AIFM1
Chr XXLRapoptosis inducing factor mitochondria associated 1
Also known as: AIF, AUNX1, CMT2D, CMTX4, COWCK, COXPD6, DFNX5, NADMR
AIFM1 encodes a mitochondrial flavoprotein that functions as an NADH oxidoreductase essential for respiratory chain biogenesis and also regulates apoptosis through caspase-independent DNA fragmentation. X-linked recessive mutations cause a spectrum of disorders including combined oxidative phosphorylation deficiency 6 (severe mitochondrial encephalomyopathy), Cowchock syndrome (X-linked Charcot-Marie-Tooth disease with neuropathy, deafness, and cognitive disability), X-linked deafness, and X-linked spondyloepimetaphyseal dysplasia with hypomyelinating leukodystrophy. The pathogenic mechanism involves loss of function, disrupting both mitochondrial respiratory chain function and cellular apoptotic regulation.
Moderate evidence — consider for supplementary testing
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
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
300 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 | 4 | 0 | 4 |
Likely Pathogenic | 0 | 5 | 1 | 0 | 6 |
VUS | 0 | 49 | 4 | 2 | 55 |
Likely Benign | 0 | 2 | 17 | 18 | 37 |
Benign | 0 | 0 | 1 | 2 | 3 |
Conflicting | — | 1 | |||
| Total | 0 | 56 | 27 | 22 | 106 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
AIFM1 · 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