PNPLA3
protein-codingpatatin like phospholipase domain containing 3, the group of Lipases|Patatin like phospholipase domain containing
Gene summary
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]
- C22orf20
- ADPN
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~40.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0013209
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PNPLA3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_025225.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | 7 | 12 | |||
| missense | 84 | 13 | 2 | 99 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 92 | 20 | 2 | 114 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_079501.2 | 9 | MANE Select | |
| Ensembl | ENSP00000216180.3 | 9 | MANE Select | |
| Ensembl | ENSP00000384668.2 | 2 | Standard | |
| Ensembl | ENSP00000397987.2 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glycerolipid metabolism - Homo sapiens (human)
- Eicosanoid Synthesis
- Adipogenesis
- Metabolism of lipids
- Acyl chain remodeling of DAG and TAG
Biological Process
- long-chain fatty acid metabolic process
- glycerophospholipid metabolic process
- phosphatidic acid biosynthetic process
- triglyceride biosynthetic process
- triglyceride catabolic process
Molecular Function
- 1-acylglycerol-3-phosphate O-acyltransferase activity
- lipoprotein lipase activity
- phospholipase A2 activity
- triglyceride lipase activity
- acylglycerol O-acyltransferase activity
Cellular Component
- cytoplasm
- endoplasmic reticulum membrane
- lipid droplet
- membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000216180
- Coding exons
- 9
- Length
- 40750
- Individuals with no LoFs
- 125607
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 141
- Defined
- 125748
- p
- 0.000561
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.472 | 296 | 274 | 1.08 | 0.0000152 | 3105 |
| Missense (PolyPhen) | 98 | 85.003 | 1.1529 | 958 | ||
| Synonymous | -0.396 | 122 | 117 | 1.05 | 0.00000694 | 985 |
| Loss of Function | 1.21 | 14 | 19.8 | 0.707 | 0.00000108 | 213 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00015 | 0.00012 | rare |
| Latino/Admixed American | 0.00097 | 0.00093 | rare |
| Ashkenazi Jewish | 0.00066 | 0.00060 | rare |
| East Asian | 0.00077 | 0.00076 | rare |
| Finnish | 0.00013 | 0.000092 | rare |
| European (Non-Finnish) | 0.00065 | 0.00059 | rare |
| South Asian | 0.00039 | 0.00039 | rare |
| Other | 0.0011 | 0.00098 | notable |
dbNSFP Gene Annotations
Source:
- 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.;
Recessive Scores
- pRec
- 0.160
Intolerance Scores
- LoFtool
- 0.710
- RVIS EVS
- 0.85
- RVIS percentile EVS
- 88.48
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0250
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |