SETMAR
Chr 3SET and mariner transposase domain methyltransferase
Also known as: METNASE, Mar1
The protein is a fusion methyltransferase-transposase that methylates histones H3K4 and H3K36 and functions in DNA double-strand break repair through non-homologous end joining. This gene is extremely intolerant to loss-of-function variants (pLI = 1.0), suggesting that mutations would likely cause severe developmental phenotypes, though no specific human disease has been definitively associated with SETMAR mutations to date. The gene exists as a fusion only in anthropoid primates, making it evolutionarily unique among DNA repair genes.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-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.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SETMAR · 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