ICOSLG
Chr 21ARinducible T cell costimulator ligand
Also known as: B7-H2, B7H2, B7RP-1, B7RP1, B7h, CD275, GL50, ICOS-L
ICOSLG encodes a ligand for the T-cell surface receptor ICOS that provides costimulatory signals for T-cell proliferation and cytokine secretion, induces B-cell proliferation and differentiation into plasma cells, and is required for proper neutrophil transmigration in endothelial cells. Mutations cause autosomal recessive immunodeficiency 119, affecting the immune system. The gene shows low constraint to loss-of-function variants (pLI 0.0004, LOEUF 0.92), consistent with recessive inheritance where heterozygous carriers are typically unaffected.
Primary Disease Associations & Inheritance
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
ICOSLG · 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
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools