DOCK8

Chr 9AR

dedicator of cytokinesis 8

Also known as: HEL-205, HIES2, MRD2, ZIR8

NCBI Gene: 81704ENSG00000107099UniProt: Q8NF50OMIM: 611432

This gene encodes a member of the DOCK180 family of guanine nucleotide exchange factors. Guanine nucleotide exchange factors interact with Rho GTPases and are components of intracellular signaling networks. Mutations in this gene result in the autosomal recessive form of the hyper-IgE syndrome. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Jun 2010]

OMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Hyper-IgE syndrome 2, autosomal recessive, with recurrent infectionsMIM #243700
AR
UniProtIntellectual developmental disorder, autosomal dominant 2

Clinical highlights

Gene-disease validity (ClinGen)
combined immunodeficiency due to DOCK8 deficiency · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
3
Active trials
74
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.48
LOEUF
LOF
Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.48LOEUF
pLI 0.000
Z-score 6.08
OE 0.36 (0.28–0.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
-2.54Z-score
OE missense 1.21 (1.16–1.27)
1380 obs / 1138.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.36 (0.28–0.48)
0≤0.351.4
Missense OE?1.21 (1.16–1.27)
0≤0.61.4
Synonymous OE?1.32
0≤1.21.6
LoF obs/exp: 39 / 106.9Missense obs/exp: 1380 / 1138.4Syn Z: -5.29

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

DOCK8 · protein map & ClinVar variants

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

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