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…

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

Clinical highlights

Gene–disease validity (ClinGen)

Limited · hyper-IgE recurrent infection syndrome 5, autosomal recessive · AR · ClinGen 2023

not for standalone diagnostic reporting

Active trials

154

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.81

LOEUF

Multiple*

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in IL6R?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 75

641 rare PASS variants

Rare truncating (LoF)

1 in 1,700

106 rare PASS variants

Rare synonymous (reference)

1 in 160

279 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IL6R. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 1,800
South Asian	~43k	1 in 80	1 in 2,700
Remaining (unassigned)	~30k	1 in 70	1 in 1,500
European (Finnish)	~27k	1 in 590	1 in 3,300
Admixed American	~22k	1 in 62	1 in 840
African / African American	~21k	1 in 55	1 in 1,900
East Asian	~20k	1 in 75	1 in 720
Ashkenazi Jewish	~13k	1 in 220	1 in 1,400
Middle Eastern	~2,884	1 in 96	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 10 coding exons well covered in gnomAD exomes; exon 8 marginal. Genomes: all 10.? see exons ↓