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Protein / target

Angiopoietin-related protein 3

Encoded byANGPTL3Q9Y5C1Homo sapiensSwiss-Prot
UniProt: Q9Y5C1Ensembl: ENSG00000132855HGNC: HGNC:491NCBI Gene: 27329
Clinically validated
Therapeutic maturity
1
Approved medicines
Open Targets target-level
View by indication →
9
Clinical trials
Antibody-tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Phospholipase inhibitor

Strongest disease association

Genetic Diseases, Inborn

Via encoding gene ANGPTL3 · Genetic evidence · score 0.68

Therapeutic position

Established drug target

Antibodies

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Acts in part as a hepatokine that is involved in regulation of lipid and glucose metabolism.

View complete UniProt function annotation

Acts in part as a hepatokine that is involved in regulation of lipid and glucose metabolism (PubMed:11788823, PubMed:12909640, PubMed:23661675, PubMed:25495645). Proposed to play a role in the trafficking of energy substrates to either storage or oxidative tissues in response to food intake (By similarity). Has a stimulatory effect on plasma triglycerides (TG), which is achieved by suppressing plasma TG clearance via inhibition of LPL activity. The inhibition of LPL activity appears to be an indirect mechanism involving recruitment of proprotein convertases PCSK6 and FURIN to LPL leading to cleavage and dissociation of LPL from the cell surface; the function does not require ANGPTL3 proteolytic cleavage but seems to be mediated by the N-terminal domain, and is not inhibited by GPIHBP1 (PubMed:12097324, PubMed:19318355, PubMed:20581395). Can inhibit endothelial lipase, causing increased plasma levels of high density lipoprotein (HDL) cholesterol and phospholipids (PubMed:17110602, PubMed:19028676). Can bind to adipocytes to activate lipolysis, releasing free fatty acids and glycerol (PubMed:12565906). Suppresses LPL specifically in oxidative tissues which is required to route very low density lipoprotein (VLDL)-TG to white adipose tissue (WAT) for storage in response to food; the function may involve cooperation with circulating, liver-derived ANGPTL8 and ANGPTL4 expression in WAT (By similarity). Contributes to lower plasma levels of low density lipoprotein (LDL)-cholesterol by a mechanism that is independent of the canonical pathway implicating APOE and LDLR. May stimulate hypothalamic LPL activity (By similarity)

Subcellular location

SecretedCell projection, lamellipodium
Domains and Gene Ontology detail (37)

Domains & features

Fibrinogen C-terminal

Gene Ontology

  • Ccell surface
  • Cearly endosome
  • Cextracellular matrix
  • Cextracellular region
  • Cextracellular space
  • CGolgi apparatus
  • Clamellipodium
  • Fenzyme inhibitor activity
  • Fgrowth factor activity
  • Fheparin binding
  • Fintegrin binding
  • Flipase binding

460 aa · 54 kDa

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Lipid & lipoprotein metabolismUniProt · GOCell migrationGO
View supporting evidence

Lipid & lipoprotein metabolism

  • ·Acts in part as a hepatokine that is involved in regulation of lipid and glucose metabol…
  • ·cholesterol homeostasis
  • ·cholesterol metabolic process
  • ·fatty acid metabolic process

Cell migration

  • ·positive regulation of cell migration

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Approved medicines with mapped indications

1 medicine · 3 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Hypercholesterolemia1 medicine
evinacumab
Hyperlipoproteinemia Type II1 medicine
evinacumab
Broader indication categories (1)
Cardiovascular Diseases1 medicine
evinacumab

Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.

Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

1

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

evinacumab
Narrow target profileApprovedInhibitor

Angiopoietin-related protein 3 inhibitor

Indicated for Hypercholesterolemia, Hyperlipoproteinemia Type II, Cardiovascular Diseases

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene ANGPTL3

Gene-level evidence surfaced through the gene ANGPTL3that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Familial hypercholesterolemia
0.76Well supported

Clinical evidence dominant · Open Targets 0.52

Genetic Diseases, Inborn
0.68Moderately supported

Genetic evidence dominant · Open Targets 0.42

Cardiovascular Diseases
0.68Moderately supported

Clinical evidence dominant · Open Targets 0.45

Homozygous familial hypercholesterolemia
0.67Moderately supported

Clinical evidence dominant · Open Targets 0.48

Genetic developmental and epileptic encephalopathy
0.64Moderately supported

Genetic evidence dominant · Open Targets 0.39

View evidence synthesis (5)
Familial hypercholesterolemiaWell supported
0.76
agreement 0.66–0.86
Clinical55%Genetic28%Animal model15%Literature3%

Open Targets aggregate 0.52 · 4 independent evidence families

Genetic Diseases, InbornModerately supported
0.68
agreement 0.54–0.82
Genetic99%Literature1%

Open Targets aggregate 0.42 · 2 independent evidence families

Cardiovascular DiseasesModerately supported
0.68
agreement 0.57–0.78
Clinical55%Genetic42%Literature3%

Open Targets aggregate 0.45 · 3 independent evidence families

Homozygous familial hypercholesterolemiaModerately supported
0.67
agreement 0.55–0.80
Clinical70%Animal model28%Literature2%

Open Targets aggregate 0.48 · 3 independent evidence families

Genetic developmental and epileptic encephalopathyModerately supported
0.64
agreement 0.52–0.76
Genetic100%

Open Targets aggregate 0.39 · 1 independent evidence family

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Familial hypercholesterolemia0.52
Homozygous familial hypercholesterolemia0.48
Cardiovascular Diseases0.45
Metabolic Diseases0.44
Genetic Diseases, Inborn0.42
Genetic developmental and epileptic encephalopathy0.39
Hyperlipidemias0.34
Disorder of lipid metabolism0.31

Drug development

3 compounds recorded · 1 approved · 1 in clinical development · 1 earlier-stage

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (3)
VUPANORSEN SODIUMUnknown
VUPANORSENPhase 2
EVINACUMABApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Antibodies — Strong

Approved Drug and UniProt loc high conf support this modality.

Protein degraders — Emerging

Feasibility evidence (half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (5)
AB · Approved DrugAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Half-life Data

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

9

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamic Effects of ANGPTL3 Inhibition With Either Small-Interfering RNA Alone or in Combination With an ANGPTL3 Antibody in Participants With Diabetic Kidney DiseasePHASE2

RECRUITING · via evinacumab · NCT07271186

Safety and Effectiveness of Evinacumab for the Treatment of Homozygous Familial Hypercholesterolemia in a Real Life Setting in CanadaPHASE3

COMPLETED · via evinacumab · NCT05611528

A Three-Part, Single-Arm, Open-Label Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Evinacumab in Pediatric Patients With Homozygous Familial HypercholesterolemiaPHASE3

COMPLETED · via evinacumab · NCT04233918

An Open-Label Study to Evaluate the Long-Term Safety and Efficacy of Evinacumab in Patients With Homozygous Familial HypercholesterolemiaPHASE3

COMPLETED · via evinacumab · NCT03409744

View all trials (5)
A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Evinacumab in Patients With Homozygous Familial HypercholesterolemiaPHASE3

COMPLETED · via evinacumab · NCT03399786

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Evinacumab in Patients With Severe Hypertriglyceridemia for the Prevention of Recurrent Acute PancreatitisPHASE2

TERMINATED · via evinacumab · NCT04863014

A Phase 2, Randomized, Placebo-Controlled Study of Safety and Efficacy, Following Repeat-Dose Administration of Evinacumab (Anti-ANGPTL3) in Patients With Severe Hypertriglyceridemia (sHTG) at Risk for Acute PancreatitisPHASE2

COMPLETED · via evinacumab · NCT03452228

A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Varying Doses and Dose Regimens of Evinacumab in Patients With Persistent Hypercholesterolemia Despite Maximally Tolerated Lipid Modifying TherapyPHASE2

COMPLETED · via evinacumab · NCT03175367

A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of Evinacumab in Healthy Japanese and Caucasian SubjectsPHASE1

COMPLETED · via evinacumab · NCT03146416

ClinicalTrials.gov via the drug-target graph.

What's happening now

1

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Regulatory approval2021-06-17

    Approval: Evkeeza (EMA)

    ema · regulatory · ema · via evinacumab

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.