DOCK3

Chr 3AR

dedicator of cytokinesis 3

Also known as: MOCA, NEDIDHA, PBP

NCBI Gene: 1795ENSG00000088538UniProt: Q8IZD9OMIM: 603123

DOCK3 encodes a guanine nucleotide exchange factor that activates Rac1 and induces axonal outgrowth in the central nervous system through stimulation of the WAVE complex. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia. The gene is highly constrained against loss-of-function variants (pLI >0.99, LOEUF 0.158), indicating that functional copies are critical for normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.161 OMIM phenotype
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.
📋
ClinVar Variants
25 unique Pathogenic / Likely Pathogenic· 238 VUS of 358 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
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
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
LoF OE0.10 (0.06–0.16)
0≤0.351.4
Missense OE0.67 (0.63–0.71)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 11 / 115.3Missense obs/exp: 766 / 1139.9Syn Z: -0.00
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateDOCK3-related neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxiaLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.3991th %ile
GOF
0.5171th %ile
LOF
0.66top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

358 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic7
VUS238
Likely Benign44
Benign4
Conflicting3
18
Pathogenic
7
Likely Pathogenic
238
VUS
44
Likely Benign
4
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
0
11
0
18
Likely Pathogenic
6
0
1
0
7
VUS
6
224
8
0
238
Likely Benign
0
8
3
33
44
Benign
0
1
2
1
4
Conflicting
—3
Total192332534314

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
DOCK3-Associated Neurodevelopmental Disorder-Clinical Features and Molecular Basis.
Alexander MS et al.·Genes (Basel)
2023Review
Folate intake and colorectal cancer risk according to genetic subtypes defined by targeted tumor sequencing.
Aglago EK et al.·Am J Clin Nutr
2024
DOCK3-related neurodevelopmental syndrome: Biallelic intragenic deletion of DOCK3 in a boy with developmental delay and hypotonia.
Iwata-Otsubo A et al.·Am J Med Genet A
2018Case report
Biallelic loss-of-function variants in DOCK3 cause muscle hypotonia, ataxia, and intellectual disability.
Helbig KL et al.·Clin Genet
2017
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.
Liaqat K et al.·Clin Genet
2025Case report
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients