NEM4
MCID: NML005
MIFTS: 39

Nemaline Myopathy 4 (NEM4)

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

Aliases & Classifications for Nemaline Myopathy 4

MalaCards integrated aliases for Nemaline Myopathy 4:

Name: Nemaline Myopathy 4 58 12 76 30 6 15 74
Cap Myopathy 2 58 76 30 6 74
Nem4 58 12 76
Nemaline Myopathy 4, Autosomal Dominant 58 12
Tpm2-Related Nemaline Myopathy 76
Myopathy, Nemaline, Type 4 41
Nemaline Myopathy, Type 4 77
Cap Myopathy Tpm2-Related 76
Cap Myopathy 74
Cap Disease 76
Capm2 76

Characteristics:

OMIM:

58
Inheritance:
autosomal dominant

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


HPO:

33
nemaline myopathy 4:
Onset and clinical course variable expressivity childhood onset
Inheritance heterogeneous autosomal dominant inheritance


Classifications:



Summaries for Nemaline Myopathy 4

UniProtKB/Swiss-Prot : 76 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 cap myopathy and nemaline myopathy 1, and has symptoms including waddling gait An important gene associated with Nemaline Myopathy 4 is TPM2 (Tropomyosin 2), and among its related pathways/superpathways are Cell cycle and Transcriptional misregulation in cancer. Affiliated tissues include skeletal muscle, and related phenotypes are high palate and muscular hypotonia

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

Wikipedia : 77 Nemaline myopathy (also called rod myopathy or nemaline rod myopathy) is a congenital, hereditary... more...

Description from OMIM: 609285

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:

33 (show all 20)
# Description HPO Frequency HPO Source Accession
1 high palate 33 HP:0000218
2 muscular hypotonia 33 HP:0001252
3 flexion contracture 33 HP:0001371
4 feeding difficulties in infancy 33 HP:0008872
5 skeletal muscle atrophy 33 HP:0003202
6 waddling gait 33 HP:0002515
7 scapular winging 33 HP:0003691
8 motor delay 33 HP:0001270
9 kyphoscoliosis 33 HP:0002751
10 type 1 muscle fiber predominance 33 HP:0003803
11 nemaline bodies 33 HP:0003798
12 difficulty walking 33 HP:0002355
13 hyporeflexia 33 HP:0001265
14 myopathic facies 33 HP:0002058
15 facial diplegia 33 HP:0001349
16 generalized hypotonia 33 HP:0001290
17 reduced vital capacity 33 HP:0002792
18 limb muscle weakness 33 HP:0003690
19 neck muscle weakness 33 HP:0000467
20 gowers sign 33 HP:0003391

Symptoms via clinical synopsis from OMIM:

58
Abdomen Gastrointestinal:
feeding difficulties

Skeletal Spine:
kyphoscoliosis

Head And Neck Face:
facial diplegia
myopathic face

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)

Muscle Soft Tissue:
waddling gait
difficulty walking
facial diplegia
limb muscle weakness
neck muscle weakness
more
Neurologic Peripheral Nervous System:
hyporeflexia

Head And Neck Neck:
neck muscle weakness

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

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

Genetic Tests for Nemaline Myopathy 4

Genetic tests related to Nemaline Myopathy 4:

# Genetic test Affiliating Genes
1 Nemaline Myopathy 4 30 TPM2
2 Cap Myopathy 2 30

Anatomical Context for Nemaline Myopathy 4

MalaCards organs/tissues related to Nemaline Myopathy 4:

42
Skeletal Muscle

Publications for Nemaline Myopathy 4

Articles related to Nemaline Myopathy 4:

# Title Authors Year
1
Dominantly inherited distal nemaline/cap myopathy caused by a large deletion in the nebulin gene. ( 30679003 )
2018
2
Recessive MYPN mutations cause cap myopathy with occasional nemaline rods. ( 28220527 )
2017
3
The role of ultrasound in fetal congenital myopathy detection: a novel case of fetal-onset cap myopathy. ( 23804214 )
2013
4
Novel TPM3 mutation in a family with cap myopathy and review of the literature. ( 24239060 )
2013
5
Abnormal actin binding of aberrant I^-tropomyosins is a molecular cause of muscle weakness in TPM2-related nemaline and cap myopathy. ( 22084935 )
2012
6
Evidence for a dominant negative disease mechanism in cap myopathy due to TPM3. ( 20554445 )
2010
7
Cap myopathy caused by a mutation of the skeletal alpha-actin gene ACTA1. ( 20303757 )
2010
8
A TPM3 mutation causing cap myopathy. ( 19553118 )
2009

Variations for Nemaline Myopathy 4

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

76
# 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

ClinVar genetic disease variations for Nemaline Myopathy 4:

6 (show all 20)
# Gene Variation Type Significance SNP ID Assembly Location
1 TPM2 NM_003289.3(TPM2): c.440A> C (p.Gln147Pro) single nucleotide variant Pathogenic rs104894128 GRCh37 Chromosome 9, 35685483: 35685483
2 TPM2 NM_003289.3(TPM2): c.440A> C (p.Gln147Pro) single nucleotide variant Pathogenic rs104894128 GRCh38 Chromosome 9, 35685486: 35685486
3 TPM2 NM_003289.3(TPM2): c.349G> A (p.Glu117Lys) single nucleotide variant Pathogenic rs104894129 GRCh37 Chromosome 9, 35685669: 35685669
4 TPM2 NM_003289.3(TPM2): c.349G> A (p.Glu117Lys) single nucleotide variant Pathogenic rs104894129 GRCh38 Chromosome 9, 35685672: 35685672
5 TPM2 NM_003289.3(TPM2): c.121G> A (p.Glu41Lys) single nucleotide variant Pathogenic rs137853306 GRCh37 Chromosome 9, 35689262: 35689262
6 TPM2 NM_003289.3(TPM2): c.121G> A (p.Glu41Lys) single nucleotide variant Pathogenic rs137853306 GRCh38 Chromosome 9, 35689265: 35689265
7 TPM2 NM_003289.3(TPM2): c.415_417delGAG (p.Glu139del) deletion Pathogenic rs199476153 GRCh37 Chromosome 9, 35685506: 35685508
8 TPM2 NM_003289.3(TPM2): c.415_417delGAG (p.Glu139del) deletion Pathogenic rs199476153 GRCh38 Chromosome 9, 35685509: 35685511
9 TPM2 NM_003289.3(TPM2): c.145_147delAAG (p.Lys49del) deletion Pathogenic rs199476147 GRCh37 Chromosome 9, 35689236: 35689238
10 TPM2 NM_003289.3(TPM2): c.145_147delAAG (p.Lys49del) deletion Pathogenic rs199476147 GRCh38 Chromosome 9, 35689239: 35689241
11 TPM2 NM_003289.3(TPM2): c.606C> G (p.Asn202Lys) single nucleotide variant Pathogenic rs137853307 GRCh37 Chromosome 9, 35684762: 35684762
12 TPM2 NM_003289.3(TPM2): c.606C> G (p.Asn202Lys) single nucleotide variant Pathogenic rs137853307 GRCh38 Chromosome 9, 35684765: 35684765
13 TPM2 NM_003289.3(TPM2): c.20_22delAGA (p.Lys7del) deletion Pathogenic rs199476146 GRCh37 Chromosome 9, 35689793: 35689795
14 TPM2 NM_003289.3(TPM2): c.20_22delAGA (p.Lys7del) deletion Pathogenic rs199476146 GRCh38 Chromosome 9, 35689796: 35689798
15 TPM2 NM_003289.3(TPM2): c.181T> C (p.Ser61Pro) single nucleotide variant Likely pathogenic rs878854363 GRCh37 Chromosome 9, 35689202: 35689202
16 TPM2 NM_003289.3(TPM2): c.181T> C (p.Ser61Pro) single nucleotide variant Likely pathogenic rs878854363 GRCh38 Chromosome 9, 35689205: 35689205
17 TPM2 NM_213674.1(TPM2): c.826C> G (p.Gln276Glu) single nucleotide variant Uncertain significance rs376668943 GRCh38 Chromosome 9, 35682110: 35682110
18 TPM2 NM_213674.1(TPM2): c.826C> G (p.Gln276Glu) single nucleotide variant Uncertain significance rs376668943 GRCh37 Chromosome 9, 35682107: 35682107
19 TPM2 NM_001301226.1(TPM2): c.269G> A (p.Arg90His) single nucleotide variant Likely pathogenic GRCh38 Chromosome 9, 35685752: 35685752
20 TPM2 NM_001301226.1(TPM2): c.269G> A (p.Arg90His) single nucleotide variant Likely pathogenic GRCh37 Chromosome 9, 35685749: 35685749

Expression for Nemaline Myopathy 4

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

Pathways for Nemaline Myopathy 4

Pathways related to Nemaline Myopathy 4 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.32 CDKN1B MEN1
2 10.89 CDKN1B MEN1

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 negative regulation of cell proliferation GO:0008285 9.26 CDKN1B MEN1
2 negative regulation of epithelial cell proliferation GO:0050680 9.16 CDKN1B MEN1
3 negative regulation of cell cycle GO:0045786 8.96 CDKN1B MEN1
4 negative regulation of cyclin-dependent protein serine/threonine kinase activity GO:0045736 8.62 CDKN1B MEN1

Sources for Nemaline Myopathy 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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