DOCK7

Chr 1AR

dedicator of cytokinesis 7

Also known as: DEE23, EIEE23, ZIR2

The protein functions as a guanine nucleotide exchange factor that activates RAC1 and RAC3 small GTPases to regulate axon formation and neuronal polarization. Biallelic mutations cause developmental and epileptic encephalopathy 23, inherited in an autosomal recessive pattern. The pathogenic mechanism involves disrupted neuronal development due to impaired axon formation and polarization.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.381 OMIM phenotype
Clinical SummaryDOCK7
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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
23 unique Pathogenic / Likely Pathogenic· 122 VUS of 300 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Missense constrained — critical functional residues
LoF Constraint
0.38LOEUF
pLI 0.000
Z-score 7.25
OE 0.28 (0.220.38)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.42Z-score
OE missense 0.71 (0.670.75)
791 obs / 1111.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.28 (0.220.38)
00.351.4
Missense OE0.71 (0.670.75)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 34 / 119.5Missense obs/exp: 791 / 1111.9Syn Z: 0.37

ClinVar Variant Classifications

300 submitted variants in ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic10
VUS122
Likely Benign117
Benign5
Conflicting1
13
Pathogenic
10
Likely Pathogenic
122
VUS
117
Likely Benign
5
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
1
4
0
13
Likely Pathogenic
10
0
0
0
10
VUS
2
115
5
0
122
Likely Benign
0
1
66
50
117
Benign
0
0
5
0
5
Conflicting
1
Total201178050268

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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