IL23A

Summary

IL23A (interleukin 23 subunit alpha, HGNC:15488) is a protein-coding gene on chromosome 12q13.3, encoding Interleukin-23 subunit alpha (Q9NPF7). Associates with IL12B to form the pro-inflammatory cytokine IL-23 that plays different roles in innate and adaptive immunity.

This gene encodes a subunit of the heterodimeric cytokine interleukin 23 (IL23). IL23 is composed of this protein and the p40 subunit of interleukin 12 (IL12B). The receptor of IL23 is formed by the beta 1 subunit of IL12 (IL12RB1) and an IL23 specific subunit, IL23R. Both IL23 and IL12 can activate the transcription activator STAT4, and stimulate the production of interferon-gamma (IFNG). In contrast to IL12, which acts mainly on naive CD4(+) T cells, IL23 preferentially acts on memory CD4(+) T cells.

Source: NCBI Gene 51561 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 20 total
• Druggable target: yes
• MANE Select transcript: NM_016584

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15488
Approved symbol	IL23A
Name	interleukin 23 subunit alpha
Location	12q13.3
Locus type	gene with protein product
Status	Approved
Aliases	SGRF, IL23P19, IL-23, IL-23A, P19
Ensembl gene	ENSG00000110944
Ensembl biotype	protein_coding
OMIM	605580
Entrez	51561

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000228534, ENST00000619177, ENST00000622119

RefSeq mRNA: 1 — MANE Select: NM_016584 NM_016584

CCDS: CCDS8916

Canonical transcript exons

ENST00000228534 — 4 exons

Exon	Start	End
ENSE00000749561	56339426	56339524
ENSE00000749563	56339691	56339837
ENSE00001316590	56338884	56339206
ENSE00001329528	56339943	56340410

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 84.48.

FANTOM5 (CAGE): breadth broad, TPM avg 5.8975 / max 318.2930, expressed in 891 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126105	2.5994	288
126102	2.1225	655
126106	0.4544	171
126107	0.3754	143
126104	0.2696	90
126108	0.0762	43

Top tissues by expression

279 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.48	gold quality
left testis	UBERON:0004533	84.32	gold quality
right testis	UBERON:0004534	83.75	gold quality
testis	UBERON:0000473	81.29	gold quality
pancreatic ductal cell	CL:0002079	79.27	silver quality
granulocyte	CL:0000094	79.01	gold quality
sperm	CL:0000019	78.76	silver quality
male germ cell	CL:0000015	77.09	silver quality
cartilage tissue	UBERON:0002418	76.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.56	gold quality
oocyte	CL:0000023	75.16	silver quality
leukocyte	CL:0000738	74.65	gold quality
oral cavity	UBERON:0000167	74.58	silver quality
amniotic fluid	UBERON:0000173	74.39	gold quality
monocyte	CL:0000576	74.17	gold quality
mononuclear cell	CL:0000842	74.16	gold quality
blood	UBERON:0000178	71.60	gold quality
secondary oocyte	CL:0000655	70.24	gold quality
right lobe of liver	UBERON:0001114	70.01	gold quality
islet of Langerhans	UBERON:0000006	69.98	gold quality
bone marrow	UBERON:0002371	69.85	gold quality
esophagus squamous epithelium	UBERON:0006920	69.81	silver quality
epithelium of esophagus	UBERON:0001976	69.77	silver quality
cervix squamous epithelium	UBERON:0006922	68.97	gold quality
squamous epithelium	UBERON:0006914	68.92	silver quality
lymph node	UBERON:0000029	68.50	gold quality
tongue squamous epithelium	UBERON:0006919	68.22	gold quality
epithelium of nasopharynx	UBERON:0001951	67.94	silver quality
spleen	UBERON:0002106	67.94	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	67.88	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	9.23
E-ANND-3	no	2.94

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AP1, ATF2, ATF4, BATF, BCL3, CEBPD, DDIT3, E2F1, ESR1, FOS, IRF1, IRF3, IRF4, IRF6, JUN, NFKB1, NFKB2, NFKB, REL, RELA, SATB1, SMAD3, STAT3

miRNA regulators (miRDB)

30 targeting IL23A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-1909-5P	98.94	64.01	484
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-6894-5P	98.70	63.78	809
HSA-MIR-7112-3P	97.67	68.77	948
HSA-MIR-4433A-5P	96.79	65.01	599
HSA-MIR-6508-3P	96.73	65.48	576
HSA-MIR-4683	95.29	65.98	631
HSA-MIR-4301	95.00	65.22	554

Literature-anchored findings (GeneRIF, showing 40)

• Elevated expression of mRNA for IL-23(p19)was found in trigeminal ganglia of BALB/C mice infected with HSV-1 from early acute infection to the beginning of the latent phase. (PMID:12162874)
• In BALB/c mice, single chain (sc) IL-23-transduced CT26 cells grow progressively until day 26, then the tumors start to regress in most animals; scIL-23 transduction also significantly suppresses lung metastases of CT26 and B16F1 tumor cells. (PMID:12847224)
• IL-23 plays a more dominant role than IL-12 in psoriasis, a Th1 type of human inflammatory disease. (PMID:14707118)
• Macrophages produce neither IL-23 nor IL-12 but predominantly secrete IL-10. (PMID:15070757)
• IL-23 p19 mRNA is inducible in colonic myofibroblasts by IL-1beta and Tumor Necrosis Factor-alpha (PMID:15583831)
• synthesis induced by Bordetella pertussis in monocyte-derived dendritic cells (MDDC) (PMID:15731058)
• This overview provides the historical background and current understanding of the roles of IL-12, IL-23, and T-helper type 1 (TH1) cell development in inflammation and autoimmunity. (PMID:16300465)
• IL-23 plays an important role in the FasL-induced IL-17 production. (PMID:16339539)
• Augmented expression of IL-23 by keratinocytes and cutaneous antigen-presenting cells may contribute to the perpetuation of inflammatory lesions in psoriatic skin. (PMID:16424222)
• IL-23 and IL-17 have roles in inflammation [commentary] (PMID:16670765)
• An abnormal type-1 T helper (Th1) cell bias exists related to IL-23-expressing dendritic cells from multiple sclerosis (MS) patients, which may play an important role in the pathogenesis of human autoimmune diseases such as MS. (PMID:16751425)
• Increased concentrations of p40 subunit of IL-23 in follicles containing oocytes suggest an important role of this cytokine in reproduction. (PMID:16772281)
• This review summarizes information on the expression and role of IL-12 both in patients with Crohn’s diease and experimental models of colitis, thus emphasizing differences between IL-12 and IL-23 activity on the development of intestinal inflammation. (PMID:17007011)
• Abnormal IL-23 expression may play a role in the pathogenesis and progression of mycosis fungoides to Sezary syndrome. (PMID:17021762)
• c-Rel controls IL-23 p19 gene expression through two kappaB sites in the p19 promoter, and propose a c-Rel-dependent enhanceosome model for p19 gene activation. (PMID:17182554)
• IL-22 is preferentially produced by T(H)17 cells and mediates the acanthosis induced by IL-23 (PMID:17187052)
• mRNA levels of IL23 subunit p19 in active SLE patients was significantly higher compared with those in the inactive SLE patients (PMID:17564777)
• Upregulated IL-23p19 in synovial fluid may be involved in joint destruction in rheumatoid arthritis. (PMID:17763202)
• results here show that IL-23 is elevated in children with malarial anemia, and that IL-10 and IL-12 appear to have important regulatory effects on IL-23 production during childhood malaria (PMID:17945537)
• Data suggest that the p38 MAP kinase and NF-kappaB signaling pathways play an important role in regulation of IL-23p19 expression on human microglia, and are thus potential therapeutic targets in the treatment of MS. (PMID:18054783)
• These data indicate that IL23R represents a novel shared susceptibility gene as its association with inflammatory bowel disease (IBD) has recently been verified. (PMID:18180107)
• an increased expression of IL-12 p40, IL-12 p35 and IL-23 p19 mRNA was observed in bone marrow mononuclear cells and peripheral blood mononuclear cells of patients with aplastic anemia compared with the corresponding one in normal controls. (PMID:18190588)
• Immunohistochemical stainings of submandibular glands from C57BL/6.NOD-Aec1Aec2 mice and of salivary gland biopsy specimens from Sjogren’s syndrome patients revealed IL-17 and IL-23 staining within lymphocytic foci and epithelial tissues. (PMID:18311793)
• NK cells require in vivo priming with IL-12/23 to acquire their full spectrum of functional reactivity, while T cells are dependent upon IL-12/23 signals for the differentiation and/or the maintenance of CD56(+) effector memory T cells (PMID:18319400)
• The activated IL-23/IL-17 axis is important for the inflammatory immunity in systemic lupus erythematosus. (PMID:18373953)
• IL-23 stimulates survival and proliferation of Th17 cells and thus serves as a key master cytokine regulator for psoriasis (PMID:18408745)
• findings show that lactic acid secreted by tumor cells enhances the transcription of IL-23p19 and IL-23 production in monocytes/macrophages and in tumor-infiltrating immune cells that are stimulated with TLR2 and 4 ligands (PMID:18490716)
• intestinal macrophages expressing CD14 contribute to the pathogenesis of Crohn disease via IL-23/IFN-gamma axis (PMID:18497880)
• Levels of IL-23, IL-17, and IFN-gamma are elevated in Behcet disease(BD) with active uveitis. IL-23/IL-17 pathway together with IFN-gamma is associated with active intraocular inflammation in BD patients. (PMID:18579762)
• study demonstrates that oxidative stress induced by soluble cigarette smoke components potently inhibits the production of IL-12 and IL-23 by maturing dendritic cells (PMID:18606709)
• Data suggest that the structure of interleukin-23 reveals the molecular basis of p40 subunit sharing with interleukin-12. (PMID:18680750)
• Results describe the crystal structures of the pro-inflammatory cytokine interleukin-23 and its complex with a high-affinity neutralizing antibody. (PMID:18708069)
• Serum levels of anti-cyclic citrullinated peptide antibodies and IL-23p19 were higher in psoriatic arthritis patients than in rheumatoid arthritis patients. (PMID:18752933)
• Identification of potentially functional splice variants of IL23 receptor (IL-23R) will aid in understanding possible pathogenic mechanisms of IL-23R’s contribution to disease susceptibility. (PMID:18754016)
• The role of the IL23/IL17 axis in bronchiolitis obliterans syndrome after lung transplantation is reported. (PMID:18786233)
• The greatest upregulation of IL-23p19, Foxp3 and survivin mRNA was seen in colorectal carcinomas than normal mucosa. (PMID:18825388)
• Significant associations between Arg381Gln SNP and haplotypes encoding this variant were noted in psoriatic arthritis (PMID:19040306)
• IL-23 in synergy with IL-18 elicits IFN-gamma production in NK T cells but not in NK cells; upregulates IL-18Ra and CD56 expression (PMID:19088061)
• Expanded catalog of genetic loci implicated in psoriasis susceptibility. (PMID:19169254)
• Fibroblast-like synoviocytes are potently regulated by inflammatory cytokines to specifically express IL-23 p19. (PMID:19201028)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Il23a	ENSMUSG00000025383
rattus_norvegicus	Il23a	ENSRNOG00000003254

Protein

Protein identifiers

Interleukin-23 subunit alpha — Q9NPF7 (reviewed: Q9NPF7)

Alternative names: Interleukin-23 subunit p19

All UniProt accessions (1): Q9NPF7

UniProt curated annotations — full annotation on UniProt →

Function. Associates with IL12B to form the pro-inflammatory cytokine IL-23 that plays different roles in innate and adaptive immunity. Released by antigen-presenting cells such as dendritic cells or macrophages, binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R to activate JAK2 and TYK2 which then phosphorylate the receptor to form a docking site leading to the phosphorylation of STAT3 and STAT4. This process leads to activation of several pathways including p38 MAPK or NF-kappa-B and promotes the production of pro-inflammatory cytokines such as interleukin-17A/IL17A. In turn, participates in the early and effective intracellular bacterial clearance. Promotes the expansion and survival of T-helper 17 cells, a CD4-positive helper T-cell subset that produces IL-17, as well as other IL-17-producing cells.

Subunit / interactions. Heterodimer with IL12B; disulfide-linked. The heterodimer is known as interleukin IL-23. Interacts with IL23R; this interaction enables recruitment of IL12RB1.

Subcellular location. Secreted.

Tissue specificity. Secreted by activated dendritic and phagocytic cells and keratinocytes. Also expressed by dermal Langerhans cells (at protein level).

Induction. Up-regulated by a wide array of pathogens and pathogen-products together with self-signals for danger or injury. Up-regulated in psoriatic dermal tissues, in dendritic cells of multiple sclerosis patients and in tumors.

Similarity. Belongs to the IL-6 superfamily.

RefSeq proteins (1): NP_057668* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009079	4_helix_cytokine-like_core	Homologous_superfamily
IPR010831	IL-23_alpha	Family

Pfam: PF16649

UniProt features (23 total): helix 8, sequence conflict 5, turn 3, strand 3, disulfide bond 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
5MJ3	X-RAY DIFFRACTION	1.74
3D85	X-RAY DIFFRACTION	1.9
8CR8	X-RAY DIFFRACTION	2
3DUH	X-RAY DIFFRACTION	2.3
8UUI	X-RAY DIFFRACTION	2.43
5MXA	X-RAY DIFFRACTION	2.5
4GRW	X-RAY DIFFRACTION	2.55
6UIB	X-RAY DIFFRACTION	2.74
5MZV	X-RAY DIFFRACTION	2.8
3D87	X-RAY DIFFRACTION	2.9
3QWR	X-RAY DIFFRACTION	3.25
5MJ4	X-RAY DIFFRACTION	3.4
6WDQ	X-RAY DIFFRACTION	3.4
8OE4	ELECTRON MICROSCOPY	3.6
5NJD	X-RAY DIFFRACTION	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPF7-F1	80.72	0.52

Antibody-complex structures (SAbDab): 4 — 3D85, 4GRW, 5MZV, 5NJD

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (2): 73, 77–89

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-9020933	Interleukin-23 signaling

MSigDB gene sets: 440 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_POSITIVE_REGULATION_OF_CELL_FATE_COMMITMENT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE

GO Biological Process (40): positive regulation of T cell mediated cytotoxicity (GO:0001916), positive regulation of defense response to virus by host (GO:0002230), positive regulation of T-helper 1 type immune response (GO:0002827), inflammatory response (GO:0006954), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), negative regulation of interleukin-10 production (GO:0032693), positive regulation of granulocyte macrophage colony-stimulating factor production (GO:0032725), positive regulation of type II interferon production (GO:0032729), positive regulation of interleukin-10 production (GO:0032733), positive regulation of interleukin-12 production (GO:0032735), positive regulation of interleukin-17 production (GO:0032740), positive regulation of tumor necrosis factor production (GO:0032760), positive regulation of natural killer cell activation (GO:0032816), positive regulation of natural killer cell proliferation (GO:0032819), positive regulation of tissue remodeling (GO:0034105), T cell proliferation (GO:0042098), positive regulation of T cell proliferation (GO:0042102), positive regulation of activated T cell proliferation (GO:0042104), positive regulation of memory T cell differentiation (GO:0043382), innate immune response (GO:0045087), positive regulation of osteoclast differentiation (GO:0045672), positive regulation of transcription by RNA polymerase II (GO:0045944), tissue remodeling (GO:0048771), positive regulation of inflammatory response (GO:0050729), defense response to Gram-negative bacterium (GO:0050829), positive regulation of NK T cell activation (GO:0051135), positive regulation of NK T cell proliferation (GO:0051142), defense response to virus (GO:0051607), positive regulation of neutrophil chemotaxis (GO:0090023), cell surface receptor signaling pathway via STAT (GO:0097696), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224), positive regulation of T-helper 17 type immune response (GO:2000318), positive regulation of T-helper 17 cell lineage commitment (GO:2000330), immune system process (GO:0002376), immune response (GO:0006955), regulation of gene expression (GO:0010468), positive regulation of macromolecule biosynthetic process (GO:0010557), positive regulation of alpha-beta T cell activation (GO:0046635), regulation of primary metabolic process (GO:0080090), positive regulation of leukocyte differentiation (GO:1902107)

GO Molecular Function (3): cytokine activity (GO:0005125), interleukin-23 receptor binding (GO:0045519), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), endoplasmic reticulum lumen (GO:0005788), interleukin-23 complex (GO:0070743), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by Interleukins	1
Interleukin-12 family signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of cytokine production	5
interleukin-10 production	2
regulation of interleukin-10 production	2
positive regulation of lymphocyte proliferation	2
positive regulation of leukocyte mediated cytotoxicity	1
T cell mediated cytotoxicity	1
regulation of T cell mediated cytotoxicity	1
positive regulation of T cell mediated immunity	1
regulation of defense response to virus by host	1
positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
regulation of T-helper 1 type immune response	1
T-helper 1 type immune response	1
defense response	1
cell surface receptor signaling pathway via STAT	1
negative regulation of cytokine production	1
granulocyte macrophage colony-stimulating factor production	1
regulation of granulocyte macrophage colony-stimulating factor production	1
positive regulation of protein metabolic process	1
type II interferon production	1
regulation of type II interferon production	1
interleukin-12 production	1
regulation of interleukin-12 production	1
interleukin-17 production	1
regulation of interleukin-17 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
natural killer cell activation	1
regulation of natural killer cell activation	1
positive regulation of lymphocyte activation	1
natural killer cell proliferation	1
positive regulation of natural killer cell activation	1
regulation of natural killer cell proliferation	1
regulation of tissue remodeling	1
tissue remodeling	1
positive regulation of multicellular organismal process	1
T cell activation	1
lymphocyte proliferation	1
T cell proliferation	1
regulation of T cell proliferation	1

Protein interactions and networks

STRING

924 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL23A	IL12RB1	P42701	916
IL23A	IL23R	Q5VWK5	905
IL23A	IL22	Q9GZX6	890
IL23A	IL17F	Q96PD4	869
IL23A	IL17A	Q16552	867
IL23A	IL12RB2	Q99665	802
IL23A	IL27	Q8NEV9	773
IL23A	IL6	P05231	764
IL23A	IL10	P22301	727
IL23A	IL4	P05112	725
IL23A	IFNG	P01579	696
IL23A	TBX21	Q9UL17	669
IL23A	IL17RA	Q96F46	668
IL23A	IL12B	P29460	650
IL23A	IL17RC	Q8NAC3	648

IntAct

21 interactions, top by confidence:

A	B	Type	Score
IL23A	IL12B	psi-mi:“MI:0914”(association)	0.810
IL12B	IL23A	psi-mi:“MI:2364”(proximity)	0.810
IL12B	IL23A	psi-mi:“MI:0915”(physical association)	0.810
IL23A	IL12B	psi-mi:“MI:0915”(physical association)	0.810
IL12B	IL23A	psi-mi:“MI:0914”(association)	0.810
IL12B	IL23A	psi-mi:“MI:0407”(direct interaction)	0.810
PEX19	IL23A	psi-mi:“MI:0915”(physical association)	0.720
IL23A	PEX19	psi-mi:“MI:0915”(physical association)	0.720
IL23R	IL23A	psi-mi:“MI:0407”(direct interaction)	0.520
IL12RB1	IL23R	psi-mi:“MI:0915”(physical association)	0.400
IL23A	GP6	psi-mi:“MI:0915”(physical association)	0.400
IL23A	LILRA1	psi-mi:“MI:0915”(physical association)	0.400
IL23A	LILRB2	psi-mi:“MI:0915”(physical association)	0.400
IL23A	SIGLEC6	psi-mi:“MI:0915”(physical association)	0.400
IL23A	IFFO1	psi-mi:“MI:0914”(association)	0.350
IL23A	PEX19	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): IL23A (Two-hybrid), IFFO1 (Affinity Capture-MS), RNF41 (Affinity Capture-MS), RNF41 (Affinity Capture-MS), IFFO1 (Affinity Capture-MS), IL23A (FRET), IL12B (Affinity Capture-Luminescence), PEX19 (Two-hybrid), IL23R (Reconstituted Complex), IL12RB1 (Reconstituted Complex), IFFO1 (Affinity Capture-MS), RNF41 (Affinity Capture-MS), IL12B (Affinity Capture-Western), IL23A (Affinity Capture-Western), HERPUD1 (Affinity Capture-Western)

ESM2 similar proteins: A3FFS8, B4ER10, K9M1U5, O02708, O02720, O02837, P01245, P01588, P07321, P07865, P09920, P13725, P13854, P29676, P33707, P33708, P33709, P35833, P48617, P49157, P53346, Q0Z956, Q13007, Q1XG29, Q28513, Q29406, Q2XNF5, Q4T554, Q5IGQ0, Q5S1V9, Q64FU1, Q65Z15, Q6H8S9, Q6H8T0, Q6H8T1, Q6H8T2, Q6JV22, Q6LA37, Q6UXV1, Q7YRR6

Diamond homologs: Q64FU1, Q6LA37, Q91Z84, Q9EQ14, Q9N2H9, Q9NPF7

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
SATB1	“down-regulates quantity by repression”	IL23A	“transcriptional regulation”
IL23A	“form complex”	“Interleukin-23 receptor-ligand complex”	binding
IL23A	“up-regulates activity”	“Interleukin-23 receptor-ligand complex”	binding
IL23A	up-regulates	IL12RB1	binding
IL23A	up-regulates	IL23R	binding
CEBPD	“up-regulates quantity by expression”	IL23A	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

20 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

293 predictions. Top by Δscore:

Variant	Effect	Δscore
12:56339419:A:AG	acceptor_gain	1.0000
12:56339423:CAGG:C	acceptor_loss	1.0000
12:56339424:A:AT	acceptor_loss	1.0000
12:56339424:AG:A	acceptor_gain	1.0000
12:56339425:GG:G	acceptor_gain	1.0000
12:56339520:GTCAG:G	donor_gain	1.0000
12:56339689:A:AG	acceptor_gain	1.0000
12:56339690:G:GG	acceptor_gain	1.0000
12:56339690:GTTCT:G	acceptor_gain	1.0000
12:56339836:AG:A	donor_loss	1.0000
12:56339837:GG:G	donor_loss	1.0000
12:56339838:GTATG:G	donor_loss	1.0000
12:56339420:T:G	acceptor_gain	0.9900
12:56339424:A:AG	acceptor_gain	0.9900
12:56339425:G:GG	acceptor_gain	0.9900
12:56339425:GGAT:G	acceptor_gain	0.9900
12:56339425:GGATC:G	acceptor_gain	0.9900
12:56339513:G:T	donor_gain	0.9900
12:56339521:TCAG:T	donor_loss	0.9900
12:56339522:CAGG:C	donor_loss	0.9900
12:56339523:AGGTA:A	donor_loss	0.9900
12:56339525:GTA:G	donor_loss	0.9900
12:56339526:T:C	donor_loss	0.9900
12:56339687:CTA:C	acceptor_loss	0.9900
12:56339688:TAGTT:T	acceptor_loss	0.9900
12:56339689:AGTTC:A	acceptor_loss	0.9900
12:56339690:GT:G	acceptor_gain	0.9900
12:56339690:GTT:G	acceptor_gain	0.9900
12:56339690:GTTC:G	acceptor_gain	0.9900
12:56339938:TTCA:T	acceptor_loss	0.9900

AlphaMissense

1227 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:56339134:G:C	W30C	0.983
12:56339134:G:T	W30C	0.983
12:56340048:T:C	F172L	0.983
12:56340050:T:A	F172L	0.983
12:56340050:T:G	F172L	0.983
12:56339492:T:A	C77S	0.979
12:56339493:G:C	C77S	0.979
12:56339492:T:C	C77R	0.974
12:56339754:T:C	F109L	0.974
12:56339756:C:A	F109L	0.974
12:56339756:C:G	F109L	0.974
12:56339719:T:C	L97P	0.973
12:56339696:C:G	C89W	0.972
12:56340002:G:C	W156C	0.971
12:56340002:G:T	W156C	0.971
12:56339475:T:C	I71T	0.970
12:56339695:G:A	C89Y	0.970
12:56339493:G:A	C77Y	0.969
12:56339694:T:C	C89R	0.968
12:56340040:T:C	L169P	0.968
12:56339755:T:C	F109S	0.965
12:56340049:T:G	F172C	0.965
12:56340073:T:C	F180S	0.964
12:56339707:T:C	I93T	0.963
12:56340072:T:C	F180L	0.963
12:56340074:T:A	F180L	0.963
12:56340074:T:G	F180L	0.963
12:56339132:T:A	W30R	0.961
12:56339132:T:C	W30R	0.961
12:56339694:T:A	C89S	0.959

dbSNP variants (sampled 300 via entrez): RS1000462823 (12:56340550 T>C), RS1000906886 (12:56339662 C>T), RS1000918194 (12:56340135 T>C), RS1001406460 (12:56337349 C>T), RS1001440858 (12:56339322 C>A,G,T), RS1001818019 (12:56337554 T>A,C), RS1004385831 (12:56338370 C>T), RS1004438267 (12:56338889 G>A), RS1004691683 (12:56339832 C>T), RS1004788334 (12:56340425 C>T), RS1006060096 (12:56337050 G>C), RS1008070548 (12:56340554 A>G,T), RS1009041687 (12:56338059 G>A), RS1009547766 (12:56338354 C>A), RS1011376614 (12:56337106 C>T)

Disease associations

OMIM: gene MIM:605580 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000322_6	Psoriasis	1.000000e-09
GCST000833_16	Psoriasis	2.000000e-07
GCST002115_16	Axial length	4.000000e-07
GCST002738_2	Psoriasis	6.000000e-10
GCST002874_52	Psoriasis	1.000000e-10
GCST002874_53	Psoriasis	5.000000e-12
GCST003268_19	Psoriasis vulgaris	4.000000e-15
GCST003270_10	Psoriatic arthritis	5.000000e-06
GCST005527_15	Psoriasis	5.000000e-17
GCST010002_217	Refractive error	6.000000e-174

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005318	axial length measurement
EFO:1001494	psoriasis vulgaris

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2364154 (PROTEIN COMPLEX)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

93 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	affects cotreatment, decreases reaction, increases secretion, increases expression, affects expression (+2 more)	7
sodium arsenite	increases expression	3
Particulate Matter	decreases expression, increases expression	3
apilimod	affects binding, affects cotreatment, decreases reaction, increases secretion, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
Cisplatin	increases expression	2
Bucladesine	increases expression, affects cotreatment, decreases expression	2
Dust	decreases expression, increases expression	2
Methotrexate	decreases expression, increases expression	2
Nickel	increases expression	2
Silicon Dioxide	increases expression	2
Tunicamycin	increases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	increases expression	1
abemaciclib	increases expression	1
bisphenol F	decreases methylation	1
TL8-506	affects cotreatment, increases expression, increases secretion	1
triphenyl phosphate	affects expression	1
titanium dioxide	affects expression	1
decabromobiphenyl ether	affects expression	1
cinnamaldehyde	affects cotreatment, affects reaction, increases expression, affects expression, affects response to substance	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction, increases secretion	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
2-tert-butylhydroquinone	increases secretion, affects binding, decreases reaction	1
nickel sulfate	increases expression	1
resorcinol	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression, decreases reaction	1
brequinar	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8IC	Abcam HCT 116 IL23A KO	Cancer cell line	Male
CVCL_B9KL	Abcam A-549 IL23A KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.