ArticleEuropean journal of human genetics : EJHG2019
Variants in DOCK3 cause developmental delay and hypotonia.
Article in European journal of human genetics : EJHG, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- DOCKopathies: A systematic review of the clinical pathologies associated with human DOCK pathogenic variants.Human mutation · 2022Pooled it
- Alternative pre-mRNA Splicing and Gene Expression Patterns in Midbrain Lineage Cells Carrying Familial Parkinson's Disease Mutations.bioRxiv : the preprint server for biology · 2025Article
- Research-Based Whole Genome Sequencing Identifies Biallelic Loss of Function Variants in DOCK3 Gene Causing DOCK3-Related Disorder: The End of a Diagnostic Journey for This Family.Clinical genetics · 2025Article
- Heterozygous loss-of-function variants in DOCK4 cause neurodevelopmental delay and microcephaly.Human genetics · 2024Article
- Review
- Loss of ZBED6 Protects Against Sepsis-Induced Muscle Atrophy by Upregulating DOCK3-Mediated RAC1/PI3K/AKT Signaling Pathway in Pigs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Neuroprotection and axon regeneration by novel low-molecular-weight compounds through the modification of DOCK3 conformation.Cell death discovery · 2023Article
- Consequences of exposure to pollutants on respiratory health: From genetic correlations to causal relationships.PloS one · 2022Article
- Review
- Genetic Predisposition to the Mortality in Septic Shock Patients: From GWAS to the Identification of a Regulatory Variant Modulating the Activity of aInternational journal of molecular sciences · 2021Article
- Impact of integrated translational research on clinical exome sequencing.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- DOCK3 is a dosage-sensitive regulator of skeletal muscle and Duchenne muscular dystrophy-associated pathologies.Human molecular genetics · 2020Article
- RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors.The Journal of biological chemistryReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
Abstract
The DOCK3 gene encodes the Dedicator of cytokinesis 3 (DOCK3) protein, which belongs to the family of guanine nucleotide exchange factors and is expressed almost exclusively in the brain and spinal cord. We used whole exome sequencing (WES) to investigate the molecular cause of developmental delay and hypotonia in three unrelated probands. WES identified truncating and splice site variants in Patient 1 and compound heterozygous and homozygous missense variants in Patients 2 and 3, respectively. We studied the effect of the three missense variants in vitro by using site-directed mutagenesis and pull-down assay and show that the induction of Rac1 activation was significantly lower in DOCK3 mutant cells compared with wild type human DOCK3 (P < 0.05). We generated a protein model to further examine the effect of the two missense variants within or adjacent to the DHR-2 domain in DOCK3 and this model supports pathogenicity. Our results support a loss of function mechanism but the data on the patients with missense variants should be cautiously interpreted because of the variability of the phenotypes and limited number of cases. Prior studies have described DOCK3 bi-allelic loss of function variants in two families with ataxia, hypotonia, and developmental delay. Here, we report on three patients with DOCK3-related developmental delay, wide-based or uncoordinated gait, and hypotonia, further supporting DOCK3's role in a neurodevelopmental syndrome and expanding the spectrum of phenotypic and genotypic variability.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.