IL6ST

Chr 5q11.2

interleukin 6 cytokine family signal transducer

Aliases:: GP130, CD130, sGP130, IL-6RB
MANE:: ENST00000381298.7

OMIM: 600694 ↗NCBI: 3572 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

IL6ST · P40189

v62025-08-01

Predicted Aligned Error matrix for IL6ST — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

74.6/ 100

Confident

918 residues

Confidence breakdown

Very high(≥ 90)49%
Confident(70–90)18%
Low(50–70)4%
Very low(< 50)28%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

COVID-19 research
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rare syndromic craniosynostosis or isolated multisuture synostosis
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

Autosomal recessive hyper-IgE syndrome
0.70
Stuve-Wiedemann syndrome 2
0.67
hyper-IgE recurrent infection syndrome 4A, autosomal dominant
0.66
neuromyelitis optica
0.57
immunodeficiency 94 with autoinflammation and dysmorphic facies
0.42
immune system disorder
0.38
hepatocellular adenoma
0.37
Eczematoid dermatitis
0.37
Increased total eosinophil count
0.37
colon adenocarcinoma
0.37

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Interleukin-6 receptor subunit beta

Functions as a shared signal-transducing subunit not only for IL6 but also for other cytokine receptor complexes, including IL6, LIF, OSM, CNTF, IL11, CTF1, BSF3, MT-RNR2/humanin, CLCF1 and the heterodimeric complex CRLF1-CLCF1 (PubMed:11285233, PubMed:11294841, PubMed:1542794, PubMed:19386761, PubMed:2261637, PubMed:27384491, PubMed:36930708, PubMed:39532904, PubMed:8272873, PubMed:8999038, PubMed:9030543, PubMed:9188471). Engages site 2 of CNTF, CLCF1, LIF, and IL-6, and site 3 of IL27 and IL6 (PubMed:36930708). Initiates signal transmission through three mechanisms (PubMed:11285233, PubMed:11294841, PubMed:1542794, PubMed:19386761, PubMed:19915009, PubMed:2261637, PubMed:23294003). Binding of cytokines, such as IL6 or IL11 to the alpha-chains of their specific cell surface receptor triggers homodimerization of IL6ST/gp130 (PubMed:19915009, PubMed:2261637, PubMed:23294003, PubMed:8637716). In contrast, binding of other IL-6 family cytokines can result in the formation of a IL6ST/gp130 heterodimer with another signal-transducing receptor, such as LIFR or OSMR (PubMed:1542794, PubMed:39532904, PubMed:8999038, PubMed:9030543, PubMed:9188471). Moreover, binding of CNTF or CLCF1 or the heterodimeric complex CRLF1-CLCF1 or MT-RNR2/humanin to the non-signaling receptor CNTFR induces heterodimerization of the IL6ST/gp130 with LIFR or IL27RA/WSX1 (in the case of MT-RNR2/humanin) (PubMed:11285233, PubMed:11294841, PubMed:19386761). Mechanistically, homodimerization or heterodimerization of IL6ST/gp130 activate JAK tyrosine kinases bound to their intracellular domains (PubMed:11294841, PubMed:19915009, PubMed:2261637, PubMed:23294003, PubMed:27384491, PubMed:8272873, PubMed:9030543, PubMed:9188471). These kinases subsequently phosphorylate the homodimer or heterodimer form of IL6ST/gp130 (PubMed:11285233, PubMed:11294841, PubMed:19915009, PubMed:23294003, PubMed:25731159, PubMed:9030543). The tyrosine phosphorylated signaling receptors serve in turn as docking sites for recruitment and activation of signal transducer and activators of transcription (STATs) (PubMed:11285233, PubMed:11294841, PubMed:19386761, PubMed:19915009, PubMed:23294003, PubMed:25731159, PubMed:27384491, PubMed:9030543, PubMed:9188471). The IL6 signaling pathway induces, in parallel, the expression of two cytokine receptor signaling inhibitors, SOCS1 and SOCS3, which inhibit JAK and terminate the activity of the IL6 signaling pathway as a negative feedback loop (By similarity). Also activates the yes-associated protein 1 (YAP) and NOTCH pathways to control inflammation-induced epithelial regeneration, independently of STAT3 (By similarity). Mediates signals which regulate immune response, hematopoiesis, pain control and bone metabolism (By similarity). Has a role in embryonic development (By similarity). Essential for survival of motor and sensory neurons and for differentiation of astrocytes (By similarity). Required for expression of TRPA1 in nociceptive neurons (By similarity). Required for the maintenance of PTH1R expression in the osteoblast lineage and for the stimulation of PTH-induced osteoblast differentiation (By similarity). Required for normal trabecular bone mass and cortical bone composition (By similarity)