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GeneE
26 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
DMPK
DM1 protein kinase
Chromosome 19 Β· 19q13.32
NCBI Gene: 1760Ensembl: ENSG00000104936.21HGNC: HGNC:2933UniProt: B4DM55
177PubMed Papers
21Diseases
0Drugs
183Pathogenic Variants
FUNCTIONAL ROLE
Kinase
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
myosin phosphatase regulator activityregulation of heart contractionprotein phosphorylationmitochondrial outer membranemyotonic dystrophy type 1Steinert myotonic dystrophyBethlem myopathy 1ABethlem myopathy
✦AI Summary

DMPK is a serine/threonine protein kinase primarily expressed in skeletal, cardiac, and smooth muscle that maintains muscle structure and function through multiple mechanisms. The protein regulates myosin phosphorylation by phosphorylating PPP1R12A to inhibit myosin phosphatase activity, and phosphorylates PLN to regulate sarcoplasmic reticulum calcium uptake and cardiac contractility 1. DMPK also modulates nuclear envelope integrity and muscle-specific gene expression during myocyte differentiation [UniProt annotation]. DMPK mutations cause myotonic dystrophy type 1 (DM1), the most prevalent adult-onset muscular dystrophy, through CTG trinucleotide repeat expansion in the DMPK 3' untranslated region 2. This expansion triggers a toxic RNA gain-of-function mechanism rather than simple protein loss, disrupting RNA splicing through MBNL1 protein sequestration and causing widespread cellular dysfunction 3. DM1 manifests as a multisystem disorder affecting skeletal and cardiac muscle, the central nervous system, and other organs, with phenotypic variability including myotonia, cataracts, cardiac arrhythmias, and testicular atrophy 1. Recent therapeutic advances targeting miR-23b and miR-218 to restore MBNL1 expression show promise in correcting DM1 cellular defects across varying repeat sizes 4, while optical genome mapping now enables accurate repeat expansion measurement for improved diagnosis 5.

Sources cited
1
DMPK is a Ser/Thr kinase expressed in skeletal, cardiac, and smooth muscle; CTG repeat expansion causes DM1 with myotonia, cataracts, cardiac arrhythmia, and testicular atrophy
PMID: 18583094
2
DM1 is caused by CTG repeat expansion in DMPK gene on chromosome 19; DM1 is the most prevalent adult-onset muscular dystrophy
PMID: 16265841
3
DM1 is mediated by toxic RNA gain-of-function mechanism disrupting RNA splicing; causes multisystem disorder affecting muscles, CNS, and heart
PMID: 40983775
4
AntimiRs targeting miR-23b and miR-218 boost MBNL1 expression and correct DM1 cellular defects across CTG repeat expansions
PMID: 39383229
5
Optical genome mapping accurately measures DMPK repeat expansions and detects somatic instability with 98.8% sensitivity
PMID: 40113266
Disease Associationsβ“˜21
myotonic dystrophy type 1Open Targets
0.75Strong
Steinert myotonic dystrophyOpen Targets
0.72Strong
Bethlem myopathy 1AOpen Targets
0.28Weak
Bethlem myopathyOpen Targets
0.28Weak
coronary artery diseaseOpen Targets
0.27Weak
hypertrophic cardiomyopathyOpen Targets
0.27Weak
cholelithiasisOpen Targets
0.22Weak
diabetic retinopathyOpen Targets
0.22Weak
psoriatic arthritisOpen Targets
0.21Weak
gallstonesOpen Targets
0.20Weak
genetic disorderOpen Targets
0.19Weak
myocardial infarctionOpen Targets
0.19Weak
neurodegenerative diseaseOpen Targets
0.18Weak
chronic obstructive pulmonary diseaseOpen Targets
0.17Weak
myotonic dystrophyOpen Targets
0.16Weak
catecholaminergic polymorphic ventricular tachycardia 1Open Targets
0.13Weak
Noonan syndromeOpen Targets
0.12Weak
acute myeloid leukemiaOpen Targets
0.08Suggestive
Late-onset distal myopathy, Markesbery-Griggs typeOpen Targets
0.08Suggestive
Distal myopathy, Nonaka typeOpen Targets
0.07Suggestive
Dystrophia myotonica 1UniProt
Pathogenic Variants183
Single allelePathogenic
Male infertility
β˜…β˜†β˜†β˜†2025
NM_004409.5(DMPK):c.281CAG[81] (p.Thr93_Gly94insAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAla)Likely pathogenic
Bethlem myopathy 1A
β˜…β˜†β˜†β˜†2023β†’ Residue 93
NM_004409.5(DMPK):c.*224CTG[58]Pathogenic
Steinert myotonic dystrophy syndrome
β˜…β˜†β˜†β˜†2019
NM_004409.5(DMPK):c.*224CTG[330]Pathogenic
Steinert myotonic dystrophy syndrome
β˜…β˜†β˜†β˜†2019
NM_004409.5(DMPK):c.*224CTG[57]Pathogenic
Steinert myotonic dystrophy syndrome
β˜…β˜†β˜†β˜†2019
NM_004409.5(DMPK):c.*224CTG[55]Pathogenic
Steinert myotonic dystrophy syndrome
β˜…β˜†β˜†β˜†2019
NM_004409.5(DMPK):c.*224CTG[75]Pathogenic
Steinert myotonic dystrophy syndrome
β˜…β˜†β˜†β˜†2019
NM_004409.5(DMPK):c.*224CTG[56]Pathogenic
Steinert myotonic dystrophy syndrome
β˜…β˜†β˜†β˜†2019
NM_004409.5(DMPK):c.*224CTG[73]Pathogenic
Steinert myotonic dystrophy syndrome
β˜…β˜†β˜†β˜†2019
NM_004409.5(DMPK):c.*224CTG[280]Pathogenic
Steinert myotonic dystrophy syndrome
β˜…β˜†β˜†β˜†2019
NM_004409.5(DMPK):c.*224CTG[42]Pathogenic
Steinert myotonic dystrophy syndrome
β˜…β˜†β˜†β˜†2019
NM_004409.5(DMPK):c.*224CTG[41]Pathogenic
Steinert myotonic dystrophy syndrome
β˜…β˜†β˜†β˜†2019
NM_004409.5(DMPK):c.*224CTG[45]Pathogenic
Steinert myotonic dystrophy syndrome
β˜…β˜†β˜†β˜†2019
NM_004409.5(DMPK):c.*224CTG[51]Pathogenic
Steinert myotonic dystrophy syndrome
β˜…β˜†β˜†β˜†2019
NM_004409.5(DMPK):c.*224CTG[46]Pathogenic
Steinert myotonic dystrophy syndrome
β˜…β˜†β˜†β˜†2019
NM_004409.5(DMPK):c.*224CTG[52]Pathogenic
Steinert myotonic dystrophy syndrome
β˜…β˜†β˜†β˜†2019
NM_004409.5(DMPK):c.*224CTG[65]Pathogenic
Steinert myotonic dystrophy syndrome
β˜…β˜†β˜†β˜†2019
NM_004409.5(DMPK):c.*224CTG[72]Pathogenic
Steinert myotonic dystrophy syndrome
β˜…β˜†β˜†β˜†2019
NM_004409.5(DMPK):c.*224CTG[31]Pathogenic
Steinert myotonic dystrophy syndrome
β˜…β˜†β˜†β˜†2019
NM_004409.5(DMPK):c.*224CTG[61]Pathogenic
Steinert myotonic dystrophy syndrome
β˜…β˜†β˜†β˜†2019
View on ClinVar β†—
Related Genes
CELF1Protein interaction99%CNBPProtein interaction96%ATP2A1Protein interaction94%CLCN1Protein interaction94%MBNL1Protein interaction94%SIX5Protein interaction86%
Tissue Expression6 tissues
Heart
100%
Ovary
39%
Lung
33%
Liver
12%
Brain
8%
Bone Marrow
4%
Gene Interaction Network
Click a node to explore
DMPKCELF1CNBPATP2A1CLCN1MBNL1SIX5
PROTEIN STRUCTURE
Preparing viewer…
PDB1WT6 Β· 1.60 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.67LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.50 [0.37–0.67]
RankingsWhere DMPK stands among ~20K protein-coding genes
  • #2,460of 20,598
    Most Researched177 Β· top quartile
  • #387of 5,498
    Most Pathogenic Variants183 Β· top 10%
  • #4,931of 17,882
    Most Constrained (LOEUF)0.67
Genes detectedDMPK
Sources retrieved26 papers
Response timeβ€”
πŸ“„ Sources
26β–Ό
1
Myotonic dystrophy type 2: the 2020 update.
PMID: 33458578
Acta Myol Β· 2020
1.00
2
Myotonic dystrophy type 1: clinical diversity, molecular insights and therapeutic perspectives.
PMID: 40983775
Nat Rev Neurol Β· 2025
0.90
3
Myotonic dystrophies.
PMID: 16265841
Chang Gung Med J Β· 2005
0.80
4
Myotonic dystrophy: candidate small molecule therapeutics.
PMID: 28780071
Drug Discov Today Β· 2017
0.72
5
AntimiR treatment corrects myotonic dystrophy primary cell defects across several CTG repeat expansions with a dual mechanism of action.
PMID: 39383229
Sci Adv Β· 2024
0.70