SAMD12
Chr 8ADsterile alpha motif domain containing 12
Also known as: BAFME, BAFME1, FAME, FAME1, FCMTE1, MEBA
SAMD12 encodes a protein predicted to function in cell surface receptor protein tyrosine kinase signaling at the cytoplasmic side of the plasma membrane. Mutations cause familial adult myoclonic epilepsy type 1, which follows autosomal dominant inheritance with adult onset as the name suggests. The gene shows tolerance to loss-of-function variants (pLI 0.001, LOEUF 1.14), indicating that complete loss of protein function may not be the primary disease mechanism.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative 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
SAMD12 · 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