MTFR1L
Chr 1mitochondrial fission regulator 1 like
Also known as: FAM54B, HYST1888, MST116, MSTP116
MTFR1L encodes a mitochondrial protein that regulates mitochondrial morphology and mediates stress-induced mitochondrial fragmentation by controlling OPA1 levels in response to metabolic changes. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly and brain atrophy, typically presenting in infancy. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.61), and the disorder primarily affects the central nervous system with severe neurodevelopmental impairment.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
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
60 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 | 5 | 0 | 5 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 36 | 6 | 0 | 42 |
Likely Benign | 1 | 3 | 0 | 1 | 5 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 1 | 39 | 11 | 1 | 52 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MTFR1L · 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