IL27RA
Chr 19ARinterleukin 27 receptor subunit alpha
Also known as: CRL1, IL-27RA, IL27R, TCCR, WSX1, zcytor1
The IL27RA protein functions as a receptor for IL-27 and requires IL6ST/GP130 for signal transduction, playing a key role in regulating Th1-type immune responses and innate defense mechanisms. Autosomal recessive mutations cause Immunodeficiency 134, which is characterized by specific susceptibility to Epstein-Barr virus infections. This gene is extremely intolerant to loss-of-function variants (pLI near 0), indicating that complete loss of protein function is likely pathogenic.
Primary Disease Associations & Inheritance
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
138 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 | 0 | 0 | 15 | 0 | 15 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 87 | 3 | 0 | 90 |
Likely Benign | 0 | 8 | 0 | 2 | 10 |
Benign | 0 | 1 | 1 | 2 | 4 |
Conflicting | — | 3 | |||
| Total | 0 | 96 | 20 | 4 | 123 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
IL27RA · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools