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 |