Human Gene Module / Chromosome 6 / DST

DSTDystonin

Score
4
Minimal Evidence Criteria 4.1
Autism Reports / Total Reports
3 / 4
Rare Variants / Common Variants
9 / 0
Aliases
DST, RP3-361I14.2,  BP240,  BPA,  BPAG1,  CATX-15,  CATX15,  D6S1101,  DMH,  DT,  HSAN6,  MACF2
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
6p12.1
Associated Disorders
-
Relevance to Autism

Five case-specific loss-of-function variants were identified in the DST gene following the sequencing of 215 synaptic genes in 147 cases with ASD, 273 cases with schizophrenia, and 287 controls (Kenny et al., 2013).

Molecular Function

Cytoskeletal linker protein that acts as an integrator of intermediate filaments, actin and microtubule cytoskeleton networks. Isoform 7 regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. Defects in this gene are associated with hereditary sensory and autonomic neuropathy 6 (HSAN6) [MIM:614653], a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities.

Reports related to DST (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders. Kenny EM , et al. (2013) Yes -
2 Support De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder. Dong S , et al. (2014) Yes -
3 Support The contribution of de novo coding mutations to autism spectrum disorder. Iossifov I , et al. (2014) Yes -
4 Support Large-scale discovery of novel genetic causes of developmental disorders. Deciphering Developmental Disorders Study (2014) No -
Rare Variants   (9)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
TA>T - frameshift_variant Unknown - Unknown 24126926 Kenny EM , et al. (2013)
G>A p.Gln2285Ter stop_gained Unknown - Unknown 24126926 Kenny EM , et al. (2013)
c.4831-2A>G - splice_site_variant Unknown - Unknown 24126926 Kenny EM , et al. (2013)
c.6048+1->AG - splice_site_variant Unknown - Unknown 24126926 Kenny EM , et al. (2013)
c.5662G>T p.Glu1888Ter stop_gained Unknown - Unknown 24126926 Kenny EM , et al. (2013)
11319+AAAC (delGTTT) 3773-! frameshift_variant De novo - Simplex 25284784 Dong S , et al. (2014)
c.13296A>T p.Glu4432Asp missense_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.9776A>G p.His3259Arg missense_variant De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
c.7538T>C p.Ile2513Thr missense_variant De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
Common Variants  

No common variants reported.

SFARI Gene score
4

Minimal Evidence

Five case-specific loss-of-function variants were identified in the DST gene following the sequencing of 215 synaptic genes in 147 cases with ASD, 273 cases with schizophrenia, and 287 controls (Kenny et al., 2013); these variants were identified in two ASD cases and three SCZ cases and were not observed in the control cohort.

Score Delta: Score remained at 4

4

Minimal Evidence

See all Category 4 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as 'acc" in the score cards) could also boost a gene from category 4 to 3.

1/1/2016
4
icon
4

Score remained at 4

Description

Five case-specific loss-of-function variants were identified in the DST gene following the sequencing of 215 synaptic genes in 147 cases with ASD, 273 cases with schizophrenia, and 287 controls (Kenny et al., 2013); these variants were identified in two ASD cases and three SCZ cases and were not observed in the control cohort.

7/1/2015
icon
4

Increased from to 4

Description

Five case-specific loss-of-function variants were identified in the DST gene following the sequencing of 215 synaptic genes in 147 cases with ASD, 273 cases with schizophrenia, and 287 controls (Kenny et al., 2013); these variants were identified in two ASD cases and three SCZ cases and were not observed in the control cohort.

Krishnan Probability Score

Score 0.54929652142797

Ranking 1378/25841 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 0.99999999999999

Ranking 20/18225 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 0.92997999192357

Ranking 11308/18665 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).
Larsen Cumulative Evidence Score

Score 8

Ranking 222/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Zhang D Score

Score 0.13521668776383

Ranking 5453/20870 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.
CNVs associated with DST(1 CNVs)
6p12.1 15 Deletion-Duplication 24  /  184
Submit New Gene

Report an Error