IL12B interleukin 12B [Homo sapiens (human)] - Gene

Summary

Official Symbol: IL12Bprovided by HGNC
Official Full Name: interleukin 12Bprovided by HGNC
Primary source: HGNC:HGNC:5970
See related: Ensembl:ENSG00000113302 MIM:161561; AllianceGenome:HGNC:5970
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CLMF; NKSF; CLMF2; IMD28; IMD29; NKSF2; IL-12B
Summary: 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]
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: 5q33.3

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (159314780..159330487, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (159843275..159858983, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (158741788..158757495, complement)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Interleukin gene polymorphisms and alopecia areata: A systematic review and meta-analysis.
Title: Interleukin gene polymorphisms and alopecia areata: A systematic review and meta-analysis.
Association between interleukin-12 +1188A/C polymorphism and the risk of tuberculosis: A meta-analysis.
Title: Association between interleukin-12 +1188A/C polymorphism and the risk of tuberculosis: A meta-analysis.
IL-12 reprograms CAR-expressing natural killer T cells to long-lived Th1-polarized cells with potent antitumor activity.
Title: IL-12 reprograms CAR-expressing natural killer T cells to long-lived Th1-polarized cells with potent antitumor activity.
Variants of IL6, IL10, FCN2, RNASE3, IL12B and IL17B loci are associated with Schistosoma mansoni worm burden in the Albert Nile region of Uganda.
Title: Variants of IL6, IL10, FCN2, RNASE3, IL12B and IL17B loci are associated with Schistosoma mansoni worm burden in the Albert Nile region of Uganda.
IL12B and IL17 genes polymorphisms associated with differential susceptibility to juvenile idiopathic arthritis and juvenile-onset systemic lupus erythematosus in Chinese children.
Title: IL12B and IL17 genes polymorphisms associated with differential susceptibility to juvenile idiopathic arthritis and juvenile-onset systemic lupus erythematosus in Chinese children.
IL-12 and IL-23 pathway inhibition in inflammatory bowel disease.
Title: IL-12 and IL-23 pathway inhibition in inflammatory bowel disease.
Elevated expression of interleukin-27, IL-35, and decreased IL-12 in patients with thyroid-associated ophthalmopathy.
Title: Elevated expression of interleukin-27, IL-35, and decreased IL-12 in patients with thyroid-associated ophthalmopathy.
Interleukin 12B rs3212227 and rs6887695 single nucleotide polymorphisms are associated with the susceptibility to preeclampsia: Genetic, haplotype and bioinformatics analysis.
Title: Interleukin 12B rs3212227 and rs6887695 single nucleotide polymorphisms are associated with the susceptibility to preeclampsia: Genetic, haplotype and bioinformatics analysis.
Association between gene polymorphisms of IL-12, IL-12 receptor and IL-27 and organ involvement in Iranian endometriosis patients.
Title: Association between gene polymorphisms of IL-12, IL-12 receptor and IL-27 and organ involvement in Iranian endometriosis patients.
[IFN-gamma and IL-12 from Concentrated Ascites in Patients with Pancreatic Cancer Exerts Growth Inhibitory Effects against Pancreatic Cancer Cells].
Title: [IFN-γ and IL-12 from Concentrated Ascites in Patients with Pancreatic Cancer Exerts Growth Inhibitory Effects against Pancreatic Cancer Cells].

Submit: New GeneRIF Correction See all GeneRIFs (405)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency MedGen: C4013948 OMIM: 614890 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Discovery of six new susceptibility loci and analysis of pleiotropic effects in leprosy. EBI GWAS Catalog EBI GWAS CatalogPubMed
Fucosyltransferase 2 (FUT2) non-secretor status is associated with Crohn's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic association with overall survival of taxane-treated lung cancer patients - A genome-wide association study in human lymphoblastoid cell lines followed by a clinical association study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. EBI GWAS Catalog EBI GWAS CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. EBI GWAS Catalog EBI GWAS CatalogPubMed
Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21. EBI GWAS Catalog EBI GWAS CatalogPubMed
Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
HIV/tuberculosis coinfection upregulates IL12B expression in pleural fluid mononuclear cells (PFMC) isolated from antiretroviral-naive coinfected patients (relative to patients infected with only tuberculosis)	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Levels of IL-12 in LPS-treated myeloid dendritic cells are modulated in the presence of HIV-1 gp120	PubMed
	env	HIV-1 gp120 inhibits early and late production of interleukin (IL)-12 by peripheral blood mononuclear cells (PBMC)	PubMed
	env	Secretion of IL-12 is found in macrophages primed with gamma interferon (IFN-gamma) and subsequently treated with gp120	PubMed
	env	Apoptosis of CD4+ lymphocytes induced by HIV-1 gp120 cross-linking to CD4 is inhibited by IL-12	PubMed
	env	HIV-gp120 induces a significant IL-10 synthesis, which in turn inhibits IL-12 subunits mRNA accumulation and protein secretion after Staphylococcus aureus strain cowan I (SAC)-activation	PubMed
Envelope surface glycoprotein gp160, precursor	env	IL-7 and IL-12 significantly augment proliferative responses to HIV-1 gp160	PubMed
	env	Chimeric HIV-1 gp140 - CD40L trimers can target and activate dendritic cells to release IL-6, IL-10 and IL-12	PubMed
Nef	nef	HIV-1 Nef specifically incorporates CSF2, PPBP (NAP2), CCL5, TNF, FAS, CXCL1, IL12B, MIF and OSM into plasma extracellular vesicles from HIV-1 infected patient samples	PubMed
	nef	IL-12 and GM-CSF increase the magnitude of the specific immune response with higher breadth by targeting HIV-1 Nef peptides (amino acids 9-23, 11-26, 140-155, 179-193, and 181-195)	PubMed
	nef	HIV-1 Nef upregulates IL-12 release in immature human and macaque dendritic cells	PubMed
	nef	IL-1beta, IL-12, and IL-15 are factors involved in the upregulation of IFN-gamma expression in coculture between Nef-pulsed iDCs and NK cells	PubMed
Tat	tat	HIV-1 Tat upregulates IL-12 expression in Jurkat T-cells, Raji B-cells, monocyte-derived dendritic cells, and primary human Muller glia	PubMed
	tat	Wild-type Tat but not Cys-22 and oxidized Tat induces CD1A-expressing monocyte-derived dendritic cells (MDDC) maturation and increases the production of cytokines TNF-alpha, IL-12, MIP-1alpha, and MIP-1beta	PubMed
	tat	HIV-1 Tat downregulates IL-12 production by human dendritic cells by blocking extracellular calcium influx	PubMed
	tat	HIV-1 Tat downregulates IL-12 production by human peripheral blood mononuclear cells (PBMCs)	PubMed
Vpr	vpr	HIV-1 Vpr downregulates the expression of IL12B in human monocyte-derived dendritic cells	PubMed
matrix	gag	HIV-1 Matrix upregulates levels of IL-2, IL-12 and IL-15 in natural killer cells and induces natural killer cell proliferation	PubMed
reverse transcriptase	gag-pol	The addition of anti-IFN-gamma antibodies block the IL-12-induced downregulation of HIV-1 RT activity in HIV-1-infected macrophages	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G10637 (e-PCR)
- UniSTS:60436

SGC35786 (e-PCR)
- UniSTS:51991

NoName (e-PCR)
- UniSTS:480804

RH17728 (e-PCR)
- UniSTS:24645

NoName (e-PCR)
- UniSTS:481890

IL12B_146 (e-PCR)
- UniSTS:277362

D5S1480 (e-PCR), detects polymorphism
- UniSTS:80294

PMC321570P1 (e-PCR)
- UniSTS:273112

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
contributes_to cytokine activity	IDA Inferred from Direct Assay more info	PubMed
enables cytokine activity	IDA Inferred from Direct Assay more info	PubMed
enables cytokine binding	IBA Inferred from Biological aspect of Ancestor more info
enables cytokine receptor activity	IBA Inferred from Biological aspect of Ancestor more info
contributes_to growth factor activity	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables interleukin-12 alpha subunit binding	IPI Inferred from Physical Interaction more info	PubMed
contributes_to interleukin-12 receptor binding	TAS Traceable Author Statement more info	PubMed
enables interleukin-12 receptor binding	TAS Traceable Author Statement more info	PubMed
contributes_to interleukin-23 receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in T cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in T-helper 1 type immune response	TAS Traceable Author Statement more info	PubMed
involved_in T-helper cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
involved_in cellular response to type II interferon	IEA Inferred from Electronic Annotation more info
involved_in cytokine-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in defense response to Gram-negative bacterium	IDA Inferred from Direct Assay more info	PubMed
involved_in defense response to protozoan	IEA Inferred from Electronic Annotation more info
involved_in defense response to virus	IEA Inferred from Electronic Annotation more info
involved_in interleukin-12-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in natural killer cell activation	IDA Inferred from Direct Assay more info	PubMed
involved_in natural killer cell activation involved in immune response	IEA Inferred from Electronic Annotation more info
acts_upstream_of negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of inflammatory response to antigenic stimulus	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of interleukin-10 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of interleukin-17 production	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of protein secretion	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of smooth muscle cell proliferation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of negative regulation of vascular endothelial growth factor signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of NK T cell activation	IC Inferred by Curator more info	PubMed
involved_in positive regulation of NK T cell activation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of NK T cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of T cell mediated cytotoxicity	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of T cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of T-helper 1 type immune response	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of T-helper 1 type immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of T-helper 17 cell lineage commitment	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of T-helper 17 type immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of activated T cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of activation of Janus kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell adhesion	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of defense response to virus by host	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of defense response to virus by host	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of granulocyte macrophage colony-stimulating factor production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of inflammatory response	IC Inferred by Curator more info	PubMed
involved_in positive regulation of interleukin-10 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interleukin-10 production	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of interleukin-12 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interleukin-17 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of lymphocyte proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of memory T cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of mononuclear cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of natural killer cell activation	IC Inferred by Curator more info	PubMed
involved_in positive regulation of natural killer cell activation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of natural killer cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of non-canonical NF-kappaB signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of osteoclast differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of smooth muscle cell apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of tissue remodeling	IC Inferred by Curator more info	PubMed
involved_in positive regulation of tumor necrosis factor production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of type II interferon production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of type II interferon production	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of tyrosine phosphorylation of STAT protein	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cytokine production	TAS Traceable Author Statement more info	PubMed
involved_in regulation of tyrosine phosphorylation of STAT protein	IDA Inferred from Direct Assay more info	PubMed
involved_in response to UV-B	IDA Inferred from Direct Assay more info	PubMed
involved_in sexual reproduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in cytosol	TAS Traceable Author Statement more info
located_in endoplasmic reticulum lumen	TAS Traceable Author Statement more info
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular space	TAS Traceable Author Statement more info	PubMed
part_of interleukin-12 complex	IDA Inferred from Direct Assay more info	PubMed
part_of interleukin-23 complex	IDA Inferred from Direct Assay more info	PubMed
located_in late endosome lumen	TAS Traceable Author Statement more info
part_of receptor complex	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: interleukin-12 subunit beta

Names: CLMF p40; IL-12 subunit p40; IL12, subunit p40; NK cell stimulatory factor chain 2; cytotoxic lymphocyte maturation factor 40 kDa subunit; interleukin 12, p40; interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40); interleukin-12 beta chain; natural killer cell stimulatory factor, 40 kD subunit

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009618.1 RefSeqGene

Range

5001..20691

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_71

mRNA and Protein(s)

NM_002187.3 → NP_002178.2 interleukin-12 subunit beta precursor

See identical proteins and their annotated locations for NP_002178.2

Status: REVIEWED

Source sequence(s)

AC011418, M65272, M65290

Consensus CDS

CCDS4346.1

UniProtKB/Swiss-Prot

P29460

Related

ENSP00000231228.2, ENST00000231228.3

Conserved Domains (4) summary

smart00408
Location:42 → 90

IGc2; Immunoglobulin C-2 Type

cd00063
Location:235 → 325

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

pfam10420
Location:126 → 216

IL12p40_C; Cytokine interleukin-12p40 C-terminus

cd00096
Location:38 → 41

Ig; Ig strand A' [structural motif]