LIFR
LIFR (Leukaemia inhibitory factor receptor) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Melanoma and Small-cell lung cancer.
Overview
Functions as a membrane-bound signal-transducing subunit either in complex with IL6ST/gp130 or as part of the ciliary neurotrophic factor receptor (CNTFR) complex composed by CNTFR, IL6ST/gp130 and LIFR. Signal transmission is initiated either by binding directly to cytokines, such as OSM or LIF or CTF1, or through the binding of other cytokines, like CNTF, CLCF1 or the heterodimeric complex CRLF1-CLCF1 to the non-signalling receptor CNTFR; ligand binding induces heterodimerisation of IL6ST/gp130 and LIFR which activates JAK tyrosine kinases bound to their intracellular domains. These kinases subsequently phosphorylate the homodimer or heterodimer form of IL6ST/gp130.
Open Targets scores its association with cancer at 0.58 (direct and indirect evidence; datatypes literature 0.98, animal model 0.57, genetic association 0.17, somatic mutation 0.73). IntOGen calls it a driver in 2 cohorts (1 activating, 0 loss-of-function), covering Melanoma, Small Cell Lung Cancer.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · LIFR (Leukaemia inhibitory factor receptor) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Melanoma and Small-cell lung cancer.
- 1 · What it is
LIFR (Leukaemia inhibitory factor receptor) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Melanoma and Small-cell lung cancer.
- 2 · What goes wrong in cancer
Functions as a membrane-bound signal-transducing subunit either in complex with IL6ST/gp130 or as part of the ciliary neurotrophic factor receptor (CNTFR) complex composed by CNTFR, IL6ST/gp130 and LIFR.
- 3 · How drugs use it
No product in this corpus aims at LIFR yet. Drugs fit a pocket that exists only in one shape of the mutant protein and hold it there, off.
External identifiers
Sources: HGNC HGNC:6597 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P42702 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000113594 (association with cancer (MONDO_0004992) 0.58; (GraphQL API, CC0)); IntOGen LIFR (driver in 2 cohorts (Act 1, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Functions as a membrane-bound signal-transducing subunit either in complex with IL6ST/gp130 or as part of the ciliary neurotrophic factor receptor (CNTFR) complex composed by CNTFR, IL6ST/gp130 and LIFR. Signal transmission is initiated either by binding directly to cytokines, such as OSM or LIF or CTF1, or through the binding of other cytokines, like CNTF, CLCF1 or the heterodimeric complex CRLF1-CLCF1 to the non-signalling receptor CNTFR; ligand binding induces heterodimerisation of IL6ST/gp130 and LIFR which activates JAK tyrosine kinases bound to their intracellular domains. These kinases subsequently phosphorylate the homodimer or heterodimer form of IL6ST/gp130. The tyrosine phosphorylated signalling receptors serve in turn as docking sites for recruitment and activation of signal transducer and activators of transcription (STATs). Engages sites 3 of ligands cytokines. Could inhibit the biological activity of LIF by blocking its binding to receptors on target cells. Location: Cell membrane; Secreted (UniProt). Locus 5p13.1 (HGNC).
- Melanoma: IntOGen driver in 1 cohort (MEL)
- Small-cell lung cancer: IntOGen driver in 1 cohort (SCLC)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it an activating (Act) driver in 1 cohort; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"LIFR" OR ABSTRACT:"LIFR" OR TITLE:"LIF receptor subunit alpha" OR ABSTRACT:"LIF receptor subunit alpha" OR TITLE:"Leukemia inhibitory factor receptor" OR ABSTRACT:"Leukemia inhibitory factor receptor" OR TITLE:"CD118" OR ABSTRACT:"CD118") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about LIFR, not a curated reading list.