Human Gene Module / Chromosome 10 / DOCK1

DOCK1Dedicator of cytokinesis 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 4
Rare Variants / Common Variants
4 / 0
Aliases
DOCK1, DOCK180,  ced5
Associated Syndromes
-
Chromosome Band
10q26.2
Associated Disorders
-
Relevance to Autism

A loss-of-function variant in the DOCK1 gene was identified in an ASD proband and an ASD-affected mother, but not in an unaffected sibling (Griswold et al., 2015). A de novo missense variant in this gene was also identifed in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014).

Molecular Function

This gene encodes a member of the dedicator of cytokinesis protein family. Dedicator of cytokinesis proteins act as guanine nucleotide exchange factors for small Rho family G proteins. The encoded protein regulates the small GTPase Rac, thereby influencing several biological processes, including phagocytosis and cell migration.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to DOCK1 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Primary Targeted massively parallel sequencing of autism spectrum disorder-associated genes in a case control cohort reveals rare loss-of-function risk variants Griswold AJ , et al. (2015) Yes -
3 Support Meta-Analyses Support Previous and Novel Autism Candidate Genes: Outcomes of an Unexplored Brazilian Cohort da Silva Montenegro EM , et al. (2019) Yes -
4 Support - Soo-Whee Kim et al. (2024) Yes -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1884C>T p.Leu628= synonymous_variant De novo - - 39334436 Soo-Whee Kim et al. (2024)
c.5348C>T p.Pro1783Leu missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.3747G>A p.Lys1249= stop_gained Familial Maternal Simplex 26185613 Griswold AJ , et al. (2015)
c.4838C>T p.Pro1613Leu missense_variant De novo - Simplex 31696658 da Silva Montenegro EM , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A loss-of-function variant in the DOCK1 gene was identified in an ASD proband and an ASD-affected mother, but not in an unaffected sibling (Griswold et al., 2015). A de novo missense variant in this gene was also identifed in an ASD proband from the Simons Simplex Collection (Iossifov 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

A loss-of-function variant in the DOCK1 gene was identified in an ASD proband and an ASD-affected mother, but not in an unaffected sibling (Griswold et al., 2015). A de novo missense variant in this gene was also identifed in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A loss-of-function variant in the DOCK1 gene was identified in an ASD proband and an ASD-affected mother, but not in an unaffected sibling (Griswold et al., 2015). A de novo missense variant in this gene was also identifed in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014).

Reports Added
[Meta-Analyses Support Previous and Novel Autism Candidate Genes: Outcomes of an Unexplored Brazilian Cohort.2019] [New Scoring Scheme]
7/1/2015
icon
4

Increased from to 4

Description

A loss-of-function variant in the DOCK1 gene was identified in an ASD proband and an ASD-affected mother, but not in an unaffected sibling (Griswold et al., 2015). A de novo missense variant in this gene was also identifed in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014).

Krishnan Probability Score

Score 0.49582955977547

Ranking 2785/25841 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 0.36842317046063

Ranking 6128/18225 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 0.94981235914008

Ranking 18242/18665 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 -0.091854976354927

Ranking 12043/20870 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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