IL12A Gene: Interleukin-12 Subunit Alpha - Function, Disease Associations, and Expression
Comprehensive biomedical overview of IL12A, encoding the p35 subunit of IL-12, with roles in immune regulation, autoimmunity, and cancer.
Gene Information Card
| Symbol | IL12A |
|---|---|
| Full Name | Interleukin 12 subunit alpha |
| Gene Type | protein coding |
| Chromosomal Location | 3q25.33 (GRCh38: chr3:159,988,835-159,996,019) |
| NCBI Gene ID | 3592 ncbi.nlm.nih.gov/gene/3592 |
| Ensembl ID | ENSG00000168811 |
| UniProt ID | P29459 |
| OMIM ID | 161560 |
| HGNC ID | 5970 |
| Aliases | CLMF p35, IL-12A, NKSF1, p35 |
Description
The IL12A gene encodes the p35 subunit of interleukin-12 (IL-12), a heterodimeric cytokine composed of p35 (IL-12A) and p40 (IL-12B). IL-12 is produced by antigen-presenting cells and plays a critical role in promoting Th1 immune responses, enhancing cytotoxic T cell and NK cell activity, and inducing interferon-gamma (IFN-gamma) production. IL12A is also a subunit of IL-35, an immunosuppressive cytokine. The gene is located on chromosome 3q25.33 and is expressed in various immune and non-immune tissues. Dysregulation of IL12A has been implicated in autoimmune diseases, infectious diseases, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autoimmune diseases (e.g., multiple sclerosis, rheumatoid arthritis) | IL12A variants may alter IL-12 production, affecting Th1/Th17 balance and inflammatory responses. | GWAS and case-control studies (e.g., PMID: 19010703, 20453841) |
| Infectious diseases (e.g., tuberculosis, leishmaniasis) | IL-12 is essential for host defense; reduced IL-12 activity impairs IFN-gamma-mediated immunity. | Functional studies and genetic association (e.g., PMID: 14694169) |
| Cancer (e.g., colorectal, lung, melanoma) | IL-12 can promote anti-tumor immunity, but chronic inflammation may contribute to tumorigenesis; IL12A expression varies by tumor type. | Expression studies and clinical trials (e.g., PMID: 24675833) |
| Inflammatory bowel disease (IBD) | IL-12 p70 drives intestinal inflammation; IL12A variants may influence susceptibility. | GWAS (e.g., PMID: 21102463) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 8.9 | Medium |
| Spleen | 7.2 | Medium |
| Bone marrow | 5.4 | Low |
| Lung | 3.1 | Low |
| Small intestine | 2.8 | Low |
| Brain | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Monocytes | 12.5 | High expression; induced by LPS/IFN-gamma |
| Dendritic cells | 10.2 | High expression upon activation |
| B cells | 4.3 | Moderate expression |
| T cells | 1.2 | Low expression; mainly in activated subsets |
| NK cells | 0.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs3212227 (3'UTR) | SNP | Allele frequency: A=0.25 (global) | Associated with altered IL-12 levels and disease susceptibility (e.g., asthma, cancer) |
| rs17860508 (5' flanking) | SNP | Allele frequency: C=0.30 (global) | May affect promoter activity and IL12A expression |
| c.315C>T (p.Ser105=) | Synonymous | Rare (MAF<0.01) | No known functional effect |
| c.467A>G (p.Asn156Ser) | Missense | Very rare (MAF<0.001) | Potential impact on protein stability; clinical significance uncertain |
Mutation functional classification
Loss of Function (LOF)
Rare deleterious variants that impair IL-12 p70 secretion or receptor binding, leading to immunodeficiency and increased susceptibility to mycobacterial infections.
Gain of Function (GOF)
Not well characterized; some promoter variants may increase IL12A expression, potentially enhancing inflammatory responses.
Dominant Negative (DN)
No dominant-negative mutations reported for IL12A; however, mutations affecting heterodimer formation could theoretically interfere with IL-12 function.
View complete mutation data：
Gene Ontology (GO)
| • cytokine activity | • interleukin-12 receptor binding |
| • protein heterodimerization activity | • extracellular space |
| • immune response | • cell surface receptor signaling pathway |
| • positive regulation of T cell proliferation | • positive regulation of interferon-gamma production |
Pathways
• IL-12 signaling pathway (KEGG hsa04620)
• Th1 and Th2 cell differentiation (KEGG hsa04658)
• Cytokine-cytokine receptor interaction (KEGG hsa04060)
• Toll-like receptor signaling pathway (KEGG hsa04620)
• JAK-STAT signaling pathway (KEGG hsa04630)
Protein Summary
The IL12A protein (p35) is a 219-amino-acid polypeptide (mature form ~197 aa) that contains an immunoglobulin-like domain and is structurally related to type I cytokines. It is synthesized as a precursor with a signal peptide and is secreted as a heterodimer with p40 (IL12B) to form IL-12 p70. The p35 subunit is essential for IL-12 biological activity, binding to IL-12 receptor beta 1 and beta 2. IL-12 p70 activates STAT4, leading to IFN-gamma production and Th1 differentiation. Additionally, p35 can pair with EBI3 to form IL-35, an immunosuppressive cytokine. Post-translational modifications include N-glycosylation, which is critical for secretion and stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IL12A Knockout HEK293 Cell Line | EDJ-KQ480 | Human | 3592 | Details Get a Quote |
| IL12A Knockout A-549 Cell Line | EDJ-KQ18792 | Human | 3592 | Details Get a Quote |
| IL12A Knockout HCT 116 Cell Line | EDJ-KQ18793 | Human | 3592 | Details Get a Quote |
| IL12A Knockout HeLa Cell Line | EDJ-KQ53647 | Human | 3592 | Details Get a Quote |
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