CRLF2
Chr Ycytokine receptor like factor 2
Also known as: CRL2, CRLF2Y, TSLPR
The protein functions as a receptor for thymic stromal lymphopoietin (TSLP) and forms a complex with IL7R to activate STAT3, STAT5, and JAK2 pathways that control cell proliferation and hematopoietic system development. Rearrangements of this gene with immunoglobulin heavy chain or P2RY8 genes are associated with B-progenitor acute lymphoblastic leukemia and Down syndrome-associated ALL. The gene shows low constraint against loss-of-function variants, consistent with its primary role in hematologic malignancies rather than developmental disorders.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
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
CRLF2 · 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