PNPLA3

Chr 22

patatin like domain 3, 1-acylglycerol-3-phosphate O-acyltransferase

Also known as: ADPN, C22orf20, iPLA(2)epsilon

NCBI Gene: 80339 ENSG00000100344 UniProt: Q9NST1

The protein functions as a triacylglycerol lipase and CoA-dependent acyltransferase that catalyzes phosphatidic acid synthesis and mediates lipid metabolism in adipocytes. Mutations cause autosomal recessive early-onset familial hypertriglyceridemia and contribute to nonalcoholic fatty liver disease susceptibility. The gene shows high constraint against loss-of-function variants, indicating that complete loss of protein function is likely severely deleterious.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a triacylglycerol lipase that mediates triacylglycerol hydrolysis in adipocytes. The encoded protein, which appears to be membrane bound, may be involved in the balance of energy usage/storage in adipocytes. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNon-alcoholic fatty liver disease 1

Active trials

277

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.10

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.10LOEUF

pLI 0.000

Z-score 1.21

OE 0.71 (0.47–1.10)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.47Z-score

OE missense 1.08 (0.98–1.19)

296 obs / 274.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.71 (0.47–1.10)

0≤0.351.4

Missense OE?1.08 (0.98–1.19)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 14 / 19.8Missense obs/exp: 296 / 274.0Syn Z: -0.40

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

PNPLA3 · protein map & ClinVar variants

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

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

CirrhosisMASLD

DEFINITION OF THE GENOMIC LANDSCAPE OF MASLD

RECRUITING

NCT07249112Phase NAFondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoStarted 2025-09-01

genetic and somatic variants involved in its progression toward advanced fibrosis and hepatocellular carcinoma

Polycystic Ovary Syndrome (PCOS)Metabolic Dysfunction-Associated Steatotic Liver DiseasePediatric Obesity

Biomarker Panel for PCOS-Associated Liver Steatosis in Adolescent Girls (COMPASS-pedPCOS)

NOT YET RECRUITING

NCT07731373Kayseri City HospitalStarted 2026-09-01

Extended Serum Biomarker and Hormonal PanelLiver Elastography with Controlled Attenuation ParameterTargeted Genotyping of PNPLA3 rs738409 and HSD17B13 rs72613567

MASLD/MASH (Metabolic Dysfunction-Associated Steatotic Liver Disease / Metabolic Dysfunction-Associated Steatohepatitis)

Study of PNPLA3 Genetic Polymorphisms in Patients With Non-Alcoholic Fatty Liver Disease in an Ultramarine Population (AdipoDROMExpo)

RECRUITING

NCT07330830Centre Hospitalier Universitaire de la GuadeloupeStarted 2025-11-26

MASLD - Metabolic Dysfunction-Associated Steatotic Liver DiseaseCirrhosisAdvanced Fibrosis

MASLD in Type 2 Diabetes in Primary Care - a Follow-up Study

ENROLLING BY INVITATION

NCT07312136Linkoeping UniversityStarted 2025-12-16

NAFLDLiver FibrosesCardiovascular Diseases

Liver Damage and Cardiometabolic Disorders in NAFLD

RECRUITING

NCT04036357University of Roma La SapienzaStarted 2011-11

NAFLD

Human Liver ORganoids as a Model to Study the Development of Non-Alcoholic SteatOhepatitis (NASH)

RECRUITING

NCT06856252Phase NAFondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoStarted 2021-07-01

Liver resection to isolate cells

B Acute Lymphoblastic LeukemiaB Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1B Acute Lymphoblastic Leukemia, BCR-ABL1-Like

Studying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma

ACTIVE NOT RECRUITING

NCT05602194Phase PHASE3Children's Oncology GroupStarted 2023-08-24

Biospecimen CollectionCalaspargase PegolLevocarnitine

Fatty Liver Disease

The Role of Sugars in Fat Accumulation in the Liver

RECRUITING

NCT06751862Phase NAInstitute for Clinical and Experimental MedicineStarted 2024-06-20

150g of fat with glucose150g of fat with fructose150g of fat with sucrose

Daily Step CountMASLDBMI

The Efficacy of Pedometer-motivated Physical Activity for the Management of Patients With MASLD.

ENROLLING BY INVITATION

NCT06334666Phase NAMahidol UniversityStarted 2024-08-01

Encourage using pedometer

NASHHCCGenetic Predisposition

Evaluation of Risk of hEpatocellular Carcinoma

RECRUITING

NCT06523179Phase NAFondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoStarted 2018-01-01

quantify the impact of genetic risk factors

Healthy VolunteersMetabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

A Trial to Learn if ALN-PNP is Safe and Well Tolerated in Healthy Adults and Adult Participants With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

RECRUITING

NCT05648214Phase PHASE1, PHASE2Regeneron PharmaceuticalsStarted 2022-12-27

ALN-PNPPlacebo (PB)

Chronic Liver Disease and Cirrhosis

Influence of Donor and Recipient Genetic Polymorphisms on Graft Steatosis After Liver Transplant

RECRUITING

NCT07685353Institute of Liver and Biliary Sciences, IndiaStarted 2026-07-07

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3