DOCK6

Chr 19AR

dedicator of cytokinesis 6

The protein acts as a guanine nucleotide exchange factor that activates CDC42 and RAC1 small GTPases, regulating actin cytoskeletal reorganization and neurite outgrowth. Biallelic mutations cause Adams-Oliver syndrome 2, a congenital disorder characterized by scalp defects and limb malformations, inherited in an autosomal recessive pattern. The gene shows moderate constraint against loss-of-function variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.721 OMIM phenotype
Clinical SummaryDOCK6
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Gene-Disease Validity (ClinGen)
Adams-Oliver syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.72LOEUF
pLI 0.000
Z-score 3.96
OE 0.58 (0.470.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.43Z-score
OE missense 0.89 (0.850.93)
1160 obs / 1305.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.58 (0.470.72)
00.351.4
Missense OE0.89 (0.850.93)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 59 / 102.2Missense obs/exp: 1160 / 1305.9Syn Z: 0.72
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongDOCK6-related Adams-Oliver syndromeLOFAR

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

DN
0.6064th %ile
GOF
0.6443th %ile
LOF
0.3550th %ile

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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

DOCK6 · 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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