DMPK

Summary

DMPK (DM1 protein kinase, HGNC:2933) is a protein-coding gene on chromosome 19q13.32, encoding Myotonin-protein kinase (Q09013). Non-receptor serine/threonine protein kinase which is necessary for the maintenance of skeletal muscle structure and function.

The protein encoded by this gene is a serine-threonine kinase that is closely related to other kinases that interact with members of the Rho family of small GTPases. Substrates for this enzyme include myogenin, the beta-subunit of the L-type calcium channels, and phospholemman. The 3’ untranslated region of this gene contains 5-38 copies of a CTG trinucleotide repeat. Expansion of this unstable motif to 50-5,000 copies causes myotonic dystrophy type I, which increases in severity with increasing repeat element copy number. Repeat expansion is associated with condensation of local chromatin structure that disrupts the expression of genes in this region. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.

Source: NCBI Gene 1760 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myotonic dystrophy type 1 (Definitive, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 152 total — 9 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 52
• Druggable target: yes — 20 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004409

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2933
Approved symbol	DMPK
Name	DM1 protein kinase
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	DMK, DM1PK, MDPK, MT-PK
Ensembl gene	ENSG00000104936
Ensembl biotype	protein_coding
OMIM	605377
Entrez	1760

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 21 protein_coding, 20 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000291270, ENST00000343373, ENST00000354227, ENST00000447742, ENST00000458663, ENST00000588522, ENST00000593574, ENST00000595361, ENST00000596067, ENST00000596686, ENST00000596920, ENST00000597660, ENST00000598180, ENST00000598191, ENST00000598272, ENST00000599002, ENST00000599392, ENST00000600370, ENST00000600757, ENST00000674226, ENST00000682259, ENST00000682273, ENST00000682335, ENST00000682436, ENST00000682529, ENST00000682898, ENST00000682994, ENST00000683086, ENST00000683830, ENST00000684007, ENST00000684672, ENST00000902145, ENST00000902146, ENST00000902147, ENST00000902148, ENST00000902149, ENST00000902150, ENST00000902151, ENST00000902152, ENST00000902153, ENST00000947411, ENST00000947412, ENST00000947413, ENST00000947414

RefSeq mRNA: 14 — MANE Select: NM_004409 NM_001081560, NM_001081562, NM_001081563, NM_001288764, NM_001288765, NM_001288766, NM_001424162, NM_001424163, NM_001424164, NM_001424165, NM_001424166, NM_001424168, NM_001424169, NM_004409

CCDS: CCDS12674, CCDS46117, CCDS46118, CCDS74400

Canonical transcript exons

ENST00000291270 — 15 exons

Exon	Start	End
ENSE00002858732	45782193	45782490
ENSE00003484367	45777667	45777873
ENSE00003494201	45778493	45778641
ENSE00003494269	45771771	45771928
ENSE00003515823	45779439	45779522
ENSE00003525807	45774949	45775034
ENSE00003534388	45778127	45778220
ENSE00003554377	45779778	45779869
ENSE00003592282	45771568	45771665
ENSE00003609541	45777327	45777590
ENSE00003610901	45771350	45771396
ENSE00003615528	45770971	45771060
ENSE00003640441	45769717	45770640
ENSE00003653656	45772641	45772752
ENSE00003672131	45779264	45779359

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 98.88.

FANTOM5 (CAGE): breadth broad, TPM avg 3.6691 / max 107.5367, expressed in 801 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181569	3.2481	774
181568	0.2289	101
208866	0.1108	53
181571	0.0814	31

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.88	gold quality
right coronary artery	UBERON:0001625	98.80	gold quality
mucosa of stomach	UBERON:0001199	98.78	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.73	gold quality
lower esophagus	UBERON:0013473	98.72	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.72	gold quality
popliteal artery	UBERON:0002250	98.54	gold quality
tibial artery	UBERON:0007610	98.54	gold quality
right atrium auricular region	UBERON:0006631	98.46	gold quality
aorta	UBERON:0000947	98.37	gold quality
ascending aorta	UBERON:0001496	98.33	gold quality
thoracic aorta	UBERON:0001515	98.33	gold quality
descending thoracic aorta	UBERON:0002345	98.23	gold quality
left uterine tube	UBERON:0001303	98.22	gold quality
body of uterus	UBERON:0009853	98.14	gold quality
left coronary artery	UBERON:0001626	98.05	gold quality
heart left ventricle	UBERON:0002084	98.00	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.82	gold quality
right adrenal gland cortex	UBERON:0035827	97.77	gold quality
right adrenal gland	UBERON:0001233	97.76	gold quality
gastrocnemius	UBERON:0001388	97.67	gold quality
cardiac ventricle	UBERON:0002082	97.66	gold quality
coronary artery	UBERON:0001621	97.65	gold quality
left adrenal gland cortex	UBERON:0035825	97.65	gold quality
left adrenal gland	UBERON:0001234	97.64	gold quality
cardiac atrium	UBERON:0002081	97.48	gold quality
adenohypophysis	UBERON:0002196	97.37	gold quality
right uterine tube	UBERON:0001302	97.26	gold quality
muscle of leg	UBERON:0001383	96.98	gold quality
heart	UBERON:0000948	96.88	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.12

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CNBP, CTCF, MBD2, PDX1, SP1, SPEN, TCF3, ZNF91

miRNA regulators (miRDB)

29 targeting DMPK, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-12114	98.70	63.45	730
HSA-MIR-6855-5P	97.51	66.03	830
HSA-MIR-4264	96.35	64.76	1480
HSA-MIR-6815-5P	96.05	65.55	662
HSA-MIR-6865-5P	96.05	65.58	675
HSA-MIR-3170	95.84	64.32	721
HSA-MIR-6835-5P	95.81	64.27	500
HSA-MIR-4707-5P	90.95	65.69	110
HSA-MIR-4787-5P	89.08	66.18	88
HSA-MIR-1538	85.86	60.08	75

Literature-anchored findings (GeneRIF, showing 40)

• eight years’ experience of direct molecular testing for myotonic dystrophy in Wales (PMID:11748308)
• Gene for myotonic dystrophy (PMID:11766468)
• presymptomatic testing in myotonic dystrophy: genetic counselling approaches (PMID:11768386)
• trinucleotide repeat contraction of a paternal expanded DMPK allele back to the normal range detected in the fetus: a pitfall in prenatal diagnosis of myotonic dystrophy (PMID:11768387)
• negative linear correlation of age at onset and average expansion size in juvenile-adult DM1 patients (35 out of 46) whose progenitor allele is less than 245 repeats long (PMID:11793472)
• conclude that mutant DMPK 3’-UTR transcripts disrupt myoblast differentiation by reducing MyoD levels below a threshold required to activate the differentiation program (PMID:12427866)
• Levels of this enzyme are altered, along with muscle development, in congenital myotonic dystrophy. (PMID:12598332)
• These studies indicate that homologous recombination strongly destabilizes long tracts of CTG repeats from DMPK (PMID:12697816)
• enhancement of activity through homodimerization of coiled-coil regions (PMID:12832055)
• the N-terminus of DMPK plays an important role in DMPK kinase activity, and that the C-terminus of DMPK determines the intracellular localization of the protein (PMID:14607980)
• DMPK mutant RNA binds and sequesters transcription factors (TFs) with up to 90% depletion of selected TFs from active chromatin (PMID:14657503)
• used transgenic DM1 mice carrying more than 300 unstable CTG repeats within their large human genomic environment to investigate the dynamics of CTG repeat germinal mosaicism in males (PMID:14701736)
• Ribozymes can be applied to repair mutations at the RNA level, and therefore can restore normal cellular functions in myotonic dystrophy. (PMID:15017064)
• The number of CTG repeats in the normal or mutational range of DM1PK gene is associated with neither idiopathic male subfertility nor with clinical characteristics of male subfertility. (DM1PK) (PMID:15284213)
• Continuous overexpression of hDMPK generated pathologic hypertrophic cardiomyopathy and myotonic muscle myopathy in transgenic mice. (PMID:15317754)
• Trinucleotide Repeat Expansion at 3 untranslated region of myotonic dystrophy protein kinase is associated with myotonic dystrophy (PMID:15462191)
• In twenty-six individuals from a family with DM, the CTG repeats in DMPK were found in normal range. (PMID:15476170)
• preliminary X-ray analysis of the coiled-coil domain of dystrophia myotonica kinase (PMID:15583383)
• DMPK phosphorylates phospholamban and regulates calcium uptake in cardiomyocyte sarcoplasmic reticulum (PMID:15598648)
• with DMPK in myotonic dystrophy cells, there may be a link between processing of the shRNA and nuclear import or a separate pathway for processing shRNAs in the nuclei (PMID:15722335)
• Transfected into Saccharomyces cerevisiae overexpresses two forms of human DMPK, full-length (DMFL) and a C-terminal truncated form (DMTand affects growth and cell morphology. (PMID:15894391)
• role in muscle differentiation by controlling the rearrangement of the cytoskeleton that takes place during elongation and fusion of myblasts into myotubes (PMID:16099181)
• Myotonic dystrophy is an autosomal dominant disease caused by a trinucleotide repeat-expansion, cytosine-thymine-guanine (CTG)n, in the 3’ untranslated region of a gene encoding DMPK. (PMID:16193250)
• Our findings indicate that the coiled-coil domain modulates myotonic dystrophy protein kinase multimerization, substrate binding, kinase activity and subcellular localization characteristics. (PMID:16519679)
• coordinated physical and functional interactions between hnRNP H, CUG-BP1 and MBNL1 dictate IR splicing in normal and DM1 myoblasts (PMID:16946708)
• It is important to use more than one linked polymorphic marker in PGD-PCR protocols to identify the DM1 mutation. (PMID:17192963)
• Subjects who presented large CTG expansion in regions of the DMPK gene correlated with significant extensive cognitive deficits in intelligence scales. (PMID:17433680)
• the expanded CUG repeats in DMPK mRNA are blocking a stage in its export pathway that would normally occur at the speckle periphery (PMID:17825047)
• In DM1, DMPK mutant transcripts detach from the gene but accumulate in granules that abut but do not enter SC-35 domains, suggesting that RNA entry into the domain is blocked. (PMID:17846170)
• subcortical WMLs are correlated with focal dementia in classic DM1(CTG repeat expansion ) patients. (PMID:18184345)
• Further studies are warranted to elucidate the molecular etiology causing neurodevelopmental symptoms such as autism spectrum disorder and mental retardation in myotonic dystrophy type 1. (PMID:18228241)
• Mutation analysis revealed 2 copies of expansion mutation of 1260 and 60 cytosine-thymine-guanine repeats in the myotonic dystrophy protein kinase gene. (PMID:18474935)
• Data show that an important instability of the CTG repeat CTG repeat in DMPK gene was detected during prolonged in vitro culture, showing stepwise increases of the repeat number in consecutive passages as well as a higher range of variability. (PMID:18577525)
• The length of the (CTG)n repetition located in the 3’UTR of the DM protein kinase gene (DMPK) is associated with the degree of splicing misregulation in myotonic dystrophy type 1. (PMID:18611984)
• In transgenic mice the respiratory impairment associated with DM-1 may be partially due to pathologic alterations in neuromuscular junctions and phrenic nerves. (PMID:18648326)
• DMPK Allelic frequencies in the Chilean sample studied were intermediate between those of the two ancestral populations (European and Pehuenche). (PMID:18798829)
• Altered splicing of Tau in DM1 is different from the fetal splicing process. (PMID:19166838)
• The crystal structure of the kinase domain of DMPK bound to the inhibitor bisindolylmaleimide VIII (BIM-8) revealed a dimeric enzyme associated by a conserved dimerization domain. (PMID:19309729)
• The identification of interruptions in the DMPK repeat has important consequences for molecular genetic testing where they can lead to false negative conclusions. (PMID:19514047)
• DMPK is a kinase with pronounced expression in diverse muscle and neural tissues that are affected in myotonic dystrophy type 1 (PMID:19626675)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dmpk	ENSMUSG00000030409
rattus_norvegicus	Dmpk	ENSRNOG00000015085
drosophila_melanogaster	CG32944	FBGN0052944
drosophila_melanogaster	dop	FBGN0267390
caenorhabditis_elegans		WBGENE00002192
caenorhabditis_elegans	wts-1	WBGENE00007047
caenorhabditis_elegans		WBGENE00010838
caenorhabditis_elegans		WBGENE00011992

Paralogs (13): MAST4 (ENSG00000069020), MAST2 (ENSG00000086015), MAST3 (ENSG00000099308), SGK2 (ENSG00000101049), SGK3 (ENSG00000104205), MAST1 (ENSG00000105613), SGK1 (ENSG00000118515), MASTL (ENSG00000120539), LATS1 (ENSG00000131023), LATS2 (ENSG00000150457), STK32B (ENSG00000152953), STK32C (ENSG00000165752), STK32A (ENSG00000169302)

Protein

Protein identifiers

Myotonin-protein kinase — Q09013 (reviewed: Q09013)

Alternative names: DM-kinase, DM1 protein kinase, DMPK, Myotonic dystrophy protein kinase

All UniProt accessions (7): Q09013, E5KR05, E5KR06, E5KR07, K7EQX1, M0QXJ9, M0R1F3

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Homodimer; homodimerization stimulates the kinase activity. Interacts with HSPB2; may enhance DMPK kinase activity. Interacts with PLN; phosphorylates PLN. May interact with RAC1; may regulate DMPK kinase activity. Interacts with LMNA; may regulate nuclear envelope stability.

Subcellular location. Endoplasmic reticulum membrane. Nucleus outer membrane. Mitochondrion outer membrane. Sarcoplasmic reticulum membrane. Cell membrane. Cytoplasm. Cytosol Mitochondrion membrane Mitochondrion membrane.

Tissue specificity. Most isoforms are expressed in many tissues including heart, skeletal muscle, liver and brain, except for isoform 2 which is only found in the heart and skeletal muscle, and isoform 14 which is only found in the brain, with high levels in the striatum, cerebellar cortex and pons.

Post-translational modifications. Phosphorylated. Autophosphorylates. Phosphorylation by RAF1 may result in activation of DMPK. Proteolytic processing of the C-terminus may remove the transmembrane domain and release the kinase from membranes stimulating its activity.

Disease relevance. 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. The disease is caused by variants 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.

Activity regulation. Coiled-coil-mediated oligomerization enhances the catalytic activity. Proteolytic processing of the C-terminus may release the protein from membranes and constitute a mean to regulate the enzyme. May be regulated by HSPB2, RAC1, RAF1 and G-protein second messengers.

Domain organisation. The coiled coil domain is required for homodimerization and regulates the enzymatic activity.

Similarity. Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. DMPK subfamily.

Isoforms (12)

UniProt ID	Names	Canonical?
Q09013-9	1, DMPK A	yes
Q09013-11	2, DMPK B
Q09013-16	3, DMPK C
Q09013-15	4, DMPK D
Q09013-10	5, DMPK E
Q09013-12	6, DMPK F
Q09013-1	7
Q09013-2	8
Q09013-5	9
Q09013-6	10
Q09013-7	11
Q09013-8	12

RefSeq proteins (14): NP_001075029, NP_001075031, NP_001075032, NP_001275693, NP_001275694, NP_001275695, NP_001411091, NP_001411092, NP_001411093, NP_001411094, NP_001411095, NP_001411097, NP_001411098, NP_004400* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR014930	Myotonic_dystrophy_kinase_coil	Domain
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR050839	Rho-assoc_Ser/Thr_Kinase	Family

Pfam: PF00069, PF08826

Enzyme classification (BRENDA):

• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
KKRAARATSNVFA	0.013–0.045	3
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (62 total): helix 23, strand 9, splice variant 8, turn 5, modified residue 3, topological domain 2, sequence variant 2, domain 2, binding site 2, chain 1, transmembrane region 1, mutagenesis site 1, sequence conflict 1, coiled-coil region 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1WT6	X-RAY DIFFRACTION	1.6
2VD5	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q09013-F1	78.91	0.53

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 195 (proton acceptor)

Ligand- & substrate-binding residues (2): 77–85; 100

Post-translational modifications (3): 216, 228, 234

Mutagenesis-validated functional residues (1):

Position	Phenotype
100	loss of kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5578775	Ion homeostasis

MSigDB gene sets: 0 (showing top):

GO Biological Process (10): regulation of sodium ion transport (GO:0002028), protein phosphorylation (GO:0006468), intracellular calcium ion homeostasis (GO:0006874), nuclear envelope organization (GO:0006998), regulation of heart contraction (GO:0008016), muscle cell apoptotic process (GO:0010657), regulation of myotube differentiation (GO:0010830), regulation of skeletal muscle contraction by calcium ion signaling (GO:0014722), regulation of excitatory postsynaptic membrane potential involved in skeletal muscle contraction (GO:0014853), regulation of synapse structural plasticity (GO:0051823)

GO Molecular Function (10): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), myosin phosphatase regulator activity (GO:0017020), metal ion binding (GO:0046872), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (14): nuclear outer membrane (GO:0005640), mitochondrial outer membrane (GO:0005741), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), nuclear membrane (GO:0031965), sarcoplasmic reticulum membrane (GO:0033017), nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), sarcoplasmic reticulum (GO:0016529), mitochondrial membrane (GO:0031966)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cardiac conduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
organelle membrane	3
cytoplasm	3
cellular anatomical structure	3
intracellular membrane-bounded organelle	3
skeletal muscle contraction	2
protein kinase activity	2
organelle outer membrane	2
nuclear outer membrane-endoplasmic reticulum membrane network	2
sodium ion transport	1
regulation of metal ion transport	1
phosphorylation	1
protein modification process	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
nucleus organization	1
endomembrane system organization	1
membrane organization	1
heart contraction	1
regulation of blood circulation	1
apoptotic process	1
myotube differentiation	1
regulation of striated muscle cell differentiation	1
regulation of skeletal muscle contraction	1
calcium-mediated signaling	1
regulation of skeletal muscle contraction by neural stimulation via neuromuscular junction	1
modulation of excitatory postsynaptic potential	1
regulation of synapse organization	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
myosin phosphatase activity	1
protein phosphatase regulator activity	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1

Protein interactions and networks

STRING

2398 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DMPK	MBNL1	Q9NR56	939
DMPK	CELF1	Q92879	925
DMPK	CNBP	P20694	916
DMPK	CLCN1	P35523	878
DMPK	MBNL2	Q5VZF2	850
DMPK	MBNL3	Q9NUK0	845
DMPK	SIX5	Q8N196	832
DMPK	DMWD	Q09019	760
DMPK	ATP2A1	O14983	740
DMPK	YIPF7	Q8N8F6	728
DMPK	CELF2	O95319	662
DMPK	TNNT2	P45379	650
DMPK	LDB3	O75112	640
DMPK	CEBPD	P49716	622
DMPK	RYR1	P21817	608

IntAct

28 interactions, top by confidence:

A	B	Type	Score
ATXN1	DMPK	psi-mi:“MI:0915”(physical association)	0.670
DMPK	PPP1R12A	psi-mi:“MI:0217”(phosphorylation reaction)	0.570
PPP1R12A	DMPK	psi-mi:“MI:0217”(phosphorylation reaction)	0.570
	DMPK	psi-mi:“MI:0915”(physical association)	0.560
DMPK	PLN	psi-mi:“MI:0217”(phosphorylation reaction)	0.560
PLN	DMPK	psi-mi:“MI:0217”(phosphorylation reaction)	0.560
HSP90AB1	DMPK	psi-mi:“MI:0915”(physical association)	0.400
GEMIN4	DMPK	psi-mi:“MI:0915”(physical association)	0.370
ANXA7	DMPK	psi-mi:“MI:0915”(physical association)	0.370
PIN1	DMPK	psi-mi:“MI:0915”(physical association)	0.370
DMPK	RPS10	psi-mi:“MI:0915”(physical association)	0.370
SMN1	DMPK	psi-mi:“MI:0915”(physical association)	0.370
TK1	DMPK	psi-mi:“MI:0915”(physical association)	0.370
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
	DMPK	psi-mi:“MI:0915”(physical association)	0.000
DMPK		psi-mi:“MI:0915”(physical association)	0.000
DMPK	GABARAP	psi-mi:“MI:0915”(physical association)	0.000
UBQLN4	DMPK	psi-mi:“MI:0915”(physical association)	0.000
ATN1	DMPK	psi-mi:“MI:0915”(physical association)	0.000
ATXN1	DMPK	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (41): DMPK (Affinity Capture-Western), PLN (Affinity Capture-Western), PLN (Biochemical Activity), MAP2K7 (Negative Genetic), DMPK (Negative Genetic), PTK6 (Negative Genetic), DMPK (Negative Genetic), TST (Negative Genetic), DMPK (Negative Genetic), KSR1 (Negative Genetic), DMPK (Negative Genetic), NPEPPS (Negative Genetic), DMPK (Negative Genetic), DMPK (Two-hybrid), HSPB2 (Affinity Capture-Western)

ESM2 similar proteins: A0JP70, A1XQU1, A5LHX3, O14976, O23712, O24361, O35955, O43304, O55234, O95248, O95382, O95398, P28062, P28063, P28064, P28072, P28074, P28075, P30656, P34065, P40306, P51656, P51657, P54265, P70195, Q09013, Q0P595, Q2TBP0, Q32KL2, Q3MHN0, Q3T0T1, Q3T112, Q4KM35, Q54BC8, Q5R8S2, Q5W416, Q60692, Q6NYX6, Q6ZPG2, Q7DLS1

Diamond homologs: A0A7J6K7I9, A0A7J6K7Y0, A0A7J6KD88, A8X775, B1WAR9, C4YRB7, D2HXI8, E1C2I2, E9PSL7, G1X456, G5EGQ3, M3TYT0, O00506, O01583, O01700, O14578, O54874, O61267, O75116, O77819, O80902, O88643, O97627, P05131, P0CY23, P0CY24, P13677, P21146, P25098, P26817, P26818, P32865, P34100, P35465, P38070, P48562, P49025, P49673, P54265, P70335

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
DMPK	up-regulates	PLN	phosphorylation
DMPK	up-regulates	SRF	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

152 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	2
Uncertain significance	101
Likely benign	22
Benign	6

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
187920	NM_004409.5(DMPK):c.*224CTG[132]	Pathogenic
523754	NC_000019.10:g.45770205_45770264CAG[(53_67)]CAGGCC[(53_67)]CAG[(180_230)]	Pathogenic
523755	NC_000019.10:g.45770205_45770264CAG[(41_59)]CGG[1]CAG[(200_300)]	Pathogenic
523760	NM_004409.5(DMPK):c.*224CTG[288]	Pathogenic
805866	NM_004409.4:c.*224_*283CTG[(192_602)]CCG[1]CTG[8]CCG[2]CTG[2]CCG[1]CTG[4]CCG[1]CTG[30]	Pathogenic
805867	NM_004409.4:c.*224_*283CTG[329]NNN[(?)]CCG[1]CTG[1]CCG[1]CTG[1]CCG[1]CTG[4]CCG[1]CTG[1]CCG[1]CTG[1]CCG[1]CTG[4]CCG[1]CTG[1]CCG[1]CTG[18]	Pathogenic
805868	NM_004409.4:c.*224_*283CTG[(510_860)]CCG[1]CTG[1]CCG[1]CTG[1]CCG[1]CTG[2]CCG[3]CTG[1]CCG[1]CTG[4]CCG[1]CTG[1]CCG[1]CTG[18]	Pathogenic
805869	NM_004409.4:c.*224_*283CTG[(271_852)]CCG[1]CTG[17]CCG[1]CTG[29]	Pathogenic
973609	NC_000019.9:g.46273465GCA[(49_?)]	Pathogenic
3775836	NM_004409.5(DMPK):c.281CAG[81] (p.Thr93_Gly94insAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAlaAla)	Likely pathogenic
805865	NM_004409.4:c.*224CTG[173_283]CCG[1]CTG[8]CCG[2]CTG[2]CCG[1]CTG[4]CCG[1]CTG[30]	Likely pathogenic

SpliceAI

2044 predictions. Top by Δscore:

Variant	Effect	Δscore
19:45770766:CAG:C	donor_gain	1.0000
19:45771564:TCACC:T	donor_loss	1.0000
19:45771566:A:AC	donor_gain	1.0000
19:45771566:AC:A	donor_gain	1.0000
19:45771566:ACC:A	donor_loss	1.0000
19:45771567:C:CA	donor_gain	1.0000
19:45771567:CC:C	donor_gain	1.0000
19:45771567:CCT:C	donor_gain	1.0000
19:45771567:CCTG:C	donor_gain	1.0000
19:45771661:GTTGA:G	acceptor_gain	1.0000
19:45771662:TTGA:T	acceptor_gain	1.0000
19:45771663:TGA:T	acceptor_gain	1.0000
19:45771664:GA:G	acceptor_gain	1.0000
19:45771664:GAC:G	acceptor_loss	1.0000
19:45771665:AC:A	acceptor_loss	1.0000
19:45771666:C:CC	acceptor_gain	1.0000
19:45771667:T:G	acceptor_loss	1.0000
19:45771668:G:C	acceptor_gain	1.0000
19:45771668:G:GC	acceptor_gain	1.0000
19:45771765:CCCGA:C	donor_loss	1.0000
19:45771766:CCGA:C	donor_loss	1.0000
19:45771767:CGA:C	donor_loss	1.0000
19:45771768:GACC:G	donor_loss	1.0000
19:45771770:C:CT	donor_loss	1.0000
19:45771925:CAGC:C	acceptor_gain	1.0000
19:45771929:C:CC	acceptor_gain	1.0000
19:45771930:T:A	acceptor_loss	1.0000
19:45771931:G:GC	acceptor_gain	1.0000
19:45772636:CTTA:C	donor_gain	1.0000
19:45772638:TACTG:T	donor_loss	1.0000

AlphaMissense

4043 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:45778164:T:A	D213V	1.000
19:45778164:T:G	D213A	1.000
19:45778211:T:A	K197N	1.000
19:45778211:T:G	K197N	1.000
19:45778218:T:G	D195A	1.000
19:45778493:C:A	R194M	1.000
19:45778613:C:T	G154E	1.000
19:45779475:C:A	K100N	1.000
19:45779475:C:G	K100N	1.000
19:45779784:G:C	F82L	1.000
19:45779784:G:T	F82L	1.000
19:45779786:A:G	F82L	1.000
19:45779797:C:T	G78E	1.000
19:45777372:G:C	F367L	0.999
19:45777372:G:T	F367L	0.999
19:45777373:A:C	F367C	0.999
19:45777374:A:G	F367L	0.999
19:45777715:G:C	F278L	0.999
19:45777715:G:T	F278L	0.999
19:45777717:A:G	F278L	0.999
19:45777763:C:A	W262C	0.999
19:45777763:C:G	W262C	0.999
19:45777765:A:G	W262R	0.999
19:45777765:A:T	W262R	0.999
19:45777852:C:G	G233R	0.999
19:45778151:G:C	C217W	0.999
19:45778163:G:C	D213E	0.999
19:45778163:G:T	D213E	0.999
19:45778164:T:C	D213G	0.999
19:45778165:C:G	D213H	0.999

dbSNP variants (sampled 300 via entrez): RS1000180256 (19:45784098 C>T), RS1000219437 (19:45782465 TCCCTGGCTGTC>T), RS1000529688 (19:45770517 G>A), RS1000779803 (19:45773862 T>TG), RS1000786177 (19:45776635 T>C), RS1000812041 (19:45778378 C>CCG), RS1000921913 (19:45776787 T>C), RS1000937485 (19:45770863 C>T), RS1001277241 (19:45774245 C>G,T), RS1001326694 (19:45774483 C>T), RS1001347018 (19:45779565 C>G), RS1001410910 (19:45769669 G>C), RS1001479405 (19:45770982 G>A), RS1001637903 (19:45783798 A>G), RS1001837963 (19:45769888 T>C,G)

Disease associations

OMIM: gene MIM:605377 | disease phenotypes: MIM:160900, MIM:163950, MIM:600996, MIM:604772, MIM:158810

GenCC curated gene-disease

Disease	Classification	Inheritance
myotonic dystrophy type 1	Definitive	Autosomal dominant

Mondo (5): myotonic dystrophy type 1 (MONDO:0008056), Noonan syndrome (MONDO:0018997), catecholaminergic polymorphic ventricular tachycardia 1 (MONDO:0011484), Bethlem myopathy 1A (MONDO:0024530), myotonic dystrophy (MONDO:0016107)

Orphanet (5): Steinert myotonic dystrophy (Orphanet:273), Noonan syndrome (Orphanet:648), Catecholaminergic polymorphic ventricular tachycardia (Orphanet:3286), Bethlem muscular dystrophy (Orphanet:610), Myotonic dystrophy (Orphanet:206647)

HPO phenotypes

52 total (30 of 52 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000029	Testicular atrophy
HP:0000135	Hypogonadism
HP:0000256	Macrocephaly
HP:0000297	Facial hypotonia
HP:0000518	Cataract
HP:0000729	Autistic behavior
HP:0000736	Short attention span
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0000805	Enuresis
HP:0001081	Cholelithiasis
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001262	Excessive daytime somnolence
HP:0001290	Generalized hypotonia
HP:0001319	Neonatal hypotonia
HP:0001324	Muscle weakness
HP:0001349	Facial diplegia
HP:0001513	Obesity
HP:0001558	Decreased fetal movement
HP:0001561	Polyhydramnios
HP:0001622	Premature birth
HP:0001643	Patent ductus arteriosus
HP:0001671	Abnormal cardiac septum morphology
HP:0001883	Talipes
HP:0002014	Diarrhea
HP:0002015	Dysphagia
HP:0002019	Constipation
HP:0002020	Gastroesophageal reflux

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007612_3	Chronic obstructive pulmonary disease or coronary artery disease (pleiotropy)	1.000000e-08
GCST012099_24	Hypertrophic cardiomyopathy (sarcomere negative)	7.000000e-07

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D009223	Myotonic Dystrophy	C05.651.534.500.500; C05.651.662.750; C10.574.500.547; C10.668.491.175.500.500; C10.668.491.606.750; C16.320.400.542; C16.320.577.500
D009634	Noonan Syndrome	C05.660.207.690; C14.240.400.787; C14.280.400.787; C16.131.240.400.784; C16.131.621.207.690; C17.300.690
C563409	Arrhythmogenic Right Ventricular Dysplasia, Familial, 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5320 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

20 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 337,581 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL2103743	TOFACITINIB CITRATE	4	1,672
CHEMBL221959	TOFACITINIB	4	10,408
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL939	GEFITINIB	4	117,814
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL384304	RG-547	2	93
CHEMBL445813	AT-7519	2	2,614
CHEMBL513909	BI-2536	2	895
CHEMBL607707	PELITINIB	2	6,340
CHEMBL1908397	KW-2449	1	622

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs672348	DMPK		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — GEK subfamily

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
RKI-1447	Inhibition	7.47	pIC50

Binding affinities (BindingDB)

9 measured of 9 human assays (9 total across all organisms); most potent 9 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
BMS-354825	KD	27 nM
PKC-412	KD	190 nM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.1^{7,14}.0^{2,6}.0^{8,13}.0^{22,27}]nonacosa-1(28),2(6),7(29),8(13),9,11,22(27),23,25-nonaene-3,5-dione	KD	700 nM
ERLOTINIB HYDROCHLORIDE	KD	1200 nM
GEFITINIB	IC50	2300 nM	US-9416123: Kinase modulators for the treatment of cancer
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 nM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S)-3-hydroxy-1-methyl-4-piperidinyl]-1-benzopyran-4-one	KD	5300 nM

ChEMBL bioactivities

47 potent at pChembl≥5 of 47 total, top 38 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.46	Kd	3.5	nM	STAUROSPORINE
7.52	Kd	30	nM	CHEMBL5633837
7.47	IC50	34.06	nM	CHEMBL3218297
7.23	Kd	59	nM	PELITINIB
7.19	IC50	64.6	nM	CHEMBL4439133
7.05	Kd	90	nM	CHEMBL4465866
7.04	Kd	92	nM	CHEMBL379218
7.04	Kd	91	nM	BOSUTINIB
7.03	Kd	94	nM	CHEMBL4576489
6.98	IC50	105	nM	STAUROSPORINE
6.95	IC50	113	nM	STAUROSPORINE
6.85	Kd	140	nM	CHEMBL1241674
6.62	IC50	242	nM	STAUROSPORINE
6.62	Kd	240	nM	LESTAURTINIB
6.55	Kd	280	nM	RUBOXISTAURIN
6.21	Kd	610	nM	RG-547
6.19	Kd	650	nM	ALVOCIDIB
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
6.00	Kd	1000	nM	FEDRATINIB
5.96	Kd	1100	nM	AT-7519
5.92	Kd	1200	nM	TOFACITINIB CITRATE
5.92	Kd	1200	nM	JNJ-7706621
5.92	Kd	1200	nM	TOFACITINIB
5.89	Kd	1300	nM	DASATINIB
5.86	IC50	1380	nM	CHEMBL3715238
5.85	Kd	1400	nM	CRIZOTINIB
5.82	IC50	1500	nM	CHEMBL5202142
5.68	Kd	2100	nM	TAE-684
5.66	Kd	2200	nM	ENZASTAURIN
5.54	Kd	2900	nM	ERLOTINIB
5.54	Kd	2900	nM	BI-2536
5.46	Kd	3500	nM	RUXOLITINIB
5.42	Kd	3800	nM	MIDOSTAURIN
5.42	Kd	3800	nM	KW-2449
5.16	Kd	6900	nM	GEFITINIB
5.16	Kd	7000	nM	CANERTINIB

PubChem BioAssay actives

44 with measured affinity, of 818 total; 32 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	435285: Binding constant for DMPK kinase domain	kd	0.0035	uM
2-[2-methyl-5-[3-(3,4,5-trimethoxyphenyl)-2H-pyrazolo[3,4-b]pyridin-5-yl]anilino]ethanol	2137769: Binding affinity to human DMPK assessed as dissociation constant by Adp-glo assay	kd	0.0300	uM
1-[(3-hydroxyphenyl)methyl]-3-(4-pyridin-4-yl-1,3-thiazol-2-yl)urea;methanesulfonic acid	1119784: Inhibition of DMPK (unknown origin)	ic50	0.0341	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	435285: Binding constant for DMPK kinase domain	kd	0.0590	uM
6-(5-methyl-1H-pyrazol-4-yl)-2-[(2S)-piperidin-2-yl]-3H-thieno[3,2-d]pyrimidin-4-one;dihydrochloride	1528734: Inhibition of kinase tracer 236 binding to recombinant full-length human GST-tagged DMPK expressed in baculovirus expression system by Lanthascreen Eu kinase binding assay	ic50	0.0646	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526233: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged DMPK (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0900	uM
Bosutinib	624950: Binding constant for DMPK kinase domain	kd	0.0910	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	624950: Binding constant for DMPK kinase domain	kd	0.0920	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526233: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged DMPK (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0940	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	624950: Binding constant for DMPK kinase domain	kd	0.1400	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507901: Binding affinity to DMPK	kd	0.2400	uM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione	435285: Binding constant for DMPK kinase domain	kd	0.2800	uM
[4-amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl]-(2,3-difluoro-6-methoxyphenyl)methanone	624950: Binding constant for DMPK kinase domain	kd	0.6100	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	435285: Binding constant for DMPK kinase domain	kd	0.6500	uM
Fedratinib	624950: Binding constant for DMPK kinase domain	kd	1.0000	uM
4-[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-1H-imidazol-5-yl]pyridine	1646093: Inhibition of human DMPK	ic50	1.0000	uM
4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide	624950: Binding constant for DMPK kinase domain	kd	1.1000	uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	435285: Binding constant for DMPK kinase domain	kd	1.2000	uM
Tofacitinib	624950: Binding constant for DMPK kinase domain	kd	1.2000	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	435285: Binding constant for DMPK kinase domain	kd	1.3000	uM
5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine	1491956: Inhibition of full length recombinant human DMPK expressed in baculovirus expression system by FRET assay	ic50	1.3800	uM
Crizotinib	624950: Binding constant for DMPK kinase domain	kd	1.4000	uM
methyl N-[4-[5-[(2S)-2-amino-2,4-dimethylpentoxy]-6-(difluoromethyl)-2-pyridinyl]-2-pyridinyl]carbamate	1904681: Inhibition of DMPK1 (unknown origin)	ic50	1.5000	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	624950: Binding constant for DMPK kinase domain	kd	2.1000	uM
3-(1-methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione	624950: Binding constant for DMPK kinase domain	kd	2.2000	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	624950: Binding constant for DMPK kinase domain	kd	2.9000	uM
Erlotinib	435285: Binding constant for DMPK kinase domain	kd	2.9000	uM
Ruxolitinib	624950: Binding constant for DMPK kinase domain	kd	3.5000	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624950: Binding constant for DMPK kinase domain	kd	3.8000	uM
Midostaurin	435285: Binding constant for DMPK kinase domain	kd	3.8000	uM
Gefitinib	435285: Binding constant for DMPK kinase domain	kd	6.9000	uM
N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide	624950: Binding constant for DMPK kinase domain	kd	7.0000	uM

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
beta-lapachone	increases expression	1
arsenite	decreases methylation	1
Am 580	decreases expression	1
prothioconazole	decreases expression	1
Rosiglitazone	decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Quercetin	increases expression	1
Smoke	decreases expression	1
Dronabinol	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	increases expression	1
Cyclosporine	increases expression	1
Gold Compounds	increases expression	1
Asbestos, Serpentine	decreases methylation	1
Asbestos, Crocidolite	decreases methylation	1
Asbestos, Amosite	decreases methylation	1
Cadmium Chloride	increases abundance, increases expression	1

ChEMBL screening assays

210 unique, capped per target: 210 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1021464	Binding	Inhibition of DMPK assessed as enzyme activity relative to control	Examining the chirality, conformation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550). — J Med Chem

Cellosaurus cell lines

85 cell lines: 25 transformed cell line, 23 induced pluripotent stem cell, 16 embryonic stem cell, 14 finite cell line, 4 cancer cell line, 3 telomerase immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_7376	GM03132	Finite cell line	Male
CVCL_7404	GM03987	Finite cell line	Male
CVCL_7405	GM04033	Finite cell line	Male
CVCL_9854	VUB19_DM1	Embryonic stem cell	Female
CVCL_9859	VUB24_DM1	Embryonic stem cell	Female
CVCL_A251	KCL018	Embryonic stem cell	Female
CVCL_AW53	GM04567	Transformed cell line	Female
CVCL_AW55	GM04647	Finite cell line	Male
CVCL_AW56	GM04648	Transformed cell line	Male
CVCL_AW58	GM05151	Finite cell line	Male

Clinical trials (associated diseases)

131 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01939561	PHASE3	COMPLETED	Lamotrigine as Treatment of Myotonia
NCT05532813	PHASE3	RECRUITING	Evaluation of the Efficacy and Safety of Metformin in the Myotonic Dystrophy Type 1 (Steinert’s Disease)
NCT05848830	PHASE3	UNKNOWN	Home-based Training and Supplementation in DM1 Patients
NCT06411288	PHASE3	ACTIVE_NOT_RECRUITING	Global Study of Del-desiran for the Treatment of DM1
NCT07008469	PHASE3	ENROLLING_BY_INVITATION	Global Open-Label Extension Study of Del-desiran for the Treatment of DM1
NCT07486934	PHASE3	RECRUITING	Efficacy, Safety, and Tolerability of Zeleciment Basivarsen (DYNE-101) in Participants With Myotonic Dystrophy Type 1
NCT00452725	PHASE3	COMPLETED	Effect of MAXOMAT ® on the Growth of Small Children to NOONAN’s Syndrome
NCT01529840	PHASE3	COMPLETED	Somatropin Effect on Linear Growth and Final Height in Subjects With Noonan Syndrome
NCT01529944	PHASE3	COMPLETED	Genetic Testing of Noonan Subjects Previously Treated With Norditropin®. An Extension to Trial GHNOO-1658
NCT01927861	PHASE3	COMPLETED	Investigating the Long-term Efficacy and Safety of Two Doses of NN-220 (Somatropin) in Short Stature Due to Noonan Syndrome
NCT02713945	PHASE3	COMPLETED	Treatment With HMG-COA Reductase Inhibitor of Growth and Bone Abnormalities in Children With Noonan Syndrome
NCT05723835	PHASE3	ACTIVE_NOT_RECRUITING	A Research Study Looking at How Safe Somapacitan is and How Well it Works in Children Who Need Help to Grow - REAL 9
NCT04624750	PHASE3	COMPLETED	Open Label Study in Adolescents and Children With Myotonic Disorders
NCT04700046	PHASE3	WITHDRAWN	Study to Investigate the Efficacy and Safety of Mexiletine in Patients With Myotonic Dystrophy Type 1 and Type 2
NCT06523400	PHASE3	RECRUITING	The Efficacy and Safety of Once Daily Mexiletine PR in Patients With Myotonic Dystrophy Type 1 and Type 2
NCT06549400	PHASE3	ENROLLING_BY_INVITATION	An Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Once Daily Mexiletine PR in Patients With Myotonic Dystrophy Type 1 and Type 2 Who Have Completed MEX-DM-302 Study.
NCT00577577	PHASE2	COMPLETED	Safety and Efficacy Study of Recombinant Human Insulin-Like Growth Factor-I/Recombinant Human Insulin-Like Growth Factor Binding Protein-3 (rhIGF-I/rhIGFBP-3) In Myotonic Dystrophy Type 1
NCT02858908	PHASE2	COMPLETED	Study of Tideglusib in Adolescent and Adult Patients With Myotonic Dystrophy
NCT04886518	PHASE2	COMPLETED	Safety and Efficacy of Pitolisant on Excessive Daytime Sleepiness and Other Non-Muscular Symptoms in Patients With Myotonic Dystrophy Type 1
NCT05479981	PHASE2	COMPLETED	Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients
NCT06667453	PHASE2	RECRUITING	A Clinical Study of PGN-EDODM1 in People With Myotonic Dystrophy Type 1
NCT06926621	PHASE2	ENROLLING_BY_INVITATION	A Study of Long-term Safety and Efficacy of VX-670 in Participants With Myotonic Dystrophy Type I
NCT07220603	PHASE2	RECRUITING	An Open-Label Extension Study of PGN-EDODM1 in People With Myotonic Dystrophy Type 1 (FREEDOM-OLE)
NCT00351221	PHASE2	TERMINATED	Research Study Using Recombinant Human Insulin-Like Growth Factor-1/Recombinant Human Insulin-Like Growth Factor Binding Protein-3 for Children With Noonan Syndrome
NCT06555237	PHASE2	RECRUITING	MEK Inhibitors for the Treatment of Hypertrophic Cardiomyopathy in Patients With RASopathies
NCT06668805	PHASE2	RECRUITING	A Study of Vosoritide in Children With Noonan Syndrome With Inadequate Growth During or After Human Growth Hormone Treatment
NCT05122975	PHASE2	TERMINATED	Treatment of an Inherited Ventricular Arrhythmia
NCT06005428	PHASE2	TERMINATED	Effectiveness of CRD-4730 in Participants With Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
NCT01406873	PHASE2	COMPLETED	Clinical Efficacy Trial of Mexiletine for Myotonic Dystrophy Type 1
NCT02251457	PHASE1	COMPLETED	Study of Ranolazine in Myotonia Congenita, Paramyotonia Congenita and Myotonic Dystrophy Type 1
NCT06204809	PHASE1	COMPLETED	Safety, Tolerability, PK, and PD Study of PGN-EDODM1 in Participants With Myotonic Dystrophy Type 1
NCT07075965	PHASE1	NOT_YET_RECRUITING	Calcium Channel Blocker in Myotonic Dystrophy Type 1
NCT03959189	PHASE1	COMPLETED	Safety, Tolerability and Pharmacokinetics of ERX-963 in Adults With Myotonic Dystrophy Type 1
NCT02312011	PHASE1/PHASE2	COMPLETED	A Safety andTolerability Study of Multiple Doses of ISIS-DMPKRx in Adults With Myotonic Dystrophy Type 1
NCT05027269	PHASE1/PHASE2	COMPLETED	Study of AOC 1001 in Adult Myotonic Dystrophy Type 1 (DM1) Patients
NCT05481879	PHASE1/PHASE2	RECRUITING	Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-101 in Participants With Myotonic Dystrophy Type 1
NCT06138743	PHASE1/PHASE2	RECRUITING	Study of ARO-DM1 in Subjects With Type 1 Myotonic Dystrophy
NCT06185764	PHASE1/PHASE2	RECRUITING	A Phase 1/2 Study of VX-670 in Adult Participants With Myotonic Dystrophy 1 (DM1)
NCT06300307	PHASE1/PHASE2	RECRUITING	Study of ATX-01 in Participants With DM1
NCT00082108	Not specified	RECRUITING	Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Registry