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.

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.

04-01-2017
4

Initial score established: 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.

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

Report an Error