MTERF3
Chr 8mitochondrial transcription termination factor 3
Also known as: CGI-12, MTERFD1
This protein binds mitochondrial promoter DNA and regulates transcription initiation, maintaining 16S rRNA levels and functioning in mitochondrial ribosome assembly and respiratory complex formation. Mutations cause autosomal recessive mitochondrial disorders affecting multiple organ systems. The gene shows tolerance to loss-of-function variants (LOEUF 1.276), suggesting complete loss of function may be compatible with survival in some cases.
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
100 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 36 | 0 | 36 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 47 | 3 | 0 | 50 |
Likely Benign | 0 | 1 | 0 | 0 | 1 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 0 | 48 | 42 | 0 | 90 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MTERF3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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