IL22RA2

Chr 6

interleukin 22 receptor subunit alpha 2

Also known as: CRF2-10, CRF2-S1, CRF2X, IL-22BP, IL-22R-alpha-2, IL-22RA2, ZCYTOR16

NCBI Gene: 116379ENSG00000164485UniProt: Q969J5

This gene encodes a member of the class II cytokine receptor family. The encoded soluble protein specifically binds to and inhibits interleukin 22 activity by blocking the interaction of interleukin 22 with its cell surface receptor. The encoded protein may be important in the regulation of inflammatory response, and has been implicated in the regulation of tumorigenesis in the colon. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2013]

49
ClinVar variants
16
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— IL22RA2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 30 VUS of 49 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.86LOEUF
pLI 0.000
Z-score -1.36
OE 1.38 (0.97–1.86)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.14Z-score
OE missense 1.03 (0.90–1.19)
145 obs / 140.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.38 (0.97–1.86)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.03 (0.90–1.19)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.80
0≤1.21.6
LoF obs/exp: 21 / 15.3Missense obs/exp: 145 / 140.5Syn Z: 1.10

ClinVar Variant Classifications

49 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
VUS30
Likely Benign3
16
Pathogenic
30
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
0
0
0
VUS
0
28
2
0
30
Likely Benign
0
2
1
0
3
Benign
0
0
0
0
0
Total03019049

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

View in ClinVar →

Protein Context — Lollipop Plot

IL22RA2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The Rare IL22RA2 Signal Peptide Coding Variant rs28385692 Decreases Secretion of IL-22BP Isoform-1, -2 and -3 and Is Associated with Risk for Multiple Sclerosis.
Gómez-Fernández P et al.·Cells
2020
Circulating apelin, IL22RA2 and VEGF in pre-capillary pulmonary hypertension.
Csósza G et al.·Physiol Int
2023
IL-22RA2 Is a SMAD7 Target Mediating the Alleviation of Dermatitis and Psoriatic Phenotypes in Mice.
Ke Y et al.·J Invest Dermatol
2023
Deletion of the entire interferon-γ receptor 1 gene causing complete deficiency in three related patients.
de Vor IC et al.·J Clin Immunol
2016Cohort
Newborn DNA methylation and asthma acquisition across adolescence and early adulthood.
Li L et al.·Clin Exp Allergy
2022
Genetic and Clinical Characteristics of Patients in the Middle East With Multisystem Inflammatory Syndrome in Children.
Abuhammour W et al.·JAMA Netw Open
2022Cohort
Assessment of microRNA-related SNP effects in the 3' untranslated region of the IL22RA2 risk locus in multiple sclerosis.
Lill CM et al.·Neurogenetics
2014
A Functional IL22 Polymorphism (rs2227473) Is Associated with Predisposition to Childhood Cerebral Malaria.
Marquet S et al.·Sci Rep
2017Functional
Serum pharmacodynamic biomarkers for chronic corticosteroid treatment of children.
Hathout Y et al.·Sci Rep
2016
Cytokine and Chemokine-Associated Signatures Underlying Dermal Invasion and Skin Metastasis in Melanoma.
Koroknai V et al.·Int J Mol Sci
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Acute-On-Chronic Liver FailureAlcoholic HepatitisLiver Cirrhosis, Alcoholic

A-TANGO Phase 2 Study

NOT YET RECRUITING
NCT06890039Phase PHASE2Yaqrit LtdStarted 2025-09-01
PlaceboTAK-242G-CSF (Filgrastim)

External Resources

Links to major genomics databases and tools