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 56 12 73 29 6 15 71
Cap Myopathy 2 56 73 29 6 71
Nemaline Myopathy 4, Autosomal Dominant 56 12 29
Nem4 56 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:

56
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 nemaline myopathy and myopathy, and has symptoms including waddling gait An important gene associated with Nemaline Myopathy 4 is TPM2 (Tropomyosin 2). The drugs Anti-Bacterial Agents and Antibiotics, Antitubercular have been mentioned in the context of this disorder. Affiliated tissues include skeletal muscle, and related phenotypes are muscular hypotonia 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, 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 25)
# Related Disease Score Top Affiliating Genes
1 nemaline myopathy 29.9 TPM2 KLHL41
2 myopathy 28.5 TPM2 LMOD3 KLHL41 KBTBD13
3 congenital fiber-type disproportion 28.2 TPM2 LMOD3 KLHL41 KBTBD13
4 cap myopathy 11.8
5 nemaline myopathy 1 11.5
6 myopathy, congenital 10.1
7 myopathy, congenital, with fiber-type disproportion 9.9
8 alkuraya-kucinskas syndrome 9.8
9 distal arthrogryposis 9.8
10 congenital amyoplasia 9.8
11 severe congenital nemaline myopathy 9.7 LMOD3 KLHL41
12 arthrogryposis, distal, type 1a 9.7
13 cryopyrin-associated periodic syndrome 9.7
14 hypotonia 9.7
15 typical congenital nemaline myopathy 9.5 TPM2 LMOD3 KLHL41
16 multiple pterygium syndrome, escobar variant 9.4 TPM2 LMOD3 KLHL41
17 nemaline myopathy 11, autosomal recessive 9.4 LMOD3 KBTBD13
18 childhood-onset nemaline myopathy 9.4 TPM2 KLHL41 KBTBD13
19 centronuclear myopathy 9.4 TPM2 KBTBD13
20 nemaline myopathy 8 9.3 LMOD3 KBTBD13
21 nemaline myopathy 9 9.2 LMOD3 KLHL41 KBTBD13
22 nemaline myopathy 3 9.1 LMOD3 KLHL41 KBTBD13
23 nemaline myopathy 10 9.1 LMOD3 KLHL41 KBTBD13
24 nemaline myopathy 2 9.1 LMOD3 KLHL41 KBTBD13
25 congenital structural myopathy 8.9 TPM2 LMOD3 KLHL41 KBTBD13

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

Symptoms via clinical synopsis from OMIM:

56
Abdomen Gastrointestinal:
feeding difficulties

Skeletal Spine:
kyphoscoliosis

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)

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

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

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 Anti-Bacterial Agents
2 Antibiotics, Antitubercular

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
2 Study of Progression of Hospitalized Community Acquired Pneumonia - Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis Recruiting NCT02782013

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:

(show all 11)
# Title Authors PMID Year
1
K7del is a common TPM2 gene mutation associated with nemaline myopathy and raised myofibre calcium sensitivity. 56 6
23378224 2013
2
Novel deletion of lysine 7 expands the clinical, histopathological and genetic spectrum of TPM2-related myopathies. 56 6
23413262 2013
3
Cap disease due to mutation of the beta-tropomyosin gene (TPM2). 56 6
19345583 2009
4
New morphologic and genetic findings in cap disease associated with beta-tropomyosin (TPM2) mutations. 6 56
19047562 2008
5
Congenital myopathy with nemaline rods and cap structures caused by a mutation in the beta-tropomyosin gene (TPM2). 6 56
17846275 2007
6
Cap disease caused by heterozygous deletion of the beta-tropomyosin gene TPM2. 6 56
17434307 2007
7
Mutations in the beta-tropomyosin (TPM2) gene--a rare cause of nemaline myopathy. 56 6
11738357 2002
8
Clinical utility gene card for: nemaline myopathy. 6
22510848 2012
9
Nemaline Myopathy – ARCHIVED CHAPTER, FOR HISTORICAL REFERENCE ONLY 6
20301465 2002
10
"Cap disease": new congenital myopathy. 56
7196531 1981
11
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 34) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# 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.121G>A (p.Glu41Lys)SNV Pathogenic 12464 rs137853306 9:35689262-35689262 9:35689265-35689265
4 TPM2 NM_213674.1(TPM2):c.412_414GAG[1] (p.Glu139del)short repeat Pathogenic 12465 rs199476153 9:35685506-35685508 9:35685509-35685511
5 TPM2 NM_213674.1(TPM2):c.142_144AAG[1] (p.Lys49del)short repeat Pathogenic 12466 rs199476147 9:35689236-35689238 9:35689239-35689241
6 TPM2 NM_213674.1(TPM2):c.640-215C>GSNV Pathogenic 12467 rs137853307 9:35684762-35684762 9:35684765-35684765
7 TPM2 NM_213674.1(TPM2):c.14_16AGA[2] (p.Lys7del)short repeat Pathogenic 140486 rs199476146 9:35689793-35689795 9:35689796-35689798
8 TPM2 NM_213674.1(TPM2):c.181T>C (p.Ser61Pro)SNV Likely pathogenic 224658 rs878854363 9:35689202-35689202 9:35689205-35689205
9 TPM2 NM_213674.1(TPM2):c.269G>A (p.Arg90His)SNV Likely pathogenic 617588 rs1563929454 9:35685749-35685749 9:35685752-35685752
10 TPM2 NM_213674.1(TPM2):c.374+9G>CSNV Conflicting interpretations of pathogenicity 458723 rs200730708 9:35685635-35685635 9:35685638-35685638
11 TPM2 NM_003289.4(TPM2):c.558C>T (p.Ala186=)SNV Conflicting interpretations of pathogenicity 914400 9:35685271-35685271 9:35685274-35685274
12 TPM2 NM_213674.1(TPM2):c.639+248C>TSNV Conflicting interpretations of pathogenicity 366770 rs763429317 9:35684813-35684813 9:35684816-35684816
13 TPM2 NM_213674.1(TPM2):c.-10C>ASNV Conflicting interpretations of pathogenicity 366771 rs372751531 9:35689824-35689824 9:35689827-35689827
14 TPM2 NM_213674.1(TPM2):c.773-971A>CSNV Conflicting interpretations of pathogenicity 366766 rs781513152 9:35683131-35683131 9:35683134-35683134
15 TPM2 NM_213674.1(TPM2):c.-92C>TSNV Uncertain significance 366773 rs886063906 9:35689906-35689906 9:35689909-35689909
16 TPM2 NM_213674.1(TPM2):c.-158C>ASNV Uncertain significance 366774 rs886063907 9:35689972-35689972 9:35689975-35689975
17 TPM2 NM_213674.1(TPM2):c.-238C>TSNV Uncertain significance 366775 rs886063908 9:35690052-35690052 9:35690055-35690055
18 TPM2 NM_213674.1(TPM2):c.-118G>ASNV Uncertain significance 914913 9:35689932-35689932 9:35689935-35689935
19 TPM2 NM_213674.1(TPM2):c.-142C>TSNV Uncertain significance 912958 9:35689956-35689956 9:35689959-35689959
20 TPM2 NM_213674.1(TPM2):c.826C>G (p.Gln276Glu)SNV Uncertain significance 548556 rs376668943 9:35682107-35682107 9:35682110-35682110
21 TPM2 NM_213674.1(TPM2):c.773-897A>GSNV Uncertain significance 366765 rs879505630 9:35683057-35683057 9:35683060-35683060
22 TPM2 NM_213674.1(TPM2):c.772+1002C>ASNV Uncertain significance 140496 rs199476157 9:35683241-35683241 9:35683244-35683244
23 TPM2 NM_003289.4(TPM2):c.*199C>TSNV Uncertain significance 914860 9:35682957-35682957 9:35682960-35682960
24 TPM2 NM_003289.4(TPM2):c.*194C>TSNV Uncertain significance 914861 9:35682962-35682962 9:35682965-35682965
25 TPM2 NM_003289.4(TPM2):c.*22C>ASNV Uncertain significance 912915 9:35683134-35683134 9:35683137-35683137
26 TPM2 NM_003289.4(TPM2):c.760G>A (p.Asp254Asn)SNV Uncertain significance 913283 9:35684255-35684255 9:35684258-35684258
27 TPM2 NM_003289.4(TPM2):c.569G>A (p.Cys190Tyr)SNV Uncertain significance 913284 9:35684799-35684799 9:35684802-35684802
28 TPM2 NM_213674.1(TPM2):c.773-1038C>TSNV Benign/Likely benign 366767 rs201215303 9:35683198-35683198 9:35683201-35683201
29 TPM2 NM_213674.1(TPM2):c.-65C>TSNV Benign 366772 rs377242459 9:35689879-35689879 9:35689882-35689882
30 TPM2 NM_213674.1(TPM2):c.-135T>ASNV Benign 670242 9:35689949-35689949 9:35689952-35689952
31 TPM2 NM_213674.1(TPM2):c.-136T>ASNV Benign 670241 9:35689950-35689950 9:35689953-35689953
32 TPM2 NM_213674.1(TPM2):c.-137T>ASNV Benign 670240 9:35689951-35689951 9:35689954-35689954
33 TPM2 NM_213674.1(TPM2):c.773-989C>TSNV Benign 94121 rs79882576 9:35683149-35683149 9:35683152-35683152
34 TPM2 NM_003289.4(TPM2):c.*8G>ASNV Benign 94122 rs56249943 9:35683148-35683148 9:35683151-35683151

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

Cellular components related to Nemaline Myopathy 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 M band GO:0031430 8.62 LMOD3 KLHL41

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 9.32 TPM2 LMOD3
2 muscle contraction GO:0006936 9.26 TPM2 LMOD3
3 skeletal muscle fiber development GO:0048741 9.16 LMOD3 KLHL41
4 striated muscle contraction GO:0006941 8.96 LMOD3 KLHL41
5 myofibril assembly GO:0030239 8.62 LMOD3 KLHL41

Sources for Nemaline Myopathy 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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