tests related to Nemaline Myopathy 4:

# Genetic test Affiliating Genes
1 Nemaline Myopathy 4 28 TPM2
2 Cap Myopathy 2 28
3 Nemaline Myopathy 4, Autosomal Dominant 28

Anatomical Context for Nemaline Myopathy 4

Organs/tissues related to Nemaline Myopathy 4:

MalaCards : Skeletal Muscle, Prostate, Pituitary
ODiseA: Skeletal Muscle

Publications for Nemaline Myopathy 4

Articles related to Nemaline Myopathy 4:

(show top 50) (show all 56)
# Title Authors PMID Year
1
Cap disease due to mutation of the beta-tropomyosin gene (TPM2). 62 57 5
19345583 2009
2
New morphologic and genetic findings in cap disease associated with beta-tropomyosin (TPM2) mutations. 62 57 5
19047562 2008
3
Congenital myopathy with nemaline rods and cap structures caused by a mutation in the beta-tropomyosin gene (TPM2). 62 57 5
17846275 2007
4
Cap disease caused by heterozygous deletion of the beta-tropomyosin gene TPM2. 62 57 5
17434307 2007
5
K7del is a common TPM2 gene mutation associated with nemaline myopathy and raised myofibre calcium sensitivity. 57 5
23378224 2013
6
Novel deletion of lysine 7 expands the clinical, histopathological and genetic spectrum of TPM2-related myopathies. 57 5
23413262 2013
7
Mutations in the beta-tropomyosin (TPM2) gene--a rare cause of nemaline myopathy. 57 5
11738357 2002
8
"Cap disease": new congenital myopathy. 62 57
7196531 1981
9
Phenotype-driven variant filtration strategy in exome sequencing toward a high diagnostic yield and identification of 85 novel variants in 400 patients with rare Mendelian disorders. 5
34008892 2021
10
A mutation of beta-tropomyosin gene in a Chinese family with distal arthrogryposis type I. 5
31966463 2017
11
Early-Onset Myopathies: Clinical Findings, Prevalence of Subgroups and Diagnostic Approach in a Single Neuromuscular Referral Center in Germany. 5
29172004 2017
12
Targeted Re-Sequencing Emulsion PCR Panel for Myopathies: Results in 94 Cases. 5
27854218 2016
13
Frequency and phenotype of patients carrying TPM2 and TPM3 gene mutations in a cohort of 94 patients with congenital myopathy. 5
24507666 2014
14
Mutations in repeating structural motifs of tropomyosin cause gain of function in skeletal muscle myopathy patients. 5
23886664 2013
15
Somatic mosaicism in TPM2-related myopathy with nemaline rods and cap structures. 5
23015096 2013
16
Mutations in TPM2 and congenital fibre type disproportion. 5
22832343 2012
17
[MEN for multiple endocrin neoplasms: When evokate MEN? Update 2022]. 62
36307322 2022
18
Novel autosomal dominant TPM3 mutation causes a combined congenital fibre type disproportion-cap disease histological pattern. 62
35688744 2022
19
Pretreatment visceral metastases in castration resistant metastatic prostate cancer: role in prediction versus actual site of disease progression. 62
35836271 2022
20
Markov State Modelling of Disease Courses and Mortality Risks of Patients with Community-Acquired Pneumonia. 62
32121038 2020
21
Establishment of a human induced pluripotent stem cell line (SDQLCHi004-A) from a patient with nemaline myopathy-4 disease carrying heterozygous mutation in TPM2 gene. 62
31526942 2019
22
Relative Clinical and Cost Burden of Community-Acquired Pneumonia Hospitalizations in Older Adults in the United States-A Cross-Sectional Analysis. 62
30200286 2018
23
The reason for the low Ca2+-sensitivity of thin filaments associated with the Glu41Lys mutation in the TPM2 gene is "freezing" of tropomyosin near the outer domain of actin and inhibition of actin monomer switching off during the ATPase cycle. 62
29792862 2018
24
A novel TPM2 gene splice-site mutation causes severe congenital myopathy with arthrogryposis and dysmorphic features. 62
27726070 2017
25
Complication of Community-Acquired Pneumonia (Including Cardiac Complications). 62
27960213 2016
26
Improving outcomes in community-acquired pneumonia. 62
26859379 2016
27
[The three-category classification of severe acute pancreatitis: a single-center pilot study]. 62
25623558 2014
28
ROBO1, a tumor suppressor and critical molecular barrier for localized tumor cells to acquire invasive phenotype: study in African-American and Caucasian prostate cancer models. 62
24752651 2014
29
Corticosteroids in the treatment of severe community-acquired pneumonia. 62
24817026 2014
30
Combined cap disease and nemaline myopathy in the same patient caused by an autosomal dominant mutation in the TPM3 gene. 62
24095155 2013
31
Mechanism of recruitment and activation of the endosome-associated deubiquitinase AMSH. 62
24151880 2013
32
Community-acquired pneumonia. 62
23422417 2013
33
BMI1 polycomb group protein acts as a master switch for growth and death of tumor cells: regulates TCF4-transcriptional factor-induced BCL2 signaling. 62
23671559 2013
34
Myopathies associated with β-tropomyosin mutations. 62
22749895 2012
35
Functional effects of congenital myopathy-related mutations in gamma-tropomyosin gene. 62
22749829 2012
36
Whole-Body muscle MRI in a series of patients with congenital myopathy related to TPM2 gene mutations. 62
22980765 2012
37
Protein aggregation in congenital myopathies. 62
22172423 2011
38
Ten-year outcomes: the clinical utility of single photon emission computed tomography/computed tomography capromab pendetide (Prostascint) in a cohort diagnosed with localized prostate cancer. 62
20961696 2011
39
[Congenital myopathies - skeletal muscle diseases related to disorder of actin filament structure and functions]. 62
21677359 2011
40
Angiogenesis as a strategic target for prostate cancer therapy. 62
19536866 2010
41
A TPM3 mutation causing cap myopathy. 62
19553118 2009
42
RHAMM (CD168) is overexpressed at the protein level and may constitute an immunogenic antigen in advanced prostate cancer disease. 62
19724689 2009
43
TPM3 mutation in one of the original cases of cap disease. 62
19487656 2009
44
[Familial pituitary adenomas]. 62
18990538 2009
45
Genetic variation for resistance to ergot (Claviceps purpurea [Fr.] Tul.) among full-sib families of five populations of winter rye (Secale cereale L.). 62
18797841 2008
46
Thin filament proteins mutations associated with skeletal myopathies: defective regulation of muscle contraction. 62
18574571 2008
47
The role of extracellular matrix metalloproteinase inducer protein in prostate cancer progression. 62
18273614 2008
48
Residual prostate cancer after radiotherapy: a study of radical cystoprostatectomy specimens. 62
18289645 2008
49
Tropomyosins in skeletal muscle diseases. 62
19209820 2008
50
Skeletal muscle disease due to mutations in tropomyosin, troponin and cofilin. 62
19181092 2008

Variations for Nemaline Myopathy 4

ClinVar genetic disease variations for Nemaline Myopathy 4:

5 (show all 38)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TPM2 NM_003289.4(TPM2):c.440A>C (p.Gln147Pro) SNV Pathogenic
12461 rs104894128 GRCh37: 9:35685483-35685483
GRCh38: 9:35685486-35685486
2 TPM2 NM_003289.4(TPM2):c.121G>A (p.Glu41Lys) SNV Pathogenic
12464 rs137853306 GRCh37: 9:35689262-35689262
GRCh38: 9:35689265-35689265
3 TPM2 NM_003289.4(TPM2):c.14AGA[2] (p.Lys7del) MICROSAT Pathogenic
140486 rs199476146 GRCh37: 9:35689793-35689795
GRCh38: 9:35689796-35689798
4 TPM2 NM_003289.4(TPM2):c.349G>A (p.Glu117Lys) SNV Pathogenic
12462 rs104894129 GRCh37: 9:35685669-35685669
GRCh38: 9:35685672-35685672
5 TPM2 NM_003289.4(TPM2):c.412GAG[1] (p.Glu139del) MICROSAT Pathogenic
Pathogenic
12465 rs199476153 GRCh37: 9:35685506-35685508
GRCh38: 9:35685509-35685511
6 TPM2 NM_003289.4(TPM2):c.782A>G (p.Tyr261Cys) SNV Pathogenic
977300 rs1824676022 GRCh37: 9:35683229-35683229
GRCh38: 9:35683232-35683232
7 TPM2 NM_003289.4(TPM2):c.142AAG[1] (p.Lys49del) MICROSAT Pathogenic
12466 rs199476147 GRCh37: 9:35689236-35689238
GRCh38: 9:35689239-35689241
8 TPM2 NM_003289.4(TPM2):c.606C>G (p.Asn202Lys) SNV Pathogenic
12467 rs137853307 GRCh37: 9:35684762-35684762
GRCh38: 9:35684765-35684765
9 TPM2 NM_003289.4(TPM2):c.463G>A (p.Ala155Thr) SNV Likely Pathogenic
569587 rs1563929039 GRCh37: 9:35685460-35685460
GRCh38: 9:35685463-35685463
10 TPM2 NM_213674.1(TPM2):c.773-2A>C SNV Likely Pathogenic
1299603 GRCh37: 9:35682162-35682162
GRCh38: 9:35682165-35682165
11 TPM2 NM_003289.4(TPM2):c.181T>C (p.Ser61Pro) SNV Likely Pathogenic
224658 rs878854363 GRCh37: 9:35689202-35689202
GRCh38: 9:35689205-35689205
12 TPM2 NM_003289.4(TPM2):c.269G>A (p.Arg90His) SNV Likely Pathogenic
617588 rs1563929454 GRCh37: 9:35685749-35685749
GRCh38: 9:35685752-35685752
13 TPM2 NM_003289.4(TPM2):c.*22C>A SNV Uncertain Significance
912915 rs1824669468 GRCh37: 9:35683134-35683134
GRCh38: 9:35683137-35683137
14 TPM2 NM_003289.4(TPM2):c.773-3C>A SNV Uncertain Significance
140496 rs199476157 GRCh37: 9:35683241-35683241
GRCh38: 9:35683244-35683244
15 TPM2 NM_003289.4(TPM2):c.760G>A (p.Asp254Asn) SNV Uncertain Significance
913283 rs1419786293 GRCh37: 9:35684255-35684255
GRCh38: 9:35684258-35684258
16 TPM2 NM_003289.4(TPM2):c.569G>A (p.Cys190Tyr) SNV Uncertain Significance
913284 rs1369077598 GRCh37: 9:35684799-35684799
GRCh38: 9:35684802-35684802
17 TPM2 NM_003289.4(TPM2):c.-92C>T SNV Uncertain Significance
366773 rs886063906 GRCh37: 9:35689906-35689906
GRCh38: 9:35689909-35689909
18 TPM2 NM_003289.4(TPM2):c.*99A>G SNV Uncertain Significance
366765 rs879505630 GRCh37: 9:35683057-35683057
GRCh38: 9:35683060-35683060
19 TPM2 NM_003289.4(TPM2):c.*199C>T SNV Uncertain Significance
914860 rs965743785 GRCh37: 9:35682957-35682957
GRCh38: 9:35682960-35682960
20 TPM2 NM_003289.4(TPM2):c.*194C>T SNV Uncertain Significance
914861 rs561175276 GRCh37: 9:35682962-35682962
GRCh38: 9:35682965-35682965
21 TPM2 NM_003289.4(TPM2):c.773-5C>G SNV Uncertain Significance
1028593 rs1230541017 GRCh37: 9:35683243-35683243
GRCh38: 9:35683246-35683246
22 TPM2 NM_213674.1(TPM2):c.-142C>T SNV Uncertain Significance
912958 rs1825166266 GRCh37: 9:35689956-35689956
GRCh38: 9:35689959-35689959
23 TPM2 NM_213674.1(TPM2):c.-118G>A SNV Uncertain Significance
914913 rs986048371 GRCh37: 9:35689932-35689932
GRCh38: 9:35689935-35689935
24 TPM2 NM_213674.1(TPM2):c.-238C>T SNV Uncertain Significance
366775 rs886063908 GRCh37: 9:35690052-35690052
GRCh38: 9:35690055-35690055
25 TPM2 NM_213674.1(TPM2):c.-158C>A SNV Uncertain Significance
366774 rs886063907 GRCh37: 9:35689972-35689972
GRCh38: 9:35689975-35689975
26 TPM2 NM_213674.1(TPM2):c.826C>G (p.Gln276Glu) SNV Uncertain Significance
548556 rs376668943 GRCh37: 9:35682107-35682107
GRCh38: 9:35682110-35682110
27 TPM2 NM_003289.4(TPM2):c.564-9C>T SNV Likely Benign
366770 rs763429317 GRCh37: 9:35684813-35684813
GRCh38: 9:35684816-35684816
28 TPM2 NM_003289.4(TPM2):c.*25A>C SNV Likely Benign
366766 rs781513152 GRCh37: 9:35683131-35683131
GRCh38: 9:35683134-35683134
29 TPM2 NM_003289.4(TPM2):c.-10C>A SNV Likely Benign
366771 rs372751531 GRCh37: 9:35689824-35689824
GRCh38: 9:35689827-35689827
30 TPM2 NM_003289.4(TPM2):c.558C>T (p.Ala186=) SNV Likely Benign
914400 rs746177794 GRCh37: 9:35685271-35685271
GRCh38: 9:35685274-35685274
31 TPM2 NM_003289.4(TPM2):c.-65C>T SNV Benign
366772 rs377242459 GRCh37: 9:35689879-35689879
GRCh38: 9:35689882-35689882
32 TPM2 NM_003289.4(TPM2):c.*7C>T SNV Benign
94121 rs79882576 GRCh37: 9:35683149-35683149
GRCh38: 9:35683152-35683152
33 TPM2 NM_003289.4(TPM2):c.813C>T (p.Ser271=) SNV Benign
366767 rs201215303 GRCh37: 9:35683198-35683198
GRCh38: 9:35683201-35683201
34 TPM2 NM_003289.4(TPM2):c.*8G>A SNV Benign
94122 rs56249943 GRCh37: 9:35683148-35683148
GRCh38: 9:35683151-35683151
35 TPM2 NM_003289.4(TPM2):c.374+9G>C SNV Benign
458723 rs200730708 GRCh37: 9:35685635-35685635
GRCh38: 9:35685638-35685638
36 TPM2 NM_213674.1(TPM2):c.-135T>A SNV Benign
670242 rs3793538 GRCh37: 9:35689949-35689949
GRCh38: 9:35689952-35689952
37 TPM2 NM_213674.1(TPM2):c.-136T>A SNV Benign
670241 rs3793539 GRCh37: 9:35689950-35689950
GRCh38: 9:35689953-35689953
38 TPM2 NM_213674.1(TPM2):c.-137T>A SNV Benign
670240 rs3793540 GRCh37: 9:35689951-35689951
GRCh38: 9:35689954-35689954

UniProtKB/Swiss-Prot genetic disease variations for Nemaline Myopathy 4:

73
# Symbol AA change Variation ID SNP ID
1 TPM2 p.Glu117Ala VAR_013468
2 TPM2 p.Gln147Pro VAR_013469 rs104894128
3 TPM2 p.Glu41Lys VAR_070978 rs137853306
4 TPM2 p.Arg133Trp VAR_070981 rs137853305
5 TPM2 p.Asn202Lys VAR_070983 rs137853307
6 TPM2 p.Ala3Gly VAR_071486
7 TPM2 p.Asp14Val VAR_071488
8 TPM2 p.Leu143Pro VAR_071494
9 TPM2 p.Leu148Pro VAR_071495

Expression for Nemaline Myopathy 4

Search GEO for disease gene expression data for Nemaline Myopathy 4.

Pathways for Nemaline Myopathy 4

GO Terms for Nemaline Myopathy 4

Sources for Nemaline Myopathy 4

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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