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

  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

  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

  LMNA*

Prelamin-A/C

Nuclear membrane structure

4%

  WWTR1 (TAZ)

Tafazzin (WW domain-containing transcription regulator protein 1)

Associated with syndromic DCM (for example, Barth syndrome). X-linked

  RBM20

RNA-binding protein 20

Regulates splicing of cardiac genes

2%

  PLN

Cardiac phospholamban

Sarcoplasmic reticulum calcium regulator; inhibits SERCA2a pump

<1%

Linked to an arrhythmogenic phenotype

  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

  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]

  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

  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)

  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