IL23R

Chr 1

interleukin 23 receptor

Also known as: PSORS7

NCBI Gene: 149233ENSG00000162594UniProt: Q5VWK5

This protein associates with IL12RB1 to form the interleukin-23 receptor, which binds IL-23 and mediates stimulation of T-cells, NK cells, and certain macrophage/myeloid cells through the Jak-Stat signaling cascade. Mutations in this gene are associated with protection against inflammatory bowel disease and psoriasis rather than causing disease. The gene is not highly constrained against loss-of-function variants, consistent with protective rather than pathogenic effects of certain mutations.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

{Inflammatory bowel disease 17, protection against}MIM #612261
{Psoriasis, protection against}MIM #605606
5
Active trials
45
Pubs (1 yr)
25
P/LP submissions
0%
P/LP missense
0.61
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— IL23R
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
25 unique Pathogenic / Likely Pathogenic· 256 VUS of 476 total submissions
💊
Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.61LOEUF
pLI 0.001
Z-score 3.22
OE 0.37 (0.23–0.61)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.08Z-score
OE missense 0.83 (0.75–0.92)
264 obs / 318.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.37 (0.23–0.61)
0≤0.351.4
Missense OE0.83 (0.75–0.92)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 11 / 30.0Missense obs/exp: 264 / 318.4Syn Z: -0.02
DN
0.78top 25%
GOF
0.83top 10%
LOF
0.2288th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

476 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic2
VUS256
Likely Benign163
Benign21
Conflicting6
23
Pathogenic
2
Likely Pathogenic
256
VUS
163
Likely Benign
21
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
23
0
23
Likely Pathogenic
0
0
2
0
2
VUS
8
221
21
6
256
Likely Benign
0
6
65
92
163
Benign
1
5
9
6
21
Conflicting
—6
Total9232120104471

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

IL23R · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
IL23R as an indicator of immune infiltration and poor prognosis in intrahepatic cholangiocarcinoma: a bioinformatics analysis
Zhang LT et al.·Transl Cancer Res
2023
Determination of IL-23 receptor expression and gene polymorphism (rs1884444) in Iranian patients with ankylosing spondylitis
Mellati A et al.·BMC Rheumatol
2024Cohort
Dietary mercury intake, the IL23R rs10889677 polymorphism, and the risk of gastric cancer in a Korean population: a hospital-based case-control study
Kim JH et al.·Epidemiol Health
2024
Targeted Sequencing of Cytokine-Induced PI3K-Related Genes in Ulcerative Colitis, Colorectal Cancer and Colitis-Associated Cancer
Razali NN et al.·Int J Mol Sci
2022
Identification of an Induced Orthosteric Pocket in IL-23: A New Avenue for Non-biological Therapeutic Targeting
Lecomte FC et al.·ACS Chem Biol
2025
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Deep learning-guided discovery of IL23/IL23R macromolecular inhibitors: An integrative framework combining virtual screening and experimental validation.
Manan A et al.·Int J Biol Macromol
2026
Ectopic co-expression of canonical and LINE1 and THE1A-exonizing IL23R transcripts in sarcoid myopathy.
Iida A et al.·J Hum Genet
2026
Homozygosity for the Common IL23R R381Q Variant Associates with Increased Susceptibility to Chronic Mucocutaneous Candidiasis.
Gerbaux M et al.·Eur J Immunol
2025Open Access
A hybrid protocol for peptide development: integrating deep generative models and physics simulations for biomolecular design targeting IL23R/IL23.
Qayyum N et al.·Int J Biol Macromol
2025Functional
Mendelian randomization analysis identifies ERAP1 and IL23R as potential drug targets for ankylosing spondylitis.
Wu W et al.·Life Sci
2025
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients