Human Gene Module / Chromosome 2 / EXOC6B

EXOC6Bexocyst complex component 6B

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 5
Rare Variants / Common Variants
7 / 0
Aliases
EXOC6B, SEC15B,  SEC15L2
Associated Syndromes
-
Chromosome Band
2p13.2
Associated Disorders
ASD, EPS
Relevance to Autism

The EXOC6B gene was found to be disrupted by a de novo balanced translocation t(2;8)(p13.2;q22.1) in a female patient with a severe clinical phenotype including intellectual disability, epilepsy, behavioral features resembling autism, and minor dysmorphic features (Fruhmesser et al., 2013).

Molecular Function

Component of the exocyst complex involved in the docking of exocytic vesicles with fusion 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 EXOC6B (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Disruption of EXOC6B in a patient with developmental delay, epilepsy, and a de novo balanced t(2;8) translocation Frhmesser A , et al. (2013) No Epilepsy
2 Support Phenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.2 Wen J , et al. (2013) No ASD
3 Support Whole-Genome Sequencing of Cytogenetically Balanced Chromosome Translocations Identifies Potentially Pathological Gene Disruptions and Highlights the Importance of Microhomology in the Mechanism of Formation Nilsson D , et al. (2016) Yes -
4 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
5 Support - Zhou X et al. (2022) Yes -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - - 23837398 Wen J , et al. (2013)
- - translocation De novo - - 27862604 Nilsson D , et al. (2016)
- - copy_number_loss De novo - Simplex 23837398 Wen J , et al. (2013)
- - translocation De novo - Simplex 23422942 Frhmesser A , et al. (2013)
c.1293C>G p.Asp431Glu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1551A>G p.Leu517%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.499G>C p.Glu167Gln missense_variant De novo - Multiplex 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

The EXOC6B gene was found to be disrupted by a de novo balanced translocation t(2;8)(p13.2;q22.1) in a female patient with a severe clinical phenotype including intellectual disability, epilepsy, behavioral features resembling autism, and minor dysmorphic features (Fruhmesser et al., 2013). Another de novo translocation with a breakpoint disrupting the EXOC6B gene [46,XY,t(2;21)(p13;p11.2)dn] identified in a male case (841-95D) presenting with autism and ADHD in Nilsson et al., 2017. De novo deletions involving the EXOC6B gene were identified in individuals with intellectual disability and either a diagnosis of autism or autistic features in Wen et al., 2013.

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

The EXOC6B gene was found to be disrupted by a de novo balanced translocation t(2;8)(p13.2;q22.1) in a female patient with a severe clinical phenotype including intellectual disability, epilepsy, behavioral features resembling autism, and minor dysmorphic features (Fruhmesser et al., 2013). Another de novo translocation with a breakpoint disrupting the EXOC6B gene [46,XY,t(2;21)(p13;p11.2)dn] identified in a male case (841-95D) presenting with autism and ADHD in Nilsson et al., 2017. De novo deletions involving the EXOC6B gene were identified in individuals with intellectual disability and either a diagnosis of autism or autistic features in Wen et al., 2013.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

The EXOC6B gene was found to be disrupted by a de novo balanced translocation t(2;8)(p13.2;q22.1) in a female patient with a severe clinical phenotype including intellectual disability, epilepsy, behavioral features resembling autism, and minor dysmorphic features (Fruhmesser et al., 2013). Another de novo translocation with a breakpoint disrupting the EXOC6B gene [46,XY,t(2;21)(p13;p11.2)dn] identified in a male case (841-95D) presenting with autism and ADHD in Nilsson et al., 2017. De novo deletions involving the EXOC6B gene were identified in individuals with intellectual disability and either a diagnosis of autism or autistic features in Wen et al., 2013.

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

The EXOC6B gene was found to be disrupted by a de novo balanced translocation t(2;8)(p13.2;q22.1) in a female patient with a severe clinical phenotype including intellectual disability, epilepsy, behavioral features resembling autism, and minor dysmorphic features (Fruhmesser et al., 2013). Another de novo translocation with a breakpoint disrupting the EXOC6B gene [46,XY,t(2;21)(p13;p11.2)dn] identified in a male case (841-95D) presenting with autism and ADHD in Nilsson et al., 2017. De novo deletions involving the EXOC6B gene were identified in individuals with intellectual disability and either a diagnosis of autism or autistic features in Wen et al., 2013.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
7/1/2018
icon
4

Increased from to 4

Description

The EXOC6B gene was found to be disrupted by a de novo balanced translocation t(2;8)(p13.2;q22.1) in a female patient with a severe clinical phenotype including intellectual disability, epilepsy, behavioral features resembling autism, and minor dysmorphic features (Fruhmesser et al., 2013). Another de novo translocation with a breakpoint disrupting the EXOC6B gene [46,XY,t(2;21)(p13;p11.2)dn] identified in a male case (841-95D) presenting with autism and ADHD in Nilsson et al., 2017. De novo deletions involving the EXOC6B gene were identified in individuals with intellectual disability and either a diagnosis of autism or autistic features in Wen et al., 2013.

Krishnan Probability Score

Score 0.44726386037116

Ranking 13432/25841 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 0.66629805167812

Ranking 4662/18225 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 0.72919492829867

Ranking 1367/18665 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 0.22297114486238

Ranking 3890/20870 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
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