IL12B
Interleukin-12 subunit beta
Also known as: CLMF, CLMF2, IL-12B, IL12B_HUMAN, NKSF, NKSF2
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P29460
- Gene
- IL12B
- Ensembl
- ENSG00000113302
- Chromosome
- 5
- Canonical length
- 328 aa
- Protein class
- Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins
- Secretome location
- Secreted to blood
OverviewNCBI Gene
This gene encodes a subunit of interleukin 12, a cytokine that acts on T and natural killer cells, and has a broad array of biological activities. Interleukin 12 is a disulfide-linked heterodimer composed of the 40 kD cytokine receptor like subunit encoded by this gene, and a 35 kD subunit encoded by IL12A. This cytokine is expressed by activated macrophages that serve as an essential inducer of Th1 cells development. This cytokine has been found to be important for sustaining a sufficient number of memory/effector Th1 cells to mediate long-term protection to an intracellular pathogen. Overexpression of this gene was observed in the central nervous system of patients with multiple sclerosis (MS), suggesting a role of this cytokine in the pathogenesis of the disease. The promoter polymorphism of this gene has been reported to be associated with the severity of atopic and non-atopic asthma in children. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
328 residues, UniProt reviewed canonical sequence.
>P29460|IL12B
1 MCHQQLVISW FSLVFLASPL VAIWELKKDV YVVELDWYPD APGEMVVLTC DTPEEDGITW
61 TLDQSSEVLG SGKTLTIQVK EFGDAGQYTC HKGGEVLSHS LLLLHKKEDG IWSTDILKDQ
121 KEPKNKTFLR CEAKNYSGRF TCWWLTTIST DLTFSVKSSR GSSDPQGVTC GAATLSAERV
181 RGDNKEYEYS VECQEDSACP AAEESLPIEV MVDAVHKLKY ENYTSSFFIR DIIKPDPPKN
241 LQLKPLKNSR QVEVSWEYPD TWSTPHSYFS LTFCVQVQGK SKREKKDRVF TDKTSATVIC
301 RKNASISVRA QDRYYSSSWS EWASVPCSLocalizationUniProt · AlphaFold · HPA
Whether an antibody against IL12B can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Secreted
- Secreted
- Yes
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.33
- Highest tissue expression
- 1.2 nTPM
Expression across tissuesHPA
Tissue
- thymus: 1.2 nTPM
- lymph node: 0.4 nTPM
- spleen: 0.4 nTPM
- bone marrow: 0.3 nTPM
- skin: 0.3 nTPM
- appendix: 0.2 nTPM
Single-cell type
- renal collecting duct intercalated cells: 0.6 nCPM
- thyrotrophs: 0.6 nCPM
- mesothelial cells: 0.3 nCPM
- somatotrophs: 0.3 nCPM
- macrophages: 0.2 nCPM
- microglia: 0.2 nCPM
Immune cell
- basophil: 0.6 nTPM
- neutrophil: 0.6 nTPM
- memory B-cell: 0.2 nTPM
- classical monocyte: 0.1 nTPM
- NK-cell: 0.1 nTPM
- eosinophil: 0 nTPM
Brain region
- cerebellum: 3 nTPM
- cerebral cortex: 2.3 nTPM
- white matter: 2.1 nTPM
- pons: 2 nTPM
- basal ganglia: 1.9 nTPM
- hippocampal formation: 1.9 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about IL12B.
Disease | AllUniProt
Conditions IL12B is implicated in, by any mechanism.
- Immunodeficiency 29 (IMD29) MIM:614890
- Psoriasis 11 (PSORS11) MIM:612599
Disease | GeneticClinVar
18 pathogenic / likely-pathogenic of 246 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency
- IL12B-related disorder
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.92
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.57
- DepMap mean gene effect
- 0.08
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- cell migration
- cell surface receptor signaling pathway via JAK-STAT
- cellular response to lipopolysaccharide
- cellular response to type II interferon
- defense response to Gram-negative bacterium
- defense response to protozoan
- defense response to virus
- interleukin-12-mediated signaling pathway
- natural killer cell activation
- natural killer cell activation involved in immune response
- negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis
- negative regulation of inflammatory response to antigenic stimulus
- negative regulation of interleukin-10 production
- negative regulation of interleukin-17 production
- negative regulation of protein secretion
- negative regulation of smooth muscle cell proliferation
- negative regulation of vascular endothelial growth factor signaling pathway
- oocyte development
- positive regulation of activated T cell proliferation
- positive regulation of cell adhesion
- positive regulation of defense response to virus by host
- positive regulation of granulocyte macrophage colony-stimulating factor production
- positive regulation of inflammatory response
- positive regulation of interleukin-10 production
- positive regulation of interleukin-12 production
- positive regulation of interleukin-17 production
- positive regulation of lymphocyte proliferation
- positive regulation of memory T cell differentiation
- positive regulation of mononuclear cell proliferation
- positive regulation of natural killer cell activation
- positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target
- positive regulation of natural killer cell proliferation
- positive regulation of NK T cell activation
- positive regulation of NK T cell proliferation
- positive regulation of non-canonical NF-kappaB signal transduction
- positive regulation of osteoclast differentiation
- positive regulation of smooth muscle cell apoptotic process
- positive regulation of T cell mediated cytotoxicity
- positive regulation of T cell proliferation
- positive regulation of T-helper 1 type immune response
- positive regulation of T-helper 17 cell lineage commitment
- positive regulation of T-helper 17 type immune response
- positive regulation of tissue remodeling
- positive regulation of tumor necrosis factor production
- positive regulation of type II interferon production
- regulation of cytokine production
- response to UV-B
- T cell proliferation
- T-helper 1 type immune response
- T-helper cell differentiation
Molecular functions
- cytokine activity
- cytokine receptor activity
- identical protein binding
- interleukin-12 receptor binding
- protein heterodimerization activity
- protein-containing complex binding
- interleukin-12 alpha subunit binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Long hematopoietin receptor, soluble alpha chain, conserved site
- Immunoglobulin subtype 2
- Fibronectin type III
- Immunoglobulin-like domain
- Immunoglobulin-like fold
- Fibronectin type III superfamily
- Immunoglobulin-like domain superfamily
- Interleukin-12
- Interleukin-12 beta
- Interleukin-12 beta, central domain
- Cytokine interleukin-12p40 C-terminus
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of IL12B in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads IL12B as an antibody target. Whether an autoantibody or antibody against IL12B could matter depends on whether native IL12B is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
IL12B is annotated as secreted, so native IL12B circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.
Annotation status
The present source text does not explicitly label IL12B as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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