C1RL
Chr 12complement C1r subcomponent like
Also known as: C1RL1, C1RLP, C1r-LP, CLSPa
The protein mediates proteolytic cleavage of haptoglobin in the endoplasmic reticulum and has predicted serine-type endopeptidase activity involved in zymogen activation. Mutations cause autosomal recessive anhaptoglobinemia, characterized by complete absence of serum haptoglobin. This gene shows very low constraint to loss-of-function variation (pLI near 0), consistent with the recessive inheritance pattern observed clinically.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
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
C1RL · 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