# Histone methyltransferase SMYD1: playing a crucial role in disease progression **Authors:** Lingqian Duan, Yang Lou, Kan Huang, Kailing Pan, Xianguo Chen PMC · DOI: 10.3389/fmolb.2026.1769660 · Frontiers in Molecular Biosciences · 2026-02-09 ## TL;DR This paper reviews how the histone methyltransferase SMYD1 contributes to disease progression and highlights its potential as a therapeutic target. ## Contribution The paper provides a comprehensive review of SMYD1's roles in various diseases and its potential as a therapeutic target. ## Key findings - SMYD1 influences chromatin structure and gene expression, impacting cell proliferation and differentiation. - SMYD1 is involved in the progression of cancer, cardiovascular diseases, and metabolic disorders. - Modulation of SMYD1 affects cell cycle regulation, apoptosis, and inflammation. ## Abstract Histone methyltransferase SET and MYND domain-containing 1 (SMYD1), a member of the SMYD family, catalyzes the methylation of lysine residues on histone proteins. This modification is pivotal in regulating chromatin structure and gene expression, influencing processes such as cell proliferation, differentiation, and development. Primarily expressed in muscle tissues, SMYD1 plays a crucial role in muscle development and function. However, accumulating evidence suggests its involvement in the progression of various diseases, including cancer, cardiovascular diseases, and metabolic disorders. By modulating key signaling pathways and gene expression profiles, SMYD1 affects cellular processes such as cell cycle regulation, apoptosis, and inflammation. This review aims to explore the multifaceted roles of SMYD1 in disease progression, highlighting its potential as a therapeutic target. Understanding the molecular mechanisms underlying the effects of SMYD1 will be essential for developing strategies to manipulate its activity for disease prevention and treatment. ## Linked entities - **Genes:** SMYD1 (SET and MYND domain containing 1) [NCBI Gene 150572] - **Diseases:** cancer (MONDO:0004992) ## Full-text entities - **Genes:** H2-M3 (histocompatibility 2, M region locus 3) [NCBI Gene 14991] {aka H-2M3, Hmt, M3a, MuprM3, MuprM301, MuprM302}, GATA4 (GATA binding protein 4) [NCBI Gene 2626] {aka ASD2, TACHD, TOF, VSD1}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, P2rx7 (purinergic receptor P2X, ligand-gated ion channel, 7) [NCBI Gene 18439] {aka P2X(7), P2X7R}, SMYD2 (SET and MYND domain containing 2) [NCBI Gene 56950] {aka HSKM-B, KMT3C, ZMYND14}, PRDM9 (PR/SET domain 9) [NCBI Gene 56979] {aka KMT8B, MEISETZ, MSBP3, PFM6, ZNF899}, HSP90AA1 (heat shock protein 90 alpha family class A member 1) [NCBI Gene 3320] {aka EL52, HEL-S-65p, HSP86, HSP89A, HSP90A, HSP90N}, OPA1 (OPA1 mitochondrial dynamin like GTPase) [NCBI Gene 4976] {aka BERHS, MGM1, MTDPS14, MTDPS14A, MTDPS14B, NPG}, CHD4 (chromodomain helicase DNA binding protein 4) [NCBI Gene 1108] {aka CHD-4, Mi-2b, Mi2-BETA, SIHIWES}, Myog (myogenin) [NCBI Gene 17928] {aka MYF4, bHLHc3, myo}, Naca (nascent polypeptide-associated complex alpha polypeptide) [NCBI Gene 17938] {aka Gm1878, mKIAA0363, skNAC}, NKX2-5 (NK2 homeobox 5) [NCBI Gene 1482] {aka CHNG5, CSX, CSX1, HLHS2, NKX2.5, NKX2E}, Atf6 (activating transcription factor 6) [NCBI Gene 304962], Tgfb3 (transforming growth factor, beta 3) [NCBI Gene 21809] {aka TGF-beta-3, Tgfb-3}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, Cox4i1 (cytochrome c oxidase subunit 4I1) [NCBI Gene 12857] {aka COX, COX IV-1, COXIV, Cox4, Cox4a, IV-1}, SMYD3 (SET and MYND domain containing 3) [NCBI Gene 64754] {aka KMT3E, ZMYND1, ZNFN3A1, bA74P14.1}, GATA5 (GATA binding protein 5) [NCBI Gene 140628] {aka CHTD5, GATAS, bB379O24.1}, HDGF (heparin binding growth factor) [NCBI Gene 3068] {aka HMG1L2}, MYOG (myogenin) [NCBI Gene 4656] {aka MYF4, bHLHc3, myf-4}, H3c7 (H3 clustered histone 7) [NCBI Gene 260423] {aka H3.2-221, H3c13, H3c14, H3c15, H3c2, H3c3}, MIR206 (microRNA 206) [NCBI Gene 406989] {aka MIRN206, miRNA206, mir-206}, Ppargc1a (peroxisome proliferative activated receptor, gamma, coactivator 1 alpha) [NCBI Gene 19017] {aka A830037N07Rik, Gm11133, PGC-1, PPARGC-1-alpha, Pgc-1alpha, Pgc1}, smyd1a (SET and MYND domain containing 1a) [NCBI Gene 321245] {aka sb:cb405, smyd1, wu:fc09a05, zgc:77936}, Smyd1 (SET and MYND domain containing 1) [NCBI Gene 12180] {aka 4632404M21Rik, Bop, Zmynd18}, Ckm (creatine kinase, muscle) [NCBI Gene 12715] {aka CPK-M, Ckmm, M-CK, MCK}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56718] {aka Frap1, RAFT1}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, Myoz1 (myozenin 1) [NCBI Gene 59011] {aka 2310001N11Rik, FATZ, Myoz}, Cd8b1 (CD8 subunit beta 1) [NCBI Gene 12526] {aka Cd8b, Ly-3, Ly-C, Lyt-3}, MB (myoglobin) [NCBI Gene 4151] {aka MYOSB, PVALB}, Opa1 (OPA1, mitochondrial dynamin like GTPase) [NCBI Gene 74143] {aka 1200011N24Rik, lilr3, mKIAA0567}, HAND2-AS1 (HAND2 antisense RNA 1) [NCBI Gene 79804] {aka DEIN, NBLA00301, UPH}, CKM (creatine kinase, M-type) [NCBI Gene 1158] {aka CKMM, CPK-M, M-CK}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Gsk3b (glycogen synthase kinase 3 beta) [NCBI Gene 56637] {aka 7330414F15Rik, 8430431H08Rik, GSK-3, GSK-3beta, GSK3}, TRIB3 (tribbles pseudokinase 3) [NCBI Gene 57761] {aka C20orf97, NIPK, SINK, SKIP3, TRB3}, Trp53-ps (transformation related protein 53, pseudogene) [NCBI Gene 22060], Spag5 (sperm associated antigen 5) [NCBI Gene 54141] {aka D11Bhm180e, Deepest, MAP126, Mastrin, S17}, Atf6 (activating transcription factor 6) [NCBI Gene 226641] {aka 9130025P16Rik, 9630036G24, Atf6alpha, ESTM49}, Nppa (natriuretic peptide type A) [NCBI Gene 230899] {aka ANP, Anf, CDD, Pnd}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, hsp90aa1.1 (heat shock protein 90, alpha (cytosolic), class A member 1, tandem duplicate 1) [NCBI Gene 30591] {aka fb17b01, hsp90, hsp90a, hsp90a.1, hsp90alpha, wu:fb17b01}, Hdgf (heparin binding growth factor) [NCBI Gene 15191] {aka D3Ertd299e}, unc45b (unc-45 myosin chaperone B) [NCBI Gene 266640] {aka Unc-45B, cb393, fb37f02, unc45r, wu:fa05a03, wu:fa10f03}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, Smyd1 (SET and MYND domain containing 1) [NCBI Gene 297333], IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, MEF2A (myocyte enhancer factor 2A) [NCBI Gene 4205] {aka ADCAD1, RSRFC4, RSRFC9, mef2}, MYH6 (myosin heavy chain 6) [NCBI Gene 4624] {aka ASD3, CMD1EE, CMH14, MYHC, MYHCA, SSS3}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56717] {aka 2610315D21Rik, FRAP, FRAP2, Frap1, RAFT1, RAPT1}, Isl1 (ISL1 transcription factor, LIM/homeodomain) [NCBI Gene 16392], SMYD1 (SET and MYND domain containing 1) [NCBI Gene 150572] {aka BOP, KMT3D, ZMYND18, ZMYND22}, Myoz1 (myozenin 1) [NCBI Gene 498440] {aka RGD1561064} - **Diseases:** BC (MESH:D001943), infarct (MESH:D007238), biventricular heart failure (MESH:D006333), ductal carcinoma (MESH:D044584), cardiac defects (MESH:D006331), hypertrophic cardiomyopathy (MESH:D002312), muscle-related diseases (MESH:D009135), cardiac hypertrophy (MESH:D006332), urinary system diseases (MESH:D014570), development (MESH:D002658), neuromuscular atrophy (MESH:D009468), HCC (MESH:D006528), pulmonary hypertension (MESH:D006976), metastasis (MESH:D009362), MCAO (MESH:D020244), leukemia (MESH:D007938), ischemic stroke (MESH:D002544), myocardial hypertrophy (MESH:D006984), ischemic injury (MESH:D017202), dilated cardiomyopathy (MESH:D002311), urethral closure dysfunction (MESH:D014522), cardiovascular diseases (MESH:D002318), congenital heart defects (MESH:D006330), lobular carcinoma (MESH:D018275), hypoxic (MESH:D002534), neurological diseases (MESH:D020271), RMS (MESH:D012208), GC (MESH:D013274), stroke (MESH:D020521), SUI (MESH:D014550), metabolic disorders (MESH:D008659), cardiotoxicity (MESH:D066126), defects (MESH:D000013), inflammation (MESH:D007249), neurodegenerative diseases (MESH:D019636), developmental abnormalities (MESH:D006130), mitochondrial dysfunction (MESH:D028361), PD (MESH:D010300), cancer (MESH:D009369), HD (MESH:D006816), medullary carcinoma (MESH:D018276), urethral sphincter muscle fiber injury (MESH:D014526), AD (MESH:D000544) - **Chemicals:** lysine (MESH:D008239), calcium (MESH:D002118), AZ50552 (-), DOX (MESH:D004317), fatty acid (MESH:D005227), leucine (MESH:D007930), oxygen (MESH:D010100), anthracycline (MESH:D018943) - **Species:** Danio rerio (leopard danio, species) [taxon 7955], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090] - **Mutations:** S103, S103A - **Cell lines:** C2C12 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0188) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12926172/full.md ## Figures 1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12926172/full.md ## References 55 references — full list in the complete paper: https://tomesphere.com/paper/PMC12926172/full.md --- Source: https://tomesphere.com/paper/PMC12926172