IL6R

Chr 1AR

interleukin 6 receptor

Also known as: CD126, HIES5, IL-1Ra, IL-6R, IL-6R-1, IL-6RA, IL6Q, IL6QTL

NCBI Gene: 3570ENSG00000160712UniProt: P08887

This gene encodes a subunit of the interleukin 6 (IL6) receptor complex. Interleukin 6 is a potent pleiotropic cytokine that regulates cell growth and differentiation and plays an important role in the immune response. The IL6 receptor is a protein complex consisting of this protein and interleukin 6 signal transducer (IL6ST/GP130/IL6-beta), a receptor subunit also shared by many other cytokines. Dysregulated production of IL6 and this receptor are implicated in the pathogenesis of many diseases, such as multiple myeloma, autoimmune diseases and prostate cancer. Alternatively spliced transcript variants encoding distinct isoforms have been identified in this gene. A pseudogene of this gene is found on chromosome 9. [provided by RefSeq, Aug 2020]

Primary Disease Associations & Inheritance

[Interleukin 6, serum level of, QTL]MIM #614752
[Interleukin-6 receptor, soluble, serum level of, QTL]MIM #614689
Hyper-IgE syndrome 5, autosomal recessive, with recurrent infectionsMIM #618944
AR
12
Active trials
15
Pathogenic / LP
348
ClinVar variants
6
Pubs (1 yr)
0.7
Missense Z
0.81
LOEUF
Clinical Summary— IL6R
🧬
Gene-Disease Validity (ClinGen)
hyper-IgE recurrent infection syndrome 5, autosomal recessive · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 148 VUS of 348 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.81LOEUF
pLI 0.000
Z-score 2.23
OE 0.49 (0.31–0.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.69Z-score
OE missense 0.89 (0.80–0.98)
254 obs / 286.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.49 (0.31–0.81)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.80–0.98)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 11 / 22.4Missense obs/exp: 254 / 286.8Syn Z: -0.20
DN
0.74top 25%
GOF
0.73top 25%
LOF
0.2871th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

348 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic2
VUS148
Likely Benign162
Benign22
Conflicting1
13
Pathogenic
2
Likely Pathogenic
148
VUS
162
Likely Benign
22
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
12
0
13
Likely Pathogenic
0
0
2
0
2
VUS
6
123
16
3
148
Likely Benign
0
9
61
92
162
Benign
0
0
15
7
22
Conflicting
—1
Total6133106102348

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

IL6R · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Anterior Cruciate Ligament Injuries

Biologic Therapy to Prevent Osteoarthritis After ACL Injury

RECRUITING
NCT03968913Phase EARLY_PHASE1University of California, Los AngelesStarted 2021-09-15
Anakinra injectionsterile saline injection
Multiple SclerosisSpasticity

miR-142-3p as Potential Biomarker of Synaptopathy in MS

RECRUITING
NCT03999788Phase NANeuromed IRCCSStarted 2019-12-10
lumbar puncture and blood withdrawalIntermittent theta burst stimulation (iTBS) therapeutic protocol for spasticity
Osteoarthritis, Knee

Study to Evaluate the Safety and Tolerability of FX201 in Patients with Osteoarthritis of the Knee

ACTIVE NOT RECRUITING
NCT04119687Phase PHASE1Pacira Pharmaceuticals, IncStarted 2020-03-02
FX201
Facioscapulohumeral Muscular Dystrophy 1

Study to Evaluate the Efficacy and Safety of Satralizumab in FSHD1

ACTIVE NOT RECRUITING
NCT06222827Phase PHASE2Centre Hospitalier Universitaire de NiceStarted 2024-01-24
Satralizumab Prefilled SyringePlacebo Comparator
Congenital Adrenal Hyperplasia (CAH)

Fertility And Sexual Function In CAH: CALLIOPE

RECRUITING
NCT07099456University of Roma La SapienzaStarted 2024-11-01
Endometriosis

Developing a Complex ex Vivo Endometrial Tissue Model to Improve Endometriosis Care

RECRUITING
NCT06331676Phase NAHospices Civils de LyonStarted 2024-06-21
Tissue collectionData collection
Healthy

Pulmonary Immune Cell-microbiome Interactions in the Healthy Lung

RECRUITING
NCT05846620Hvidovre University HospitalStarted 2023-04-17
Bronchoalveolar lavage
Type 2 DiabetesInflammationInsulin Sensitivity/Resistance

Targeting Risk Factors for Diabetes in Subjects With Normal Blood Cholesterol Using Omega-3 Fatty Acids

RECRUITING
NCT04485871Phase NAInstitut de Recherches Cliniques de MontrealStarted 2019-12-19
Omega-3 fatty acids
Hand OsteoarthritisErosive Osteoarthritis

Methotrexate in Erosive Inflammatory Hand Osteoarthritis

ACTIVE NOT RECRUITING
NCT04579848Phase PHASE4Diakonhjemmet HospitalStarted 2021-08-12
Methotrexate TabletsPlaceboFolic Acid 1 MG
Systemic Histiocytosis (Disorder)

Biomarkers in Systemic Histiocytosis

NOT YET RECRUITING
NCT07157683Assistance Publique - Hôpitaux de ParisStarted 2025-10-01
Biospecimen collection
Chronic Post Operative Pain

Cytokine Alterations and Chronic Post-Surgical Pain

NOT YET RECRUITING
NCT06418295London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sStarted 2026-01-01
Unilateral thoracotomy
Healthy AdultsHigh AltitudeIsolation, Social

Human Milk Oligosaccharides (HMOs) and Gut Microbiota, Immune System in Antarctica

ENROLLING BY INVITATION
NCT06133530Phase NAIU University of Applied SciencesStarted 2023-09-24
Human milk oligosaccharidesMaltose
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Place of anti-IL6R in the therapeutic strategy in NMOSD-AQP4+, MOGAD, and NMOSD double-seronegative patients.
Comet C et al.·Mult Scler
2026Cohort
A multi-omics approach uncovers causality of IL6R on endotypes of subclinical carotid atherosclerosis and the possible role of the IL6R/OSMR pathway.
Chen QS et al.·Cardiovasc Res
2025Open Access
DNA methylation of the IL6R gene moderates the association between biopsychosocial factors and depression.
Kusuma RM et al.·Transl Psychiatry
2025Open Access
BCL6, DUSP3, and IL6R Are Identified as Shared Druggable Immune-Regulatory Axis in Atrial Fibrillation and Atherosclerosis Through Integrative In Silico and In Vitro Analysis.
Zheng H et al.·Hum Mutat
2025Open Access
Molecular characterization and functional prioritization of CD46, IL6R, KLRC1, LEAP2 and SMOX as candidate targets in acute kidney injury.
Liu J et al.·Int J Biol Macromol
2025Functional
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients