DOCK4
Homo sapiens
Gene Name: Dedicator of cytokinesis 4
Aliases: WUGSC:H_GS034D21.1
Chromosome No: 7
Chromosome Band: 7q31.1
Genetic Category: Genetic association/multigenic CNV--Genetic association-Rare single gene variant-Functional-Rare single gene variant/Functional
Aliases: WUGSC:H_GS034D21.1
Chromosome No: 7
Chromosome Band: 7q31.1
Genetic Category: Genetic association/multigenic CNV--Genetic association-Rare single gene variant-Functional-Rare single gene variant/Functional
Summary Statistics:
ASD Reports: 12
Recent Reports: 2
Annotated variants: 21
Associated CNVs: 5
Evidence score: 3
ASD Reports: 12
Recent Reports: 2
Annotated variants: 21
Associated CNVs: 5
Evidence score: 3
Gene Score: 4
Associated Disorders: |
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Relevance to Autism
Assocation between the DOCK4 gene and ASD has been observed in two studies (Maestrini et al., 2010; Liang et al., 2014). Deletions involving the DOCK4 gene has also been implicated in ASD and dyslexia (Maestrini et al., 2010; Pagnamenta et al., 2010).
Molecular Function
Involved in regulation of adherens junction between cells. Plays a role in cell migration. Functions as a guanine nucleotide exchange factor (GEF), which activates Rap1 small GTPase by exchanging bound GDP for free GTP.
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L-DOCK4 gene region in autism ...
ASD
Positive Association
A Pooled Genome-Wide Association Study of Asperger Syndrome.
ASD
Asperger syndrome
Positive Association
Family-based association study of ZNF533, DOCK4 and IMMP2L gene polymorphisms linked to autism in a northeastern Chinese Han population.
ASD
Support
Characterization of a family with rare deletions in CNTNAP5 and DOCK4 suggests novel risk loci for autism and dyslexia.
Dyslexia
Support
Heterozygous loss-of-function variants in DOCK4 cause neurodevelopmental delay and microcephaly
DD
ASD or autistic features, ADHD, ID, epilepsy/seizu
Support
Deficiency of Autism-Related Gene Dock4 Leads to Impaired Spatial Memory and Hippocampal Function in Mice at Late Middle Age
ASD
Support
Autism-like social deficit generated by Dock4 deficiency is rescued by restoration of Rac1 activity and NMDA receptor function.
Support
Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder.
ASD
Support
The contribution of de novo coding mutations to autism spectrum disorder
ASD
Recent Recommendation
Rac GEF Dock4 interacts with cortactin to regulate dendritic spine formation.
Recent Recommendation
The atypical guanine nucleotide exchange factor Dock4 regulates neurite differentiation through modulation of Rac1 GTPase and actin dynamics.
Rare
Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
GEN603R011b
missense_variant
c.758C>T
p.Pro253Leu
Familial
Paternal
Simplex
GEN603R015
stop_gained
c.2770C>T
p.Arg924Ter
Unknown
Not maternal
Multiplex
GEN603R016
frameshift_variant
c.3937del
p.Asp1313ThrfsTer27
Familial
Maternal
Simplex
Common
Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
GEN603C001
intron_variant
rs2217262
c.37+49780T>G
Risk allele, A
Combined sample of IMGSAC primary sample, IMGSAC replication sample, and 96 Northern Dutch samples (515-516 affected individuals)
Discovery
GEN603C002
intron_variant
rs2217262
c.37+49780T>G
A/C; risk allele, A
Combined sample of IMGSAC primary and replication samples (420-421 cases, 368 controls)
Replication
GEN603C003
intron_variant
rs2217262
c.37+49780T>G
A/C
Discovery cohort: 370 ASD child-parent trios of Han Chinese descent
Replication
GEN603C004
intron_variant
rs7785891
c.38-88385G>C
294 cases (254 male, 40 female) with diagnosis of Asperger syndrome (DSM-IV or ICD-10 criteria) and 318 controls (250 male, 68 female), all of Caucasian ancestry
Discovery