Human Gene Module / Chromosome 19 / DMPK

DMPKdystrophia myotonica-protein kinase

SFARI Gene Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
6 / 12
Rare Variants / Common Variants
11 / 1
EAGLE Score
3.75
Limited Learn More
Aliases
DMPK, DM,  DM1,  DMK,  MDPK,  DM1PK,  MT-PK
Associated Syndromes
-
Chromosome Band
19q13.32
Associated Disorders
DD/NDD, ASD
Genetic Category
Rare Single Gene Mutation, Syndromic
Relevance 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.

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

1

High Confidence

See all Category 1 Genes

We 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
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1

Score remained at 1

Description

Myotonic dystrophy gene associated with autism.

7/1/2020
1
icon
1

Score remained at 1

Description

Myotonic dystrophy gene associated with autism.

10/1/2019
S
icon
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
icon
S

Increased from S to S

Description

Myotonic dystrophy gene associated with autism.

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.
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
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