GeneBe

PNPLA3

patatin like phospholipase domain containing 3, the group of Lipases|Patatin like phospholipase domain containing

Basic information

Region (hg38): 22:43923792-43964488

Previous symbols: [ "C22orf20", "ADPN" ]

Links

ENSG00000100344 ∙ NCBI:80339 ∙ OMIM:609567 ∙ HGNC:18590 ∙ Uniprot:Q9NST1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PNPLA3 gene.

  • not_specified (71 variants)
  • NAFLD1 (40 variants)
  • not_provided (17 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PNPLA3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000025225.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
4
clinvar
7
clinvar
 11
missense
75
clinvar
12
clinvar
2
clinvar
 89
nonsense
0
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
0
Total 0 0 80 19 2
Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
PNPLA3protein_codingprotein_codingENST00000216180 940750
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
5.74e-80.66312560701411257480.000561
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.4722962741.080.00001523105
Missense in Polyphen9885.0031.1529958
Synonymous-0.3961221171.050.00000694985
Loss of Function1.211419.80.7070.00000108213

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001120.00109
Ashkenazi Jewish0.0006580.000595
East Asian0.0007700.000761
Finnish0.0001280.0000924
European (Non-Finnish)0.0006540.000589
Middle Eastern0.0007700.000761
South Asian0.0003920.000392
Other0.001100.000978

dbNSFP

Source: dbNSFP

Function
FUNCTION: Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and precursor for both triglycerides and glycerophospholipids. Does not esterify other lysophospholipids. Acyl donors are long chain (at least C16) fatty acyl-CoAs: arachidonoyl-CoA, linoleoyl-CoA, oleoyl-CoA and at a lesser extent palmitoyl-CoA (PubMed:22560221). Additionally possesses low triacylglycerol lipase and CoA-independent acylglycerol transacylase activities and thus may play a role in acyl-chain remodeling of triglycerides (PubMed:15364929, PubMed:20034933, PubMed:22560221). {ECO:0000269|PubMed:15364929, ECO:0000269|PubMed:20034933, ECO:0000269|PubMed:22560221}.;
Disease
DISEASE: Non-alcoholic fatty liver disease 1 (NAFLD1) [MIM:613282]: A condition characterized by accumulation of triglycerides in the liver. It is associated with adverse metabolic consequences, including insulin resistance and dyslipidemia. In a subset of individuals, hepatic steatosis promotes an inflammatory response in the liver, referred to as steatohepatitis, which can progress to cirrhosis and liver cancer. NAFLD is the most common form of liver disease in Western countries. {ECO:0000269|PubMed:18820647, ECO:0000269|PubMed:19224197, ECO:0000269|PubMed:19738004, ECO:0000269|PubMed:27288299}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
Pathway
Glycerolipid metabolism - Homo sapiens (human);Eicosanoid Synthesis;Adipogenesis;Metabolism of lipids;Acyl chain remodeling of DAG and TAG;Metabolism;triacylglycerol degradation;Glycerophospholipid biosynthesis;Phospholipid metabolism (Consensus)

Recessive Scores

pRec
0.160

Intolerance Scores

loftool
0.710
rvis_EVS
0.85
rvis_percentile_EVS
88.48

Haploinsufficiency Scores

pHI
0.137
hipred
N
hipred_score
0.179
ghis
0.414

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.0250

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Pnpla3
Phenotype
homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); liver/biliary system phenotype;

Gene ontology

Biological process
long-chain fatty acid metabolic process;glycerophospholipid metabolic process;phosphatidic acid biosynthetic process;triglyceride biosynthetic process;triglyceride catabolic process;lipid droplet organization;triglyceride acyl-chain remodeling;acylglycerol acyl-chain remodeling;lipid homeostasis
Cellular component
cytoplasm;endoplasmic reticulum membrane;lipid droplet;membrane;integral component of membrane
Molecular function
1-acylglycerol-3-phosphate O-acyltransferase activity;lipoprotein lipase activity;phospholipase A2 activity;triglyceride lipase activity;acylglycerol O-acyltransferase activity;lysophosphatidic acid binding;long-chain fatty acyl-CoA binding;lysophosphatidic acid acyltransferase activity;mono-olein transacylation activity;diolein transacylation activity