CALCRL
Chr 2ARcalcitonin receptor like receptor
Also known as: CGRPR, CRLR, LMPHM8
The protein functions as a G protein-coupled receptor that forms complexes with receptor-activity-modifying proteins (RAMPs) to bind calcitonin gene-related peptide and adrenomedullin, activating cAMP-dependent signaling pathways. Mutations cause lymphatic malformation with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants, indicating critical importance for normal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, loss-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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CALCRL · 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
i-NEED: NEw migrainE Drugs Database
RECRUITINGMolecular Phenotyping of Migraine Patients According to Sex and Age Through CGRP Quantification
RECRUITINGChinese Real-world Study of Treatment of Vestibular Migraine
NOT YET RECRUITINGReal-world Prospective Study on the Use of Anti-CGRP Drugs in Migraine
RECRUITINGExternal Resources
Links to major genomics databases and tools