DOCK5

Chr 8

dedicator of cytokinesis 5

NCBI Gene: 80005ENSG00000147459UniProt: Q9H7D0

This gene encodes a member of the dedicator of cytokinesis protein family. Members of this family act as guanine nucleotide exchange factors for small Rho family G proteins. The protein encoded by this gene is thought to associate with adaptors CRK and CRKL, and function in regulation of intestinal epithelial cell spreading and migration on collagen IV. Similar proteins in mouse and zebrafish also function in myoblast fusion. [provided by RefSeq, Oct 2016]

Research Assistant →
0
Active trials
9
Pubs (1 yr)
81
P/LP submissions
0%
P/LP missense
0.44
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— DOCK5
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
81 unique Pathogenic / Likely Pathogenic· 285 VUS of 448 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.44LOEUF
pLI 0.000
Z-score 6.40
OE 0.33 (0.26–0.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.05Z-score
OE missense 0.91 (0.86–0.96)
907 obs / 1000.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.33 (0.26–0.44)
0≤0.351.4
Missense OE0.91 (0.86–0.96)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 36 / 107.7Missense obs/exp: 907 / 1000.4Syn Z: 0.36
DN
0.6842th %ile
GOF
0.6540th %ile
LOF
0.3258th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

448 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic77
Likely Pathogenic4
VUS285
Likely Benign18
Benign5
77
Pathogenic
4
Likely Pathogenic
285
VUS
18
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
77
0
77
Likely Pathogenic
0
0
4
0
4
VUS
0
276
9
0
285
Likely Benign
0
9
2
7
18
Benign
0
1
2
2
5
Total0286949389

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

View in ClinVar →

Protein Context — Lollipop Plot

DOCK5 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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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
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