DOCK7

Chr 1AR

dedicator of cytokinesis 7

Also known as: DEE23, EIEE23, ZIR2

NCBI Gene: 85440ENSG00000116641UniProt: Q96N67

The protein encoded by this gene is a guanine nucleotide exchange factor (GEF) that plays a role in axon formation and neuronal polarization. The encoded protein displays GEF activity toward RAC1 and RAC3 Rho small GTPases but not toward CDC42. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 23MIM #615859
AR
668
ClinVar variants
50
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DOCK7
🧬
Gene-Disease Validity (ClinGen)
developmental and epileptic encephalopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
📋
ClinVar Variants
50 Pathogenic / Likely Pathogenic· 294 VUS of 668 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
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.
0.38LOEUF
pLI 0.000
Z-score 7.25
OE 0.28 (0.22–0.38)
Moderately constrained

More LoF-intolerant than ~75% 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.
3.42Z-score
OE missense 0.71 (0.67–0.75)
791 obs / 1111.9 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.0.28 (0.22–0.38)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.67–0.75)
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.0.98
0≤1.21.6
LoF obs/exp: 34 / 119.5Missense obs/exp: 791 / 1111.9Syn Z: 0.37

ClinVar Variant Classifications

668 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic19
VUS294
Likely Benign314
Benign9
Conflicting1
31
Pathogenic
19
Likely Pathogenic
294
VUS
314
Likely Benign
9
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
1
14
0
31
Likely Pathogenic
17
0
2
0
19
VUS
1
271
21
1
294
Likely Benign
0
3
154
157
314
Benign
0
0
9
0
9
Conflicting
—1
Total34275200158668

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

View in ClinVar →

Protein Context — Lollipop Plot

DOCK7 · protein map & ClinVar variants

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

Gene2Phenotype Curations

DOCK7-related epileptic encephalopathy, early infantile

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental and epileptic encephalopathy 23

MIM #615859

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Characteristic facial features and cortical blindness distinguish the DOCK7-related epileptic encephalopathy.
Haberlandt E et al.·Mol Genet Genomic Med
2021Case report
Homozygosity for a Novel DOCK7 Variant Due to Segmental Uniparental Isodisomy of Chromosome 1 Associated with Early Infantile Epileptic Encephalopathy (EIEE) and Cortical Visual Impairment.
Kivrak Pfiffner F et al.·Int J Mol Sci
2022Case report
Shared genetic correlations between kidney diseases and sepsis.
Zhang T et al.·Front Endocrinol (Lausanne)
2024Meta-analysis
The ErbB2-Dock7 Signaling Axis Mediates Excessive Cell Morphogenesis Induced by Autism Spectrum Disorder- and Intellectual Disability-Associated Sema5A p.Arg676Cys.
Takahashi M et al.·Int J Mol Sci
2025
Mutations in DOCK7 in individuals with epileptic encephalopathy and cortical blindness.
Perrault I et al.·Am J Hum Genet
2014
Post-GWAS methodologies for localisation of functional non-coding variants: ANGPTL3.
Oldoni F et al.·Atherosclerosis
2016Functional
Importance of targeted next-generation sequencing in pediatric patients with developmental epileptic encephalopathy.
Bariş S et al.·Rev Assoc Med Bras (1992)
2023Cohort
Construction and Validation of Early Warning Model of Lung Cancer Based on Machine Learning: A Retrospective Study.
Ye S et al.·Technol Cancer Res Treat
2022Functional
Fine-mapping in African Americans of 8 recently discovered genetic loci for plasma lipids: the Jackson Heart Study.
Keebler ME et al.·Circ Cardiovasc Genet
2010
An Agonistic Monoclonal Antibody Targeting cMet Attenuates Inflammation and Up-Regulates Collagen Synthesis and Angiogenesis in Type 2 Diabetic Mice Wounds.
Choi MH et al.·Plast Reconstr Surg
2022
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