KREMEN2
Chr 16kringle containing transmembrane protein 2
Also known as: KRM2
This gene encodes a transmembrane receptor for Dickkopf proteins that cooperates with DKK1/2 to inhibit Wnt/beta-catenin signaling by promoting endocytosis of Wnt receptors LRP5 and LRP6, playing important roles in limb development and bone formation regulation. Mutations in KREMEN2 cause autosomal recessive ectodermal dysplasia with syndactyly. The gene shows tolerance to loss-of-function variants (LOEUF 0.917), suggesting that complete loss of function may be required for disease manifestation.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is gain-of-function.
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
KREMEN2 · 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