IL12A interleukin 12A [Homo sapiens (human)] - Gene

Summary

Official Symbol: IL12Aprovided by HGNC
Official Full Name: interleukin 12Aprovided by HGNC
Primary source: HGNC:HGNC:5969
See related: Ensembl:ENSG00000168811 MIM:161560; AllianceGenome:HGNC:5969
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: P35; CLMF; NFSK; NKSF1; IL-12A
Summary: This gene encodes a subunit of a cytokine that acts on T and natural killer cells, and has a broad array of biological activities. The cytokine is a disulfide-linked heterodimer composed of the 35-kD subunit encoded by this gene, and a 40-kD subunit that is a member of the cytokine receptor family. This cytokine is required for the T-cell-independent induction of interferon (IFN)-gamma, and is important for the differentiation of both Th1 and Th2 cells. The responses of lymphocytes to this cytokine are mediated by the activator of transcription protein STAT4. Nitric oxide synthase 2A (NOS2A/NOS2) is found to be required for the signaling process of this cytokine in innate immunity. [provided by RefSeq, Jul 2008]
Expression: Broad expression in esophagus (RPKM 2.2), lung (RPKM 1.4) and 19 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3q25.33

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (159988835..159996019)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (162763550..162770734)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (159706622..159713806)

Chromosome 3 - NC_000003.12 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?

The effects of IL-27 and IL-35 gene variation and expression levels on the susceptibility and clinical manifestations of pulmonary tuberculosis.
Title: The effects of IL-27 and IL-35 gene variation and expression levels on the susceptibility and clinical manifestations of pulmonary tuberculosis.
Signaling pathways underlying TGF-beta mediated suppression of IL-12A gene expression in monocytes.
Title: Signaling pathways underlying TGF-β mediated suppression of IL-12A gene expression in monocytes.
Altered Gene Expression of IL-35 and IL-36alpha in the Skin of Patients with Atopic Dermatitis.
Title: Altered Gene Expression of IL-35 and IL-36α in the Skin of Patients with Atopic Dermatitis.
IL-8 and IL-12p70 are associated with pelvic pain among infertile women with endometriosis.
Title: IL-8 and IL-12p70 are associated with pelvic pain among infertile women with endometriosis.
Human interleukin-12alpha and EBI3 are cytokines with anti-inflammatory functions.
Title: Human interleukin-12α and EBI3 are cytokines with anti-inflammatory functions.
A Meta-Analysis of the Association Between Genetic Polymorphisms in IL-12, IL-17, and IL-21 and Risk of Hepatitis B Virus Infection.
Title: A Meta-Analysis of the Association Between Genetic Polymorphisms in IL-12, IL-17, and IL-21 and Risk of Hepatitis B Virus Infection.
Immunomodulatory effect of IL-35 gene-transfected mesenchymal stem cells on allergic asthma.
Title: Immunomodulatory effect of IL-35 gene-transfected mesenchymal stem cells on allergic asthma.
[Expression of Tregs and IL-35 in Peripheral Blood of Patients with Newly Diagnosed Acute Myeloid Leukemia].
Title: [Expression of Tregs and IL-35 in Peripheral Blood of Patients with Newly Diagnosed Acute Myeloid Leukemia].
Interleukin-35 ameliorates cardiovascular disease by suppressing inflammatory responses and regulating immune homeostasis.
Title: Interleukin-35 ameliorates cardiovascular disease by suppressing inflammatory responses and regulating immune homeostasis.
Interleukin 35 regulates interleukin 17 expression and T helper 17 in patients with proliferative diabetic retinopathy.
Title: Interleukin 35 regulates interleukin 17 expression and T helper 17 in patients with proliferative diabetic retinopathy.

Submit: New GeneRIF Correction See all GeneRIFs (283)

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

EBI GWAS Catalog

Description
Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies. 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 analysis identifies new susceptibility loci for Beh&#x000e7;et's disease and epistasis between HLA-B*51 and ERAP1. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Multiple common variants for celiac disease influencing immune gene expression. EBI GWAS Catalog EBI GWAS CatalogPubMed
Newly identified genetic risk variants for celiac disease related to the immune response. EBI GWAS Catalog EBI GWAS CatalogPubMed
Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants. 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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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	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	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
	nef	HIV-1 Nef upregulates IL-12 release in immature human and macaque dendritic 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 impairs NK cell function through cytokine dysregulation, including diminshed expression of CD107a, reduced production of IFN-gamma, differential regulation of IL-12 and TGF-beta, and activation of the Smad3 signalling pathway	PubMed
	vpr	The C-terminal domain or the R90 residue of HIV-1 Vpr are important for Vpr-mediated IL-12 degradation via ubiquitin-dependent pathway	PubMed
	vpr	HIV-1 Vpr downregulates the production of interleukin 12 (IL-12) in dendritic cells	PubMed
	vpr	HIV-1 Vpr suppresses expression and secretion of IL-12 subunit p35 and IL-12 holo-protein, but not IL-12 subunit p40	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

PMC105864P1 (e-PCR)
- UniSTS:270118

NoName (e-PCR)
- UniSTS:488050

GDB:252062 (e-PCR)
- UniSTS:156323

SHGC-12751 (e-PCR)
- UniSTS:32985

RH17729 (e-PCR)
- UniSTS:66784

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
contributes_to cytokine activity	TAS Traceable Author Statement more info	PubMed
contributes_to growth factor activity	IDA Inferred from Direct Assay more info	PubMed
contributes_to growth factor activity	NAS Non-traceable Author Statement more info	PubMed
enables interleukin-12 beta subunit binding	IPI Inferred from Physical Interaction more info	PubMed
enables interleukin-12 receptor binding	NAS Non-traceable Author Statement more info	PubMed
enables interleukin-27 binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein 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

Process	Evidence Code	Pubs
involved_in cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to virus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in defense response to Gram-positive bacterium	IEP Inferred from Expression Pattern more info	PubMed
involved_in extrinsic apoptotic signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in immune response	TAS Traceable Author Statement more info	PubMed
involved_in interleukin-12-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
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 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	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of T cell mediated cytotoxicity	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 dendritic cell chemotaxis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of lymphocyte proliferation	IDA Inferred from Direct Assay more info	PubMed
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	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of natural killer cell mediated cytotoxicity	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 smooth muscle cell apoptotic process	IDA Inferred from Direct Assay 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 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 response to lipopolysaccharide	IDA Inferred from Direct Assay more info	PubMed
involved_in response to virus	IEP Inferred from Expression Pattern more info	PubMed

Component	Evidence Code	Pubs
located_in endoplasmic reticulum lumen	TAS Traceable Author Statement 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	IDA Inferred from Direct Assay more info	PubMed
part_of interleukin-12 complex	IDA Inferred from Direct Assay more info	PubMed
part_of interleukin-12 complex	NAS Non-traceable Author Statement more info	PubMed
located_in late endosome lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: interleukin-12 subunit alpha

Names: CLMF p35; IL-12, subunit p35; IL35 subunit; NF cell stimulatory factor chain 1; NK cell stimulatory factor chain 1; cytotoxic lymphocyte maturation factor 1, p35; cytotoxic lymphocyte maturation factor 35 kDa subunit; interleukin 12, p35; interleukin 12A (natural killer cell stimulatory factor 1, cytotoxic lymphocyte maturation factor 1, p35); interleukin-12 alpha chain

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_033022.2 RefSeqGene

Range

5002..12186

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000882.4 → NP_000873.2 interleukin-12 subunit alpha isoform 1 precursor

See identical proteins and their annotated locations for NP_000873.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AC010370, AW472810, BC104982, M65291

Consensus CDS

CCDS3187.1

UniProtKB/TrEMBL

E9PGR3, O60595

Related

ENSP00000303231.2, ENST00000305579.7

Conserved Domains (1) summary

pfam03039
Location:51 → 253

IL12; Interleukin-12 alpha subunit
NM_001354582.2 → NP_001341511.1 interleukin-12 subunit alpha isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AC010370

UniProtKB/TrEMBL

E9PGR3

Related

ENSP00000419046.2, ENST00000466512.1

Conserved Domains (1) summary

pfam03039
Location:51 → 239

IL12; Interleukin-12 alpha subunit
NM_001354583.2 → NP_001341512.1 interleukin-12 subunit alpha isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (3) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AC010370

UniProtKB/TrEMBL

E7ENE1

Related

ENSP00000420184.2, ENST00000480787.5

Conserved Domains (1) summary

pfam03039
Location:51 → 215

IL12; Interleukin-12 alpha subunit
NM_001397992.1 → NP_001384921.1 interleukin-12 subunit alpha isoform 4 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript. The encoded isoform (4) uses a downstream in-frame start codon and is shorter than isoform 1.

Source sequence(s)

AC010370, M65291

Consensus CDS

CCDS93420.1

UniProtKB/Swiss-Prot

P29459, Q96QZ1

Related

ENSP00000514529.1, ENST00000699704.1

Conserved Domains (1) summary

pfam03039
Location:17 → 219

IL12; Interleukin-12 alpha subunit