Target Information

Target General Information

Target ID

T63214

Target Name

1-acylglycerol-3-phosphate O-acyltransferase PNPLA3 messenger RNA (PNPLA3 mRNA)

Synonyms

Acylglycerol transacylase (mRNA); Adiponutrin (mRNA); ADPN (mRNA); Calcium-independent phospholipase A2-epsilon (mRNA); iPLA2-epsilon (mRNA); Lysophosphatidic acid acyltransferase (mRNA); Patatin-like phospholipase domain-containing protein 3 (mRNA)

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Gene Name

PNPLA3

Target Type

Clinical trial target

[1]

Disease

[+] 1 Target-related Diseases

Non-alcoholic fatty liver disease [ICD-11: DB92]

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). In vitro may express hydrolytic activity against glycerolipids triacylglycerol, diacylglycerol and monoacylglycerol, with a strong preference for oleic acid as the acyl moiety (PubMed:21878620). However, the triacylglycerol hydrolase activity is controversial and may be very low (PubMed:22560221). Possesses phospholipase A2 activity (PubMed:15364929). {ECO:0000269|PubMed:15364929, ECO:0000269|PubMed:20034933, ECO:0000269|PubMed:21878620, ECO:0000269|PubMed:22560221}.

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BioChemical Class

mRNA target

UniProt ID

PLPL3_HUMAN

EC Number

EC 2.3.1.51; EC 3.1.1.3; EC 3.1.1.4

Sequence

MYDAERGWSLSFAGCGFLGFYHVGATRCLSEHAPHLLRDARMLFGASAGALHCVGVLSGI
PLEQTLQVLSDLVRKARSRNIGIFHPSFNLSKFLRQGLCKCLPANVHQLISGKIGISLTR
VSDGENVLVSDFRSKDEVVDALVCSCFIPFYSGLIPPSFRGVRYVDGGVSDNVPFIDAKT
TITVSPFYGEYDICPKVKSTNFLHVDITKLSLRLCTGNLYLLSRAFVPPDLKVLGEICLR
GYLDAFRFLEEKGICNRPQPGLKSSSEGMDPEVAMPSWANMSLDSSPESAALAVRLEGDE
LLDHLRLSILPWDESILDTLSPRLATALSEEMKDKGGYMSKICNLLPIRIMSYVMLPCTL
PVESAIAIVQRLVTWLPDMPDDVLWLQWVTSQVFTRVLMCLLPASRSQMPVSSQQASPCT
PEQDWPCWTPCSPKGCPAETKAEATPRSILRSSLNFFLGNKVPAGAEGLSTFPSFSLEKS
L

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Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 2 Clinical Trial Drugs

ION839

Drug Info

Phase 2

Non-alcoholic steatohepatitis

[2]

AMG 609

Drug Info

Phase 1

Non-alcoholic steatohepatitis

[3]

References

Top

REF 1

Clinical pipeline report, company report or official report of Ionis

REF 2

ClinicalTrials.gov (NCT05809934) A Randomised, Double-blind, Placebo-controlled, Multi-centre Phase 2b Study to Evaluate the Efficacy, Safety and Tolerability of AZD2693 in Participants With Non-cirrhotic Non-alcoholic Steatohepatitis (NASH) With Fibrosis Who Are Carriers of the PNPLA3 rs738409 148M Risk Allele. U.S.National Institutes of Health.

REF 3

ClinicalTrials.gov (NCT04857606) A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 609 in Subjects With Non-alcoholic Fatty Liver Disease. U.S.National Institutes of Health.

REF 4

Insights into the molecular targets and emerging pharmacotherapeutic interventions for nonalcoholic fatty liver disease. Metabolism. 2022 Jan;126:154925.

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