AIF1

Chr 6

allograft inflammatory factor 1

Also known as: AIF-1, IBA1, IRT-1, IRT1

NCBI Gene: 199ENSG00000204472UniProt: P55008

This gene encodes a protein that binds actin and calcium. This gene is induced by cytokines and interferon and may promote macrophage activation and growth of vascular smooth muscle cells and T-lymphocytes. Polymorphisms in this gene may be associated with systemic sclerosis. Alternative splicing results in multiple transcript variants, but the full-length and coding nature of some of these variants is not certain. [provided by RefSeq, Jan 2016]

34
ClinVar variants
7
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— AIF1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 22 VUS of 34 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.
1.62LOEUF
pLI 0.000
Z-score 0.15
OE 0.95 (0.57–1.62)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.22Z-score
OE missense 0.93 (0.77–1.13)
72 obs / 77.3 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.0.95 (0.57–1.62)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.77–1.13)
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.0.62
0≤1.21.6
LoF obs/exp: 9 / 9.5Missense obs/exp: 72 / 77.3Syn Z: 1.71

ClinVar Variant Classifications

34 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic3
VUS22
Likely Benign5
4
Pathogenic
3
Likely Pathogenic
22
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
3
0
3
VUS
0
8
14
0
22
Likely Benign
0
1
4
0
5
Benign
0
0
0
0
0
Total0925034

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

View in ClinVar →

Protein Context — Lollipop Plot

AIF1 · 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
Identification of novel therapeutic targets for chronic kidney disease and kidney function by integrating multi-omics proteome with transcriptome.
Si S et al.·Genome Med
2024
Proteome-wide Mendelian randomization identifies therapeutic targets for ankylosing spondylitis.
Zhao W et al.·Front Immunol
2024
Heat-shock chaperone HSPB1 mitigates poly-glycine-induced neurodegeneration via restoration of autophagic flux.
Ding N et al.·Autophagy
2025
Targeting allograft inflammatory factor 1 reprograms kidney macrophages to enhance repair.
Husain I et al.·J Clin Invest
2025
Multi-omic biomarkers associated with multiple sclerosis: from Mendelian randomization to drug prediction.
Yang W et al.·Sci Rep
2025
Novel genetic insight for psoriasis: integrative genome-wide analyses in 863 080 individuals and proteome-wide Mendelian randomization.
Liu S et al.·Brief Bioinform
2024
Genetic associations in ankylosing spondylitis: circulating proteins as drug targets and biomarkers.
Zhang Y et al.·Front Immunol
2024
Hofbauer cell alterations and potential role in the pathophysiology of HELLP syndrome.
Ezaki A et al.·Hum Cell
2025
Increased adipose catecholamine levels and protection from obesity with loss of Allograft Inflammatory Factor-1.
Chinnasamy P et al.·Nat Commun
2023
Improving immunotherapy responses by dual inhibition of macrophage migration inhibitory factor and PD-1.
Tran TT et al.·JCI Insight
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Pc-AIF1 Is Expressed in Hemocyte-Rich and Neural Tissues and Links Immune Response and Regeneration in the Snail Model Pomacea canaliculata.
Ferri A et al.·Int J Mol Sci
2025🔓 Open AccessFunctional
AIF1 Regulates the Progression of Esophageal Squamous Cell Carcinoma Through Negative Regulation of Immune T Cell Efflux Function by TIGIT Signal.
Lyu X et al.·Dig Dis Sci
2025
Identification of AIF1 as a protein target of notoginsenosides in brain tissue of mice with intracerebral hemorrhage based on hapten immunoaffinity fishing technique.
Chen F et al.·J Ginseng Res
2025🔓 Open Access
Cnaphalocrocis medinalis granulovirus regulates apoptosis by targeting AIF1 and ASPP1 through tca-miR-3885-5p and tca-miR-3897-3p to promote infection.
Zhang N et al.·Pestic Biochem Physiol
2024
Copper Sulfate Combined with Photodynamic Therapy Enhances Antifungal Effect by Downregulating AIF1.
Zhang M et al.·J Fungi (Basel)
2024🔓 Open Access
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