IL23A

Chr 12

interleukin 23 subunit alpha

Also known as: IL-23, IL-23A, IL23P19, P19, SGRF

NCBI Gene: 51561ENSG00000110944UniProt: Q9NPF7

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. [provided by RefSeq, Jul 2008]

26
ClinVar variants
6
Pathogenic / LP
0.36
pLI score
5
Active trials
Clinical Summary— IL23A
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 19 VUS of 26 total submissions
💊
Clinical Trials
5 active or recruiting trials — 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.
0.71LOEUF
pLI 0.358
Z-score 2.13
OE 0.23 (0.09–0.71)
Tolerant

Typical tolerance to LoF variation

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.
1.19Z-score
OE missense 0.67 (0.55–0.81)
67 obs / 100.7 exp
Tolerant

Mild missense constraint

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.0.23 (0.09–0.71)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.55–0.81)
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.0.73
0≤1.21.6
LoF obs/exp: 2 / 8.9Missense obs/exp: 67 / 100.7Syn Z: 1.30

ClinVar Variant Classifications

26 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
VUS19
Benign1
6
Pathogenic
19
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
0
0
0
VUS
0
16
3
0
19
Likely Benign
0
0
0
0
0
Benign
0
0
0
1
1
Total0169126

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

View in ClinVar →

Protein Context — Lollipop Plot

IL23A · 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
Role of the IL-23/IL-17 Pathway in Rheumatic Diseases: An Overview.
Schinocca C et al.·Front Immunol
2021Review
IL-23 inhibition for chronic inflammatory disease.
Jairath V et al.·Lancet
2024Review
Endothelial TFEB signaling-mediated autophagic disturbance initiates microglial activation and cognitive dysfunction.
Lu Y et al.·Autophagy
2023
Uveitis genetics.
Hou S et al.·Exp Eye Res
2020Review
Single-cell transcriptomics applied to emigrating cells from psoriasis elucidate pathogenic versus regulatory immune cell subsets.
Kim J et al.·J Allergy Clin Immunol
2021
AR(+)TREM2(+) macrophage induced pathogenic immunosuppression promotes prostate cancer progression.
Wang Q et al.·Nat Commun
2025
Single-cell transcriptomics identifies pathogenic T-helper 17.1 cells and pro-inflammatory monocytes in immune checkpoint inhibitor-related pneumonitis.
Franken A et al.·J Immunother Cancer
2022
CCR7(+) dendritic cells expressing both IL-23A and IL-12B potentially contribute to psoriasis relapse.
Sun Y et al.·Nat Commun
2025
Biomarkers of disease progression in people with psoriasis: a scoping review.
Ramessur R et al.·Br J Dermatol
2022Review
Genetics of psoriatic arthritis.
O'Rielly DD et al.·Best Pract Res Clin Rheumatol
2014Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Chemotherapy-induced high expression of IL23A enhances efficacy of anti-PD-1 therapy in TNBC by co-activating the PI3K-AKT signaling pathway of CTLs.
Pan F et al.·Sci Rep
2024🔓 Open Access
Helicobacter pylori with trx1 high expression promotes gastric diseases via upregulating the IL23A/NF-κB/IL8 pathway.
Guan X et al.·Helicobacter
2024
Mucosal IL23A expression predicts the response to Ustekinumab in inflammatory bowel disease.
Nishioka K et al.·J Gastroenterol
2021
Single-cell analysis of human skin identifies CD14+ type 3 dendritic cells co-producing IL1B and IL23A in psoriasis.
Nakamizo S et al.·J Exp Med
2021🔓 Open Access
CD4+ and CD25+ T-cell response to short-time interferon-beta therapy on IL10, IL23A and FOXP3 genes in multiple sclerosis patients.
Gezmis H et al.·Int J Clin Pract
2021Cohort
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Migraine DisordersPainAutoimmune Diseases

The Role of Cytokines and Regulatory T Lymphocytes in Migraine Pathophysiology.

RECRUITING
NCT06426316Phase NAUniversity Hospital, Clermont-FerrandStarted 2025-06-02
Blood test
Systemic Histiocytosis (Disorder)

Biomarkers in Systemic Histiocytosis

NOT YET RECRUITING
NCT07157683Assistance Publique - Hôpitaux de ParisStarted 2025-10-01
Biospecimen collection
Chronic Post Operative Pain

Cytokine Alterations and Chronic Post-Surgical Pain

NOT YET RECRUITING
NCT06418295London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sStarted 2026-01-01
Unilateral thoracotomy
Post-Acute COVID-19 Syndrome

A Study of Apabetalone in Subjects With Long -COVID

RECRUITING
NCT06590324Phase PHASE2, PHASE3Resverlogix CorpStarted 2025-04-15
Apabetalone
Chronic Spontaneous Urticaria (CSU)Hidradenitis Suppurativa (HS)Psoriasis (PsO)

SKIN Disease Profiling by an Exploratory, pRospective, Biomarker Study in dermatoloGY Practice (SKINERGY)

RECRUITING
NCT07021495Leiden University Medical CenterStarted 2025-07-29

External Resources

Links to major genomics databases and tools