AIFM1

Chr XXLR

apoptosis 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.

Summary from RefSeq, OMIM, UniProt, Mechanism
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Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 6MIM #300816
XLR
Cowchock syndromeMIM #310490
XLR
Deafness, X-linked 5MIM #300614
XLR
Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophyMIM #300232
XLR
UniProtCharcot-Marie-Tooth disease, X-linked recessive, 4, with or without cerebellar ataxia
0
Active trials
53
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.23
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryAIFM1
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Gene-Disease Validity (ClinGen)
Leigh syndrome · XLModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📖
GeneReview available — AIFM1
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.23LOEUF
pLI 0.998
Z-score 4.45
OE 0.07 (0.030.23)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.49Z-score
OE missense 0.55 (0.470.63)
130 obs / 238.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.07 (0.030.23)
00.351.4
Missense OE0.55 (0.470.63)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 2 / 26.9Missense obs/exp: 130 / 238.4Syn Z: 0.57
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongAIFM1-related combined oxidative phosphorylation deficiencyOTHERXLR
DN
0.3992th %ile
GOF
0.4579th %ile
LOF
0.67top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.23

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

0 submitted variants 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗