IL6R

Chr 1AR

interleukin 6 receptor

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

NCBI Gene: 3570 ENSG00000160712 UniProt: P08887 OMIM: 147880

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 0.813 OMIM phenotypes

Clinical Summary— IL6R

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Gene-Disease Validity (ClinGen)

hyper-IgE recurrent infection syndrome 5, autosomal recessive · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 143 VUS of 342 total submissions

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Clinical Trials

12 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.81LOEUF

pLI 0.000

Z-score 2.23

OE 0.49 (0.31–0.81)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.69Z-score

OE missense 0.89 (0.80–0.98)

254 obs / 286.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.31–0.81)

0≤0.351.4

Missense OE?0.89 (0.80–0.98)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 11 / 22.4Missense obs/exp: 254 / 286.8Syn Z: -0.20

This gene — mechanism propensity

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

342 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS143

Likely Benign162

Benign22

Conflicting1

Pathogenic

143

VUS

162

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	0	0	0	0	0
VUS	7	124	9	3	143
Likely Benign	0	9	60	93	162
Benign	0	0	15	7	22
Conflicting	—				1
Total	7	134	84	103	329

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap IL6R — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →