IL23R

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0009897 external side of plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: IL23R is a type I transmembrane receptor localized at the cell surface of immune cells. The extracellular domain faces outward and has been structurally resolved by X-ray crystallography and cryo-EM (PMID:29287995). IBA annotation based on phylogenetic inference from related cytokine receptors is consistent with experimental evidence. Reason: IL23R is experimentally confirmed at the cell surface (PMID:12023369). Its extracellular Ig-like and FNIII domains face the external side of the plasma membrane to engage IL-23. The IBA annotation is appropriate and consistent with direct evidence. Supporting Evidence: PMID:12023369 Anti-IL-12Rbeta1 and anti-IL-23R Abs block IL-23 responses of an NK cell line and Ba/F3 cells expressing the two receptor chains. PMID:29287995 IL-23R bound to IL-23 exclusively via its N-terminal immunoglobulin domain.
GO:0019221 cytokine-mediated signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: IL23R is a core component of the IL-23 cytokine signaling pathway. Upon IL-23 binding, it signals through JAK2/TYK2-STAT3 (PMID:12023369). This IBA is well-supported phylogenetically across the type I cytokine receptor family. Reason: This is a correct and appropriately general annotation. IL23R directly participates in IL-23-mediated cytokine signaling, its core function. The more specific term GO:0038155 (interleukin-23-mediated signaling pathway) is also annotated separately with IDA evidence. Supporting Evidence: PMID:12023369 IL-23 activates the same Jak-stat signaling molecules as IL-12: Jak2, Tyk2, and stat1, -3, -4, and -5, but stat4 activation is substantially weaker and different DNA-binding stat complexes form in response to IL-23 compared with IL-12.
GO:0008284 positive regulation of cell population proliferation	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: IL-23 signaling through IL23R promotes proliferation of memory T cells and other immune cell populations (PMID:11114383, PMID:12023369). The IBA annotation is phylogenetically inferred from related cytokine receptors that promote cell proliferation. Reason: While IL-23 signaling does promote proliferation of T cells and NK-like T cells, this is a downstream consequence of cytokine receptor signaling rather than a core molecular function of IL23R itself. The term is accurate but represents a broad biological outcome rather than the receptor's primary role. Supporting Evidence: PMID:11114383 IL-23 induces strong proliferation of mouse memory (CD4(+)CD45Rb(low)) T cells, a unique activity of IL-23 as IL-12 has no effect on this cell population.
GO:0019955 cytokine binding	IBA GO_REF:0000033	ACCEPT	Summary: IL23R binds IL-23 via its N-terminal Ig-like domain. Crystal structures confirm direct binding of IL23R to the p19 subunit of IL-23 (PMID:29287995). The IBA at the level of cytokine binding is correct but more specific terms exist. Reason: IL23R does bind IL-23, a cytokine. While more specific terms (GO:0042019 interleukin-23 binding, GO:0042020 interleukin-23 receptor activity) are also annotated, this broader IBA annotation captures the general cytokine-binding function appropriately at the family level. Supporting Evidence: PMID:12023369 Human IL-23, but not IL-12, exhibits detectable affinity for human IL-23R. PMID:29287995 IL-23R bound to IL-23 exclusively via its N-terminal immunoglobulin domain.
GO:0004925 prolactin receptor activity	IBA GO_REF:0000033	REMOVE	Summary: This annotation infers prolactin receptor activity for IL23R based on phylogenetic relationship to the prolactin receptor (PRLR). While IL23R and PRLR are both type I cytokine receptors, IL23R does not bind prolactin and has no demonstrated prolactin receptor activity. Reason: Retain removal of this ligand-specific assignment: IL23R has a structurally established IL-23p19 recognition mechanism (PMID:29287995), whereas the GOA source PTN000547909 is grounded in PRLR/prolactin evidence. The existing OpenScientist report supports that functional mismatch, but its k-mer similarity and absence-of-annotations arguments are not decisive evidence of loss. PMID:12023369 compares IL-23 with IL-12, not prolactin; it must not be described as a negative prolactin-binding assay. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE WRONG ORTHOLOG OR PARALOG Sources checked: PANTHER:PTN000547909 · PANTHER prolactin-receptor source node SUPPORTS SOURCE BUT NOT TARGET GOA traces the GO:0004925 IBA to a PRLR/prolactin-receptor source node; that source supports prolactin receptor activity, but the ligand-specific activity should not transfer to IL23R. UniProtKB:P16471 · human PRLR SUPPORTS SOURCE BUT NOT TARGET PRLR is a true prolactin receptor, whereas IL23R binds IL-23 p19 and functions in the IL-23 receptor complex. Supporting Evidence: PMID:12023369 Human IL-23, but not IL-12, exhibits detectable affinity for human IL-23R. file:human/IL23R/IL23R-hypotheses/function-hypothesis-go-0004925/openscientist.md The GO:0004925 annotation should be removed as an erroneous phylogenetic propagation.
GO:0005143 interleukin-12 receptor binding	IBA GO_REF:0000033	ACCEPT	Summary: IL23R contributes to IL-12 receptor binding in the sense that IL-23 shares the p40 subunit with IL-12 and IL23R pairs with IL12RB1 (the shared IL-12 receptor chain). The IBA annotation with contributes_to qualifier reflects that IL23R is part of a complex that engages IL-12-family cytokine receptor components. Reason: GO:0005143 means binding to an interleukin-12 receptor. The direct IPI row cites partner P42701/IL12RB1, which also pairs with IL23R in the IL-23 receptor complex (PMID:12023369). This is receptor-subunit association, not IL-12 cytokine binding. The IBA correctly lists the target itself among descendant experimental sources; that is experimental grounding, not circularity. Supporting Evidence: PMID:12023369 IL-23R pairs with IL-12Rbeta1
GO:0042019 interleukin-23 binding	IBA GO_REF:0000033	ACCEPT	Summary: IL23R contributes to IL-23 binding as part of the IL23R:IL12RB1 heterodimer. IL23R binds IL-23 p19 directly, while IL12RB1 engages p40 (PMID:29287995). The contributes_to qualifier reflects that full IL-23 binding requires both receptor chains. Reason: The IBA annotation with contributes_to is correct. IL23R directly binds the p19 subunit of IL-23, but the full high-affinity binding of IL-23 requires both IL23R and IL12RB1. This is confirmed by structural studies. Supporting Evidence: PMID:29287995 IL-23R bound to IL-23 exclusively via its N-terminal immunoglobulin domain. PMID:12023369 Human IL-23, but not IL-12, exhibits detectable affinity for human IL-23R.
GO:0072536 interleukin-23 receptor complex	IBA GO_REF:0000033	ACCEPT	Summary: IL23R is a defining component of the interleukin-23 receptor complex, which consists of IL23R and IL12RB1 together with bound IL-23 (PMID:12023369). The IBA annotation is fully consistent with experimental evidence. Reason: IL23R is the IL-23-specific subunit of the IL-23 receptor complex. This is its core localization when engaged in signaling. The annotation is also supported by IDA evidence from PMID:12023369. Supporting Evidence: PMID:12023369 IL-23R pairs with IL-12Rbeta1 to confer IL-23 responsiveness on cells expressing both subunits.
GO:0017046 peptide hormone binding	IBA GO_REF:0000033	UNDECIDED	Summary: The broader peptide-hormone-binding term needs an independent ligand-scope judgment. Reason: GO:0017046 is binding to a peptide with hormonal activity in animals. It is broader than prolactin binding, and cytokine versus hormone terminology is not an absolute molecular exclusion. The existing OpenScientist report explicitly accepts this term as general, while the GOA trace uses the PRLR-seeded PTN000547909. Neither fact independently demonstrates whether IL-23 meets the intended hormonal scope; retain uncertainty rather than importing the prolactin-specific removal automatically. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN000547909 · PTN000547909 UNRESOLVED The source supports PRLR binding to prolactin; the broader term requires a separate judgment about hormonal activity of the actual IL23R ligand. It is not equivalent to prolactin binding. Supporting Evidence: file:human/IL23R/IL23R-hypotheses/function-hypothesis-go-0004925/openscientist.md GO:0017046 — peptide hormone binding [IBA] (acceptable — general term)
GO:0038161 prolactin signaling pathway	IEA GO_REF:0000108	REMOVE	Summary: This IEA annotation is derived by logical inference from the erroneous IBA annotation of prolactin receptor activity (GO:0004925). IL23R does not participate in prolactin signaling. Reason: This is a cascade error. The IBA annotation of prolactin receptor activity for IL23R is incorrect (IL23R does not bind prolactin), and this IEA was automatically inferred from that erroneous annotation. IL23R signals through the IL-23/JAK2/TYK2/STAT3 pathway, not prolactin signaling. Propagation Review Root cause: SOURCE BAD Failure modes: CIRCULAR PROPAGATION FUNCTIONAL DIVERGENCE Sources checked: GO:0004925 · IL23R prolactin receptor activity annotation SOURCE BAD GOA derives this prolactin-signaling IEA from the erroneous IL23R GO:0004925 annotation, so the pathway inference inherits the bad source. Supporting Evidence: PMID:12023369 IL-23 activates the same Jak-stat signaling molecules as IL-12: Jak2, Tyk2, and stat1, -3, -4, and -5, but stat4 activation is substantially weaker and different DNA-binding stat complexes form in response to IL-23 compared with IL-12.
GO:0002376 immune system process	IEA GO_REF:0000043	ACCEPT	Summary: IL23R is annotated to the Immunity keyword in UniProt, from which this IEA is derived. IL23R is indeed a core component of the immune system, functioning in innate and adaptive immunity through IL-23 signaling. Reason: While very broad, this IEA is correct. IL23R functions exclusively in the immune system, driving Th17/type 17 immune responses. More specific immune process annotations exist alongside this one. Supporting Evidence: PMID:12023369 IL-23R pairs with IL-12Rbeta1 to confer IL-23 responsiveness on cells expressing both subunits.
GO:0005886 plasma membrane	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation of IL23R to the plasma membrane based on automated mapping from UniProt subcellular location. IL23R is a single-pass type I transmembrane protein localized to the plasma membrane (PMID:12023369). Reason: Correct. IL23R is a transmembrane receptor at the plasma membrane. This is also supported by multiple TAS and IDA annotations for the same term. Supporting Evidence: PMID:12023369 IL-23R pairs with IL-12Rbeta1 to confer IL-23 responsiveness on cells expressing both subunits.
GO:0006954 inflammatory response	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: IEA from UniProt Inflammatory response keyword. IL-23 signaling through IL23R is a major driver of inflammatory responses, particularly in autoimmune and autoinflammatory diseases. Reason: While IL-23 signaling is strongly linked to inflammatory responses and IL23R variants are associated with inflammatory bowel disease and psoriasis, the inflammatory response is a downstream consequence of IL-23-mediated Th17 activation rather than the core molecular function of IL23R. The annotation is not wrong but is peripheral. Supporting Evidence: PMID:16482511 These data support the role of IL-23 in inflammation through stimulating IL-17 production by T lymphocytes, and importantly indicate a novel regulatory function for IL-12 by specifically suppressing IL-17 secretion.
GO:0045087 innate immune response	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: IEA from UniProt Innate immunity keyword. IL23R is expressed on innate immune cells including gamma-delta T cells, ILC3s, and NKT cells, and IL-23 signaling plays a role in innate immune defense. Reason: IL23R is expressed on innate immune cells and IL-23 signaling contributes to innate immunity. However, the primary role of IL23R is as a cytokine receptor that transduces IL-23 signals; the innate immune response is a downstream biological context. The annotation is acceptable but not core. Supporting Evidence: PMID:12023369 The ability of cells to respond to IL-23 or IL-12 correlates with expression of IL-23R or IL-12Rbeta2, respectively.
GO:0005515 protein binding	IPI PMID:12023369 A receptor for the heterodimeric cytokine IL-23 is composed ...	REMOVE	Summary: Generic protein binding is not a useful molecular-function annotation. Reason: The interaction evidence is not being declared false; specific receptor/ligand signaling functions are already captured, and generic protein binding is removed under project policy. Supporting Evidence: PMID:12023369 IL-23R associates constitutively with Jak2 and in a ligand-dependent manner with stat3.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	REMOVE	Summary: Generic protein binding is not a useful molecular-function annotation. Reason: The interaction evidence is not being declared false; specific receptor/ligand signaling functions are already captured, and generic protein binding is removed under project policy. Supporting Evidence: PMID:25416956 Here, we describe a systematic map of ?14,000 high-quality human binary protein-protein interactions.
GO:0005886 plasma membrane	IPI PMID:11114383 Novel p19 protein engages IL-12p40 to form a cytokine, IL-23...	ACCEPT	Summary: ComplexPortal annotation of the mature IL23R chain to the plasma membrane. IL-23 receptor complex is on the cell surface where it binds extracellular IL-23. Oppmann et al. (2000) described IL-23 and its receptor biology. Reason: IL23R is a type I transmembrane receptor at the plasma membrane. Multiple lines of evidence support this localization. Supporting Evidence: PMID:12023369 IL-23R pairs with IL-12Rbeta1 to confer IL-23 responsiveness on cells expressing both subunits.
GO:0006955 immune response	NAS PMID:19088061 IL-23 modulates CD56+/CD3- NK cell and CD56+/CD3+ NK-like T ...	KEEP AS NON CORE	Summary: NAS annotation from ComplexPortal. Van de Wetering et al. (2009) showed IL-23 modulates NK and NK-like T cell function as part of the immune response. IL23R mediates immune cell activation. Reason: Correct but very broad. Immune response is a general consequence of IL-23 signaling through IL23R. More specific immune process annotations are present. Supporting Evidence: PMID:19088061 Our findings show that IL-23 and IL-18 synergistically elicit IFN-gamma production in NK-like T cells but not in NK cells.
GO:0032729 positive regulation of type II interferon production	IDA PMID:12023369 A receptor for the heterodimeric cytokine IL-23 is composed ...	ACCEPT	Summary: ComplexPortal IDA annotation. Parham et al. (2002) showed that IL-23 signaling through IL23R promotes IFN-gamma (type II interferon) production, similar to but distinct from IL-12 responses. Reason: IL-23 signaling through IL23R promotes IFN-gamma production in T cells and NK cells. This is a well-established downstream effect of IL-23 receptor engagement, supported by the original characterization paper and confirmed in multiple cell types. Supporting Evidence: PMID:12023369 IL-23 activates the same Jak-stat signaling molecules as IL-12: Jak2, Tyk2, and stat1, -3, -4, and -5, but stat4 activation is substantially weaker and different DNA-binding stat complexes form in response to IL-23 compared with IL-12. PMID:11114383 Similar to IL-12, human IL-23 stimulates IFN-gamma production and proliferation in PHA blast T cells, as well as in CD45RO (memory) T cells.
GO:0032740 positive regulation of interleukin-17 production	NAS PMID:16482511 Divergent effects of IL-12 and IL-23 on the production of IL...	ACCEPT	Summary: ComplexPortal NAS annotation. Hoeve et al. (2006) demonstrated that IL-23, in contrast to IL-12, enhances IL-17 secretion by human T cells. This is the defining function of IL-23 in Th17 biology. Reason: Promotion of IL-17 production is one of the most important downstream effects of IL-23 signaling through IL23R. This is the basis for the IL-23/Th17 axis that drives autoimmune inflammation. Supporting Evidence: PMID:16482511 These data support the role of IL-23 in inflammation through stimulating IL-17 production by T lymphocytes, and importantly indicate a novel regulatory function for IL-12 by specifically suppressing IL-17 secretion.
GO:0042102 positive regulation of T cell proliferation	IDA PMID:11114383 Novel p19 protein engages IL-12p40 to form a cytokine, IL-23...	ACCEPT	Summary: ComplexPortal IDA annotation. Oppmann et al. (2000) showed that IL-23 uniquely stimulates memory T cell proliferation, a property not shared with IL-12. Reason: IL-23 signaling through IL23R drives T cell proliferation, particularly of memory T cells. This is a well-established downstream effect directly demonstrated in the discovery paper for IL-23. Supporting Evidence: PMID:11114383 IL-23 induces strong proliferation of mouse memory (CD4(+)CD45Rb(low)) T cells, a unique activity of IL-23 as IL-12 has no effect on this cell population.
GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT	IDA PMID:12023369 A receptor for the heterodimeric cytokine IL-23 is composed ...	ACCEPT	Summary: ComplexPortal IDA annotation. Parham et al. (2002) demonstrated that IL-23 binding to IL23R activates JAK2, TYK2, and STAT1/3/4/5 signaling, with predominant STAT3 activation. Reason: This is a core function of IL23R. Upon IL-23 binding, IL23R constitutively associates with JAK2 and activates JAK-STAT signaling. This annotation accurately describes that IL23R positively regulates JAK-STAT signaling. Supporting Evidence: PMID:12023369 IL-23R associates constitutively with Jak2 and in a ligand-dependent manner with stat3.
GO:0051142 positive regulation of NK T cell proliferation	NAS PMID:19088061 IL-23 modulates CD56+/CD3- NK cell and CD56+/CD3+ NK-like T ...	KEEP AS NON CORE	Summary: ComplexPortal NAS annotation. Van de Wetering et al. (2009) showed that IL-23 modulates NK-like T cell function, including promoting IFN-gamma production and CD56 upregulation. Reason: IL-23 does modulate NKT cell function, but the primary evidence from van de Wetering et al. focuses more on cytokine production than proliferation per se. The annotation is plausible but represents a secondary cell-type-specific effect rather than a core function of IL23R. Supporting Evidence: PMID:19088061 Our findings show that IL-23 and IL-18 synergistically elicit IFN-gamma production in NK-like T cells but not in NK cells.
GO:2000318 positive regulation of T-helper 17 type immune response	NAS PMID:16482511 Divergent effects of IL-12 and IL-23 on the production of IL...	ACCEPT	Summary: ComplexPortal NAS annotation. IL-23 is the key cytokine for maintaining and expanding Th17 responses. Hoeve et al. (2006) demonstrated IL-23 promotes IL-17 production by T cells. Reason: Promotion of Th17 responses is the defining biological role of IL-23 signaling through IL23R. IL-23 is essential for stabilizing the Th17 lineage and maintaining IL-17 production. Supporting Evidence: PMID:16482511 These data support the role of IL-23 in inflammation through stimulating IL-17 production by T lymphocytes, and importantly indicate a novel regulatory function for IL-12 by specifically suppressing IL-17 secretion.
GO:0032819 positive regulation of natural killer cell proliferation	TAS PMID:19088061 IL-23 modulates CD56+/CD3- NK cell and CD56+/CD3+ NK-like T ...	KEEP AS NON CORE	Summary: BHF-UCL TAS annotation. Van de Wetering et al. (2009) examined IL-23 effects on NK and NKT cells, showing differential modulation compared to IL-12. Reason: IL-23 effects on NK cell proliferation are less well established than its effects on T cells. Van de Wetering et al. showed IL-23 modulates NK cell function but the proliferative effects were more pronounced for NKT cells. This is a secondary, cell-type-specific effect. Supporting Evidence: PMID:19088061 Our findings show that IL-23 and IL-18 synergistically elicit IFN-gamma production in NK-like T cells but not in NK cells.
GO:0051135 positive regulation of NK T cell activation	TAS PMID:19088061 IL-23 modulates CD56+/CD3- NK cell and CD56+/CD3+ NK-like T ...	KEEP AS NON CORE	Summary: BHF-UCL TAS annotation. Van de Wetering et al. (2009) showed IL-23 activates NKT cells, synergizing with IL-18 for IFN-gamma production and upregulating CD56. Reason: IL-23 does activate NKT cells, but this represents one of several cell types responsive to IL-23. The primary role of IL23R in Th17 biology is more central. Supporting Evidence: PMID:19088061 IL-23 and IL-18 synergistically elicit IFN-gamma production in NK-like T cells but not in NK cells. In contrast, IL-12 together with IL-18-induced secretion of IFN-gamma in both populations.
GO:0097696 cell surface receptor signaling pathway via STAT	TAS PMID:19088061 IL-23 modulates CD56+/CD3- NK cell and CD56+/CD3+ NK-like T ...	ACCEPT	Summary: BHF-UCL TAS annotation. IL23R signals through the JAK-STAT pathway, predominantly activating STAT3 (PMID:12023369). This annotation is consistent with the well-established signaling mechanism. Reason: STAT signaling is a core downstream pathway of IL23R. Upon IL-23 binding, IL23R activates STAT3 and to a lesser extent STAT4. This is well supported by the original receptor characterization. Supporting Evidence: PMID:12023369 IL-23 activates the same Jak-stat signaling molecules as IL-12: Jak2, Tyk2, and stat1, -3, -4, and -5, but stat4 activation is substantially weaker and different DNA-binding stat complexes form in response to IL-23 compared with IL-12.
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	IC PMID:12023369 A receptor for the heterodimeric cytokine IL-23 is composed ...	ACCEPT	Summary: BHF-UCL IC annotation inferred from IL-23 binding (GO:0042019). Parham et al. (2002) directly demonstrated JAK2/TYK2 and STAT activation by IL-23 through IL23R. Reason: JAK-STAT signaling is the canonical signaling mechanism of IL23R. IL23R constitutively associates with JAK2, and IL-23 binding activates JAK2/TYK2 leading to STAT3/STAT4 phosphorylation. This is a core biological process annotation. Supporting Evidence: PMID:12023369 IL-23R associates constitutively with Jak2 and in a ligand-dependent manner with stat3.
GO:0004896 cytokine receptor activity	IDA PMID:29287995 Structural Activation of Pro-inflammatory Human Cytokine IL-...	ACCEPT	Summary: UniProt IDA annotation. Bloch et al. (2018) solved the crystal structure of IL-23 bound to IL23R, demonstrating it is a functional cytokine receptor that binds IL-23 via its N-terminal Ig domain and enables signaling. Reason: Cytokine receptor activity is the core molecular function of IL23R. The structural data from Bloch et al. provides direct evidence that IL23R functions as a cytokine receptor. A more specific annotation (GO:0042020 interleukin-23 receptor activity) also exists. Deep research confirms IL23R as the signaling chain of the IL-23 receptor complex with JAK2/TYK2 coupling (IL23R-deep-research-falcon.md). Supporting Evidence: PMID:29287995 IL-23R bound to IL-23 exclusively via its N-terminal immunoglobulin domain. file:human/IL23R/IL23R-deep-research-falcon.md IL23R is the signaling chain of the IL-23 receptor complex. Upon IL-23 binding, IL23R:IL12RB1 engagement triggers JAK2/TYK2 activation, predominantly STAT3 signaling.
GO:0009986 cell surface	IDA PMID:12023369 A receptor for the heterodimeric cytokine IL-23 is composed ...	ACCEPT	Summary: UniProt IDA annotation. Parham et al. (2002) demonstrated IL23R at the cell surface using anti-IL23R antibodies that block IL-23 responses in NK cells and Ba/F3 cells. Reason: IL23R is a cell surface receptor. Antibody blocking experiments in the original characterization paper confirm cell surface localization. Supporting Evidence: PMID:12023369 Anti-IL-12Rbeta1 and anti-IL-23R Abs block IL-23 responses of an NK cell line and Ba/F3 cells expressing the two receptor chains.
GO:0038155 interleukin-23-mediated signaling pathway	IDA PMID:29287995 Structural Activation of Pro-inflammatory Human Cytokine IL-...	ACCEPT	Summary: UniProt IDA annotation. Bloch et al. (2018) provided structural and functional evidence that IL23R directly mediates IL-23 signaling by binding IL-23 p19 and restructuring it to enable IL12RB1 recruitment. Reason: This is the most specific and accurate biological process annotation for IL23R. The interleukin-23-mediated signaling pathway is the primary biological process in which IL23R functions. Supporting Evidence: PMID:29287995 IL-23R bound to IL-23 exclusively via its N-terminal immunoglobulin domain.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-8950269	ACCEPT	Summary: Reactome TAS annotation from the IL-23 signaling pathway model (STAT3/STAT4 phosphorylation step). IL23R is part of the plasma membrane receptor complex in IL-23 signaling. Reason: Correct. IL23R is a transmembrane receptor at the plasma membrane. The Reactome pathway model accurately places IL23R at the plasma membrane.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-8952749	ACCEPT	Summary: Reactome TAS annotation from the STAT4 binding step in IL-23 signaling. Duplicate plasma membrane annotation from a different Reactome reaction. Reason: Correct but redundant with other plasma membrane annotations. IL23R is a plasma membrane receptor.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-8952823	ACCEPT	Summary: Reactome TAS annotation from the STAT dissociation step in IL-23 signaling. Duplicate plasma membrane annotation from a different Reactome reaction. Reason: Correct but redundant with other plasma membrane annotations.
GO:0043235 receptor complex	IDA PMID:23382219 Structural basis for endosomal trafficking of diverse transm...	ACCEPT	Summary: MGI IDA annotation citing Ghai et al. (2013), a paper about PX-FERM protein-mediated endosomal trafficking. The paper identifies SNX17 binding to NPxY/NxxY motifs in various transmembrane cargos. IL23R may be among the putative cargo molecules identified. Reason: IL23R forms part of a receptor complex (the IL-23 receptor complex with IL12RB1). While the cited paper focuses on endosomal trafficking rather than receptor complex assembly per se, the annotation to receptor complex is correct -- IL23R is indeed part of a receptor complex. This is also more specifically captured by GO:0072536 (interleukin-23 receptor complex). Supporting Evidence: PMID:12023369 IL-23R pairs with IL-12Rbeta1 to confer IL-23 responsiveness on cells expressing both subunits.
GO:2000318 positive regulation of T-helper 17 type immune response	ISS GO_REF:0000024	ACCEPT	Summary: BHF-UCL ISS annotation transferred from mouse IL23R (Q9EQ14). IL-23 signaling through IL23R is essential for Th17 immune responses in both human and mouse. Reason: The Th17 response is the defining biological role of IL-23/IL23R signaling. The ISS transfer from mouse is well supported by human evidence including IL-23-driven IL-17 production and the protective effect of IL23R R381Q in autoimmune disease. Supporting Evidence: PMID:16482511 These data support the role of IL-23 in inflammation through stimulating IL-17 production by T lymphocytes, and importantly indicate a novel regulatory function for IL-12 by specifically suppressing IL-17 secretion.
GO:2000330 positive regulation of T-helper 17 cell lineage commitment	ISS GO_REF:0000024	ACCEPT	Summary: BHF-UCL ISS annotation transferred from mouse IL23R (Q9EQ14). IL-23 signaling is critical for Th17 lineage commitment and maintenance, distinct from Th17 differentiation initiation (which requires IL-6 and TGF-beta). Reason: IL-23 signaling through IL23R stabilizes and maintains Th17 cell identity. While IL-6/TGF-beta initiate Th17 differentiation, IL-23 is required for terminal Th17 commitment and function. This is well supported by mouse knockout studies and human genetic data. Supporting Evidence: PMID:16482511 These data support the role of IL-23 in inflammation through stimulating IL-17 production by T lymphocytes, and importantly indicate a novel regulatory function for IL-12 by specifically suppressing IL-17 secretion.
GO:0032693 negative regulation of interleukin-10 production	IMP PMID:16751425 IL-23 is increased in dendritic cells in multiple sclerosis ...	KEEP AS NON CORE	Summary: BHF-UCL IMP annotation. Vaknin-Dembinsky et al. (2006) showed that IL-23 suppression in dendritic cells from MS patients leads to increased IL-10 production, implying IL-23 signaling negatively regulates IL-10 production. Reason: IL-23 signaling does suppress IL-10 production, which is consistent with its pro-inflammatory role. However, IL-10 regulation is a downstream effect of IL-23 signaling rather than a core function of the IL-23 receptor itself. The evidence is from dendritic cells where IL-23 antisense oligos increased IL-10 output. Supporting Evidence: PMID:16751425 increased IL-10 and decreased TNF-alpha production
GO:0032725 positive regulation of granulocyte macrophage colony-stimulating factor production	IC PMID:20027291 Salmonella induced IL-23 and IL-1beta allow for IL-12 produc...	KEEP AS NON CORE	Summary: BHF-UCL IC annotation inferred from IL-23 binding. Van de Wetering et al. (2009, PMID:20027291) showed Salmonella-induced IL-23 and IL-1beta drive IFN-gamma and GM-CSF production through CD56+ cells. Reason: GM-CSF production is a downstream consequence of IL-23 signaling in the context of bacterial infection. It is not a core function of IL23R but rather one of several cytokines induced by IL-23 pathway activation. Supporting Evidence: PMID:20027291 The findings implicate a positive feedback loop in which IL-23 can enhance its release via induction of IFN-gamma and GM-CSF.
GO:0032729 positive regulation of type II interferon production	TAS PMID:19088061 IL-23 modulates CD56+/CD3- NK cell and CD56+/CD3+ NK-like T ...	ACCEPT	Summary: BHF-UCL TAS annotation. Van de Wetering et al. (2009) showed IL-23 promotes IFN-gamma production in NKT cells synergistically with IL-18. Reason: IFN-gamma production is a well-established downstream effect of IL-23 signaling through IL23R, demonstrated in multiple cell types. This TAS annotation provides additional evidence line for the same GO term. Supporting Evidence: PMID:19088061 Our findings show that IL-23 and IL-18 synergistically elicit IFN-gamma production in NK-like T cells but not in NK cells.
GO:0032729 positive regulation of type II interferon production	IC PMID:20027291 Salmonella induced IL-23 and IL-1beta allow for IL-12 produc...	ACCEPT	Summary: BHF-UCL IC annotation inferred from IL-23 binding. Van de Wetering et al. (2009) showed Salmonella-induced IL-23 drives IFN-gamma production through CD56+ cells. Reason: Consistent with the IDA and TAS annotations for the same term. IL-23 signaling promotes IFN-gamma production across multiple cell types and experimental contexts. Supporting Evidence: PMID:20027291 IFN-gamma production in human CD56(+) cells in an IL-23 and IL-1beta-dependent but IL-12-independent manner.
GO:0032735 positive regulation of interleukin-12 production	IDA PMID:20027291 Salmonella induced IL-23 and IL-1beta allow for IL-12 produc...	KEEP AS NON CORE	Summary: BHF-UCL IDA annotation. Van de Wetering et al. (2009) showed that Salmonella-induced IL-23 drives a feedback loop where IL-23-stimulated IFN-gamma enables monocytes to produce IL-12. Reason: IL-12 production is an indirect downstream effect of IL-23 signaling through an IFN-gamma feedback loop in the context of Salmonella infection. This is not a direct function of IL23R but rather a consequence of the immune amplification circuit. Supporting Evidence: PMID:20027291 Salmonella induced IL-23 and IL-1beta allow for IL-12 production by monocytes and Mphi1 through induction of IFN-gamma in CD56 NK/NK-like T cells.
GO:0032740 positive regulation of interleukin-17 production	IC PMID:17888176 IL-23 induces human osteoclastogenesis via IL-17 in vitro, a...	ACCEPT	Summary: BHF-UCL IC annotation inferred from IL-23 binding. Yago et al. (2007) showed IL-23 elevated the ratio of IL-17 to IFN-gamma production in activated T cells. Reason: IL-17 induction is the hallmark downstream effect of IL-23 signaling through IL23R, central to the IL-23/Th17 axis. Multiple independent studies confirm this. Supporting Evidence: PMID:17888176 we found the ratio of production levels of IL-17 to those of IFN-gamma from activated human T cells was elevated at 1 to 10 ng/ml IL-23.
GO:0042102 positive regulation of T cell proliferation	IC PMID:12023369 A receptor for the heterodimeric cytokine IL-23 is composed ...	ACCEPT	Summary: BHF-UCL IC annotation inferred from IL-23 binding. Parham et al. (2002) showed IL-23 stimulates T cell responses through IL23R. Reason: T cell proliferation is a direct consequence of IL-23 receptor engagement. The original IL23R characterization paper demonstrated this activity. Supporting Evidence: PMID:12023369 Human and mouse IL-23 exhibit some activities similar to IL-12, but differ in their capacities to stimulate particular populations of memory T cells.
GO:0042104 positive regulation of activated T cell proliferation	IC PMID:11114383 Novel p19 protein engages IL-12p40 to form a cytokine, IL-23...	ACCEPT	Summary: BHF-UCL IC annotation inferred from IL-23 binding. Oppmann et al. (2000) showed IL-23 uniquely stimulates memory (activated) T cell proliferation. Reason: IL-23 uniquely stimulates memory T cell proliferation, distinguishing it from IL-12. This is one of the defining biological activities of IL-23 signaling. Supporting Evidence: PMID:11114383 IL-23 induces strong proliferation of mouse memory (CD4(+)CD45Rb(low)) T cells, a unique activity of IL-23 as IL-12 has no effect on this cell population.
GO:0045672 positive regulation of osteoclast differentiation	IC PMID:17888176 IL-23 induces human osteoclastogenesis via IL-17 in vitro, a...	KEEP AS NON CORE	Summary: BHF-UCL IC annotation inferred from IL-23 binding. Yago et al. (2007) showed IL-23 induces human osteoclastogenesis via IL-17 in vitro. Reason: IL-23-driven osteoclast differentiation occurs indirectly through IL-17 induction. This is a secondary downstream effect relevant to rheumatoid arthritis pathology but not a core function of IL23R. Supporting Evidence: PMID:17888176 This study demonstrates that IL-23 stimulates the differentiation of human osteoclasts from peripheral blood mononuclear cells (PBMC).
GO:0050829 defense response to Gram-negative bacterium	IC PMID:15114670 Commensal Gram-negative bacteria prime human dendritic cells...	KEEP AS NON CORE	Summary: BHF-UCL IC annotation inferred from IL-23 binding. Smits et al. (2004) showed Gram-negative bacteria prime dendritic cells for enhanced IL-23 production, which drives Th1 development. Reason: IL-23 is produced in response to Gram-negative bacteria and contributes to defense through Th17/Th1 activation. However, the defense response is a broad biological outcome rather than a core function of IL23R. The cited paper is about IL-23 production by DCs, not IL23R function per se. Supporting Evidence: PMID:15114670 all Gram-negative bacteria (GnB) primed moDC for enhanced Th1 cell development, which was dependent on IL-12 and an additional unidentified cofactor.
GO:0072536 interleukin-23 receptor complex	IDA PMID:12023369 A receptor for the heterodimeric cytokine IL-23 is composed ...	ACCEPT	Summary: BHF-UCL IDA annotation. Parham et al. (2002) directly demonstrated that IL23R pairs with IL12RB1 to form the IL-23 receptor complex. Reason: This is a core component annotation. IL23R is a defining subunit of the interleukin-23 receptor complex, directly demonstrated in the original receptor characterization paper. Supporting Evidence: PMID:12023369 IL-23R pairs with IL-12Rbeta1 to confer IL-23 responsiveness on cells expressing both subunits.
GO:0002230 positive regulation of defense response to virus by host	IDA PMID:12421946 Regulation of virus-induced IL-12 and IL-23 expression in hu...	KEEP AS NON CORE	Summary: BHF-UCL IDA annotation. Pirhonen et al. (2002) showed that human macrophages produce IL-23 in response to viral infection (Sendai virus), and IL-23 enhances IFN-gamma production by NK cells, promoting antiviral defense. Reason: IL-23 signaling contributes to antiviral defense through IFN-gamma promotion in NK cells. However, the cited paper primarily demonstrates IL-23 production by macrophages rather than direct IL23R-mediated antiviral activity. This is a downstream consequence of IL-23 signaling rather than a core function. Supporting Evidence: PMID:12421946 Sendai virus stimulates the expression of p19 and p40 mRNAs in macrophages.
GO:0002827 positive regulation of T-helper 1 type immune response	IDA PMID:15114670 Commensal Gram-negative bacteria prime human dendritic cells...	KEEP AS NON CORE	Summary: BHF-UCL IDA annotation. Smits et al. (2004) showed Gram-negative bacteria prime dendritic cells for IL-23 production that enhances Th1 development. Reason: IL-23 can promote Th1 responses, but the primary role of IL-23/IL23R signaling is in Th17 biology. Th1 promotion is a secondary effect, partly mediated through IFN-gamma induction. The cited paper is primarily about DC biology rather than IL23R function directly. Supporting Evidence: PMID:15114670 GnB-matured moDC expressed elevated levels of p19 and p28 mRNA, the critical subunits of IL-23 and IL-27, respectively, suggesting that the IL-12 family members may jointly be responsible for their Th1-driving capacity.
GO:0001916 positive regulation of T cell mediated cytotoxicity	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: BHF-UCL ISS annotation transferred from mouse IL23R (Q9EQ14). IL-23 may promote cytotoxic T cell function, but this is not a well-characterized primary activity of IL23R. Reason: T cell mediated cytotoxicity is a downstream immune effector function that may be enhanced by IL-23 signaling, but it is not a core function of IL23R. The ISS transfer from mouse is reasonable but represents a peripheral activity.
GO:0002230 positive regulation of defense response to virus by host	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: BHF-UCL ISS annotation transferred from mouse IL23R (Q9EQ14). Consistent with the IDA annotation from PMID:12421946 showing IL-23 contributes to antiviral defense. Reason: Duplicate evidence line for the same annotation also supported by IDA from PMID:12421946. Antiviral defense is not a core function of IL23R.
GO:0002827 positive regulation of T-helper 1 type immune response	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: BHF-UCL ISS annotation transferred from mouse IL23R (Q9EQ14). Consistent with IDA annotation from PMID:15114670. Reason: Duplicate evidence line. Th1 promotion is a secondary effect of IL-23 signaling. The primary axis is Th17.
GO:0043382 positive regulation of memory T cell differentiation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: BHF-UCL ISS annotation transferred from mouse IL23R (Q9EQ14). IL-23 uniquely stimulates memory T cells (PMID:11114383), which is consistent with a role in memory T cell differentiation. Reason: IL-23 does preferentially act on memory T cells, but memory T cell differentiation is a downstream consequence of IL-23 signaling. The primary role of IL23R is in Th17 maintenance and cytokine receptor signaling. Supporting Evidence: PMID:11114383 IL-23 induces strong proliferation of mouse memory (CD4(+)CD45Rb(low)) T cells, a unique activity of IL-23 as IL-12 has no effect on this cell population.
GO:0005143 interleukin-12 receptor binding	IPI PMID:12023369 A receptor for the heterodimeric cytokine IL-23 is composed ...	ACCEPT	Summary: BHF-UCL IPI annotation with contributes_to qualifier. IL23R pairs with IL12RB1 (the shared IL-12 receptor beta 1 chain), contributing to a complex that has IL-12 receptor binding capacity through the p40 subunit. Reason: GO:0005143 means binding to an interleukin-12 receptor. The direct IPI row cites partner P42701/IL12RB1, which also pairs with IL23R in the IL-23 receptor complex (PMID:12023369). This is receptor-subunit association, not IL-12 cytokine binding. The IBA correctly lists the target itself among descendant experimental sources; that is experimental grounding, not circularity. Supporting Evidence: PMID:12023369 IL-23R pairs with IL-12Rbeta1
GO:0042019 interleukin-23 binding	IPI PMID:12023369 A receptor for the heterodimeric cytokine IL-23 is composed ...	ACCEPT	Summary: BHF-UCL IPI annotation with contributes_to qualifier. Parham et al. (2002) showed IL-23 has detectable affinity for IL23R alone, but full binding requires the IL23R:IL12RB1 heterodimer. Reason: The contributes_to qualifier is correct. IL23R directly binds the p19 subunit, while IL12RB1 binds the p40 subunit. Together they form the complete IL-23 binding site. Supporting Evidence: PMID:12023369 Human IL-23, but not IL-12, exhibits detectable affinity for human IL-23R.
GO:0042020 interleukin-23 receptor activity	IDA PMID:12023369 A receptor for the heterodimeric cytokine IL-23 is composed ...	ACCEPT	Summary: BHF-UCL IDA annotation with contributes_to qualifier. Parham et al. (2002) demonstrated that IL23R pairs with IL12RB1 to form the functional IL-23 receptor, conferring IL-23 responsiveness. Reason: This is the most specific molecular function annotation for IL23R. The contributes_to qualifier is appropriate because full IL-23 receptor activity requires both IL23R and IL12RB1 subunits. IL23R alone has partial activity; the heterodimer is needed for full signaling. Supporting Evidence: PMID:12023369 IL-23R pairs with IL-12Rbeta1 to confer IL-23 responsiveness on cells expressing both subunits.
GO:0032496 response to lipopolysaccharide	IDA PMID:12023369 A receptor for the heterodimeric cytokine IL-23 is composed ...	KEEP AS NON CORE	Summary: BHF-UCL IDA annotation. Parham et al. (2002) studied IL23R expression and response in cells stimulated with LPS and other stimuli. IL23R expression may be upregulated by LPS in certain immune cell types. Reason: Response to LPS is a stimulus-response annotation that reflects IL23R expression regulation rather than IL23R's core signaling function. LPS can induce IL-23 production and modulate IL23R expression, but this represents the inflammatory context rather than the receptor's primary activity. Supporting Evidence: PMID:12023369 The ability of cells to respond to IL-23 or IL-12 correlates with expression of IL-23R or IL-12Rbeta2, respectively.
GO:0032729 positive regulation of type II interferon production	IDA PMID:11114383 Novel p19 protein engages IL-12p40 to form a cytokine, IL-23...	ACCEPT	Summary: BHF-UCL IDA annotation. Oppmann et al. (2000) showed IL-23 promotes IFN-gamma production in activated T cells. Reason: IFN-gamma promotion is a well-established downstream effect of IL-23 signaling through IL23R, demonstrated in the original IL-23 discovery paper. Supporting Evidence: PMID:11114383 Similar to IL-12, human IL-23 stimulates IFN-gamma production and proliferation in PHA blast T cells, as well as in CD45RO (memory) T cells.
GO:0034341 response to type II interferon	IDA PMID:12023369 A receptor for the heterodimeric cytokine IL-23 is composed ...	KEEP AS NON CORE	Summary: BHF-UCL IDA annotation. Parham et al. (2002) showed that IFN-gamma can modulate IL23R expression and the ability of cells to respond to IL-23. Reason: Response to IFN-gamma reflects transcriptional regulation of IL23R expression rather than a core function of IL23R itself. IFN-gamma upregulates IL23R in some contexts, but this is a regulatory input not a core activity. Supporting Evidence: PMID:12023369 The ability of cells to respond to IL-23 or IL-12 correlates with expression of IL-23R or IL-12Rbeta2, respectively.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-447130	ACCEPT	Summary: Reactome TAS annotation from the IL-23 binding reaction in the Reactome pathway model. IL23R is located at the plasma membrane. Reason: Correct. Duplicate plasma membrane annotation from a different Reactome pathway step.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6790022	ACCEPT	Summary: Reactome TAS annotation from the STAT3-upregulated plasma membrane proteins pathway. IL23R is at the plasma membrane. Reason: Correct. IL23R is a plasma membrane protein. This Reactome step captures IL23R in the context of STAT3-regulated expression.

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

OpenScientist

📚 Additional Documentation

Notes

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