Human Gene Module / Chromosome 10 / EXOC6

EXOC6exocyst complex component 6

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
6 / 0
Aliases
EXOC6, RP11-348J12.4A,  SEC15,  SEC15L,  SEC15L1,  SEC15L3,  Sec15p,  EXOC6
Associated Syndromes
-
Chromosome Band
10q23.33
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; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014).

Molecular Function

The product of this gene belongs to the SEC15 family. This protein is essential for vesicular traffic from the Golgi apparatus to the cell surface in yeast. It is one of the components of a multiprotein complex required for exocytosis.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to EXOC6 (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 - Tuncay IO et al. (2022) Yes ADHD, DD, ID
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
c.2404C>T p.Gln802Ter stop_gained De novo - - 35982159 Zhou X et al. (2022)
c.1779T>C p.Ala593%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.392T>C p.Ile131Thr missense_variant Unknown - Unknown 25549968 Li J , et al. (2015)
c.1724A>G p.Gln575Arg missense_variant Unknown - Unknown 25549968 Li J , et al. (2015)
c.937-397G>C - intron_variant Familial Both parents Simplex 35190550 Tuncay IO et al. (2022)
c.1295+1914G>A - intron_variant Familial Both parents Simplex 35190550 Tuncay IO 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; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). Both of the non-synonymous variants in EXOC6 identified in this study were absent in 1000 Genomes (as of Jan/ Feb. 2013) and had GERP++ conservation scores > 5.7; however, both variants were also reported in dbSNP.

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
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; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). Both of the non-synonymous variants in EXOC6 identified in this study were absent in 1000 Genomes (as of Jan/ Feb. 2013) and had GERP++ conservation scores > 5.7; however, both variants were also reported in dbSNP.

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; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). Both of the non-synonymous variants in EXOC6 identified in this study were absent in 1000 Genomes (as of Jan/ Feb. 2013) and had GERP++ conservation scores > 5.7; however, both variants were also reported in dbSNP.

Reports Added
[New Scoring Scheme]
10/1/2018
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; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). Both of the non-synonymous variants in EXOC6 identified in this study were absent in 1000 Genomes (as of Jan/ Feb. 2013) and had GERP++ conservation scores > 5.7; however, both variants were also reported in dbSNP.

Krishnan Probability Score

Score 0.44824341010592

Ranking 11679/25841 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.
Original Source
ExAC Score

Score 0.028160635100107

Ranking 9107/18225 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
Original Source
Sanders TADA Score

Score 0.94538061997355

Ranking 16447/18665 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).
Original Source
Zhang D Score

Score 0.43296035289686

Ranking 1089/20870 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.
Original Source
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
APLNR Apelin receptor Human Protein Binding 187 P35414
C19ORF75 SIGLEC family-like protein 1 Human Protein Binding 284369 Q8N7X8
C9ORF89 Bcl10-interacting CARD protein Human Protein Binding 84270 Q96LW7-2
CD70 CD70 molecule Human Protein Binding 970 P32970
EXOC2 exocyst complex component 2 Human Protein Binding 55770 B2RBE6
RAP1A RAP1A, member of RAS oncogene family Human Protein Binding 5906 P62834
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