AIFM3

Chr 22

AIF family member 3

Also known as: AIFL

NCBI Gene: 150209ENSG00000183773UniProt: Q96NN9

Predicted to enable oxidoreductase activity, acting on NAD(P)H. Involved in execution phase of apoptosis. Located in cytosol; endoplasmic reticulum; and mitochondrial inner membrane. [provided by Alliance of Genome Resources, Jul 2025]

523
ClinVar variants
266
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— AIFM3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
266 Pathogenic / Likely Pathogenic· 137 VUS of 523 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.99LOEUF
pLI 0.000
Z-score 1.61
OE 0.72 (0.53–0.99)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.00Z-score
OE missense 0.86 (0.78–0.94)
329 obs / 384.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.72 (0.53–0.99)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.78–0.94)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 27 / 37.7Missense obs/exp: 329 / 384.0Syn Z: 0.12

ClinVar Variant Classifications

523 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic233
Likely Pathogenic33
VUS137
Likely Benign3
Benign1
233
Pathogenic
33
Likely Pathogenic
137
VUS
3
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
233
0
233
Likely Pathogenic
0
0
33
0
33
VUS
0
90
47
0
137
Likely Benign
0
1
1
1
3
Benign
0
0
1
0
1
Total0913151407

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

AIFM3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical implications of a novel prognostic factor AIFM3 in breast cancer patients.
Zheng A et al.·BMC Cancer
2019Cohort
Knockdown of integrin β1 inhibits proliferation and promotes apoptosis in bladder cancer cells.
Wang JF et al.·Biofactors
2025
Genetic Drivers of Kidney Defects in the DiGeorge Syndrome.
Lopez-Rivera E et al.·N Engl J Med
2017
Integrated analysis of a competing endogenous RNA network reveals key lncRNAs as potential prognostic biomarkers for human bladder cancer.
Zhu N et al.·Medicine (Baltimore)
2018
Unveiling immune-metabolic interaction in Atherosclerosis via Comprehensive Landscape of Hub Genes and Immune Microenvironment.
Liu F et al.·Heart Surg Forum
2023
Atypical nested 22q11.2 duplications between LCR22B and LCR22D are associated with neurodevelopmental phenotypes including autism spectrum disorder with incomplete penetrance.
Woodward KJ et al.·Mol Genet Genomic Med
2019Case report
Prioritizing Genetic Contributors to Cortical Alterations in 22q11.2 Deletion Syndrome Using Imaging Transcriptomics.
Forsyth JK et al.·Cereb Cortex
2021
Esophageal Adenocarcinoma-Derived Extracellular Vesicle MicroRNAs Induce a Neoplastic Phenotype in Gastric Organoids.
Ke X et al.·Neoplasia
2017
MLPA analysis of 32 foetuses with a congenital heart defect and 1 foetus with renal defects - pilot study. The significant frequency rate of presented pathological CNV.
Stefekova A et al.·Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Expression Pattern of AIFM3, VGLL4, and WNT4 in Patients with Different Stages of Colorectal Cancer.
Bevanda D et al.·Cancers (Basel)
2025🔓 Open AccessCohort
Bioinformatic Prediction of Novel Signaling Pathways of Apoptosis-inducing Factor, Mitochondrion-associated 3 (AIFM3) and Their Roles in Metastasis of Cholangiocarcinoma Cells.
Chua-On D et al.·Cancer Genomics Proteomics
2022
CRKL, AIFM3, AIF, BCL2, and UBASH3A during Human Kidney Development.
Lozic M et al.·Int J Mol Sci
2021🔓 Open Access
Comprehensive Assessment of Copy Number Alterations Uncovers Recurrent AIFM3 and DLK1 Copy Gain in Medullary Thyroid Carcinoma.
Araujo AN et al.·Cancers (Basel)
2021🔓 Open Access
Apoptosis-Inducing Factor, Mitochondrion-Associated 3 (AIFM3) Protein Level in the Sera as a Prognostic Marker of Cholangiocarcinoma Patients.
Chua-On D et al.·Biomolecules
2020🔓 Open AccessCohort
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools