IL27

interleukin 27, the group of Interleukins

Basic information

Region (hg38): 16:28499362-28512051

Previous symbols: [ "IL30" ]

Links

ENSG00000197272 ∙ NCBI:246778 ∙ OMIM:608273 ∙ HGNC:19157 ∙ Uniprot:Q8NEV9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IL27 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IL27 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			10	3	1	14
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding						0
Total	0	0	10	3	1

Variants in IL27

This is a list of pathogenic ClinVar variants found in the IL27 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-28499657-C-G		not specified	Uncertain significance (Jan 17, 2024)
16-28499686-G-A		not specified	Uncertain significance (Apr 06, 2024)
16-28499696-G-C		not specified	Uncertain significance (Nov 14, 2023)
16-28499775-G-A		not specified	Uncertain significance (Jun 13, 2024)
16-28499821-C-T		not specified	Uncertain significance (Oct 20, 2021)
16-28499829-A-G		not specified	Likely benign (Sep 19, 2023)
16-28499872-C-T		not specified	Uncertain significance (Feb 26, 2024)
16-28499895-G-A		not specified	Uncertain significance (Nov 07, 2022)
16-28502022-G-T		not specified	Uncertain significance (Dec 20, 2021)
16-28503702-C-T		not specified	Likely benign (Jun 22, 2021)
16-28503781-G-C		not specified	Uncertain significance (Sep 26, 2023)
16-28503792-G-A		not specified	Uncertain significance (Jul 13, 2021)
16-28503873-C-T			Uncertain significance (Apr 01, 2022)
16-28503907-A-C			Benign (Jul 15, 2020)
16-28503951-C-T		not specified	Likely benign (Aug 28, 2023)
16-28504012-C-G		not specified	Uncertain significance (Sep 25, 2023)
16-28506801-G-T		not specified	Uncertain significance (Jul 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IL27	protein_coding	protein_coding	ENST00000356897	5	12690

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.782	0.216	125527	0	2	125529	0.00000797

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.08	112	149	0.750	0.00000971	1512
Missense in Polyphen		17	37.205	0.45693		437
Synonymous	1.32	53	66.8	0.794	0.00000386	538
Loss of Function	2.54	1	9.40	0.106	5.04e-7	87

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000883	0.00000881
Middle Eastern	0.00	0.00
South Asian	0.0000336	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Associates with EBI3 to form the IL-27 interleukin, a heterodimeric cytokine which functions in innate immunity. IL-27 has pro- and anti-inflammatory properties, that can regulate T- helper cell development, suppress T-cell proliferation, stimulate cytotoxic T-cell activity, induce isotype switching in B-cells, and that has diverse effects on innate immune cells. Among its target cells are CD4 T-helper cells which can differentiate in type 1 effector cells (TH1), type 2 effector cells (TH2) and IL17 producing helper T-cells (TH17). It drives rapid clonal expansion of naive but not memory CD4 T-cells. It also strongly synergizes with IL-12 to trigger interferon-gamma/IFN-gamma production of naive CD4 T-cells, binds to the cytokine receptor WSX-1/TCCR which appears to be required but not sufficient for IL-27-mediated signal transduction. IL-27 potentiate the early phase of TH1 response and suppress TH2 and TH17 differentiation. It induces the differentiation of TH1 cells via two distinct pathways, p38 MAPK/TBX21- and ICAM1/ITGAL/ERK-dependent pathways. It also induces STAT1, STAT3, STAT4 and STAT5 phosphorylation and activates TBX21/T-Bet via STAT1 with resulting IL12RB2 up- regulation, an event crucial to TH1 cell commitment. It suppresses the expression of GATA3, the inhibitor TH1 cells development. In CD8 T-cells, it activates STATs as well as GZMB. IL-27 reveals to be a potent inhibitor of TH17 cell development and of IL-17 production. Indeed IL27 alone is also able to inhibit the production of IL17 by CD4 and CD8 T-cells. While IL-27 suppressed the development of proinflammatory Th17 cells via STAT1, it inhibits the development of anti-inflammatory inducible regulatory T-cells, iTreg, independently of STAT1. IL-27 has also an effect on cytokine production, it suppresses proinflammatory cytokine production such as IL2, IL4, IL5 and IL6 and activates suppressors of cytokine signaling such as SOCS1 and SOCS3. Apart from suppression of cytokine production, IL-27 also antagonizes the effects of some cytokines such as IL6 through direct effects on T- cells. Another important role of IL-27 is its antitumor activity as well as its antiangiogenic activity with activation of production of antiangiogenic chemokines such as IP-10/CXCL10 and MIG/CXCL9. In vein endothelial cells, it induces IRF1/interferon regulatory factor 1 and increase the expression of MHC class II transactivator/CIITA with resulting up-regulation of major histocompatibility complex class II. IL-27 also demonstrates antiviral activity with inhibitory properties on HIV-1 replication. {ECO:0000269|PubMed:12121660, ECO:0000269|PubMed:14565860, ECO:0000269|PubMed:17068156, ECO:0000269|PubMed:18191724}.
• Pathway: JAK-STAT-Core;Interleukin-12 family signaling;Signaling by Interleukins;Cytokine Signaling in Immune system;Immune System;Interleukin-27 signaling;IL27-mediated signaling events (Consensus)

Intolerance Scores

• loftool: 0.149
• rvis_EVS: 0.22
• rvis_percentile_EVS: 67.92

Haploinsufficiency Scores

• pHI: 0.0846
• hipred: N
• hipred_score: 0.370
• ghis: 0.436

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.903

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Il27
• Phenotype: homeostasis/metabolism phenotype; immune system phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: positive regulation of defense response to virus by host;inflammatory response;response to bacterium;regulation of signaling receptor activity;regulation of T cell proliferation;positive regulation of interferon-gamma biosynthetic process;innate immune response;regulation of T-helper 1 cell differentiation;interleukin-27-mediated signaling pathway
• Cellular component: extracellular region;extracellular space;endoplasmic reticulum lumen;cytosol
• Molecular function: signaling receptor binding;cytokine activity;protein binding;interleukin-27 receptor binding