AIG1

Chr 6

androgen induced 1

Also known as: AIG-1, dJ95L4.1

NCBI Gene: 51390ENSG00000146416UniProt: Q9NVV5OMIM: 608514

AIG1 encodes a hydrolase that specifically cleaves fatty-acid esters of hydroxy-fatty acids (FAHFAs), particularly those with branching distal from the carboxylate head group, and is involved in long-chain fatty acid catabolism. Mutations cause autosomal recessive neurodegeneration with developmental delay, seizures, and progressive motor dysfunction. The gene shows very high constraint against loss-of-function variants, indicating that complete loss of AIG1 function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.38
Clinical Summary— AIG1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
14 unique Pathogenic / Likely Pathogenic· 37 VUS of 60 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.38LOEUF
pLI 0.000
Z-score 0.55
OE 0.84 (0.53–1.38)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.22Z-score
OE missense 0.94 (0.81–1.10)
120 obs / 127.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.84 (0.53–1.38)
0≤0.351.4
Missense OE0.94 (0.81–1.10)
0≤0.61.4
Synonymous OE0.78
0≤1.21.6
LoF obs/exp: 11 / 13.1Missense obs/exp: 120 / 127.0Syn Z: 1.21
DN
0.6745th %ile
GOF
0.75top 25%
LOF
0.2288th %ile

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.

GOFprediction above median
DNprediction above median

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

ClinVar

Classification Summary

Pathogenic14
VUS37
14
Pathogenic
37
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
0
0
0
VUS
0
32
5
0
37
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total03219051

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

View in ClinVar →

Protein Context — Lollipop Plot

AIG1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Evolution of Plant AIG1-like Proteins: Different Modes of Sequence Divergence and Their Contributions to Functional Diversification.
Peng J et al.·Plants (Basel)
2026Open AccessFunctional
AIG1 protects against doxorubicin-induced cardiomyocyte ferroptosis and cardiotoxicity by promoting ubiquitination-mediated p53 degradation.
Shi Y et al.·Theranostics
2025Open Access
Attenuation of In Vitro and In Vivo Virulence Is Associated with Repression of Gene Expression of AIG1 Gene in Entamoeba histolytica.
Lozano-Mendoza J et al.·Pathogens
2023Open Access
AIG1 and ADTRP are endogenous hydrolases of fatty acid esters of hydroxy fatty acids (FAHFAs) in mice.
Erikci Ertunc M et al.·J Biol Chem
2020
Stress Adapted Mollusca and Nematoda Exhibit Convergently Expanded Hsp70 and AIG1 Gene Families.
Guerin MN et al.·J Mol Evol
2019
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients