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MFM2
MCID: MYP082
MIFTS: 42

Myopathy, Myofibrillar, 2 (MFM2)

Categories: Cancer diseases, Cardiovascular diseases, Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes
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Aliases & Classifications for Myopathy, Myofibrillar, 2

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MalaCards integrated aliases for Myopathy, Myofibrillar, 2:

Name: Myopathy, Myofibrillar, 2 58 76
Alpha-B Crystallinopathy 58 12 76 30 6 74
Myopathy, Myofibrillar, Alpha-B Crystallin-Related 58 13
Myofibrillar Myopathy 2 12 15
Mfm2 58 76
Myopathy, Myofibrillar, with or Without Cataract and/or Cardiomyopathy 58
Myopathy, Desmin-Related, Associated with Mutation in the Cryab Gene 58
Myofibrillar Myopathy with or Without Cataract and/or Cardiomyopathy 76
Myopathy Desmin-Related Associated with Mutation in the Cryab Gene 76
Alpha-B Crystallin-Related Late-Onset Distal Myopathy 60
Myopathy Cardioskeletal Desmin-Related with Cataract 76
Myofibrillar Myopathy Alpha-B Crystallin-Related 76
Alpha-B Crystallin-Related Late-Onset Myopathy 60
Alpha-B Crystallinopathy with Cataract 76
Desmin-Related Myopathy with Cataract 76
Late-Onset Distal Crystallinopathy 60
Mfm Alpha-B Crystallin-Related 76
Myopathy, Myofibrillar, Type 2 41

Characteristics:

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
adult onset
slowly progressive
clinical variability
two patients without cardiomyopathy or cataracts have been reported


HPO:

33
myopathy, myofibrillar, 2:
Onset and clinical course adult onset slow progression
Inheritance autosomal dominant inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Cancer diseases
Anatomical: Neuronal diseases Muscle diseases Cardiovascular diseases
See all MalaCards categories (disease lists)
ICD10: 35
Orphanet: 60  
Rare neurological diseases


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Summaries for Myopathy, Myofibrillar, 2

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OMIM : 58 Alpha-B crystallin-related myofibrillar myopathy is an autosomal dominant muscular disorder characterized by adult onset of progressive muscle weakness affecting both the proximal and distal muscles and associated with respiratory insufficiency, cardiomyopathy, and cataracts. There is phenotypic variability both within and between families (Fardeau et al., 1978; Selcen and Engel, 2003). A homozygous founder mutation in the CRYAB gene has been identified in Canadian aboriginal infants of Cree origin who have a severe fatal infantile hypertonic form of myofibrillar myopathy; see 613869. For a phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy, see MFM1 (601419). (608810)

MalaCards based summary : Myopathy, Myofibrillar, 2, also known as alpha-b crystallinopathy, is related to myopathy, myofibrillar, 4 and autosomal dominant limb-girdle muscular dystrophy. An important gene associated with Myopathy, Myofibrillar, 2 is CRYAB (Crystallin Alpha B), and among its related pathways/superpathways are Cytoskeletal Signaling and Apoptosis and survival Caspase cascade. Affiliated tissues include brain, and related phenotypes are dysphonia and dysphagia

Disease Ontology : 12 A myofibrillar myopathy that has material basis in heterozygous mutation in the alpha-B-crystallin gene on chromosome 11q23.

UniProtKB/Swiss-Prot : 76 Myopathy, myofibrillar, 2: A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM2 is characterized by weakness of the proximal and distal limb muscles, weakness of the neck, velopharynx and trunk muscles, hypertrophic cardiomyopathy, and cataract in a subset of patients.

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Related Diseases for Myopathy, Myofibrillar, 2

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Diseases in the Myofibrillar Myopathy family:

Myopathy, Myofibrillar, 1 Myopathy, Myofibrillar, 2
Myopathy, Myofibrillar, 3 Myopathy, Myofibrillar, 4
Myopathy, Myofibrillar, 5 Myopathy, Myofibrillar, 6
Myopathy, Myofibrillar, 7 Myopathy, Myofibrillar, 8

Diseases related to Myopathy, Myofibrillar, 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 27)
# Related Disease Score Top Affiliating Genes
1 myopathy, myofibrillar, 4 10.2 LDB3 MYOT
2 autosomal dominant limb-girdle muscular dystrophy 10.2 FLNC MYOT
3 myopathy, tubular aggregate, 1 10.1 ACTA1 FLNC
4 muscular dystrophy, limb-girdle, autosomal recessive 7 10.1 DMD MYOT
5 cardiomyopathy, dilated, 1b 10.1 DMD LDB3
6 myopathy, myofibrillar, 3 10.1 FLNC LDB3 MYOT
7 muscular dystrophy, congenital, 1b 10.0 DMD LDB3
8 restrictive cardiomyopathy 10.0 ACTA1 CRYAB FLNC
9 cardiomyopathy, dilated, 1d 10.0 DMD LDB3
10 miyoshi muscular dystrophy 10.0 DMD MYOT
11 cardiomyopathy, dilated, 1a 10.0 DMD LDB3
12 rigid spine muscular dystrophy 1 10.0 ACTA1 DMD
13 muscle tissue disease 9.9 DMD MYOT
14 familial isolated dilated cardiomyopathy 9.9 CRYAB DMD LDB3
15 myopathy, myofibrillar, 1 9.9 CRYAB FLNC LDB3 MYOT
16 myopathy, spheroid body 9.9 CRYAB FLNC LDB3 MYOT
17 pick disease of brain 9.9 APP CRYAB
18 limb-girdle muscular dystrophy 9.9 DMD FLNC MYOT
19 myopathy, congenital 9.9 ACTA1 DMD
20 congenital fiber-type disproportion 9.8 ACTA1 DMD
21 cerebral amyloid angiopathy, cst3-related 9.8 APP GSN
22 dilated cardiomyopathy 9.7 CRYAB DMD FLNC LDB3
23 myopathy 9.7 ACTA1 CRYAB FLNC LDB3 MYOT
24 muscular dystrophy 9.6 ACTA1 DMD FLNC MYOT
25 leukoencephalopathy, hereditary diffuse, with spheroids 9.6 APP CRYAB
26 muscular disease 9.5 ACTA1 DMD FLNC LDB3 MYOT
27 myofibrillar myopathy 9.3 ACTA1 CRYAB DMD FLNC LDB3 MYOT

Graphical network of the top 20 diseases related to Myopathy, Myofibrillar, 2:



Diseases related to Myopathy, Myofibrillar, 2
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Symptoms & Phenotypes for Myopathy, Myofibrillar, 2

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Human phenotypes related to Myopathy, Myofibrillar, 2:

60 33 (show all 30)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 dysphonia 60 33 hallmark (90%) Very frequent (99-80%) HP:0001618
2 dysphagia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002015
3 progressive distal muscle weakness 60 33 hallmark (90%) Very frequent (99-80%) HP:0009063
4 emg: myopathic abnormalities 60 33 frequent (33%) Frequent (79-30%) HP:0003458
5 hyporeflexia 60 33 frequent (33%) Frequent (79-30%) HP:0001265
6 axial muscle weakness 60 33 frequent (33%) Frequent (79-30%) HP:0003327
7 limb-girdle muscle weakness 60 33 frequent (33%) Frequent (79-30%) HP:0003325
8 increased variability in muscle fiber diameter 60 33 frequent (33%) Frequent (79-30%) HP:0003557
9 foot dorsiflexor weakness 60 33 frequent (33%) Frequent (79-30%) HP:0009027
10 neck muscle weakness 60 33 frequent (33%) Frequent (79-30%) HP:0000467
11 autophagic vacuoles 60 33 frequent (33%) Frequent (79-30%) HP:0003736
12 accumulation of muscle fiber desmin 60 33 frequent (33%) Frequent (79-30%) HP:0030225
13 posterior capsular cataract 60 33 frequent (33%) Frequent (79-30%) HP:0100020
14 muscle fiber inclusion bodies 60 33 frequent (33%) Frequent (79-30%) HP:0100299
15 abnormal circulating creatine kinase concentration 33 frequent (33%) HP:0040081
16 respiratory insufficiency due to muscle weakness 60 33 occasional (7.5%) Occasional (29-5%) HP:0002747
17 cardiomyopathy 60 33 occasional (7.5%) Occasional (29-5%) HP:0001638
18 muscle stiffness 60 33 occasional (7.5%) Occasional (29-5%) HP:0003552
19 difficulty walking 60 33 occasional (7.5%) Occasional (29-5%) HP:0002355
20 facial diplegia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001349
21 progressive proximal muscle weakness 60 33 occasional (7.5%) Occasional (29-5%) HP:0009073
22 cataract 33 HP:0000518
23 hypertrophic cardiomyopathy 33 HP:0001639
24 abnormal levels of creatine kinase in blood 60 Frequent (79-30%)
25 late-onset proximal muscle weakness 33 HP:0003694
26 muscular dystrophy 33 HP:0003560
27 distal muscle weakness 33 HP:0002460
28 muscle fiber splitting 33 HP:0003555
29 decreased achilles reflex 33 HP:0009072
30 elevated serum creatine kinase 33 HP:0003236

Symptoms via clinical synopsis from OMIM:

58
Respiratory:
respiratory insufficiency due to muscle weakness

Head And Neck Eyes:
cataracts

Cardiovascular Heart:
cardiomyopathy, hypertrophic

Muscle Soft Tissue:
limb-girdle muscle weakness
neck muscle weakness
autophagic vacuoles
foot drop
emg shows myopathic changes
more
Laboratory Abnormalities:
increased serum creatine kinase

Clinical features from OMIM:

608810

MGI Mouse Phenotypes related to Myopathy, Myofibrillar, 2:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 muscle MP:0005369 9.1 ACTA1 APP CRYAB DMD FLNC LDB3
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Drugs & Therapeutics for Myopathy, Myofibrillar, 2

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Search Clinical Trials , NIH Clinical Center for Myopathy, Myofibrillar, 2

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Genetic Tests for Myopathy, Myofibrillar, 2

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Genetic tests related to Myopathy, Myofibrillar, 2:

# Genetic test Affiliating Genes
1 Alpha-B Crystallinopathy 30 CRYAB
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Anatomical Context for Myopathy, Myofibrillar, 2

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MalaCards organs/tissues related to Myopathy, Myofibrillar, 2:

42
Brain
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Publications for Myopathy, Myofibrillar, 2

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Articles related to Myopathy, Myofibrillar, 2:

# Title Authors Year
1
Pharmacological chaperone for α-crystallin partially restores transparency in cataract models. ( 26542570 )
2015
2
A novel CRYAB mutation resulting in multisystemic disease. ( 21920752 )
2012
3
Infantile muscular dystrophy in Canadian aboriginals is an αB-crystallinopathy. ( 21337604 )
2011
4
Alpha B-crystallin mutation in dilated cardiomyopathy. ( 16483541 )
2006
5
Myofibrillar myopathy caused by novel dominant negative alpha B-crystallin mutations. ( 14681890 )
2003
6
Alteration of protein-protein interactions of congenital cataract crystallin mutants. ( 12601044 )
2003
7
Distinct chaperone mechanisms can delay the formation of aggresomes by the myopathy-causing R120G alphaB-crystallin mutant. ( 12812987 )
2003
8
A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy. ( 9731540 )
1998
9
Autosomal recessive, fatal infantile hypertonic muscular dystrophy among Canadian Natives. ( 8000975 )
1994
10
[A new familial muscular disorder demonstrated by the intra-sarcoplasmic accumulation of a granulo-filamentous material which is dense on electron microscopy (author's transl)]. ( 570292 )
1978
Sources

Variations for Myopathy, Myofibrillar, 2

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UniProtKB/Swiss-Prot genetic disease variations for Myopathy, Myofibrillar, 2:

76
# Symbol AA change Variation ID SNP ID
1 CRYAB p.Arg120Gly VAR_007899 rs104894201
2 CRYAB p.Asp109His VAR_069528 rs387907339

ClinVar genetic disease variations for Myopathy, Myofibrillar, 2:

6 (show all 38)
# Gene Variation Type Significance SNP ID Assembly Location
1 CRYAB NM_001885.2(CRYAB): c.358A> G (p.Arg120Gly) single nucleotide variant Pathogenic rs104894201 GRCh37 Chromosome 11, 111779658: 111779658
2 CRYAB NM_001885.2(CRYAB): c.358A> G (p.Arg120Gly) single nucleotide variant Pathogenic rs104894201 GRCh38 Chromosome 11, 111908934: 111908934
3 CRYAB NM_001885.2(CRYAB): c.464_465delCT (p.Pro155Argfs) deletion Pathogenic GRCh37 Chromosome 11, 111779551: 111779552
4 CRYAB NM_001885.2(CRYAB): c.464_465delCT (p.Pro155Argfs) deletion Pathogenic GRCh38 Chromosome 11, 111908827: 111908828
5 CRYAB NM_001885.2(CRYAB): c.451C> T (p.Gln151Ter) single nucleotide variant Pathogenic rs104894202 GRCh37 Chromosome 11, 111779565: 111779565
6 CRYAB NM_001885.2(CRYAB): c.451C> T (p.Gln151Ter) single nucleotide variant Pathogenic rs104894202 GRCh38 Chromosome 11, 111908841: 111908841
7 CRYAB NM_001885.2(CRYAB): c.60del (p.Ser21Alafs) deletion Pathogenic rs281865141 GRCh37 Chromosome 11, 111782389: 111782389
8 CRYAB NM_001885.2(CRYAB): c.60del (p.Ser21Alafs) deletion Pathogenic rs281865141 GRCh38 Chromosome 11, 111911665: 111911665
9 CRYAB NM_001885.2(CRYAB): c.343delT (p.Ser115Profs) deletion Pathogenic/Likely pathogenic rs281865142 GRCh37 Chromosome 11, 111779673: 111779673
10 CRYAB NM_001885.2(CRYAB): c.343delT (p.Ser115Profs) deletion Pathogenic/Likely pathogenic rs281865142 GRCh38 Chromosome 11, 111908949: 111908949
11 CRYAB NM_001885.2(CRYAB): c.460G> A (p.Gly154Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs150516929 GRCh37 Chromosome 11, 111779556: 111779556
12 CRYAB NM_001885.2(CRYAB): c.460G> A (p.Gly154Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs150516929 GRCh38 Chromosome 11, 111908832: 111908832
13 CRYAB NM_001885.2(CRYAB): c.325G> C (p.Asp109His) single nucleotide variant Pathogenic rs387907339 GRCh37 Chromosome 11, 111779691: 111779691
14 CRYAB NM_001885.2(CRYAB): c.325G> C (p.Asp109His) single nucleotide variant Pathogenic rs387907339 GRCh38 Chromosome 11, 111908967: 111908967
15 CRYAB NM_001885.2(CRYAB): c.152C> T (p.Pro51Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs2234704 GRCh37 Chromosome 11, 111782297: 111782297
16 CRYAB NM_001885.2(CRYAB): c.152C> T (p.Pro51Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs2234704 GRCh38 Chromosome 11, 111911573: 111911573
17 CRYAB NM_001885.2(CRYAB): c.165G> A (p.Leu55=) single nucleotide variant Benign rs2228387 GRCh37 Chromosome 11, 111782284: 111782284
18 CRYAB NM_001885.2(CRYAB): c.165G> A (p.Leu55=) single nucleotide variant Benign rs2228387 GRCh38 Chromosome 11, 111911560: 111911560
19 CRYAB NM_001885.2(CRYAB): c.324+4T> G single nucleotide variant Benign rs11603779 GRCh37 Chromosome 11, 111781047: 111781047
20 CRYAB NM_001885.2(CRYAB): c.324+4T> G single nucleotide variant Benign rs11603779 GRCh38 Chromosome 11, 111910323: 111910323
21 CRYAB NM_001885.2(CRYAB): c.60C> T (p.Pro20=) single nucleotide variant Benign rs4252582 GRCh37 Chromosome 11, 111782389: 111782389
22 CRYAB NM_001885.2(CRYAB): c.60C> T (p.Pro20=) single nucleotide variant Benign rs4252582 GRCh38 Chromosome 11, 111911665: 111911665
23 CRYAB NM_001885.2(CRYAB): c.116C> T (p.Pro39Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs149787233 GRCh38 Chromosome 11, 111911609: 111911609
24 CRYAB NM_001885.2(CRYAB): c.116C> T (p.Pro39Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs149787233 GRCh37 Chromosome 11, 111782333: 111782333
25 CRYAB NM_001885.2(CRYAB): c.*107A> G single nucleotide variant Uncertain significance rs886047686 GRCh37 Chromosome 11, 111779381: 111779381
26 CRYAB NM_001885.2(CRYAB): c.*107A> G single nucleotide variant Uncertain significance rs886047686 GRCh38 Chromosome 11, 111908657: 111908657
27 CRYAB NM_001885.2(CRYAB): c.*39T> C single nucleotide variant Uncertain significance rs782808506 GRCh37 Chromosome 11, 111779449: 111779449
28 CRYAB NM_001885.2(CRYAB): c.*39T> C single nucleotide variant Uncertain significance rs782808506 GRCh38 Chromosome 11, 111908725: 111908725
29 CRYAB NM_001885.2(CRYAB): c.102G> T (p.Glu34Asp) single nucleotide variant Uncertain significance rs886047688 GRCh37 Chromosome 11, 111782347: 111782347
30 CRYAB NM_001885.2(CRYAB): c.102G> T (p.Glu34Asp) single nucleotide variant Uncertain significance rs886047688 GRCh38 Chromosome 11, 111911623: 111911623
31 CRYAB NM_001885.2(CRYAB): c.375A> C (p.Pro125=) single nucleotide variant Uncertain significance rs886047687 GRCh37 Chromosome 11, 111779641: 111779641
32 CRYAB NM_001885.2(CRYAB): c.375A> C (p.Pro125=) single nucleotide variant Uncertain significance rs886047687 GRCh38 Chromosome 11, 111908917: 111908917
33 CRYAB NM_001885.2(CRYAB): c.*38G> C single nucleotide variant Uncertain significance rs781853968 GRCh37 Chromosome 11, 111779450: 111779450
34 CRYAB NM_001885.2(CRYAB): c.*38G> C single nucleotide variant Uncertain significance rs781853968 GRCh38 Chromosome 11, 111908726: 111908726
35 CRYAB NM_001885.2(CRYAB): c.-21C> T single nucleotide variant Benign/Likely benign rs376222434 GRCh37 Chromosome 11, 111782469: 111782469
36 CRYAB NM_001885.2(CRYAB): c.-21C> T single nucleotide variant Benign/Likely benign rs376222434 GRCh38 Chromosome 11, 111911745: 111911745
37 CRYAB NM_001885.2(CRYAB): c.115C> G (p.Pro39Ala) single nucleotide variant Uncertain significance GRCh38 Chromosome 11, 111911610: 111911610
38 CRYAB NM_001885.2(CRYAB): c.115C> G (p.Pro39Ala) single nucleotide variant Uncertain significance GRCh37 Chromosome 11, 111782334: 111782334
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Expression for Myopathy, Myofibrillar, 2

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Search GEO for disease gene expression data for Myopathy, Myofibrillar, 2.
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Pathways for Myopathy, Myofibrillar, 2

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Pathways related to Myopathy, Myofibrillar, 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Cytoskeletal Signaling 4
11.82 ACTA1 FLNC GSN
2
Apoptosis and survival Caspase cascade 23
Show member pathways
 11.39 ACTA1 APP GSN
3
Muscular Dystrophies and Dystrophin-Glycoprotein Complex 65
9.9 ACTA1 DMD
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GO Terms for Myopathy, Myofibrillar, 2

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Cellular components related to Myopathy, Myofibrillar, 2 according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.85 ACTA1 APP CRYAB DMD FLNC GSN
2 perinuclear region of cytoplasm GO:0048471 9.8 APP DMD GSN LDB3
3 axon GO:0030424 9.73 APP CRYAB DMD MYOT
4 lamellipodium GO:0030027 9.65 ACTA1 DMD GSN
5 sarcolemma GO:0042383 9.58 DMD FLNC MYOT
6 actin cytoskeleton GO:0015629 9.56 ACTA1 GSN MYOT SYNPO2
7 stress fiber GO:0001725 9.51 ACTA1 SYNPO2
8 cytoskeleton GO:0005856 9.5 ACTA1 DMD FLNC GSN LDB3 MYOT
9 costamere GO:0043034 9.46 DMD FLNC
10 astrocyte projection GO:0097449 9.37 APP DMD
11 sarcoplasm GO:0016528 9.32 FLNC GSN
12 Z disc GO:0030018 9.1 CRYAB DMD FLNC LDB3 MYOT SYNPO2

Biological processes related to Myopathy, Myofibrillar, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 aging GO:0007568 9.43 CRYAB DMD GSN
2 negative regulation of neuron differentiation GO:0045665 9.4 APP DMD
3 synapse organization GO:0050808 9.37 APP MYOT
4 muscle filament sliding GO:0030049 9.32 ACTA1 DMD
5 muscle fiber development GO:0048747 9.16 DMD FLNC
6 muscle contraction GO:0006936 9.13 ACTA1 CRYAB MYOT
7 amyloid fibril formation GO:1990000 8.62 APP GSN

Molecular functions related to Myopathy, Myofibrillar, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 structural constituent of muscle GO:0008307 9.37 DMD MYOT
2 myosin binding GO:0017022 9.32 ACTA1 DMD
3 alpha-actinin binding GO:0051393 9.26 MYOT SYNPO2
4 actin binding GO:0003779 9.26 DMD GSN MYOT SYNPO2
5 muscle alpha-actinin binding GO:0051371 9.16 LDB3 SYNPO2
6 cytoskeletal protein binding GO:0008092 8.8 CRYAB FLNC LDB3
Sources

Sources for Myopathy, Myofibrillar, 2

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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
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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