IL23A
protein-codinginterleukin 23 subunit alpha, the group of Interleukins
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to IL23A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016584.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 17 | 17 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 19 | 0 | 0 | 19 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057668.1 | 4 | MANE Select | |
| Ensembl | ENSP00000228534.4 | 4 | MANE Select | |
| Ensembl | ENSP00000801935.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Pertussis - Homo sapiens (human)
- Jak-STAT signaling pathway - Homo sapiens (human)
- Inflammatory bowel disease (IBD) - Homo sapiens (human)
- C-type lectin receptor signaling pathway - Homo sapiens (human)
- Tuberculosis - Homo sapiens (human)
Biological Process
- positive regulation of T cell mediated cytotoxicity
- positive regulation of defense response to virus by host
- positive regulation of T-helper 1 type immune response
- inflammatory response
- regulation of signaling receptor activity
Molecular Function
- cytokine activity
- protein binding
- interleukin-23 receptor binding
Cellular Component
- extracellular region
- endoplasmic reticulum lumen
- interleukin-23 complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000228534
- Coding exons
- 4
- Length
- 1531
- Individuals with no LoFs
- 125740
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125746
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.19 | 67 | 101 | 0.665 | 0.00000512 | 1219 |
| Missense (PolyPhen) | 28 | 41.105 | 0.68118 | 441 | ||
| Synonymous | 1.30 | 28 | 38.2 | 0.733 | 0.00000173 | 393 |
| Loss of Function | 2.13 | 2 | 8.86 | 0.226 | 3.79e-7 | 93 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000026 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Associates with IL12B to form the IL-23 interleukin, a heterodimeric cytokine which functions in innate and adaptive immunity. IL-23 may constitute with IL-17 an acute response to infection in peripheral tissues. IL-23 binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R, activates the Jak- Stat signaling cascade, stimulates memory rather than naive T- cells and promotes production of proinflammatory cytokines. IL-23 induces autoimmune inflammation and thus may be responsible for autoimmune inflammatory diseases and may be important for tumorigenesis. {ECO:0000269|PubMed:11114383, ECO:0000269|PubMed:12023369, ECO:0000269|PubMed:16424222}.;
Recessive Scores
- pRec
- 0.583
Intolerance Scores
- LoFtool
- 0.270
- RVIS EVS
- -0.08
- RVIS percentile EVS
- 47.79
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.929
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |