DMPKdystrophia myotonica-protein kinase
Autism Reports / Total Reports
6 / 12Rare 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, SyndromicRelevance 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.
External Links
SFARI Genomic Platforms
Reports related to DMPK (12 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 | 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 |