Table.

Frequency and Phenotype Correlates of Definitive and Putative DCM Genes

GeneProteinFrequency and Overlapping Phenotypes
SarcomereForce generation/transmission
 MYH6α-Myosin heavy chainHCM, CHD, Sick sinus syndrome
 MYH7*,β-Myosin heavy chain3%–4% of DCM; HCM, LVNC
 TPM1α-Tropomyosin1%–2% of DCM; HCM, LVNC
 ACTC1α-Cardiac actinHCM, LVNC
 TNNT2*,Cardiac troponin T3% of DCM; HCM, LVNC
 TNNC1Cardiac troponin CHCM, LVNC
 TNNI3Cardiac troponin IHCM
 MYBPC3Myosin-binding protein CHCM, LVNC
 TTN*,Titin12%–25% of DCM; HCM, tibial muscle dystrophy
 TNNI3KTroponin I–interacting kinaseConduction defect, atrial fibrillation
 MYL2Myosin light chain 2, regulatoryHCM
 MYL3Myosin light chain 3HCM
 MYLK2Myosin light chain kinase 2HCM; in panels, not reported as DCM gene
 MYOM1Myomesin 1Myofibrillar myopathy; in panels, not reported as DCM gene
 MYOZ2Myozenin 2HCM
Z diskMechanosensing/mechanosignaling
 ACTN2α-Actinin 2LVNC
 BAG3BCL2-associated athanogene 3Myofibrillar myopathy
 CRYABα-B-crystallinProtein aggregation myopathy
 TCAPTitin-cap/telethoninLGMD2G
 MYPNMyopalladinHCM, RCM
 CSRP3Muscle LIM proteinHCM
 NEXNNexilinHCM
 FHL1Four-and-a-half LIM protein1EDMD, HCM
 FHL2Four-and-a-half LIM protein 2HCM
 ANKRD1Cardiac ankyrin repeat proteinCongenital heart disease
 MURCMuscle-related coiled coil protein
 LDB3Cypher/ZASPLVNC
 NEBLNebuletteLVNC, HCM
Dystrophin complexSarcolemma, structural integrity
 DMDDystrophinDuchenne/Becker muscular dystrophy
 DTNAα-DystrobrevinLVNC
 SGCAα-SarcoglycanLGMD2D
 SGCBβ-SarcoglycanLGMD2E
 SGCDδ-SarcoglycanLGMD2F
 SGCGγ-SarcoglycanLGMD2C
 CAV3CaveolinHCM, LGMD1C, distal myopathy
 ILKIntegrin-linked kinase
 FKTNFukutinDystroglycanopathy, congenital muscular dystrophy
 FKRPFukutin-related proteinDystroglycanopathy, LGMD
CytoskeletonMechanotransduction/mechanosignaling/structural integrity
 DESDesmin<1% of DCM; desminopathies, myofibrillar myopathy
 VCLMetavinculin1% of DCM
 FLNCFilamin C1% of DCM, AR-DCM; myofibrillar myopathy, HCM, RCM
 SYNMDesmulin
 PDLIM3PDZ LIM domain protein 3
 PLEC1Plectin-1LGMD2Q, epidermolysis bullosa
DesmosomesCell–cell adhesion/mechanotransmission/mechanosignaling
 DSC2Desmocollin 2ARVC, mild palmoplantar keratoderma
 DSG2Desmoglein 2ARVC
 DSP*,Desmoplakin2% of DCM; ARVC
 PKP2Plakophilin 2ARVC
 CTNNA3Catenin α 3ARVC; in panels, not reported as DCM gene
Sarcoplasmic reticulum and cytoplasmCa homeostasis, contractility modulation, signaling
 PLNPhospholambanARVC, HCM
 RYR2Ryanodine receptor 2, Ca channelARVC, CPVT
 CALR3Calreticulin-3ARVC, HCM; in panels, not reported as DCM gene
 JPH2Junctophilin 2HCM
 DOLKDolichol kinaseCongenital disorder of glycosylation
 MAP2K1Mitogen-activated protein kinase kinase 1Noonan syndrome; in panels, not reported as DCM gene
 MAP2K2Mitogen-activated protein kinase kinase 2HCM, Noonan syndrome; in panels, not reported as DCM gene
 NRASNeuroblastoma RAS viral oncogene homologHCM, Noonan syndrome
 PRKAG2Protein kinase AMP-activated noncatalytic subunit γ 2HCM, WPW
 PTPN11Protein tyrosine phosphatase, nonreceptor type 11HCM, Noonan and Leopard syndromes
 RAF1Proto-oncogeneHCM, Noonan and Leopard syndromes
 RIT1Ras-like proteinNoonan syndrome; in panels, not reported as DCM gene
 SOS1SOS Ras/Rac guanine nucleotide exchange factor 1HCM, Noonan syndrome; in panels, not reported as DCM gene
 TRDNTriadinCVPT; in panels, not reported as DCM gene
Nuclear envelopeNuclear structural integrity, mechanotransduction, mechanosignaling
 LMNA*,Lamin A/C4%–8% of DCM; multiple phenotypes, LGMD1B, EDMD, progeria
 EMDEmerinEDMD
 LAP2/TMPOLamin-associated polypeptide 2
 SYNE1/2Nesprin 1/2EDMD, ataxia
NucleusTranscription cofactors, gene expression
 EYA4Eyes absent 4Deafness
 FOXD4Forkhead box D4
 HOPXHomeobox only protein
 NFKB1NF-κ B1
 PRDM16PR domain containing 16LVNC
 TBX20T-box 20Atrial septal defect
 ZBTB17Zinc finger and BTB domain containing protein 17
 RBM20*,RNA-binding protein 202% of DCM; RNA-binding protein of spliceosome of TTN and other proteins
 GATA4GATA-binding protein 4Atrial, ventricular septal defects, Fallot
 GATA5GATA-binding protein 6Atrial, ventricular septal defects, Fallot
 GATAD1GATA zinc finger domain protein 1
 NKX2-5Cardiac-specific homeobox 1Atrial, ventricular septal defects, Fallot, hypoplastic left heart
 ALSM1Centrosome and basal body–associated proteinAlstrom syndrome (phenocopy)
 ALPK3α-Kinase 3Pediatric cardiomyopathy
 LRRC10Leucine-rich repeat containing 10
 NPPANatriuretic paptide AAtrial fibrillation
 PLEKHM2Pleckstrin homology domainLVNC
 TGFB3Transforming growth factor β 3ARVC; in panels, not reported as DCM gene
 TMEM43Transmembrane protein 43ARVC, EDMD; in panels, not reported as DCM gene
Ion channels
 SCN5A*,Type V voltage-gated cardiac Na channel2%–3% of DCM; LQT, Brugada, atrial fibrillation, conduction defects
 ABCC9Sulfonylurea receptor 2A, component of ATP-sensitive potassium channelAtrial fibrillation, osteochondrodysplasia
 KCNQ1Potassium channelAtrial fibrillation, LQT1, short QT1, Jervell and Lange-Nielsen syndrome
 CACNA1CCalcium voltage-gated channel subunit α1 CBrugada syndrome, Timothy syndrome
 HCN4Hyperpolarization-activated cyclic nucleotide-gated potassium channel 4Brugada, Sick sinus syndrome
MitochondriaSupply and regulation of energy metabolism
 CPT2Carnitine palmitoyltransferase 2Carnitine deficiency, myopathy, lethal neonatal
 FRDA/FXNFrataxinFredreich ataxia
 DNAJC19HSP40 homolog, C193-methylglutaconic aciduria, type V
 SDHASuccinate dehydrogenaseLeigh syndrome
 SOD2Superoxide dismutase
 TAZ/G4.5TafazzinLVNC, Barth syndrome, endocardial fibroelastosis 2
 CTF1Cardiotrophin 1 cytokine
 mtDNAMitochondrial-encoded TRNA genesTypically syndromic, mitochondial myopathy; in panels, not always reported as DCM genes
 TXNRD2Thioredoxin reductase 2
Extracellular matrixCell adhesion and mechanosignaling
 LAMA2Laminin 2, merosinCongenital muscular dystrophy
 LAMA4Laminin 4
Lysosome
 LAMP2Lysosome-associated membrane protein 2Danon disease
 AGLAmylo-α-1, 6-glucosidase, 4-α-glucanotransferaseGlycogen storage disease
 BRAFB-Raf proto-oncogene, serine/threonine kinaseCardiofaciocutaneous, Leopard, Noonan syndromes
 GAAGlucosidase α, acidGlycogen storage disease
 GLAα-GalactosidaseFabry disease
Other
 PSEN1Presenillin 1, γ secretase intramembrane protease complexAlzheimer disease
 PSEN2Presenillin 2, γ secretase intramembrane protease complexAlzheimer disease
 CHRM2Cholinergic receptor muscarinic 2
 HFEHemochromatosisPhenocopy
 HRASHRas proto-oncogene, GTPaseHCM, Costello syndrome; in panels, not reported as DCM gene
 KRASKRAS proto-oncogene, GTPaseHCM, Costello syndrome; in panels, not reported as DCM gene
 MIB1Mitogen-activated protein kinase kinase 2LVNC; in panels, not reported as DCM gene
 SLC22A5Cation/carnitine transporterSkeletal myopathy
 TTRTransthyretinAmyloidosis (phenocopy)
  • AR-DCM indicates arrhythmogenic dilated cardiomyopathy; ARVC, arrhythmogenic right ventricular cardiomyopathy; CHD, coronary heart disease; CPVT, cathecolaminergic polymorphic ventricular tachycardia; DCM, dilated cardiomyopathy; EDMD, Emery–Dreifuss muscular dystrophy; HCM, hypertrophic cardiomyopathy; LGMD, limb-girdle muscular dystrophy; LVNC, left ventricular noncompaction; NF, nuclear factor; and RCM, restrictive cardiomyopathy.

  • Frequent (*), definitive (†), and putative DCM genes,14,21,25,52,53 OMIM (www.omim.org, accessed January 19, 2017); GeneCards (www.genecards.org, accessed January 19, 2017).