Table 1.
Hypertrophic cardiomyopathy-associated genes, proteins, and number of mutations described for each gene (protein location or function is also described)
| Gene | Chromosomal positiona | Protein | HCM-associated mutationsa | Location or functionb |
|---|---|---|---|---|
| ACTA1 | 1q42.13–q42.2 | Actin, alpha 1 | 1 | Sarcomere, skeletal muscle |
| ACTC1 | 15q11–q14 | Actin, alpha, cardiac muscle 1 | 25 | Sarcomere, cardiac muscle |
| ACTN2 | 1q42–q43 | Actinin, alpha 2 | 5 | Z-disk |
| ANKRD1 | 10q23.33 | Ankyrin repeat domain 1 | 3 | Z-disk and nucleus (transcription factor) |
| BRAF | 7q34 | v-Raf murine sarcoma viral oncogene homolog B1 | 1 | Cytoplasmic serine/threonine kinase |
| COA5 | 2q11.2 | Cytochrome c oxidase assembly factor 5 | 1 | Mitochondrial |
| CALM3 | 19q13.2–q13.3 | Calmodulin 3 (phosphorylase kinase, delta) | 1 | Calcium sensor and signal transducer |
| CALR3 | 19p13.11 | Calreticulin 3 | 2 | Endoplasmic reticulum chaperone |
| CASQ2 | 1p13.3–p11 | Calsequestrin 2 | 1 | Sarcoplasmic reticulum; calcium storage |
| CAV3 | 3p25 | Caveolin 3 | 1 | Plasma membrane |
| COX15 | 10q24 | Cytochrome c oxidase assembly homolog 15 | 2 | Mitochondrial respiratory chain |
| CSRP3 | 11p15.1 | Cysteine and glycine-rich protein 3 | 15 | Z-disk |
| DES | 2q35 | Desmin | 1 | Intermediate filament |
| FHL1 | Xq26 | Four and a half LIM domains 1 | 3 | Biomechanical stress sensor |
| FHOD3 | 18q12 | Formin homology 2 domain containing 3 | 1 | Actin-organizing protein |
| FXN | 9q13–q21.1 | Frataxin | 1 | Mitochondrial iron transport and respiration |
| GLA | Xq22 | Galactosidase, alpha | 765 | Lysosome |
| JPH2 | 20q13.12 | Junctophilin 2 | 6 | Junctional membrane complexes; calcium signaling |
| KLF10 | 8q22.2 | Kruppel-like factor 10 | 6 | Transcriptional repressor; inhibits cell growth |
| MAP2K1 | 15q22.1–q22.33 | Mitogen-activated protein kinase kinase 1 | 1 | MAP kinase kinase; signal transduction |
| MAP2K2 | 19p13.3 | Mitogen-activated protein kinase kinase 2 | 1 | MAP kinase kinase; signal transduction |
| MRPL3 | 3q21–q23 | Mitochondrial ribosomal protein L3 | 1 | Mitochondrial ribosomal protein |
| MTO1 | 6q13 | Mitochondrial tRNA translation optimization 1 | 2 | Mitochondrial tRNA modification |
| MYBPC3 | 11p11.2 | Myosin binding protein C, cardiac | 506 | Sarcomere |
| MYH6 | 14q12 | Alpha-myosin heavy chain | 3 | Sarcomere |
| MYH7 | 14q12 | Beta-myosin heavy chain | 491 | Sarcomere |
| MYL2 | 12q23–q24.3 | Ventricular myosin regulatory light chain | 20 | Sarcomere |
| MYL3 | 3p21.3–p21.2 | Myosin light chain 3 | 16 | Sarcomere |
| MYLK2 | 20q13.31 | Myosin light chain kinase 2 | 2 | Calcium/calmodulin-dependent kinase |
| MYO6 | 6q13 | Myosin VI | 1 | Actin-based reverse-direction motor protein |
| MYOM1 | 18p11.31 | Myomesin 1 | 1 | Sarcomere |
| MYOZ2 | 4q26–q27 | Myozenin 2 | 2 | Z-disk |
| MYPN | 10q21.3 | Myopalladin | 8 | Z-disk |
| NDUFAF1 | 15q11.2–q21.3 | NADH dehydrogenase (ubiquinone) complex I, assembly factor 1 | 2 | Mitochondrial chaperone |
| NDUFV2 | 18p11.31–p11.2 | NADH dehydrogenase (ubiquinone) flavoprotein 2 | 1 | Mitochondrial respiratory chain |
| NEXN | 1p31.1 | Nexilin | 2 | Z-disk |
| OBSCN | 1q42.13 | Obscurin | 1 | Sarcomere |
| PDLIM3 | 4q35 | PDZ and LIM domain 3 | 1 | Z-disk |
| PRKAG2 | 7q36.1 | 5′-AMP-activated protein kinase subunit gamma-2 | 7 | Energy sensor protein kinase |
| PLN | 6q22.1 | Phospholamban | 7 | Sarcoplasmic reticulum; regulates Ca2+-ATPase |
| RAF1 | 3p25 | v-Raf-1 murine leukemia viral oncogene homolog 1 | 1 | Serine/threonine-protein kinase; signal transduction |
| SLC25A3 | 12q23 | Solute carrier family 25, member 3 | 1 | Phosphate carrier protein (cytosol to mitochondria) |
| SLC25A4 | 4q35 | Solute carrier family 25, member 4 | 2 | Adenine nucleotide translocator (cytosol/mitochondria) |
| SOS1 | 2p22–p21 | Son of sevenless homolog 1 | 1 | Guanine nucleotide exchange factor for RAS proteins; signal transduction |
| SRI | 7q21.1 | Sorcin | 2 | Calcium-binding; modulates excitation-contraction coupling |
| TCAP | 17q12 | Telethonin | 7 | Z-disk |
| TNNC1 | 3p21.3–p14.3 | Troponin C | 14 | Sarcomere |
| TNNI3 | 19q13.4 | Troponin I | 70 | Sarcomere |
| TNNT2 | 1q32 | Troponin T | 90 | Sarcomere |
| TPM1 | 15q22.1 | Alpha-tropomyosin | 38 | Sarcomere |
| TRIM63 | 1p34–p33 | Tripartite motif-containing 63 | 3 | Sarcomere; regulates protein degradation |
| TTN | 2q31 | Titin | 6 | Sarcomere |
| VCL | 10q22.1–q23 | Vinculin | 1 | Sarcomere |
Notes:
a
Human genome mutation database (http://www.hgmd.cf.ac.uk/ac/index.php);
b
National Center for Biotechnology Information (http://ncbi.nlm.nih.gov/).
Abbreviations: HCM, hypertrophic cardiomyopathy; tRNA, transfer RNA; AMP, adenosine monophosphate; ATP, adenosine triphosphate.