LEMD3
Chr 12ADLEM domain containing 3
Also known as: MAN1
The protein functions as a specific repressor of TGF-beta, activin, and BMP signaling pathways at the inner nuclear membrane through interaction with R-SMAD proteins. Mutations cause Buschke-Ollendorff syndrome and osteopoikilosis with or without melorheostosis, which are skeletal disorders affecting bone development and connective tissue. The gene follows autosomal dominant inheritance and is highly constrained against loss-of-function variants.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Tolerant to missense variation
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
LEMD3 · 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