DOCK3

Chr 3

dedicator of cytokinesis 3

ENSG00000088538UniProt: Q8IZD9

Potential guanine nucleotide exchange factor (GEF). GEF proteins activate some small GTPases by exchanging bound GDP for free GTP. Its interaction with presenilin proteins as well as its ability to stimulate Tau/MAPT phosphorylation suggest that it may be involved in Alzheimer disease. Ectopic expression in nerve cells decreases the secretion of amyloid-beta APBA1 protein and lowers the rate of cell-substratum adhesion, suggesting that it may affect the function of some small GTPase involved in the regulation of actin cytoskeleton or cell adhesion receptors (By similarity)

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia
0
ClinVar variants
0
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— DOCK3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.16LOEUF
pLI 1.000
Z-score 9.00
OE 0.10 (0.06–0.16)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.94Z-score
OE missense 0.67 (0.63–0.71)
766 obs / 1139.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.10 (0.06–0.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.63–0.71)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 11 / 115.3Missense obs/exp: 766 / 1139.9Syn Z: -0.00

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

DOCK3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

DOCK3-related neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia

moderate
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. Disorders
G2P ↗
splice region variantframeshift variantstop gainedmissense variantwhole partial gene deletion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
DOCK3-Associated Neurodevelopmental Disorder-Clinical Features and Molecular Basis.
Alexander MS et al.·Genes (Basel)
2023Review
DOCK3 regulates normal skeletal muscle regeneration and glucose metabolism.
Samani A et al.·FASEB J
2023
Role of HAUS7 as a DOCK3 binding partner in facilitating axon regeneration.
Kiyota N et al.·Sci Adv
2025
DOCK3 regulates normal skeletal muscle regeneration and glucose metabolism.
Samani A et al.·bioRxiv
2023
DOCK3 is a dosage-sensitive regulator of skeletal muscle and Duchenne muscular dystrophy-associated pathologies.
Reid AL et al.·Hum Mol Genet
2020
Loss of ZBED6 Protects Against Sepsis-Induced Muscle Atrophy by Upregulating DOCK3-Mediated RAC1/PI3K/AKT Signaling Pathway in Pigs.
Liu H et al.·Adv Sci (Weinh)
2023
Dock3-NMDA receptor interaction as a target for glaucoma therapy.
Kimura A et al.·Histol Histopathol
2017Review
Dock3 Participate in Epileptogenesis Through rac1 Pathway in Animal Models.
Li J et al.·Mol Neurobiol
2016Functional
Targeted ErbB4 receptor activation ameliorates neuronal deficits via DOCK3 signaling in a transgenic mouse AD model.
Liu C et al.·Neurotherapeutics
2025Functional
Targeted activation of ErbB4 receptor ameliorates neuronal deficits and neuroinflammation in a food-borne polystyrene microplastic exposed mouse model.
Liu C et al.·J Neuroinflammation
2025Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools