DMPK

DM1 protein kinase, the group of AGC family kinases

Basic information

Region (hg38): 19:45769709-45782552

Previous symbols: [ "DM1", "DM" ]

Links

ENSG00000104936NCBI:1760OMIM:605377HGNC:2933Uniprot:Q09013AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • myotonic dystrophy type 1 (Definitive), mode of inheritance: AD
  • myotonic dystrophy type 1 (Supportive), mode of inheritance: AD
  • myotonic dystrophy type 1 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Myotonic dystrophy 1AD/ARCardiovascular; OphthalmologicIndividuals have been reported with fatal arrhythmias prior to other signs and symptoms, and cardiologic surveillance (including with EKG) and preventive measures may be beneficial; To assess for posterior capsular cataracts, segular ophthalmoscopy has been indicated, as these may require extraction if cataracts are impairing vision; if tarsorrhaphy is performed due to ptosis, it is important not to overcorrect due to risk of causing corneal abrasion secondary to lack of lid closureCardiovascular; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic1101835; 1167063; 6639233; 1346925; 1310900; 1346924; 1546326; 1346923; 1546325; 1303233; 8353490; 8503448; 8421476; 7696601; 7880334; 8071955; 7473648; 7650805; 8880582; 9106286; 9391889; 10325709; 11071501; 11807903; 15079005;15557517; 15596617; 17575483; 17663477; 18565861; 19949042; 19514047; 20018643; 20301344; 21259315; 22643181; 22995693

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DMPK gene.

  • Inborn_genetic_diseases (125 variants)
  • DMPK-related_disorder (15 variants)
  • Steinert_myotonic_dystrophy_syndrome (13 variants)
  • not_provided (12 variants)
  • not_specified (11 variants)
  • Myotonic_dystrophy (3 variants)
  • Catecholaminergic_polymorphic_ventricular_tachycardia_1 (1 variants)
  • Bethlem_myopathy_1A (1 variants)
  • Noonan_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DMPK gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004409.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
22
clinvar
2
clinvar
24
missense
107
clinvar
12
clinvar
3
clinvar
122
nonsense
1
clinvar
1
start loss
0
frameshift
2
clinvar
2
splice donor/acceptor (+/-2bp)
0
Total 0 0 110 34 5
Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
DMPKprotein_codingprotein_codingENST00000343373 1412836
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.03830.9621257240191257430.0000756
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.2853924080.9600.00002594047
Missense in Polyphen143174.970.817261734
Synonymous-2.102171811.200.00001251339
Loss of Function3.53828.20.2840.00000128319

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00007440.0000615
Ashkenazi Jewish0.00009930.0000992
East Asian0.0001650.000163
Finnish0.000.00
European (Non-Finnish)0.00009090.0000879
Middle Eastern0.0001650.000163
South Asian0.0001660.000131
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Non-receptor serine/threonine protein kinase which is necessary for the maintenance of skeletal muscle structure and function. May play a role in myocyte differentiation and survival by regulating the integrity of the nuclear envelope and the expression of muscle-specific genes. May also phosphorylate PPP1R12A and inhibit the myosin phosphatase activity to regulate myosin phosphorylation. Also critical to the modulation of cardiac contractility and to the maintenance of proper cardiac conduction activity probably through the regulation of cellular calcium homeostasis. Phosphorylates PLN, a regulator of calcium pumps and may regulate sarcoplasmic reticulum calcium uptake in myocytes. May also phosphorylate FXYD1/PLM which is able to induce chloride currents. May also play a role in synaptic plasticity. {ECO:0000269|PubMed:10811636, ECO:0000269|PubMed:10913253, ECO:0000269|PubMed:11287000, ECO:0000269|PubMed:15598648, ECO:0000269|PubMed:21457715, ECO:0000269|PubMed:21949239}.;
Disease
DISEASE: Dystrophia myotonica 1 (DM1) [MIM:160900]: A muscular disorder characterized by myotonia, muscle wasting in the distal extremities, cataract, hypogonadism, defective endocrine functions, male baldness and cardiac arrhythmias. {ECO:0000269|PubMed:1302022, ECO:0000269|PubMed:1310900, ECO:0000269|PubMed:1546326, ECO:0000269|PubMed:19514047}. Note=The disease is caused by mutations affecting the gene represented in this entry. The causative mutation is a CTG expansion in the 3'- UTR of the DMPK gene. A length exceeding 50 CTG repeats is pathogenic, while normal individuals have 5 to 37 repeats. Intermediate alleles with 35-49 triplets are not disease-causing but show instability in intergenerational transmissions. Disease severity varies with the number of repeats: mildly affected persons have 50 to 150 repeats, patients with classic DM have 100 to 1,000 repeats, and those with congenital onset can have more than 2,000 repeats. {ECO:0000269|PubMed:1310900, ECO:0000269|PubMed:19514047}.;
Pathway
Ion homeostasis;Cardiac conduction;Muscle contraction (Consensus)

Recessive Scores

pRec
0.281

Intolerance Scores

loftool
0.638
rvis_EVS
-0.77
rvis_percentile_EVS
13.15

Haploinsufficiency Scores

pHI
0.197
hipred
Y
hipred_score
0.592
ghis
0.593

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.861

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Dmpk
Phenotype
homeostasis/metabolism phenotype; muscle phenotype; normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan);

Gene ontology

Biological process
protein phosphorylation;cellular calcium ion homeostasis;nuclear envelope organization;regulation of heart contraction;muscle cell apoptotic process;regulation of myotube differentiation;regulation of skeletal muscle contraction by calcium ion signaling;peptidyl-serine phosphorylation;intracellular signal transduction;regulation of phosphoprotein phosphatase activity;regulation of cardiac conduction
Cellular component
nuclear outer membrane;endoplasmic reticulum membrane;cytosol;plasma membrane;integral component of mitochondrial outer membrane;nuclear membrane;sarcoplasmic reticulum membrane
Molecular function
protein serine/threonine kinase activity;protein binding;ATP binding;myosin phosphatase regulator activity;metal ion binding