AGPAT4

Chr 6

1-acylglycerol-3-phosphate O-acyltransferase 4

Also known as: 1-AGPAT4, LPAAT-delta, LPAAT4, LPLAT4, dJ473J16.2

NCBI Gene: 56895ENSG00000026652UniProt: Q9NRZ5

This gene encodes a member of the 1-acylglycerol-3-phosphate O-acyltransferase family. This integral membrane protein converts lysophosphatidic acid to phosphatidic acid, the second step in de novo phospholipid biosynthesis. [provided by RefSeq, Jul 2008]

73
ClinVar variants
30
Pathogenic / LP
0.10
pLI score
0
Active trials
Clinical Summary— AGPAT4
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.
📋
ClinVar Variants
30 Pathogenic / Likely Pathogenic· 40 VUS of 73 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.53LOEUF
pLI 0.102
Z-score 3.19
OE 0.27 (0.15–0.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
2.23Z-score
OE missense 0.59 (0.51–0.68)
136 obs / 231.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.27 (0.15–0.53)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.59 (0.51–0.68)
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.0.88
0≤1.21.6
LoF obs/exp: 6 / 22.2Missense obs/exp: 136 / 231.4Syn Z: 0.96

ClinVar Variant Classifications

73 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic1
VUS40
Likely Benign2
Benign1
29
Pathogenic
1
Likely Pathogenic
40
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
29
0
29
Likely Pathogenic
0
0
1
0
1
VUS
0
31
9
0
40
Likely Benign
0
2
0
0
2
Benign
0
0
1
0
1
Total03340073

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

View in ClinVar →

Protein Context — Lollipop Plot

AGPAT4 · 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
The Agpat4/LPA axis in colorectal cancer cells regulates antitumor responses via p38/p65 signaling in macrophages.
Zhang D et al.·Signal Transduct Target Ther
2020
Complex polymorphisms in endocytosis genes suggest alpha-cyclodextrin as a treatment for breast cancer.
Wittkowski KM et al.·PLoS One
2018
Multi-Omic Analysis Reveals a Lipid Metabolism Gene Signature and Predicts Prognosis and Chemotherapy Response in Thyroid Carcinoma.
Tu Y et al.·Cancer Med
2025
Linkage and exome analysis implicate multiple genes in non-syndromic intellectual disability in a large Swedish family.
Lindholm Carlström E et al.·BMC Med Genomics
2019
A Metabolism-Related Gene Prognostic Index Bridging Metabolic Signatures and Antitumor Immune Cycling in Head and Neck Squamous Cell Carcinoma.
Du K et al.·Front Immunol
2022
Microarray analysis of differentially expressed genes regulating lipid metabolism during melanoma progression.
Sumantran VN et al.·Indian J Biochem Biophys
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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