Protein / target

Interleukin-31 receptor subunit alpha

IL31RAQ8NI17Homo sapiensSwiss-Prot

UniProt: Q8NI17 Ensembl: ENSG00000164509 HGNC: HGNC:18969 NCBI Gene: 133396

Clinically validated

Therapeutic maturity

Approved medicines

Clinical trials

Antibody-tractable

Druggability

Advanced Clinical

Protein at a glance

Biological role

Transcription coactivator activity

Primary system

Immune system

Strongest disease association

familial primary localized cutaneous amyloidosis

Genetic evidence · score 0.62

Therapeutic maturity

Clinically validated target

1 approved medicine against this target

Druggability

Antibody

Open Targets tractability · Advanced Clinical

Clinical development

1 approved

22 linked trials

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

Functions as a membrane-bound signal-transducing subunit of the IL31 receptor complex (heterodimer composed of OSMR and IL31RA) which binds IL31 (PubMed:15184896, PubMed:15194700, PubMed:15627637). Functionally, IL31 signaling via OSMR/IL31RA is particularly important in skin immunity (PubMed:15184896). Mechanistically, ligand binding induces heterodimerization with OSMR, activating JAK1 and JAK2 (and to a lesser extent TYK2) associated with the intracellular domains of IL31RA and OSMR (PubMed:15194700, PubMed:15627637). These kinases phosphorylate tyrosine residues on IL31RA and OSMR, creating docking sites for STAT1, STAT3, and STAT5B, which are then phosphorylated and activated (Probable) (PubMed:11877449, PubMed:15194700, PubMed:15627637). In addition, the IL31 receptor complex activates the MAPK pathway (MAPK3/ERK1-MAPK1/ERK2) via recruitment of the adapter protein SHC1 (PubMed:15194700, PubMed:15627637). Mediates IL31-induced itch, probably in a manner dependent on cation channels TRPA1 and TRPV1 (By similarity). Positively regulates numbers and cycling status of immature subsets of myeloid progenitor cells in bone marrow in vivo and enhances myeloid progenitor cell survival in vitro (By similarity)

Subcellular location

Cell membranePresynaptic cell membraneCell projection, axon

Domains and Gene Ontology detail (29)

Domains & features

Fibronectin type-III 1Fibronectin type-III 2Fibronectin type-III 3Fibronectin type-III 4Fibronectin type-III 5

Gene Ontology

Caxon
Cexternal side of plasma membrane
Cmembrane
Cplasma membrane
Cpresynaptic membrane
Creceptor complex
Fcytokine binding
Fcytokine receptor activity
Fprotein kinase binding
Ftranscription coactivator activity
Pcell surface receptor protein tyrosine kinase signaling pathway
Pcell surface receptor signaling pathway via JAK-STAT

732 aa · 83 kDa · 12 isoforms

Biological roles

Reactome v97

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

Immune signallingGO · ReactomeSynaptic signallingUniProt · GOKinase signallingGOTranscriptional regulationGOApoptosis & cell deathGO

View supporting evidence

Immune signalling

·cytokine binding
·cytokine receptor activity
·cytokine-mediated signaling pathway
·IL-6-type cytokine receptor ligand interactions

Synaptic signalling

·Presynaptic cell membrane
·presynaptic membrane

Kinase signalling

·protein kinase binding
·positive regulation of tyrosine phosphorylation of STAT protein

Transcriptional regulation

·transcription coactivator activity
·positive regulation of DNA-templated transcription

Apoptosis & cell death

·negative regulation of apoptotic process

View underlying pathways (1)

IL-6-type cytokine receptor ligand interactions

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.

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

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

nemolizumab

Narrow target profileApprovedInhibitor

Interleukin-31 receptor subunit alpha inhibitor

Appears in clinical studies involving atopic eczema, Pruritus, prurigo nodularis, Eczematoid dermatitis

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

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

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

familial primary localized cutaneous amyloidosis0.62

Genetic · overall 0.54

placental retention0.46

Genetic · overall 0.28

rheumatic disorder0.26

Genetic · overall 0.16

palindromic rheumatism0.26

Genetic · overall 0.16

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

atopic eczema0.88

Clinical · overall 0.54

prurigo nodularis0.81

Clinical · overall 0.49

prurigo0.76

Clinical · overall 0.46

Pruritus0.71

Clinical · overall 0.43

Eczematoid dermatitis0.61

Clinical · overall 0.37

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

systemic sclerosis0.11

Literature

Show all associations

familial primary localized cutaneous amyloidosis0.54

atopic eczema0.54

prurigo nodularis0.49

prurigo0.46

Pruritus0.43

Eczematoid dermatitis0.37

placental retention0.28

rheumatic disorder0.16

palindromic rheumatism0.16

systemic sclerosis0.11

Open Targets ranks 308 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 1 total

NEMOLIZUMABApproval

atopic eczema · Pruritus · prurigo nodularis

Tractability

AB · Advanced ClinicalAB · UniProt loc high confAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMAB · Human Protein Atlas loc

Clinical trials

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

A Randomized, Single-Dose, Open-Label, Parallel-Group Study in Healthy Volunteers to Assess the Relative Bioavailability of a Subcutaneous Dose of Nemolizumab When Administered With Auto-Injector Compared to Dual-Chamber SyringePHASE1

COMPLETED · via nemolizumab · NCT05405985

A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Nemolizumab in Subjects With Moderate-to-Severe Atopic Dermatitis With Inadequate Response to or for Whom Cyclosporine A is Not Medically AdvisablePHASE3

WITHDRAWN · via nemolizumab · NCT05056779

A Multicenter, Open-Label, Single-Group Clinical Trial to Assess the Pharmacokinetics and Safety of Nemolizumab (CD14152) in Adolescent Subjects (12-17 Years) With Moderate-to-Severe Atopic DermatitisPHASE2

COMPLETED · via nemolizumab · NCT03921411

A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Nemolizumab (CD14152) in Subjects With Prurigo NodularisPHASE3

COMPLETED · via nemolizumab · NCT04501666

Randomized, Double-blind, Multi-center, Parallel-group, Placebo-controlled Dose-ranging Study to Assess the Efficacy and Safety of Nemolizumab in Moderate-to-severe Atopic Dermatitis Subjects With Severe Pruritus Receiving Topical Corticosteroids (TCS)PHASE2

COMPLETED · via nemolizumab · NCT03100344

A Prospective, Multicenter, Long-Term Study to Assess the Safety and Efficacy of Nemolizumab (CD14152) in Subjects With Prurigo NodularisPHASE3

ACTIVE_NOT_RECRUITING · via nemolizumab · NCT04204616

Show remaining trials (16)

A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Nemolizumab (CD14152) in Subjects With Prurigo NodularisPHASE3

COMPLETED · via nemolizumab · NCT04501679

A 52-week, Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study of Nemolizumab in Adult Patients With Systemic SclerosisPHASE2

RECRUITING · via nemolizumab · NCT07047690

A Double-Blind, Placebo-Controlled, Randomized Study to Assess the Durability of Effect and Safety of Nemolizumab for 24 Weeks in Subjects With Prurigo NodularisPHASE3

COMPLETED · via nemolizumab · NCT05052983

A Randomized, Double-Blind, Placebo-Controlled Study to Assess Immunization Responses in Adult and Adolescent Subjects With Moderate-to-Severe Atopic Dermatitis Treated With NemolizumabPHASE2

COMPLETED · via nemolizumab · NCT04365387

An Open-label, Phase 2 Study to Assess the Efficacy and Safety of Nemolizumab in Subjects With Systemic SclerosisPHASE2

COMPLETED · via nemolizumab · NCT05214794

A PHASE II, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTIPLE-DOSE STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND EFFICACY OF CIM331 IN ATOPIC DERMATITIS PATIENTS WHO ARE INADEQUATELY CONTROLLED BY OR INTOLERANT TO TOPICAL THERAPYPHASE2

COMPLETED · via nemolizumab · NCT01986933

A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Nemolizumab in Subjects With Moderate-to-Severe Atopic DermatitisPHASE3

COMPLETED · via nemolizumab · NCT03989349

Nemolizumab to Treat Lichen Planopilaris, a Noncontrolled, Prospective, Pilot Study.PHASE4

RECRUITING · via nemolizumab · NCT07396168

A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy and Safety of Nemolizumab in Subjects With Chronic Kidney Disease With Associated Moderate to Severe PruritusPHASE2/PHASE3

COMPLETED · via nemolizumab · NCT05075408

A Prospective, Multicenter, Long-Term Study to Assess the Safety and Efficacy of Nemolizumab (CD14152) in Subjects With Moderate-to-Severe Atopic DermatitisPHASE3

ACTIVE_NOT_RECRUITING · via nemolizumab · NCT03989206

An Exploratory Proof of Concept Study to Assess the Pharmacokinetics/Pharmacodynamics (PK/PD) of Nemolizumab in Adult Participants With Chronic Pruritus of Unknown Origin (CPUO)PHASE2

RECRUITING · via nemolizumab · NCT07074977

A Multicenter, Open-Label, Single-Group Clinical Study to Assess the Pharmacokinetics, Safety and Efficacy of Nemolizumab in Pediatric Subjects (Aged 6 to 23 Months) With Moderate-to-Severe Atopic Dermatitis Not Adequately Controlled With Topical TherapyPHASE2

NOT_YET_RECRUITING · via nemolizumab · NCT07660835

Utilization of a Cutaneous Therapy In Situ MicrodevicePHASE4

NOT_YET_RECRUITING · via nemolizumab · NCT07352566

A Multicenter, Open-Label, Single-Group Clinical Trial to Assess the Pharmacokinetics, Safety and Efficacy of Nemolizumab (CD14152) in Pediatric Subjects (Aged 2 to 11 Years) With Moderate-to-Severe Atopic DermatitisPHASE2

COMPLETED · via nemolizumab · NCT04921345

An Open-label Drug-Drug Interaction Study to Assess the Effects of Nemolizumab on Cytochrome P450 Substrates in Subjects With Moderate-to-Severe Atopic DermatitisPHASE2

COMPLETED · via nemolizumab · NCT04562116

A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Nemolizumab in Subjects With Moderate-to-Severe Atopic DermatitisPHASE3

COMPLETED · via nemolizumab · NCT03985943

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

atopic eczemaModerately supported

0.66

agreement 0.51–0.82

Clinical98%Literature2%

Open Targets aggregate 0.54 · 2 independent evidence families

familial primary localized cutaneous amyloidosisModerately supported

0.63

agreement 0.49–0.77

Genetic100%Literature0%Genetic literaturedup

Open Targets aggregate 0.54 · 2 independent evidence families · 1 not counted as duplicate

prurigo nodularisModerately supported

0.61

agreement 0.46–0.77

Clinical98%Literature2%

Open Targets aggregate 0.49 · 2 independent evidence families

prurigoModerately supported

0.57

agreement 0.41–0.73

Clinical100%

Open Targets aggregate 0.46 · 1 independent evidence family

PruritusModerately supported

0.54

agreement 0.38–0.69

Clinical98%Literature2%

Open Targets aggregate 0.43 · 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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.

Regulatory approval2025-02-12
Approval: Nemluvio (EMA)
ema · regulatory · ema · via nemolizumab
New publication2023-10-01
Phase 3 Trial of Nemolizumab in Patients with Prurigo Nodularis.
The New England journal of medicine · 2023 · 111 citations · Europe PMC · via nemolizumab
New publication2017-03-01
Anti-Interleukin-31 Receptor A Antibody for Atopic Dermatitis.
The New England journal of medicine · 2017 · 375 citations · Europe PMC · via nemolizumab

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.