PNPLA3

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

Basic information

Region (hg38): 22:43923791-43964488

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.

• NAFLD1 (76 variants)
• Inborn genetic diseases (26 variants)
• not provided (13 variants)
• Susceptibility to Nonalcoholic Fatty Liver Disease (4 variants)
• not specified (1 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	7	2	13
missense			38	8	4	50
nonsense			2			2
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2			2
non coding			22	8	7	37
Total	0	0	67	23	13

Variants in PNPLA3

This is a list of pathogenic ClinVar variants found in the PNPLA3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
22-43923800-A-T		NAFLD1	Likely benign (Jan 12, 2018)
22-43923801-G-A		NAFLD1	Likely benign (Jan 13, 2018)
22-43923804-T-C		NAFLD1	Uncertain significance (Apr 06, 2018)
22-43923843-T-C		NAFLD1	Uncertain significance (Jan 12, 2018)
22-43923868-C-G		NAFLD1	Uncertain significance (Jan 13, 2018)
22-43923872-C-G		NAFLD1	Likely benign (Jan 13, 2018)
22-43923927-C-G		not specified	Uncertain significance (Nov 07, 2022)
22-43923938-C-T			Likely benign (Sep 01, 2023)
22-43923962-C-T			Likely benign (Apr 01, 2022)
22-43923973-AC-A		NAFLD1	Uncertain significance (Nov 29, 2017)
22-43923990-C-G		not specified	Uncertain significance (Jul 16, 2021)
22-43923993-T-C		NAFLD1	Uncertain significance (Jan 13, 2018)
22-43924017-C-A		not specified	Uncertain significance (Jan 02, 2024)
22-43924026-G-T		not specified	Uncertain significance (Sep 19, 2023)
22-43924035-A-G		not specified	Uncertain significance (Apr 29, 2022)
22-43924036-T-G		not specified	Uncertain significance (Oct 25, 2022)
22-43924040-G-T		not specified	Likely benign (May 09, 2023)
22-43924047-G-T		not specified	Uncertain significance (Dec 08, 2023)
22-43924063-T-C		not specified	Uncertain significance (Aug 19, 2023)
22-43924091-C-G		not specified	Uncertain significance (Sep 27, 2021)
22-43924110-G-A		NAFLD1	Benign (Jan 12, 2018)
22-43926961-C-G		not specified	Uncertain significance (May 11, 2022)
22-43926963-T-C		NAFLD1	Likely benign (Jan 12, 2018)
22-43926968-G-A		not specified	Uncertain significance (Dec 28, 2022)
22-43926973-G-A		NAFLD1	Uncertain significance (Apr 10, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PNPLA3	protein_coding	protein_coding	ENST00000216180	9	40750

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.74e-8	0.663	125607	0	141	125748	0.000561

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.472	296	274	1.08	0.0000152	3105
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00112	0.00109
Ashkenazi Jewish	0.000658	0.000595
East Asian	0.000770	0.000761
Finnish	0.000128	0.0000924
European (Non-Finnish)	0.000654	0.000589
Middle Eastern	0.000770	0.000761
South Asian	0.000392	0.000392
Other	0.00110	0.000978

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

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