DMPKdystrophia myotonica-protein kinase
Autism Reports / Total Reports
7 / 13Rare Variants / Common Variants
11 / 1Aliases
DMPK, DM, DM1, DMK, MDPK, DM1PK, MT-PKAssociated Syndromes
-Chromosome Band
19q13.32Associated Disorders
DD/NDD, ASDGenetic Category
Rare Single Gene Mutation, Syndromic, FunctionalRelevance to Autism
This gene has been associated with syndromic autism, where a subpopulation of individuals with a given syndrome develop autism. For example, positive genetic association has been found between a triplet repeat in the DMPK gene and autism with increasing repeat expansions in a Swedish population (Ekstrom et al., 2008).
Molecular 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.
Reports related to DMPK (13 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Highly Cited | Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat | Mankodi A , et al. (2000) | No | - |
| 2 | Highly Cited | RNA leaching of transcription factors disrupts transcription in myotonic dystrophy | Ebralidze A , et al. (2003) | No | - |
| 3 | Primary | Autism spectrum conditions in myotonic dystrophy type 1: a study on 57 individuals with congenital and childhood forms | Ekstrm AB , et al. (2008) | No | ASD |
| 4 | Recent Recommendation | Expanded CTG repeats within the DMPK 3' UTR causes severe skeletal muscle wasting in an inducible mouse model for myotonic dystrophy | Orengo JP , et al. (2008) | No | - |
| 5 | Support | Synaptic, transcriptional and chromatin genes disrupted in autism | De Rubeis S , et al. (2014) | Yes | - |
| 6 | Support | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
| 7 | Support | Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks | Ruzzo EK , et al. (2019) | Yes | - |
| 8 | Recent Recommendation | Genome-wide detection of tandem DNA repeats that are expanded in autism | Trost B et al. (2020) | Yes | DD, myotonic dystrophy-1 |
| 9 | Support | - | Mojarad BA et al. (2021) | No | - |
| 10 | Support | - | Zhou X et al. (2022) | Yes | - |
| 11 | Support | - | Cirnigliaro M et al. (2023) | Yes | - |
| 12 | Recent Recommendation | - | Ã Âukasz J Sznajder et al. (2025) | Yes | - |
| 13 | Highly Cited | Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy | Philips AV , et al. (1998) | No | - |
Rare Variants (11)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.890A>G | p.Tyr297Cys | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1444C>T | p.Gln482Ter | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.120A>T | p.Pro40%3D | missense_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.1223G>T | p.Gly408Val | missense_variant | De novo | - | - | 25363760 | De Rubeis S , et al. (2014) | |
| c.1759T>C | p.Cys587Arg | missense_variant | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) | |
| c.253-2A>T | - | splice_site_variant | Familial | Maternal | Multiplex | 31398340 | Ruzzo EK , et al. (2019) | |
| c.239-3del | - | frameshift_variant | Familial | Maternal | Multiplex | 37506195 | Cirnigliaro M et al. (2023) | |
| - | - | trinucleotide_repeat_microsatellite_feature, 3_prime_UTR_variant | Unknown | - | Simplex | 32717741 | Trost B et al. (2020) | |
| - | - | trinucleotide_repeat_microsatellite_feature, 3_prime_UTR_variant | Familial | Maternal | Simplex | 32717741 | Trost B et al. (2020) | |
| - | - | trinucleotide_repeat_microsatellite_feature, 3_prime_UTR_variant | Familial | Paternal | Simplex | 33526774 | Mojarad BA et al. (2021) | |
| - | - | trinucleotide_repeat_microsatellite_feature, 3_prime_UTR_variant | Unknown | Not maternal | Multiplex | 32717741 | Trost B et al. (2020) |
Common Variants (1)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.*224_*226CTG(51_?);c.*217_*219CTG(51_?) | - | trinucleotide_repeat_microsatellite_feature, 3_prime_UTR_variant | - | - | - | 18228241 | Ekstrm AB , et al. (2008) |
SFARI Gene score
1S
High Confidence, Syndromic
Score Delta: Score remained at 1S
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."
1/1/2021
1
1
Score remained at 1
Description
Myotonic dystrophy gene associated with autism.
7/1/2020
1
1
Score remained at 1
Description
Myotonic dystrophy gene associated with autism.
10/1/2019
S
1
Increased from S to 1
New Scoring Scheme
Description
Myotonic dystrophy gene associated with autism.
Reports Added
[New Scoring Scheme]7/1/2019
S
S
Increased from S to S
Description
Myotonic dystrophy gene associated with autism.
1/1/2016
S
S
Increased from S to S
Description
Myotonic dystrophy gene associated with autism.
Reports Added
[Autism spectrum conditions in myotonic dystrophy type 1: a study on 57 individuals with congenital and childhood forms.2008] [Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy.1998] [Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat.2000] [RNA leaching of transcription factors disrupts transcription in myotonic dystrophy.2003] [Expanded CTG repeats within the DMPK 3' UTR causes severe skeletal muscle wasting in an inducible mouse model for myotonic dystrophy.2008] [Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [The contribution of de novo coding mutations to autism spectrum disorder2014]Krishnan Probability Score
Score 0.44318662906362
Ranking 16840/25841 scored genes
[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning
approach on a human brain-specific gene network. The method was first presented in Nat
Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed
in column G of supplementary table 3 (see:
http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser,
with the ability to view networks of associated ASD risk genes, can be found at
asd.princeton.edu.
ExAC Score
Score 0.033081178864131
Ranking 8961/18225 scored genes
[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has
been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by
Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at
exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of-
function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of-
function mutations in autism in such a gene would be more likely to confer risk. For a full list of
pLI scores see:
ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle
aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score
Score 0.9206984810606
Ranking 9234/18665 scored genes
[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013),
and is a statistic that integrates evidence from both de novo and transmitted mutations.
It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233
(2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper
(the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Zhang D Score
Score -0.44190745446642
Ranking 18737/20870 scored genes
[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures),
or D score, was developed to combine evidence from de novo loss-of- function mutation with
evidence from cell-type- specific gene expression in the mouse brain (specifically translational
profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with
positive D scores are more likely to be associated with autism risk, with higher-confidence genes
having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204-
215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in
supplementary table 2 from that paper.
External PIN Data
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
Interaction Table
| Interactor Symbol | Interactor Name | Interactor Organism | Interactor Type | Entrez ID | Uniprot ID |
|---|---|---|---|---|---|
| CELF1 | CUGBP, Elav-like family member 1 | Human | Protein Modification | 10658 | Q92879 |
| DMPK | dystrophia myotonica-protein kinase | Human | Protein Modification | 1760 | Q09013 |
| FXYD1 | FXYD domain containing ion transport regulator 1 | Dog | Protein Modification | 476487 | P56513 |
| HSPB2 | heat shock 27kDa protein 2 | Human | Protein Binding | 3316 | Q16082 |
| MBNL2 | muscleblind-like splicing regulator 2 | Human | RNA Binding | 10150 | Q5VZF2 |
| PLN | phospholamban | Human | Protein Modification | 5350 | P26678 |
| Ppp1r12a | protein phosphatase 1, regulatory (inhibitor) subunit 12A | Mouse | Protein Modification | 17931 | Q9DBR7 |