IL6ST

Chr 5ADAR

interleukin 6 cytokine family signal transducer

Also known as: CD130, CDW130, GP130, HIES4, HIES4A, HIES4B, IL-6RB, IMD94

NCBI Gene: 3572 ENSG00000134352 UniProt: P40189 OMIM: 600694

The protein functions as a shared signal transducer for multiple cytokines including interleukin-6, forming receptor complexes that activate JAK-STAT3 signaling pathways critical for immune response, hematopoiesis, and neuronal survival. Mutations cause hyper-IgE syndromes with recurrent infections (both autosomal dominant and recessive forms), Stüve-Wiedemann syndrome 2, and immunodeficiency with autoinflammation and dysmorphic features. This gene is highly constrained against loss-of-function variants, reflecting its essential role in cytokine signaling and development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a signal transducer shared by many cytokines, including interleukin 6 (IL6), ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), and oncostatin M (OSM). This protein functions as a part of the cytokine receptor complex. The activation of this protein is dependent upon the binding of cytokines to their receptors. vIL6, a protein related to IL6 and encoded by the Kaposi sarcoma-associated herpesvirus, can bypass the interleukin 6 receptor (IL6R) and directly activate this protein. Knockout studies in mice suggest that this gene plays a critical role in regulating myocyte apoptosis. Alternatively spliced transcript variants have been described. A related pseudogene has been identified on chromosome 17. [provided by RefSeq, May 2014]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Immunodeficiency 94 with autoinflammation and dysmorphic faciesMIM #619750

Hyper-IgE syndrome 4A, autosomal dominant, with recurrent infectionsMIM #619752

Hyper-IgE syndrome 4B, autosomal recessive, with recurrent infectionsMIM #618523

Stuve-Wiedemann syndrome 2MIM #619751

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.23

LOEUF· LoF intol.

Multiple*

Mechanism· predicted