DMPK
DM1 protein kinase, the group of AGC family kinases
Basic information
Region (hg38): 19:45769709-45782552
Previous symbols: [ "DM1", "DM" ]
Links
Phenotypes
GenCC
Source:
- 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:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Myotonic dystrophy 1 | AD/AR | Cardiovascular; Ophthalmologic | Individuals 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 closure | Cardiovascular; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic | 1101835; 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
- Steinert myotonic dystrophy syndrome (48 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.
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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 7 | |||||
| missense | 40 | 10 | 54 | |||
| nonsense | 2 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 3 | 1 | 5 | ||
| non coding | 48 | 14 | 70 | |||
| Total | 48 | 0 | 50 | 18 | 18 |
Highest pathogenic variant AF is 0.000693
Variants in DMPK
This is a list of pathogenic ClinVar variants found in the DMPK region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| DMPK | protein_coding | protein_coding | ENST00000343373 | 14 | 12836 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0383 | 0.962 | 125724 | 0 | 19 | 125743 | 0.0000756 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.285 | 392 | 408 | 0.960 | 0.0000259 | 4047 |
| Missense in Polyphen | 143 | 174.97 | 0.81726 | 1734 | ||
| Synonymous | -2.10 | 217 | 181 | 1.20 | 0.0000125 | 1339 |
| Loss of Function | 3.53 | 8 | 28.2 | 0.284 | 0.00000128 | 319 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000744 | 0.0000615 |
| Ashkenazi Jewish | 0.0000993 | 0.0000992 |
| East Asian | 0.000165 | 0.000163 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000909 | 0.0000879 |
| Middle Eastern | 0.000165 | 0.000163 |
| South Asian | 0.000166 | 0.000131 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- 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
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
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