ICOS
Chr 2ARinducible T cell costimulator
Also known as: AILIM, CD278, CVID1
The ICOS protein is a costimulatory receptor on activated T-cells that enhances T-cell responses to antigens, promotes T-cell and B-cell interactions, and is essential for normal antibody production and immune responses. Mutations cause common variable immunodeficiency, resulting in recurrent infections, hypogammaglobulinemia, and impaired antibody responses, with autosomal recessive inheritance. The gene shows low constraint to loss-of-function variants, which is consistent with the recessive inheritance pattern observed in affected patients.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
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
100 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 6 | 0 | 11 | 0 | 17 |
Likely Pathogenic | 1 | 0 | 0 | 0 | 1 |
VUS | 0 | 26 | 6 | 0 | 32 |
Likely Benign | 0 | 2 | 24 | 18 | 44 |
Benign | 0 | 0 | 2 | 0 | 2 |
| Total | 7 | 28 | 43 | 18 | 96 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ICOS · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools