Human Gene Module / Chromosome 14 / EXOC5

EXOC5exocyst complex component 5

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
2 / 2
Rare Variants / Common Variants
2 / 0
Aliases
EXOC5, HSEC10,  PRO1912,  SEC10,  SEC10L1,  SEC10P
Associated Syndromes
-
Chromosome Band
14q22.3
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.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to EXOC5 (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Primary Integrated systems analysis reveals a molecular network underlying autism spectrum disorders Li J , et al. (2015) Yes -
Rare Variants   (2)
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.1847A>G p.Glu616Gly missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
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). The EXOC5 non-synonymous variant identified in this study was not reported in 1000 Genomes (as of Jan/ Feb. 2013) or dbSNP and had a high GERP++ conservation score (5.48). A rare de novo possibly damaging missense variant in the EXOC5 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014.

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 (Li et al., 2014). The EXOC5 non-synonymous variant identified in this study was not reported in 1000 Genomes (as of Jan/ Feb. 2013) or dbSNP and had a high GERP++ conservation score (5.48). A rare de novo possibly damaging missense variant in the EXOC5 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014.

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). The EXOC5 non-synonymous variant identified in this study was not reported in 1000 Genomes (as of Jan/ Feb. 2013) or dbSNP and had a high GERP++ conservation score (5.48). A rare de novo possibly damaging missense variant in the EXOC5 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014.

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). The EXOC5 non-synonymous variant identified in this study was not reported in 1000 Genomes (as of Jan/ Feb. 2013) or dbSNP and had a high GERP++ conservation score (5.48). A rare de novo possibly damaging missense variant in the EXOC5 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014.

Krishnan Probability Score

Score 0.43647412854013

Ranking 20336/25841 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 0.99668302489269

Ranking 1396/18225 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 0.83989662737759

Ranking 3130/18665 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 0.40812614303533

Ranking 1369/20870 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
BRMS1L breast cancer metastasis-suppressor 1-like Human Protein Binding 84312 Q5PSV4
C9ORF9 chromosome 9 open reading frame 9 Human Protein Binding 11092 Q96E40
CCDC67 coiled-coil domain containing 67 Human Protein Binding 159989 Q05D60
COG6 component of oligomeric golgi complex 6 Human Protein Binding 57511 Q9Y2V7
EDRF1 chromosome 10 open reading frame 137 Human Protein Binding 26098 Q3B7T1
EPHA1 EPH receptor A1 Human Protein Binding 2041 P21709
ERP29 SERPINE1 Human Protein Binding 10961 P30040
EXOC3 exocyst complex component 3 Human Protein Binding 11336 O60645
EXOC8 exocyst complex component 8 Human Protein Binding 149371 Q8IYI6
HDDC3 HD domain containing 3 Human Protein Binding 374659 Q8N4P3
ICA1 islet cell autoantigen 1, 69kDa Human Protein Binding 3382 Q05084
KXD1 KxDL motif containing 1 Human Protein Binding 79036 Q9BQD3
MAGEA6 melanoma antigen family A, 6 Human Protein Binding 4105 P43360
NPY2R Neuropeptide Y receptor type 2 Human Protein Binding 4887 P49146
OAS1 2'-5'-oligoadenylate synthetase 1, 40/46kDa Human Protein Binding 4938 P00973
OPRM1 Mu-type opioid receptor Human Protein Binding 4988 P35372-10
PNKD Probable hydrolase PNKD Human Protein Binding 25953 Q8N490-2
PYCARD PYD and CARD domain containing Human Protein Binding 29108 Q9ULZ3
RAB4A RAB4A, member RAS oncogene family Human Protein Binding 5867 P20338
RAB4B RAB4B, member RAS oncogene family Human Protein Binding 53916 P61018
SCN2B Human Protein Binding
TTC23L tetratricopeptide repeat domain 23-like Human Protein Binding 153657 Q6PF05
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