DGAT2

Chr 11

diacylglycerol O-acyltransferase 2

Also known as: ARAT, GS1999FULL, HMFN1045

NCBI Gene: 84649ENSG00000062282UniProt: Q96PD7

This gene encodes one of two enzymes which catalyzes the final reaction in the synthesis of triglycerides in which diacylglycerol is covalently bound to long chain fatty acyl-CoAs. The encoded protein catalyzes this reaction at low concentrations of magnesium chloride while the other enzyme has high activity at high concentrations of magnesium chloride. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

91
ClinVar variants
8
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DGAT2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 59 VUS of 91 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.
1.25LOEUF
pLI 0.000
Z-score 0.66
OE 0.85 (0.59–1.25)
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.
0.82Z-score
OE missense 0.84 (0.74–0.95)
180 obs / 213.9 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.0.85 (0.59–1.25)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.74–0.95)
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.1.09
0≤1.21.6
LoF obs/exp: 19 / 22.4Missense obs/exp: 180 / 213.9Syn Z: -0.66

ClinVar Variant Classifications

91 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
VUS59
Likely Benign16
Benign4
Conflicting4
8
Pathogenic
59
VUS
16
Likely Benign
4
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
0
0
0
VUS
0
58
1
0
59
Likely Benign
0
6
2
8
16
Benign
0
1
1
2
4
Conflicting
—4
Total065121091

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

View in ClinVar →

Protein Context — Lollipop Plot

DGAT2 · 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
📖
GeneReview available — DGAT2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Integrative analysis of loss-of-function variants in clinical and genomic data reveals novel genes associated with cardiovascular traits.
Glicksberg BS et al.·BMC Med Genomics
2019
Lipid droplet accumulation mediates macrophage survival and Treg recruitment via the CCL20/CCR6 axis in human hepatocellular carcinoma.
Wang Y et al.·Cell Mol Immunol
2024
Single nucleus RNA-sequencing integrated into risk variant colocalization discovers 17 cell-type-specific abdominal obesity genes for metabolic dysfunction-associated steatotic liver disease.
Lee SHT et al.·EBioMedicine
2024
The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7.
Chen W et al.·Cardiovasc Diabetol
2024Review
The role of DGAT1 and DGAT2 in regulating tumor cell growth and their potential clinical implications.
Deng B et al.·J Transl Med
2024Review
Efficacy and safety of ervogastat alone and in combination with clesacostat in patients with biopsy-confirmed metabolic dysfunction-associated steatohepatitis and F2-F3 fibrosis (MIRNA): results from a phase 2, randomised, double-blind, double-dummy study.
Wong VW et al.·Lancet Gastroenterol Hepatol
2025Clinical trial
Antisense oligonucleotide DGAT-2 inhibitor, ION224, for metabolic dysfunction-associated steatohepatitis (ION224-CS2): results of a 51-week, multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.
Loomba R et al.·Lancet
2025Clinical trial
Regulatory T cell differentiation is controlled by αKG-induced alterations in mitochondrial metabolism and lipid homeostasis.
Matias MI et al.·Cell Rep
2021
Compound Shouwu Jiangzhi Granule regulates triacylglyceride synthesis to alleviate hepatic lipid accumulation.
Qian F et al.·Phytomedicine
2024
Genetic interaction of DGAT2 and FAAH in the development of human obesity.
Ning T et al.·Endocrine
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
ATG2A-mediated DAG transfer recruits DGAT2 for lipid droplet growth.
Elhan H et al.·Nat Struct Mol Biol
2025🔓 Open Access
miR-10c Targets dgat2 and Affects the Expression of Genes Involved in Fatty Acid and Triglyceride Metabolism in Oreochromis niloticus Under Heat Stress.
Wang W et al.·Int J Mol Sci
2025🔓 Open Access
Effect of Varying Degrees of Hepatic Impairment on the Pharmacokinetics of Ervogastat, a Diacylglycerol Acyltransferase 2 (DGAT2) Inhibitor, and Clesacostat, an Acetyl-CoA Carboxylase (ACC) Inhibitor.
Vourvahis M et al.·J Clin Pharmacol
2025
Three Distinctive Diacylglycerol Acyltransferases (DGAT1, DGAT2, and DGAT3) from Perilla frutescens and Their Potential in Metabolic Engineering for Designed Oil Production.
Zhou Y et al.·J Agric Food Chem
2025
DGAT2 reduction and lipid dysregulation drive psoriasis development in keratinocyte-specific SPRY1-deficient mice.
Li YY et al.·JCI Insight
2025🔓 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