IL22RA1

Summary

IL22RA1 (interleukin 22 receptor subunit alpha 1, HGNC:13700) is a protein-coding gene on chromosome 1p36.11, encoding Interleukin-22 receptor subunit alpha-1 (Q8N6P7). Component of the receptor for IL20, IL22 and IL24.

The protein encoded by this gene belongs to the class II cytokine receptor family, and has been shown to be a receptor for interleukin 22 (IL22). IL22 receptor is a protein complex that consists of this protein and interleukin 10 receptor, beta (IL10BR/CRFB4), a subunit also shared by the receptor complex for interleukin 10 (IL10). This gene and interleukin 28 receptor, alpha (IL28RA) form a cytokine receptor gene cluster in the chromosomal region 1p36.

Source: NCBI Gene 58985 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 119 total
• Druggable target: yes
• MANE Select transcript: NM_021258

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13700
Approved symbol	IL22RA1
Name	interleukin 22 receptor subunit alpha 1
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Aliases	CRF2-9
Ensembl gene	ENSG00000142677
Ensembl biotype	protein_coding
OMIM	605457
Entrez	58985

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000270800, ENST00000873330, ENST00000873331, ENST00000873332

RefSeq mRNA: 1 — MANE Select: NM_021258 NM_021258

CCDS: CCDS247

Canonical transcript exons

ENST00000270800 — 7 exons

Exon	Start	End
ENSE00000955798	24134211	24134386
ENSE00000955799	24128141	24128279
ENSE00000955800	24123302	24123423
ENSE00001036712	24119771	24121737
ENSE00001066332	24138582	24138714
ENSE00001066333	24137131	24137309
ENSE00001066334	24143040	24143140

Expression profiles

Bgee: expression breadth ubiquitous, 158 present calls, max score 98.19.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1027 / max 301.9451, expressed in 234 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11035	1.1027	234

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	98.19	gold quality
lower esophagus mucosa	UBERON:0035834	92.13	gold quality
jejunal mucosa	UBERON:0000399	89.72	gold quality
skin of leg	UBERON:0001511	89.66	gold quality
pancreas	UBERON:0001264	89.64	gold quality
skin of abdomen	UBERON:0001416	88.43	gold quality
zone of skin	UBERON:0000014	87.68	gold quality
upper arm skin	UBERON:0004263	87.54	silver quality
pancreatic ductal cell	CL:0002079	86.76	silver quality
ileal mucosa	UBERON:0000331	86.20	gold quality
duodenum	UBERON:0002114	85.38	gold quality
colonic mucosa	UBERON:0000317	82.57	gold quality
esophagus mucosa	UBERON:0002469	82.53	gold quality
gingival epithelium	UBERON:0001949	82.46	silver quality
upper leg skin	UBERON:0004262	82.01	gold quality
gingiva	UBERON:0001828	81.51	silver quality
mucosa of sigmoid colon	UBERON:0004993	81.21	gold quality
mucosa of transverse colon	UBERON:0004991	80.13	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.74	gold quality
rectum	UBERON:0001052	79.34	gold quality
small intestine	UBERON:0002108	79.29	gold quality
mammalian vulva	UBERON:0000997	78.63	gold quality
jejunum	UBERON:0002115	77.47	gold quality
oral cavity	UBERON:0000167	77.07	gold quality
squamous epithelium	UBERON:0006914	76.71	silver quality
islet of Langerhans	UBERON:0000006	76.58	gold quality
cervix squamous epithelium	UBERON:0006922	75.74	gold quality
epithelium of esophagus	UBERON:0001976	75.63	gold quality
tongue squamous epithelium	UBERON:0006919	75.22	silver quality
pharyngeal mucosa	UBERON:0000355	74.65	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	20.00
E-ANND-3	yes	16.20

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB

miRNA regulators (miRDB)

52 targeting IL22RA1, 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-4673	100.00	66.64	1490
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-1911-3P	99.15	66.17	528
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-485-5P	99.10	64.78	1889

Literature-anchored findings (GeneRIF, showing 40)

• study demonstrated IL-22R1 mRNA and protein expression on nasal epithelial cells; failure of medical and surgical therapy in chronic rhinosinusitis with nasal polyps is associated with significantly decreased expression of IL-22R1 (PMID:17906500)
• The islets of Langerhans are the local site for IL-22R1 expression in the human pancreas. (PMID:18376313)
• Molecular basis for the distinct affinities and specificities of IL-22 and IL-10 receptor chains that regulate cellular targeting and signal transduction to elicit effective immune responses. (PMID:18599299)
• A 1.9A crystal structure of the IL-22/IL-22R1 complex is reported. (PMID:18675809)
• identifies those amino acid side chains of IL-22 that are individually important for optimal binding to IL-22R (PMID:18675824)
• Comparison of IL-22/IL-22BP and IL-22/IL-22R1 crystal structures shows that both receptors display an overlapping IL-22 binding surface, which is consistent with the inhibitory role played by IL-22 binding protein. (PMID:19285080)
• Data show that deletion of the C-terminal part of IL-22R dramatically decreased its ability to activate STAT3. (PMID:19632985)
• Complete mda-7/IL-24 receptors (IL-22R1/IL-20R2 and IL-20R1/IL-20R2) are seldom expressed in liver cancer cell lines. (PMID:19666410)
• Increased IL-22R expression in epidermal keratinocytes contributes to the pathogenesis of psoriasis through enhancing the coordinated effects of IL-22 and IL-17, inducing the production of the IL-20 subfamily, chemokines, and growth factors. (PMID:19731362)
• Tyr251 and Tyr301 of IL-22R1 are required for Shp2 binding and IL-22-induced Erk1/2 activation. (PMID:20671117)
• This study documents a previously unknown role of IL-22R1 in inflammation and identifies the involvement of IL-22R1/IL-22 in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (PMID:20971950)
• IL-22R1 mRNA and protein expressions in HASMCs were significantly increased after stimulation by serum from asthmatic patients, but decreased after co-stimulation with dexamethasone. (PMID:21690049)
• Data show that IL-17RA, IL-17RC, IL-22R1, ERK1/2 MAPK and NF-kappaB pathways are involved in Th17 cytokine-induced proliferation. (PMID:22898922)
• serum IL-22 levels are significantly higher in patients with pituitary macroadenomas than in healthy controls and IL-22R is variably expressed in both prolactinoma and non-functioing pituitary adenoma cells. (PMID:23512698)
• the CC genotype of rs3795299 polymorphism in the IL-22R1 gene is associated with the reduced risk of IgAN, and this genetic association was supported by the higher renal expression of IL-22R1 in healthy controls compared with patients with IgAN. (PMID:23659670)
• Letter: calcipotriol inhibits the IL-22-induced epidermal hyperplasia by decreasing keratinocyte proliferation and down-modulating IL-22R expression. (PMID:23688404)
• High expression of interleukin-22 receptor is associated with pancreatic ductal adenocarcinoma. (PMID:24132627)
• IL-22 has restricted tissue specificity as its unique receptor IL-22R1 is exclusively expressed on epithelial and tissue cells, but not immune cells. (PMID:24856143)
• IL-22R1 is over-expressed in primary Sjogren’s syndrome and Sjogren-associated non-Hodgkin lymphomas and is regulated by IL-18. (PMID:25880879)
• FBXW12 functions as an E3 ligase constituent to ubiquitinate and degrade IL-22R and that therapeutic FBXW12 inhibition may enhance IL-22 signaling and bolster mucosal host defense and infection containment. (PMID:26171402)
• high expression profile of IL-22R1 in nonsmall cell lung cancer is an independent indicator of poor overall survival (PMID:26846835)
• phosphorylation of STAT3 and AKT was highly induced by treatment with IL-22 via IL-22R1. IL-22R1 was also consistently overexpressed in recurrent NSCLC tissues (PMID:26983629)
• IL-22 and its receptor have a crucial role in the development and pathogenesis of uveitis by facilitating inflammatory cell infiltration. (PMID:27166675)
• These data suggest that imbalance of IL-22/IL-22R1 signaling regulates the pathogenesis of chronic rhinosinusitis with nasal polyps, including local eosinophilia, via alteration of MUC1 expression. (PMID:27502468)
• increased expression of IL-22Ralpha therefore promotes keratinocyte proliferation and pro-inflammatory cytokine production during UVB-induced skin inflammation, suggesting that UVB facilitates skin inflammation by increasing the responsiveness of keratinocytes to IL-22 (PMID:28558005)
• found obvious statistic difference for the allele of early-onset PE/the genotype of late-onset preeclampsia (PE) and control subgroups for IL-22 rs2227485. IL-22 rs2227485 and IL-22RA1 rs3795299 may be associated with the development of PE in Chinese Han population. (PMID:29274280)
• Study shows that high expression of IL22RA1 is associated with poor prognosis in pancreatic cancer. IL22 promotes pancreatic cancer stemness via IL22RA1/STAT3 signaling, identifying the mechanism of regulation of cancer stem cells by microenvironmental factors. Moreover, STAT3 activation is indispensable for the maintenance of IL22RA1-hi cells, both in the absence or presence of IL22. (PMID:29572224)
• The IL22 gene promoter SNP rs2227473 G allele is a risk factor for intestinal tuberculosis. High IL-22 expression seems to be a protective factor for intestinal tuberculosis. IL-22R1 is not only highly expressed in epithelial cells but also, unexpectedly, expressed in Langhans giant cells, contradicting the previous view that IL-22R1 is expressed only in non-haematopoietic cells. (PMID:31171891)
• Overexpression of IL22RA1 enhanced HTFs migration and proliferation, while miR-760 and miR-215-3p mimics reversed these promotive biological roles induced by IL22RA1. In conclusion, NR_003923 and IL22RA1 might contribute to glaucoma progression and be a novel and potential biomarkers and therapeutic targets for glaucoma (PMID:31391457)
• During influenza infection, IL22RA1 is induced in the lung. (PMID:31416461)
• Association of interleukin 22 receptor subunit alpha 1 gene polymorphisms with chronic rhinosinusitis. (PMID:31879195)
• Targeting IL-22 and IL-22R protects against experimental osteoarthritis. (PMID:32636527)
• High IL-22RA1 gene expression is associated with poor outcome in muscle invasive bladder cancer. (PMID:34134925)
• Liver expression of IL-22, IL-22R1 and IL-22BP in patients with chronic hepatitis C with different fibrosis stages. (PMID:34920229)
• Increased expression of interleukin-22 and its receptor is relevant to poor prognosis in laryngeal squamous cell carcinoma: A case control trial. (PMID:34941188)
• Distinct Expression Patterns of Interleukin-22 Receptor 1 on Blood Hematopoietic Cells in SARS-CoV-2 Infection. (PMID:35422799)
• Lack of Association of Polymorphisms in IL22 and IL22RA1 Genes with Fibrosis Severity in Patients with Chronic Hepatitis C. (PMID:35838587)
• Sex-Dependent Hepatoprotective Role of IL-22 Receptor Signaling in Non-Alcoholic Fatty Liver Disease-Related Fibrosis. (PMID:35970323)
• Association of IL10RA, IL10RB, and IL22RA Polymorphisms/Haplotypes with Susceptibility to and Clinical Manifestations of SLE. (PMID:37511050)
• Pancreatic beta-cell IL-22 receptor deficiency induces age-dependent dysregulation of insulin biosynthesis and systemic glucose homeostasis. (PMID:38811550)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	il22ra2	ENSDARG00000039439
danio_rerio	ifngr2	ENSDARG00000067795
danio_rerio	ifngr1l	ENSDARG00000074488
danio_rerio	ifngr1	ENSDARG00000074771
danio_rerio	crfb16	ENSDARG00000075181
danio_rerio	ifnlr1	ENSDARG00000087131
danio_rerio	crfb15	ENSDARG00000099342
mus_musculus	Il22ra1	ENSMUSG00000037157
rattus_norvegicus	Il22ra1	ENSRNOG00000066331

Paralogs (11): IL20RA (ENSG00000016402), IFNGR1 (ENSG00000027697), IL10RA (ENSG00000110324), F3 (ENSG00000117525), IFNAR1 (ENSG00000142166), IFNAR2 (ENSG00000159110), IFNGR2 (ENSG00000159128), IL22RA2 (ENSG00000164485), IL20RB (ENSG00000174564), IFNLR1 (ENSG00000185436), IL10RB (ENSG00000243646)

Protein

Protein identifiers

Interleukin-22 receptor subunit alpha-1 — Q8N6P7 (reviewed: Q8N6P7)

Alternative names: Cytokine receptor class-II member 9, Cytokine receptor family 2 member 9, ZcytoR11

All UniProt accessions (1): Q8N6P7

UniProt curated annotations — full annotation on UniProt →

Function. Component of the receptor for IL20, IL22 and IL24. Component of IL22 receptor formed by IL22RA1 and IL10RB enabling IL22 signaling via JAK/STAT pathways. IL22 also induces activation of MAPK1/MAPK3 and Akt kinases pathways. Component of one of the receptor for IL20 and IL24 formed by IL22RA1 and IL20RB also signaling through STATs activation. Mediates IL24 antiangiogenic activity as well as IL24 inhibitory effect on endothelial cell tube formation and differentiation.

Subunit / interactions. Heterodimer with IL10RB and with IL20RB. IL22 binding to heterodimer is greater than binding to IL22RA1 alone. Interacts with FBXW12; the interaction promotes ubiquitination of IL22RA1.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in colon, liver, lung, pancreas and kidney. No expression in immune cells such as monocytes, T-cells, and NK-cells. Expressed in keratinocytes of normal skin as well as in psoriatic skin lesion. Detected in normal blood brain barrier endothelial cells as well as in multiple sclerosis lesions; Strongly expressed on central nervous system vessels within infiltrated multiple sclerosis lesions. Overexpressed in synovial fluid cells from rheumatoid arthritis and spondyloarthropathy patients.

Post-translational modifications. Ubiquitinated.

Induction. By IFNG/IFN-gamma in keratinocytes.

Miscellaneous. Failure of medical and surgical therapy in Chronic rhinosinusitis with nasal polyps is associated with decreased expression of IL22RA1.

Similarity. Belongs to the type II cytokine receptor family.

RefSeq proteins (1): NP_067081* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR050650

Pfam: PF01108

UniProt features (46 total): strand 15, sequence variant 6, helix 5, region of interest 3, modified residue 2, glycosylation site 2, disulfide bond 2, topological domain 2, mutagenesis site 2, domain 2, signal peptide 1, chain 1, sequence conflict 1, transmembrane region 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3DLQ	X-RAY DIFFRACTION	1.9
6DF3	X-RAY DIFFRACTION	2.15
3DGC	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N6P7-F1	62.69	0.37

Functional residue map

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

Post-translational modifications (2): 410, 414

Disulfide bonds (2): 71–79, 128–217

Glycosylation sites (2): 80, 172

Mutagenesis-validated functional residues (2):

Position	Phenotype
58	strongly reduced response to il22.
60	loss of response to il22.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8854691	Interleukin-20 family signaling

MSigDB gene sets: 80 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_INTERLEUKIN_4, GOBP_RESPONSE_TO_PEPTIDE, AMIT_SERUM_RESPONSE_20_MCF10A, GAURNIER_PSMD4_TARGETS, IRF7_01, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_NEGATIVE_REGULATION_OF_DEFENSE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_INFLAMMATORY_RESPONSE, TGANTCA_AP1_C, GOBP_DEFENSE_RESPONSE_TO_GRAM_NEGATIVE_BACTERIUM, IRF_Q6

GO Biological Process (5): cytokine-mediated signaling pathway (GO:0019221), negative regulation of inflammatory response (GO:0050728), defense response to Gram-negative bacterium (GO:0050829), negative regulation of cytokine production involved in inflammatory response (GO:1900016), interleukin-22-mediated signaling pathway (GO:0140865)

GO Molecular Function (5): cytokine receptor activity (GO:0004896), interferon receptor activity (GO:0004904), interleukin-20 binding (GO:0042015), interleukin-22 receptor activity (GO:0042018), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by Interleukins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytokine-mediated signaling pathway	2
cytokine binding	2
cytokine receptor activity	2
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
inflammatory response	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of inflammatory response	1
defense response to bacterium	1
negative regulation of cytokine production	1
cytokine production involved in inflammatory response	1
regulation of cytokine production involved in inflammatory response	1
transmembrane signaling receptor activity	1
immune receptor activity	1
interferon binding	1
interleukin-22 binding	1
interleukin-22-mediated signaling pathway	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1001 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL22RA1	IL10RB	Q08334	999
IL22RA1	IL20RB	Q6UXL0	999
IL22RA1	IL22	Q9GZX6	998
IL22RA1	IL10RA	Q13651	971
IL22RA1	IL24	Q13007	966
IL22RA1	IL20RA	Q9UHF4	927
IL22RA1	IL26	Q9NPH9	921
IL22RA1	IL19	Q9UHD0	871
IL22RA1	JAK1	P23458	869
IL22RA1	IL17RA	Q96F46	834
IL22RA1	STAT3	P40763	820
IL22RA1	TYK2	P29597	801
IL22RA1	IL17RC	Q8NAC3	766
IL22RA1	IL10	P22301	747
IL22RA1	STAT1	P42224	738

IntAct

26 interactions, top by confidence:

A	B	Type	Score
IL22RA1	IL22	psi-mi:“MI:0407”(direct interaction)	0.850
IL22	IL22RA1	psi-mi:“MI:0407”(direct interaction)	0.850
IL22	IL10RB	psi-mi:“MI:0915”(physical association)	0.590
IL22RA1	JPH3	psi-mi:“MI:0915”(physical association)	0.560
JPH3	IL22RA1	psi-mi:“MI:0915”(physical association)	0.560
IL22RA1	STAT3	psi-mi:“MI:0915”(physical association)	0.550
IL22	IL22RA1	psi-mi:“MI:0915”(physical association)	0.400
IL22RA1	IL22	psi-mi:“MI:0915”(physical association)	0.400
IL22RA1	IL10RB	psi-mi:“MI:0915”(physical association)	0.400
IL10RB	IL22RA1	psi-mi:“MI:0915”(physical association)	0.400
IL22RA1	IL22RA2	psi-mi:“MI:0915”(physical association)	0.400
IL20RB	IL22RA1	psi-mi:“MI:0915”(physical association)	0.400
IL22RA1	IL20RB	psi-mi:“MI:0915”(physical association)	0.400
IL22RA1	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
PRKAA1	NUP155	psi-mi:“MI:0914”(association)	0.350

BioGRID (32): IL22RA1 (Affinity Capture-Western), IL22RA1 (Biochemical Activity), IL22RA1 (Negative Genetic), IL22RA1 (Negative Genetic), IL22RA1 (Negative Genetic), VHL (Negative Genetic), IL22RA1 (Reconstituted Complex), ATP13A2 (Affinity Capture-MS), SLITRK5 (Affinity Capture-MS), CTDNEP1 (Affinity Capture-MS), CYB5R1 (Affinity Capture-MS), IL22RA1 (Affinity Capture-Western), PDZD8 (Affinity Capture-MS), FAM69A (Affinity Capture-MS), IL22 (Reconstituted Complex)

ESM2 similar proteins: A0A1B0GU29, A6NLX4, A6QNY1, A9CBA0, B7ZWI3, O14669, O88472, P14784, P16297, P25918, P26896, Q0VFL4, Q13651, Q32M26, Q38J84, Q38J85, Q3SYS8, Q58CT8, Q5BK39, Q5EAA5, Q5HZE8, Q5NCP0, Q5RCL0, Q64322, Q68DV7, Q6AXS2, Q6AXU5, Q6NUJ2, Q6UWV7, Q86UW2, Q8BHB3, Q8BLR5, Q8BSU2, Q8C353, Q8C708, Q8K1T1, Q8MII8, Q8N6P7, Q8NET5, Q8R182

Diamond homologs: K9JA28, Q3SYS8, Q7TNI4, Q80XF5, Q80XZ4, Q8N6P7, Q969J5, Q61727, Q6PHB0, Q9UHF4

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
IL22RA1	up-regulates	JAK1	binding
IL20	up-regulates	IL22RA1	binding
IL22	up-regulates	IL22RA1	binding
IL22RA1	up-regulates	STAT3
IL22RA1	up-regulates	TYK2	binding
FBXW12	“down-regulates quantity by destabilization”	IL22RA1	binding
“Cullin 1-RBX1-Skp1”	“down-regulates quantity by destabilization”	IL22RA1	polyubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	96
Likely benign	6
Benign	12

Top pathogenic / likely-pathogenic (0)

SpliceAI

1082 predictions. Top by Δscore:

Variant	Effect	Δscore
1:24128280:C:CC	acceptor_gain	1.0000
1:24134204:CA:C	donor_gain	1.0000
1:24134204:CACT:C	donor_gain	1.0000
1:24134206:CTCA:C	donor_loss	1.0000
1:24134207:TCA:T	donor_loss	1.0000
1:24134208:CACCA:C	donor_loss	1.0000
1:24134209:A:AC	donor_gain	1.0000
1:24134209:A:AG	donor_loss	1.0000
1:24134209:AC:A	donor_gain	1.0000
1:24134210:C:A	donor_loss	1.0000
1:24134210:C:CT	donor_gain	1.0000
1:24134210:CC:C	donor_gain	1.0000
1:24134210:CCA:C	donor_gain	1.0000
1:24134210:CCAT:C	donor_gain	1.0000
1:24134382:GGTAG:G	acceptor_gain	1.0000
1:24134383:GTAG:G	acceptor_gain	1.0000
1:24134384:TAG:T	acceptor_gain	1.0000
1:24134385:AG:A	acceptor_gain	1.0000
1:24134387:C:CC	acceptor_gain	1.0000
1:24134387:CT:C	acceptor_loss	1.0000
1:24134393:A:AC	acceptor_gain	1.0000
1:24134393:A:C	acceptor_gain	1.0000
1:24137129:A:AC	donor_gain	1.0000
1:24137130:C:CC	donor_gain	1.0000
1:24137130:CTGTG:C	donor_gain	1.0000
1:24138580:A:AC	donor_gain	1.0000
1:24138581:C:CC	donor_gain	1.0000
1:24138581:CGT:C	donor_gain	1.0000
1:24138583:T:TA	donor_gain	1.0000
1:24138589:A:AC	donor_gain	1.0000

AlphaMissense

3702 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:24137147:G:C	F113L	0.993
1:24137147:G:T	F113L	0.993
1:24137149:A:G	F113L	0.993
1:24138635:C:A	W41C	0.993
1:24138635:C:G	W41C	0.993
1:24137291:C:A	W65C	0.992
1:24137291:C:G	W65C	0.992
1:24138669:A:G	F30S	0.992
1:24138668:G:C	F30L	0.991
1:24138668:G:T	F30L	0.991
1:24138670:A:G	F30L	0.991
1:24138637:A:G	W41R	0.989
1:24138637:A:T	W41R	0.989
1:24138669:A:C	F30C	0.989
1:24128175:A:C	S212R	0.987
1:24128175:A:T	S212R	0.987
1:24128177:T:G	S212R	0.987
1:24137148:A:G	F113S	0.987
1:24137205:G:T	A94D	0.986
1:24128220:G:C	F197L	0.984
1:24128220:G:T	F197L	0.984
1:24128222:A:G	F197L	0.984
1:24137293:A:G	W65R	0.981
1:24137293:A:T	W65R	0.981
1:24138589:A:C	Y57D	0.979
1:24138656:G:C	N34K	0.979
1:24138656:G:T	N34K	0.979
1:24137148:A:C	F113C	0.977
1:24137244:A:G	L81P	0.977
1:24137250:C:G	C79S	0.977

dbSNP variants (sampled 300 via entrez): RS1000380436 (1:24132754 A>G), RS1000393362 (1:24138079 T>C), RS1000518767 (1:24140157 G>A), RS1000641306 (1:24121300 A>G), RS1000650102 (1:24133778 G>A), RS1000780198 (1:24128025 C>A), RS1000792823 (1:24121940 T>C), RS1000884497 (1:24122170 C>T), RS1000966826 (1:24139684 C>T), RS1000975510 (1:24127139 T>A), RS1001254196 (1:24124810 C>A,T), RS1001344391 (1:24124852 T>C), RS1001505736 (1:24133816 C>T), RS1001581563 (1:24130920 G>A), RS1001639512 (1:24124194 G>T)

Disease associations

OMIM: gene MIM:605457 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4804251 (PROTEIN COMPLEX)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs75824728	IL22RA1		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — IL-10 receptor family

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression, decreases reaction	3
Cyclosporine	decreases expression	3
Tetrachlorodibenzodioxin	increases expression, decreases expression	2
aristolochic acid I	increases expression	1
chlorophyllin	decreases reaction, increases expression	1
sodium arsenate	decreases expression, increases abundance	1
kojic acid	increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
abrine	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Rosiglitazone	decreases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Formaldehyde	increases expression	1
Methotrexate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Quercetin	decreases expression	1
Sarin	increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	affects expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A8CG	HEK-Blue IL-22	Transformed cell line	Female
CVCL_E8EF	HEK-Blue IL-20	Transformed cell line	Female

Clinical trials (associated diseases)

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