{{Rsnum
|rsid=738409
|Gene=PNPLA3
|Chromosome=22
|position=43928847
|Orientation=minus
|ReferenceAllele=C
|MissenseAllele=G
|GMAF=0.2842
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(C;C)
|geno2=(C;G)
|geno3=(G;G)
|Gene_s=PNPLA3
}}{{ population diversity
| geno1=(C;C)
| geno2=(C;G)
| geno3=(G;G)
| CEU | 3.1 | 41.5 | 55.4
| HCB | 13.3 | 42.2 | 44.4
| JPT | 22.7 | 40.9 | 36.4
| YRI | 1.6 | 22.6 | 75.8
| ASW | 0.0 | 0.0 | 0.0
| CHB | 13.3 | 42.2 | 44.4
| CHD | 0.0 | 0.0 | 0.0
| GIH | 0.0 | 0.0 | 0.0
| LWK | 0.0 | 0.0 | 0.0
| MEX | 0.0 | 0.0 | 0.0
| MKK | 0.0 | 0.0 | 0.0
| TSI | 0.0 | 0.0 | 0.0
| HapMapRevision=28
}}

[[rs738409]] is a SNP in the [[PNPLA3]] gene. In all [[HapMap]] populations the most common allele is a G on the positive strand. In the scientific literature, the less common C allele is considered normal, and linked to lower liver fat content. 

{{PMID|19946271}} In a Mestizo population, [[rs738409]] is strongly associated with alcoholic liver disease and clinically evident alcoholic cirrhosis (unadjusted odds ratio 2.25, p=1.7 x 10(-10); ancestry-adjusted OR 1.79, p=1.9 x 10(-5)).

{{PMID|19224197}} rs738409(G) increased quantitative measures of liver fat content 

[http://www.nature.com/ng/journal/v40/n12/abs/ng.257.html nature] 

[[Nonalcoholic fatty liver disease]]. 

Fat content 2x for rs738409(G;G)

rs738409(G) (I148M) was strongly associated with increased hepatic fat levels (P = 5.9 times 10-10)

{{omim
|id=228100
|desc=FATTY METAMORPHOSIS OF VISCERA
|rsnum=738409
}}
{{PMID Auto
|PMID=19651814
|Title=Dissociation between Fatty Liver and Insulin Resistance in Humans carrying a Variant of the Patatin-like Phospholipase 3 Gene
|OA=1
}}
{{PMID Auto
|PMID=19729411
|Title=Genetic Evidence for a Role of Adiponutrin in the Metabolism of Apolipoprotein B-Containing Lipoproteins
|OA=1
}}
{{PMID Auto
|PMID=19738004
|Title=A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity
|OA=1
}}
{{PMID Auto
|PMID=19844213
|Title=Morbid obesity exposes the association between PNPLA3 I148M (rs738409) and indices of hepatic injury in individuals of European descent
}}

{{PharmGKB
|RSID=rs738409
|Name_s=PNPLA3: I148M
|Gene_s=PNPLA3
|Feature=
|Evidence=PubMed ID:18820647
|Annotation=In a genome-wide association study this SNP in PNPLA3 gene was strongly associated with increased hepatic fat levels and with hepatic inflammation.
|Drugs=
|Drug Classes=
|Diseases=Fatty Liver
|Curation Level=Curated
|PharmGKB Accession ID=PA162359972
}}

{{PMID Auto
|PMID=20373368
|Title=Homozygosity for the patatin-like phospholipase-3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease
}}
{{PMID Auto
|PMID=20684021
|Title=The association of genetic variability in patatin-like phospholipase domain-containing protein 3 (PNPLA3) with histological severity of nonalcoholic fatty liver disease
|OA=1
}}
{{PMID Auto
|PMID=20826584
|Title=Specifically PNPLA3-Mediated Accumulation of Liver Fat in Obese Patients with Type 2 Diabetes
}}
{{PMID Auto
|PMID=20585554
|Title=On the use of variance per genotype as a tool to identify quantitative trait interaction effects: a report from the Women's Genome Health Study
|OA=1
}}
{{PMID Auto
|PMID=21140471
|Title=Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians
}}
{{PMID Auto
|PMID=21176169
|Title=Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease
|OA=1
}}
{{PMID Auto
|PMID=21236304
|Title=Viral Genotype-Specific Role of PNPLA3, PPARG, MTTP and IL28B in Hepatitis C Virus-Associated Steatosis
}}

{{PMID Auto
|PMID=21281435
|Title=Association of PNPLA3 with non-alcoholic fatty liver disease in a minority cohort: the Insulin Resistance Atherosclerosis Family Study
|OA=1
}}

{{omim
|id=612364
|rsnum=738409
}}

{{omim
|id=613282
|rsnum=738409
}}

{{PMID Auto
|PMID=21488075
|Title=Impact of PNPLA3 (rs738409 C&gt;G) polymorphism on fibrosis progression and steatosis in chronic hepatitis C
}}

{{PMID Auto GWAS
|PMID=21423719
|Trait=None
|Title=Genome-wide association analysis identifies variants associated with nonalcoholic Fatty liver disease that have distinct effects on metabolic traits
|RiskAllele=G
|Pval=4E-34
|OR=0.2600
|ORtxt=[0.22-0.30] unit increase (GOLD)
|OA=1
}}

{{PMID Auto
|PMID=21525193
|Title=Genetic variation in PNPLA3 (adiponutrin) confers sensitivity to weight loss-induced decrease in liver fat in humans
}}

{{PMID Auto
|PMID=21665509
|Title=Association of PNPLA3 SNP rs738409 with liver density in African Americans with type 2 diabetes mellitus
|OA=1
}}

{{PMID Auto
|PMID=22087248
|Title=The PNPLA3 rs738409 148M/M Genotype Is a Risk Factor for Liver Cancer in Alcoholic Cirrhosis but Shows No or Weak Association in Hepatitis C Cirrhosis
|OA=1
}}

{{PMID Auto
|PMID=22105854
|Title=A variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver in obese children and adolescents
|OA=1
}}

{{PMID Auto
|PMID=22110053
|Title=Genetic determinants of alcoholic liver disease
}}

{{PMID Auto
|PMID=22141340
|Title=Genetic variation in PNPLA3 but not APOC3 influences liver fat in NAFLD
}}

{{PMID Auto GWAS
|PMID=22001757
|Trait=None
|Title=Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.
|RiskAllele=G
|Pval=1E-45
|OR=6.0000
|ORtxt=None
|OA=1
}}

{{PMID Auto
|PMID=22276112
|Title=A Common Variant of PNPLA3 (p.I148M) Is Not Associated with Alcoholic Chronic Pancreatitis
|OA=1
}}

{{PMID Auto
|PMID=22634340
|Title=Association of the IL28B genotype with insulin resistance in patients with chronic hepatitis C
}}

{{PMID Auto
|PMID=22629460
|Title=Hepatic Fat Accumulation Is Modulated by the Interaction between the rs738409 Variant in the PNPLA3 Gene and the Dietary Omega6/Omega3 PUFA Intake
|OA=1
}}

{{PMID Auto
|PMID=22719190
|Title=Patatin-like phospholipase domain containing-3 gene I148M polymorphism, steatosis, and liver damage in hereditary hemochromatosis
|OA=1
}}

{{PMID Auto
|PMID=22724004
|Title=Paradoxical Lower Serum Triglyceride Levels and Higher Type 2 Diabetes Mellitus Susceptibility in Obese Individuals with the PNPLA3 148M Variant
|OA=1
}}

{{PMID Auto
|PMID=22792295
|Title=The PNPLA3 rs738409 G-Allele Associates with Reduced Fasting Serum Triglyceride and Serum Cholesterol in Danes with Impaired Glucose Regulation
|OA=1
}}

{{PMID Auto
|PMID=18728122
|Title=Polymorphisms in the adiponutrin gene are associated with increased insulin secretion and obesity.
}}

{{PMID Auto
|PMID=18940312
|Title=Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes.
|OA=1
}}

{{PMID Auto
|PMID=19524579
|Title=Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors.
}}

{{PMID Auto
|PMID=19542081
|Title=A common variant in the adiponutrin gene influences liver enzyme values.
|OA=1
}}

{{PMID Auto
|PMID=20546964
|Title=The 148M allele of the PNPLA3 gene is associated with indices of liver damage early in life.
}}

{{PMID Auto
|PMID=20648472
|Title=PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease.
|OA=1
}}

{{PMID Auto
|PMID=20648474
|Title=I148M patatin-like phospholipase domain-containing 3 gene variant and severity of pediatric nonalcoholic fatty liver disease.
}}

{{PMID Auto
|PMID=20648554
|Title=Patatin-like phospholipase domain-containing 3/adiponutrin deficiency in mice is not associated with fatty liver disease.
|OA=1
}}

{{PMID Auto
|PMID=20803499
|Title=A common variant in the patatin-like phospholipase 3 gene (PNPLA3) is associated with fatty liver disease in obese children and adolescents.
|OA=1
}}

{{PMID Auto
|PMID=20852027
|Title=Effects of PNPLA3 on liver fat and metabolic profile in Hispanic children and adolescents.
|OA=1
}}

{{PMID Auto
|PMID=20962157
|Title=Increased hepatic fat in overweight Hispanic youth influenced by interaction between genetic variation in PNPLA3 and high dietary carbohydrate and sugar consumption.
|OA=1
}}

{{PMID Auto
|PMID=21068004
|Title=Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome.
|OA=1
}}

{{PMID Auto
|PMID=21168155
|Title=A common variant in the PNPLA3 gene is a risk factor for non-alcoholic fatty liver disease in obese Taiwanese children.
}}

{{PMID Auto
|PMID=21168459
|Title=Variant adiponutrin (PNPLA3) represents a common fibrosis risk gene: non-invasive elastography-based study in chronic liver disease.
}}

{{PMID Auto
|PMID=21254164
|Title=Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians.
}}

{{PMID Auto
|PMID=21274868
|Title=Dissociation between APOC3 variants, hepatic triglyceride content and insulin resistance.
|OA=1
}}

{{PMID Auto
|PMID=21319195
|Title=Patatin-like phospholipase domain-containing 3 I148M polymorphism, steatosis, and liver damage in chronic hepatitis C.
}}

{{PMID Auto
|PMID=21334404
|Title=Common polymorphism in the PNPLA3/adiponutrin gene confers higher risk of cirrhosis and liver damage in alcoholic liver disease.
}}

{{PMID Auto
|PMID=21339799
|Title=Bioinformatics-driven identification and examination of candidate genes for non-alcoholic fatty liver disease.
|OA=1
}}

{{PMID Auto
|PMID=21381068
|Title=Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease.
}}

{{PMID Auto
|PMID=22162034
|Title=PNPLA3 (rs738409 C>G) is a common risk variant associated with hepatocellular carcinoma in alcoholic cirrhosis.
}}

{{PMID Auto
|PMID=22314430
|Title=IL28B and PNPLA3 polymorphisms affect histological liver damage in patients with non-alcoholic fatty liver disease.
}}

{{PMID Auto
|PMID=22338072
|Title=PNPLA3 is regulated by glucose in human hepatocytes, and its I148M mutant slows down triglyceride hydrolysis.
}}

{{PMID Auto
|PMID=22546774
|Title=PNPLA3 gene-by-visceral adipose tissue volume interaction and the pathogenesis of fatty liver disease: The NHLBI Family Heart Study.
|OA=1
}}

{{PMID Auto GWAS
|PMID=22719876
|Trait=None
|Title=Genetic Polymorphisms of the Human PNPLA3 Gene Are Strongly Associated with Severity of Non-Alcoholic Fatty Liver Disease in Japanese.
|RiskAllele=G
|Pval=1E-10
|OR=1.6600
|ORtxt=None
|OA=1
}}

{{GET Evidence
|gene=PNPLA3
|aa_change=Ile148Met
|aa_change_short=I148M
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs738409
|overall_frequency_n=2110
|overall_frequency_d=10758
|overall_frequency=0.196133
|n_genomes=24
|n_genomes_annotated=0
|n_haplomes=27
|n_articles=1
|n_articles_annotated=1
|in_pharmgkb=Y
|pph2_score=0.778
|nblosum100=-1
|autoscore=1
|webscore=N
}}

{{PMID Auto
|PMID=23155331
|Title=PNPLA3, the triacylglycerol synthesis/hydrolysis/storage dilemma, and nonalcoholic fatty liver disease
|OA=1
}}

{{PMID Auto
|PMID=23269818
|Title=A common variant in the peroxisome proliferator-activated receptor-γ coactivator-1α gene is associated with nonalcoholic fatty liver disease in obese children
}}

{{PMID Auto
|PMID=23418085
|Title=Interactions of allelic variance of PNPLA3 with non genetic factors in predicting NASH and non-hepatic complications of severe obesity
|OA=1
}}

{{PMID Auto
|PMID=23484035
|Title=Susceptibility and Gene Interaction Study of the Angiotensin II Type 1 Receptor (AGTR1) Gene Polymorphisms with Non-Alcoholic Fatty Liver Disease in a Multi-Ethnic Population
|OA=1
}}

{{PMID Auto
|PMID=23512881
|Title=A gene variant of PNPLA3, but not of APOC3, is associated with histological parameters of NAFLD in an obese population
}}

{{PMID Auto
|PMID=23734760
|Title=Genetic Variation in the Patatin-Like Phospholipase Domain-Containing Protein-3 (PNPLA-3) Gene in Asian Indians with Nonalcoholic Fatty Liver Disease
}}

{{PMID Auto
|PMID=24102786
|Title=PNPLA3 I148M (rs738409) genetic variant and age at onset of at-risk alcohol consumption are independent risk factors for alcoholic cirrhosis
}}

{{PMID Auto
|PMID=24114809
|Title=Association between the PNPLA3 (rs738409 C&gt;G) variant and hepatocellular carcinoma: evidence from a meta-analysis of individual participant data
}}

{{PMID Auto
|PMID=24125181
|Title=The Impact of PNPLA3 Polymorphisms on the Development of Hepatocellular Carcinoma in Patients with Chronic Hepatitis C Virus Infection
}}

{{PMID Auto
|PMID=24425067
|Title=Response to the letter of Limagne et al. PNPLA3 (rs738409 C&gt;G) variant and oxidative stress due to chronic liver damage
}}

{{PMID Auto
|PMID=24477042
|Title=Genetic variants in GCKR and PNPLA3 confer susceptibility to nonalcoholic fatty liver disease in obese individuals
}}

{{PMID Auto
|PMID=24553484
|Title=Impact of Comorbid Hepatic Steatosis on Treatment of Chronic Hepatitis C in Japanese Patients and the Relationship with Genetic Polymorphism of IL28B, PNPLA3 and LDL Receptor
}}

{{PMID Auto
|PMID=22258181
|Title=A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease.
|OA=1
}}

{{PMID Auto
|PMID=22704398
|Title=PNPLA3 I148M (rs738409) genetic variant is associated with hepatocellular carcinoma in obese individuals.
}}

{{PMID Auto
|PMID=22863264
|Title=Genetic polymorphism in cyclooxygenase-2 promoter affects hepatic inflammation and fibrosis in patients with chronic hepatitis C.
}}

{{PMID Auto
|PMID=22863562
|Title=PNPLA3 polymorphisms and liver aminotransferase levels in a Mexican American population.
|OA=1
}}

{{PMID Auto
|PMID=22869157
|Title=The impact of patatin-like phospholipase domain-containing protein 3 polymorphism on hepatocellular carcinoma prognosis.
}}

{{PMID Auto
|PMID=22878467
|Title=Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) affects hepatic VLDL secretion in humans and in vitro.
}}

{{PMID Auto
|PMID=22884299
|Title=PNPLA3, a genetic marker of progressive liver disease, still hiding its metabolic function?
}}

{{PMID Auto
|PMID=23032985
|Title=The interaction of rs738409, obesity, and alcohol: a population-based autopsy study.
}}

{{PMID Auto
|PMID=23069476
|Title=PNPLA3 rs738409, hepatocellular carcinoma occurrence and risk model prediction in patients with cirrhosis.
}}

{{PMID Auto
|PMID=23275357
|Title=The association between hepatic fat content and liver injury in obese children and adolescents: effects of ethnicity, insulin resistance, and common gene variants.
|OA=1
}}

{{PMID Auto
|PMID=23292069
|Title=Genetic signatures in choline and 1-carbon metabolism are associated with the severity of hepatic steatosis.
|OA=1
}}

{{PMID Auto
|PMID=23334462
|Title=Adipose tissue is inflamed in NAFLD due to obesity but not in NAFLD due to genetic variation in PNPLA3.
}}

{{PMID Auto
|PMID=23535911
|Title=Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB genes are associated with development and progression of nonalcoholic fatty liver disease in Japan.
}}

{{PMID Auto
|PMID=23564580
|Title=Patatin-like phospholipase domain-containing 3 I148M affects liver steatosis in patients with chronic hepatitis B.
}}

{{PMID Auto
|PMID=23776098
|Title=Genetic variation in the PNPLA3 gene and hepatocellular carcinoma in USA: risk and prognosis prediction.
|OA=1
}}

{{PMID Auto
|PMID=23800943
|Title=Association of glucokinase regulatory gene polymorphisms with risk and severity of non-alcoholic fatty liver disease: an interaction study with adiponutrin gene.
}}

{{PMID Auto
|PMID=23815500
|Title=Oxidized fatty acids: A potential pathogenic link between fatty liver and type 2 diabetes in obese adolescents?
}}

{{PMID Auto
|PMID=24799990
|Title=Pediatric non-alcoholic fatty liver disease: New insights and future directions
|OA=1
}}

{{PMID Auto
|PMID=24831885
|Title=Genetic Variants in the PNPLA3 Gene Are Associated with Nonalcoholic Steatohepatitis
}}

{{PMID Auto
|PMID=24917523
|Title=Pnpla3I148M knockin mice accumulate PNPLA3 on lipid droplets and develop hepatic steatosis
}}

{{PMID Auto
|PMID=24916969
|Title=Associations of I148M variant in PNPLA3 gene with plasma ALT levels during 2-year follow-up in normal weight and overweight children: the PANIC Study
}}

{{PMID Auto
|PMID=23872669
|Title=Patatin-like phospholipase domain-containing protein 3 rs738409-G in recipients of liver transplants is a risk factor for graft steatosis
}}

{{PMID Auto
|PMID=25069572
|Title=Role of the PNPLA3 I148M Polymorphism in Nonalcoholic Fatty Liver Disease and Fibrosis in Korea
}}

{{PMID Auto
|PMID=25074358
|Title=Association between genetic variants in PNPLA3 and serum adiponectin
}}

{{PMID Auto
|PMID=25232397
|Title=Genetic variation I148M in patatin-like phospholipase 3 gene and risk of non-alcoholic fatty liver disease among Filipinos
}}

{{PMID Auto
|PMID=24349054
|Title=No correlation between PNPLA3 rs738409 genotype and fatty liver and hepatic cirrhosis in Japanese patients with HCV
}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | HumanOmni1Quad}}