CNNM2
Chr 10ADARcyclin and CBS domain divalent metal cation transport mediator 2
Also known as: ACDP2, HOMG6, HOMGSMR, SLC70A2
CNNM2 encodes a divalent metal cation transporter that mediates epithelial transport and renal reabsorption of magnesium. Mutations cause hypomagnesemia with either isolated renal involvement or a more severe phenotype with seizures and intellectual disability, inherited in either autosomal dominant or recessive patterns. The gene is highly constrained against loss-of-function variants (pLI 0.995, LOEUF 0.267), indicating intolerance to complete protein loss.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
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
CNNM2 · 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