NEM4
MCID: NML005
MIFTS: 38

Nemaline Myopathy 4 (NEM4)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Nemaline Myopathy 4

MalaCards integrated aliases for Nemaline Myopathy 4:

Name: Nemaline Myopathy 4 57 12 73 29 6 15 71
Cap Myopathy 2 57 73 29 6 71
Nemaline Myopathy 4, Autosomal Dominant 57 12 29
Nem4 57 12 73
Tpm2-Related Nemaline Myopathy 73
Myopathy, Nemaline, Type 4 39
Nemaline Myopathy, Type 4 74
Cap Myopathy Tpm2-Related 73
Cap Myopathy 71
Cap Disease 73
Capm2 73

Characteristics:

OMIM®:

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

Miscellaneous:
variable severity
genetic heterogeneity (see )
childhood onset (range birth to 12 years)


HPO:

31
nemaline myopathy 4:
Inheritance autosomal dominant inheritance heterogeneous
Onset and clinical course variable expressivity childhood onset


Classifications:



Summaries for Nemaline Myopathy 4

UniProtKB/Swiss-Prot : 73 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.
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.

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). The drugs Antibiotics, Antitubercular and Anti-Bacterial Agents have been mentioned in the context of this disorder. Affiliated tissues include skeletal muscle, and related phenotypes are high palate and flexion contracture

Disease Ontology : 12 A nemaline myopathy that has material basis in heterozygous mutation in the TPM2 gene on chromosome 9p13.

Wikipedia : 74 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

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:

31 (show all 20)
# Description HPO Frequency HPO Source Accession
1 high palate 31 HP:0000218
2 flexion contracture 31 HP:0001371
3 feeding difficulties in infancy 31 HP:0008872
4 skeletal muscle atrophy 31 HP:0003202
5 waddling gait 31 HP:0002515
6 scapular winging 31 HP:0003691
7 motor delay 31 HP:0001270
8 kyphoscoliosis 31 HP:0002751
9 type 1 muscle fiber predominance 31 HP:0003803
10 nemaline bodies 31 HP:0003798
11 hyporeflexia 31 HP:0001265
12 limb muscle weakness 31 HP:0003690
13 reduced vital capacity 31 HP:0002792
14 generalized hypotonia 31 HP:0001290
15 difficulty walking 31 HP:0002355
16 neck muscle weakness 31 HP:0000467
17 gowers sign 31 HP:0003391
18 myopathic facies 31 HP:0002058
19 facial diplegia 31 HP:0001349
20 hypotonia 31 HP:0001252

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Muscle Soft Tissue:
waddling gait
limb muscle weakness
difficulty walking
neck muscle weakness
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 05-Mar-2021)

UMLS symptoms related to Nemaline Myopathy 4:


waddling gait

Drugs & Therapeutics for Nemaline Myopathy 4

Drugs for Nemaline Myopathy 4 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Antibiotics, Antitubercular
2 Anti-Bacterial Agents

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Evaluating the Impact of a New Model of Care Designed to Improve Evidence-based Management of Community-acquired Pneumonia Completed NCT02835040

Search NIH Clinical Center for Nemaline Myopathy 4

Genetic Tests for Nemaline Myopathy 4

Genetic tests related to Nemaline Myopathy 4:

# Genetic test Affiliating Genes
1 Nemaline Myopathy 4 29 TPM2
2 Cap Myopathy 2 29
3 Nemaline Myopathy 4, Autosomal Dominant 29

Anatomical Context for Nemaline Myopathy 4

MalaCards organs/tissues related to Nemaline Myopathy 4:

40
Skeletal Muscle

Publications for Nemaline Myopathy 4

Articles related to Nemaline Myopathy 4:

# Title Authors PMID Year
1
K7del is a common TPM2 gene mutation associated with nemaline myopathy and raised myofibre calcium sensitivity. 57 6
23378224 2013
2
Novel deletion of lysine 7 expands the clinical, histopathological and genetic spectrum of TPM2-related myopathies. 57 6
23413262 2013
3
Cap disease due to mutation of the beta-tropomyosin gene (TPM2). 6 57
19345583 2009
4
New morphologic and genetic findings in cap disease associated with beta-tropomyosin (TPM2) mutations. 6 57
19047562 2008
5
Congenital myopathy with nemaline rods and cap structures caused by a mutation in the beta-tropomyosin gene (TPM2). 6 57
17846275 2007
6
Cap disease caused by heterozygous deletion of the beta-tropomyosin gene TPM2. 6 57
17434307 2007
7
Mutations in the beta-tropomyosin (TPM2) gene--a rare cause of nemaline myopathy. 6 57
11738357 2002
8
"Cap disease": new congenital myopathy. 57
7196531 1981
9
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. 61
31526942 2019

Variations for Nemaline Myopathy 4

ClinVar genetic disease variations for Nemaline Myopathy 4:

6 (show all 36)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TPM2 NM_213674.1(TPM2):c.440A>C (p.Gln147Pro) SNV Pathogenic 12461 rs104894128 9:35685483-35685483 9:35685486-35685486
2 TPM2 NM_213674.1(TPM2):c.349G>A (p.Glu117Lys) SNV Pathogenic 12462 rs104894129 9:35685669-35685669 9:35685672-35685672
3 TPM2 NM_213674.1(TPM2):c.412_414GAG[1] (p.Glu139del) Microsatellite Pathogenic 12465 rs199476153 9:35685506-35685508 9:35685509-35685511
4 TPM2 NM_213674.1(TPM2):c.14_16AGA[2] (p.Lys7del) Microsatellite Pathogenic 140486 rs199476146 9:35689793-35689795 9:35689796-35689798
5 TPM2 NM_213674.1(TPM2):c.412_414GAG[1] (p.Glu139del) Microsatellite Pathogenic 12465 rs199476153 9:35685506-35685508 9:35685509-35685511
6 TPM2 NM_213674.1(TPM2):c.121G>A (p.Glu41Lys) SNV Pathogenic 12464 rs137853306 9:35689262-35689262 9:35689265-35689265
7 TPM2 NM_213674.1(TPM2):c.640-215C>G SNV Pathogenic 12467 rs137853307 9:35684762-35684762 9:35684765-35684765
8 TPM2 NM_213674.1(TPM2):c.142_144AAG[1] (p.Lys49del) Microsatellite Pathogenic 12466 rs199476147 9:35689236-35689238 9:35689239-35689241
9 TPM2 NM_003289.4(TPM2):c.782A>G (p.Tyr261Cys) SNV Pathogenic 977300 9:35683229-35683229 9:35683232-35683232
10 TPM2 NM_213674.1(TPM2):c.181T>C (p.Ser61Pro) SNV Likely pathogenic 224658 rs878854363 9:35689202-35689202 9:35689205-35689205
11 TPM2 NM_213674.1(TPM2):c.269G>A (p.Arg90His) SNV Likely pathogenic 617588 rs1563929454 9:35685749-35685749 9:35685752-35685752
12 TPM2 NM_003289.4(TPM2):c.*22C>A SNV Uncertain significance 912915 9:35683134-35683134 9:35683137-35683137
13 TPM2 NM_213674.1(TPM2):c.826C>G (p.Gln276Glu) SNV Uncertain significance 548556 rs376668943 9:35682107-35682107 9:35682110-35682110
14 TPM2 NM_213674.1(TPM2):c.-92C>T SNV Uncertain significance 366773 rs886063906 9:35689906-35689906 9:35689909-35689909
15 TPM2 NM_213674.1(TPM2):c.-158C>A SNV Uncertain significance 366774 rs886063907 9:35689972-35689972 9:35689975-35689975
16 TPM2 NM_213674.1(TPM2):c.773-897A>G SNV Uncertain significance 366765 rs879505630 9:35683057-35683057 9:35683060-35683060
17 TPM2 NM_213674.1(TPM2):c.-238C>T SNV Uncertain significance 366775 rs886063908 9:35690052-35690052 9:35690055-35690055
18 TPM2 NM_213674.1(TPM2):c.-118G>A SNV Uncertain significance 914913 9:35689932-35689932 9:35689935-35689935
19 TPM2 NM_003289.4(TPM2):c.*199C>T SNV Uncertain significance 914860 9:35682957-35682957 9:35682960-35682960
20 TPM2 NM_003289.4(TPM2):c.*194C>T SNV Uncertain significance 914861 9:35682962-35682962 9:35682965-35682965
21 TPM2 NM_213674.1(TPM2):c.-142C>T SNV Uncertain significance 912958 9:35689956-35689956 9:35689959-35689959
22 TPM2 NM_213674.1(TPM2):c.772+1002C>A SNV Uncertain significance 140496 rs199476157 9:35683241-35683241 9:35683244-35683244
23 TPM2 NM_003289.4(TPM2):c.760G>A (p.Asp254Asn) SNV Uncertain significance 913283 9:35684255-35684255 9:35684258-35684258
24 TPM2 NM_003289.4(TPM2):c.569G>A (p.Cys190Tyr) SNV Uncertain significance 913284 9:35684799-35684799 9:35684802-35684802
25 TPM2 NM_003289.4(TPM2):c.558C>T (p.Ala186=) SNV Likely benign 914400 9:35685271-35685271 9:35685274-35685274
26 TPM2 NM_213674.1(TPM2):c.639+248C>T SNV Likely benign 366770 rs763429317 9:35684813-35684813 9:35684816-35684816
27 TPM2 NM_213674.1(TPM2):c.-10C>A SNV Likely benign 366771 rs372751531 9:35689824-35689824 9:35689827-35689827
28 TPM2 NM_213674.1(TPM2):c.773-971A>C SNV Likely benign 366766 rs781513152 9:35683131-35683131 9:35683134-35683134
29 TPM2 NM_003289.4(TPM2):c.*8G>A SNV Benign 94122 rs56249943 9:35683148-35683148 9:35683151-35683151
30 TPM2 NM_213674.1(TPM2):c.-65C>T SNV Benign 366772 rs377242459 9:35689879-35689879 9:35689882-35689882
31 TPM2 NM_213674.1(TPM2):c.773-989C>T SNV Benign 94121 rs79882576 9:35683149-35683149 9:35683152-35683152
32 TPM2 NM_213674.1(TPM2):c.773-1038C>T SNV Benign 366767 rs201215303 9:35683198-35683198 9:35683201-35683201
33 TPM2 NM_213674.1(TPM2):c.-136T>A SNV Benign 670241 rs3793539 9:35689950-35689950 9:35689953-35689953
34 TPM2 NM_213674.1(TPM2):c.-137T>A SNV Benign 670240 rs3793540 9:35689951-35689951 9:35689954-35689954
35 TPM2 NM_213674.1(TPM2):c.374+9G>C SNV Benign 458723 rs200730708 9:35685635-35685635 9:35685638-35685638
36 TPM2 NM_213674.1(TPM2):c.-135T>A SNV Benign 670242 rs3793538 9:35689949-35689949 9:35689952-35689952

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

Biological processes related to Nemaline Myopathy 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 actin filament organization GO:0007015 8.96 TPM2 LMOD3
2 muscle contraction GO:0006936 8.62 TPM2 LMOD3

Sources for Nemaline Myopathy 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-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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