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Protein / target

Apelin receptor

Encoded byAPLNRP35414Homo sapiensSwiss-Prot
Clinical-stage
Therapeutic maturity
1
Clinical candidates
9
Clinical trials
Small-molecule tractable
Druggability
Structure with Ligand

Protein at a glance

Biological role

G protein-coupled peptide receptor

Strongest disease association

Essential Hypertension

Via encoding gene APLNR · Genetic evidence · score 0.28

Therapeutic position

Clinically advancing target

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

G protein-coupled receptor for peptide hormones apelin (APLN) and apelin receptor early endogenous ligand (APELA/ELA), that plays a role in the regulation of normal cardiovascular function and fluid homeostasis.

View complete UniProt function annotation

G protein-coupled receptor for peptide hormones apelin (APLN) and apelin receptor early endogenous ligand (APELA/ELA), that plays a role in the regulation of normal cardiovascular function and fluid homeostasis (PubMed:11090199, PubMed:22810587, PubMed:25639753, PubMed:28137936, PubMed:35817871, PubMed:38428423). When acting as apelin receptor, activates both G(i) protein pathway that inhibits adenylate cyclase activity, and the beta-arrestin pathway that promotes internalization of the receptor (PubMed:11090199, PubMed:25639753, PubMed:28137936, PubMed:35817871, PubMed:38428423). APLNR/APJ also functions as mechanoreceptor that is activated by pathological stimuli in a G protein-independent fashion to induce beta-arrestin signaling, hence eliciting cardiac hypertrophy (PubMed:22810587, PubMed:38428423). However, the presence of apelin ligand blunts cardiac hypertrophic induction from APLNR/APJ on response to pathological stimuli (PubMed:22810587, PubMed:38428423). Plays a key role in early development such as gastrulation, blood vessels formation and heart morphogenesis by acting as a APELA receptor (By similarity). May promote angioblast migration toward the embryonic midline, i.e. the position of the future vessel formation, during vasculogenesis (By similarity). Promotes sinus venosus (SV)-derived endothelial cells migration into the developing heart to promote coronary blood vessel development (By similarity). Also plays a role in various processes in adults such as regulation of blood vessel formation, blood pressure, heart contractility and heart failure (PubMed:25639753, PubMed:28137936)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (34)

Gene Ontology

  • Cplasma membrane
  • Fapelin receptor activity
  • FG protein-coupled peptide receptor activity
  • FG protein-coupled receptor activity
  • Fmechanoreceptor activity
  • Fsignaling receptor activity
  • Padenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
  • Padult heart development
  • Pangiogenesis
  • Paorta development
  • Papelin receptor signaling pathway
  • Patrioventricular valve development

380 aa · 43 kDa

Biological roles

Reactome v97

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

G protein-coupled signallingUniProt · GOTranscriptional regulationGO
View supporting evidence

G protein-coupled signalling

  • ·G protein-coupled receptor for peptide hormones apelin (APLN) and apelin receptor early…
  • ·G protein-coupled peptide receptor activity
  • ·G protein-coupled receptor activity
  • ·adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway

Transcriptional regulation

  • ·negative regulation of gene expression
  • ·regulation of gene expression
View underlying pathways (2)

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

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

APLNAPELAGNB4GNB1GNB3GNB2GNB5GNAQGNA13GNGT1APLNR

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

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.

Apelin
Narrow target profilePhase 2Agonist

Apelin receptor agonist

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 APLNR

Gene-level evidence surfaced through the gene APLNRthat 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.

Pulmonary arterial hypertension
0.30Limited support

Animal model evidence dominant · Open Targets 0.10

Essential Hypertension
0.29Limited support

Genetic evidence dominant · Open Targets 0.17

Hypertension
0.23Preliminary

Genetic evidence dominant · Open Targets 0.12

Neoplasms
0.13Preliminary

Literature evidence dominant · Open Targets 0.11 · no direct causal or clinical evidence

Diabetes Mellitus, Type 2
0.12Preliminary

Clinical evidence dominant · Open Targets 0.09

View evidence synthesis (5)
Pulmonary arterial hypertensionLimited support
0.30
agreement 0.170.42
Animal model65%Literature34%Clinical1%

Open Targets aggregate 0.10 · 3 independent evidence families

Essential HypertensionLimited support
0.29
agreement 0.160.43
Genetic93%Literature7%

Open Targets aggregate 0.17 · 2 independent evidence families

HypertensionPreliminary
0.23
agreement 0.100.37
Genetic65%Literature35%

Open Targets aggregate 0.12 · 2 independent evidence families

NeoplasmsPreliminary
0.13
agreement 0.000.41
Literature100%

Open Targets aggregate 0.11 · 1 independent evidence family · no direct causal or clinical evidence

Diabetes Mellitus, Type 2Preliminary
0.12
agreement 0.000.28
Clinical82%Literature18%

Open Targets aggregate 0.09 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. 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
Essential Hypertension0.17
Hypertension0.12
Neoplasms0.11
Pulmonary arterial hypertension0.10
Diabetes Mellitus, Type 20.09
Glioblastoma0.08
Non-alcoholic Fatty Liver Disease0.08
Coronary Artery Disease0.07
Carcinoma, Hepatocellular0.07

Drug development

1 compounds recorded · 1 in clinical development

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: these count different sets and are not a subset relation.

View all recorded compounds (1)
APELINPhase 2

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

Small moleculesEmerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (small molecule binder) — no clinical-stage drug of this modality recorded.

Other modalitiesStrong

Advanced Clinical support this modality.

View underlying tractability evidence (8)
SM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Small Molecule BinderOC · Advanced Clinical

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.

ClinicalTrials.gov via the drug-target graph.

What's happening now

3

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. New publication2024-08-09
    Impact of Smoking and Obesity on the Selected Peptide Hormones and Metabolic Parameters in the Blood of Women with Polycystic Ovary Syndrome-Preliminary Study.

    International journal of molecular sciences · 2024 · 5 citations · Europe PMC · via Apelin

  2. New publication2023-12-01
    Targeting the apelin system for the treatment of cardiovascular diseases.

    Cardiovascular research · 2023 · 59 citations · Europe PMC · via Apelin

  3. New publication2023-11-28
    Beneficial effects of Apelin-13 on metabolic diseases and exercise.

    Frontiers in endocrinology · 2023 · 12 citations · Europe PMC · via Apelin

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.