DOCK8 (Q8NF50) variants and mutations

DOCK8 (also known as Q8NF50) is a human protein-coding gene encoding a dedicator of cytokinesis protein 8 protein. It coordinates actin remodeling and signaling required for migration, survival, and immune synapse formation in lymphocytes. Biallelic loss-of-function variants cause DOCK8 deficiency, a combined immunodeficiency characterized by severe viral infections, allergy, eczema, and malignancy risk. This analysis covers 3,055 DOCK8 variants and mutations. Of these, 76% have computational variant effect predictions. Disease context includes combined immunodeficiency due to DOCK8 deficiency, Autosomal recessive hyper-IgE syndrome, and hyper-IgE syndrome. Example DOCK8 variants include M1?, M1T, and A2T.

Variant analysis overview

Gene: DOCK8
Protein: Q8NF50
UniProt accession: Q8NF50
Organism: Homo sapiens
Variants analyzed: 3055
Variant scope: all variants
Completed: 2026-08-21

Variant and mutation evidence

Variant composition: 2,987 unspecified-consequence records; 43 missense variants; 19 synonymous variants; 1 stop-gained variants; 2 frameshift variants; 2 splice-region variants; 2 substitution
Prediction scores: 2,323 variants have prediction scores (76% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: combined immunodeficiency due to DOCK8 deficiency, Autosomal recessive hyper-IgE syndrome, hyper-IgE syndrome, severe combined immunodeficiency, intellectual disability, autosomal dominant 2, squamous cell carcinoma, combined immunodeficiency, lymphoma, hereditary disease, immunodeficiency disease, hair color, autosomal dominant non-syndromic intellectual disability.

Protein structure and variant hotspots

Protein features: 2 domains; 8 post-translational modification sites.
Structural context: 781 variants have structural context.
PTM context: 13 variants overlap post-translational modification sites.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable DOCK8 variants

Examples include M1?, M1T, A2T, A2V, A2S, A2A, T3S, T3T. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

DOCK8 analysis run — DOCK8 (3,055 variants) — completed 2026-08-21