DOCK6

Chr 19AR

dedicator of cytokinesis 6

Also known as: AOS2, ZIR1

NCBI Gene: 57572ENSG00000130158UniProt: Q96HP0

This gene encodes a member of the dedicator of cytokinesis (DOCK) family of atypical guanine nucleotide exchange factors. Guanine nucleotide exchange factors interact with small GTPases and are components of intracellular signaling networks. The encoded protein is a group C DOCK protein and plays a role in actin cytoskeletal reorganization by activating the Rho GTPases Cdc42 and Rac1. Mutations in this gene are associated with Adams-Oliver syndrome 2. [provided by RefSeq, Dec 2011]

Primary Disease Associations & Inheritance

Adams-Oliver syndrome 2MIM #614219
AR
599
ClinVar variants
40
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DOCK6
🧬
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.
📋
ClinVar Variants
40 Pathogenic / Likely Pathogenic· 355 VUS of 599 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.72LOEUF
pLI 0.000
Z-score 3.96
OE 0.58 (0.47–0.72)
Tolerant

Typical tolerance to LoF variation

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.
1.43Z-score
OE missense 0.89 (0.85–0.93)
1160 obs / 1305.9 exp
Tolerant

Mild missense constraint

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.0.58 (0.47–0.72)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.85–0.93)
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.0.96
0≤1.21.6
LoF obs/exp: 59 / 102.2Missense obs/exp: 1160 / 1305.9Syn Z: 0.72

ClinVar Variant Classifications

599 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic17
VUS355
Likely Benign198
Benign2
Conflicting4
23
Pathogenic
17
Likely Pathogenic
355
VUS
198
Likely Benign
2
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
0
9
0
23
Likely Pathogenic
13
0
4
0
17
VUS
2
332
19
2
355
Likely Benign
0
3
76
119
198
Benign
0
0
1
1
2
Conflicting
—4
Total29335109122599

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

View 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.

Gene2Phenotype Curations

DOCK6-related Adams-Oliver syndrome

strong
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkinSkeletal
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Adams-Oliver syndrome 2

MIM #614219

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification and validation of a novel senescence-related biomarker for thyroid cancer to predict the prognosis and immunotherapy.
Hong K et al.·Front Immunol
2023
DOCK6 promotes chemo- and radioresistance of gastric cancer by modulating WNT/β-catenin signaling and cancer stem cell traits.
Chi HC et al.·Oncogene
2020
Attenuated clinical and osteoclastic phenotypes of Paget's disease of bone linked to the p.Pro392Leu/SQSTM1 mutation by a rare variant in the DOCK6 gene.
Dessay M et al.·BMC Med Genomics
2022
Overexpression of DOCK6 in oral squamous cell cancer promotes cellular migration and invasion and is associated with poor prognosis.
Zhang ZY et al.·Arch Oral Biol
2022
Familial Exudative Vitreoretinopathy-Like Retinal Findings in Adams-Oliver Syndrome Type 2.
Wang Y et al.·Clin Exp Ophthalmol
2025
Novel compound heterozygous DOCK6 variants expand the mutational spectrum in prenatal diagnosis of Adams-Oliver syndrome 2.
Zhong X et al.·BMC Med Genomics
2025
Intrafamilial phenotypic variability in autosomal recessive DOCK6-related Adams-Oliver syndrome.
Zepeda-Romero LC et al.·Eur J Med Genet
2022Case report
Gene Variant Spectrum in Probands With Familial Exudative Vitreoretinopathy Using an Expanded Panel.
van der Ende S et al.·Invest Ophthalmol Vis Sci
2025
DOCK6 mutations are responsible for a distinct autosomal-recessive variant of Adams-Oliver syndrome associated with brain and eye anomalies.
Sukalo M et al.·Hum Mutat
2015
A novel pathogenic variation of DOCK6 gene: the genotype-phenotype correlation in Adams-Oliver syndrome.
Nieto-Benito LM et al.·Mol Biol Rep
2023Case report
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