Skip to main content

Table 2 Genes implicated in monogenic dilated cardiomyopathy and their cellular component

From: Genetics and genomics of dilated cardiomyopathy and systolic heart failure

Gene Protein Function Estimated contribution in DCM patients and phenotypic comments
Sarcomeric
MYH7* Myosin-7 (beta myosin heavy chain) Muscle contraction Non-truncating variants: 5%
TNNT2* Troponin T, cardiac muscle (troponin T2) Muscle contraction Non-truncating variants: 3%
TTN*,# Titin Extensible scaffold/molecular spring Truncating variants: 15–25%
TPM1* Tropomyosin alpha-1 chain Muscle contraction <2%
MYBPC3 Myosin-binding protein C, cardiac type Muscle contraction Major hypertrophic cardiomyopathy gene; purported association with DCM now less likely in light of population variation data [16]
TNNC1 Troponin C, slow skeletal and cardiac muscles Muscle contraction Mutations also associated with hypertrophic cardiomyopathy
TNNI3 Troponin I, cardiac muscle Muscle contraction Mutations also associated with hypertrophic cardiomyopathy
MYL2 # Myosin regulatory light chain 2, ventricular/cardiac muscle isoform Regulation of myosin ATPase activity Mutations also associated with hypertrophic cardiomyopathy
FHOD3 # FH1/FH2 domain-containing protein 3 Sarcomere organization  
Cytoskeleton
DES* Desmin Contractile force transduction <1%
DMD* Dystrophin Contractile force transduction In patients with dystrophinopathies. X-linked
VCL Vinculin Cell–matrix and cell–cell adhesion  
Nuclear envelope
LMNA* Prelamin-A/C Nuclear membrane structure 4%
Mitochondrial
WWTR1 (TAZ) Tafazzin (WW domain-containing transcription regulator protein 1)   Associated with syndromic DCM (for example, Barth syndrome). X-linked
Spliceosomal
RBM20 RNA-binding protein 20 Regulates splicing of cardiac genes 2%
Sarcoplasmic reticulum
PLN Cardiac phospholamban Sarcoplasmic reticulum calcium regulator; inhibits SERCA2a pump <1%
Linked to an arrhythmogenic phenotype
Desomosomal
DSP* Desmoplakin Desmosomal junction protein Truncating variants: 3%
Linked to arrhythmogenic right and left ventricular cardiomyopathy
DSC-2 # Desmocollin-2 Desmosomal junction protein Linked to arrhythmogenic right and left ventricular cardiomyopathy
DSG2 # Desmoglein-2 Desmosomal junction protein Linked to arrhythmogenic right and left ventricular cardiomyopathy
PKP2 # Plakophilin-2 Desmosomal junction protein Linked to arrhythmogenic right and left ventricular cardiomyopathy; recent studies cast doubt on involvement in DCM
JUP Junction plakoglobin Desmosomal junction protein Linked to arrhythmogenic right and left ventricular cardiomyopathy
Ion channels
SCN5A Sodium channel protein type 5 subunit alpha Sodium channel <2%. Associated with atrial arrhythmias and conduction disease. Association with DCM in absence of segregation less strong in light of population variation data [16]
Z-disc
FLNC # Filamin-C Structural integrity of cardiac myocyte; actin crosslinking protein
NEBL Nebulette Z-disc protein
NEXN Nexilin Encodes a filamentous actin binding protein
CSRP3 Cysteine and glycine-rich protein 3 Mechanical stretch sensing
TCAP Telethonin Mechanical stretch sensing
LDB3 Lim domain-binding 3 Z-disc structural integrity Associated with left ventricular non-compaction phenotypes
CRYAB Alpha-crystallin B chain Heat-shock protein  
Other
BAG3 # BAG family molecular chaperone regulator 3 Inhibits apoptosis
ANKRD1 Ankyrin repeat domain-containing protein 1 Encodes CARP, a transcription coinhibitor <2%
RAF1 # RAF proto-oncogene serine/threonine-protein kinase MAP3 kinase, part of the Ras–MAPK signaling cascade ~9% in childhood-onset DCM (one study)
Transcription factors
PRDM16 # PR domain zinc finger protein 16 Transcription factor Mutations cause cardiomyopathy in 1p36 deletion syndrome; also linked to isolated DCM and left ventricular non-compaction
ZBTB17 # Zinc-finger and BTB domain-containing protein 17 Transcription factor  
TBX5 # T-box transcription factor TBX5 Transcription factor Associated with congenital heart disease; also linked to adult-onset DCM
NKX2-5 # Homeobox protein Nkx-2.5 Transcription factor Associated with congenital heart disease; also linked to adult-onset DCM
GATA4 # Transcription factor GATA-4 (GATA-binding protein 4) Transcription factor Linked to sporadic and familial DCM
TBX20 # T-box transcription factor TBX20 Transcription factor Associated with congenital heart disease; also linked to adult-onset DCM
  1. Table content adapted from Hershberger et al. [5] and Walsh et al. [16]. We have highlighted the genes with the strongest evidence linking them to dilated cardiomyopathy (DCM; marked with an asterisk) or the most recently identified genes from 2011 onwards (marked with a hash sign). Causes of predominantly autosomal recessive DCM and older gene associations that have not been replicated have not been included