Human Gene Module / Chromosome 5 / EXOC3

EXOC3exocyst complex component 3

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
6 / 0
Aliases
EXOC3, SEC6,  SEC6L1,  Sec6p
Associated Syndromes
-
Chromosome Band
5p15.33
Associated Disorders
-
Relevance to Autism

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module; sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism (Li et al., 2014).

Molecular Function

The protein encoded by this gene is a component of the exocyst complex, a multiple protein complex essential for targeting exocytic vesicles to specific docking sites on the plasma membrane.

SFARI Genomic Platforms
Reports related to EXOC3 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Integrated systems analysis reveals a molecular network underlying autism spectrum disorders Li J , et al. (2015) Yes -
2 Support - Woodbury-Smith M et al. (2022) Yes -
3 Support - Zhou X et al. (2022) Yes -
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - nonsynonymous_variant Unknown - Unknown 25549968 Li J , et al. (2015)
c.503G>A p.Arg168His missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.59_60delinsCT p.Leu20Pro missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1406C>T p.Ala469Val missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.1692A>G p.Leu564%3D synonymous_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.2196C>T p.Asp732%3D synonymous_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module; sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism (Li et al., 2014). Both of the non-synonymous variants in EXOC3 identified in this study were absent in 1000 Genomes (as of Jan/ Feb. 2013) and dbSNP and had GERP++ conservation scores > 4.9.

Score Delta: Score remained at 2

2

Strong Candidate

See all Category 2 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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module; sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism (Li et al., 2014). Both of the non-synonymous variants in EXOC3 identified in this study were absent in 1000 Genomes (as of Jan/ Feb. 2013) and dbSNP and had GERP++ conservation scores > 4.9.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module; sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism (Li et al., 2014). Both of the non-synonymous variants in EXOC3 identified in this study were absent in 1000 Genomes (as of Jan/ Feb. 2013) and dbSNP and had GERP++ conservation scores > 4.9.

Reports Added
[New Scoring Scheme]
7/1/2018
icon
4

Increased from to 4

Description

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module; sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism (Li et al., 2014). Both of the non-synonymous variants in EXOC3 identified in this study were absent in 1000 Genomes (as of Jan/ Feb. 2013) and dbSNP and had GERP++ conservation scores > 4.9.

Krishnan Probability Score

Score 0.41424217453704

Ranking 21683/25841 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 0.75523003836991

Ranking 4181/18225 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 0.94034899301545

Ranking 14535/18665 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 0.49270189741994

Ranking 576/20870 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.
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