IL6

protein-coding

interleukin 6, the group of Interferons|Interleukin 6 type cytokine family|Interleukins

Gene summary

This gene encodes a cytokine that functions in inflammation and the maturation of B cells. In addition, the encoded protein has been shown to be an endogenous pyrogen capable of inducing fever in people with autoimmune diseases or infections. The protein is primarily produced at sites of acute and chronic inflammation, where it is secreted into the serum and induces a transcriptional inflammatory response through interleukin 6 receptor, alpha. The functioning of this gene is implicated in a wide variety of inflammation-associated disease states, including suspectibility to diabetes mellitus and systemic juvenile rheumatoid arthritis. Elevated levels of the encoded protein have been found in virus infections, including COVID-19 (disease caused by SARS-CoV-2). [provided by RefSeq, Aug 2020]

Previous symbols:

IFNB2

MANE transcript

NM_000600.5

Inheritance

ClinVar variants

U:15B:7

Top phenotype

Kaposi sarcoma, susceptibility to

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr7:22,725,884-22,732,002

External References & Databases

Ensembl (ENSG00000136244)

Transcript & Mutation Effects

hg38 • Region Span ~6.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Kaposi sarcoma, susceptibility toDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007845

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IL6 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 14

not providedTotal: 5

IL6-related disorderTotal: 1

Cerebral arteriovenous malformationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000600.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar		2
missense			13 clinvar	2 clinvar	3 clinvar	18
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	15	4	3	22

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000600.5	RefSeq	NP_000591.1	5	MANE Select
ENST00000258743.10	Ensembl	ENSP00000258743.5	5	MANE Select
NM_001318095.2	RefSeq	NP_001305024.1	3	Standard
NM_001371096.1	RefSeq	NP_001358025.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Prion diseases - Homo sapiens (human)
PI3K-Akt signaling pathway - Homo sapiens (human)
Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
Pertussis - Homo sapiens (human)
Salmonella infection - Homo sapiens (human)

Biological Process

neutrophil apoptotic process
hepatic immune response
neutrophil mediated immunity
monocyte chemotaxis
positive regulation of acute inflammatory response

Molecular Function

cytokine activity
interleukin-6 receptor binding
protein binding
growth factor activity

Cellular Component

extracellular region
extracellular space
endoplasmic reticulum lumen
interleukin-6 receptor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000404625
Coding exons: 5
Length: 6119
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125741
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.00294	112	112	0.999	0.00000544	1389
Missense (PolyPhen)		28	33.596	0.83344		445
Synonymous	0.0324	43	43.3	0.994	0.00000203	415
Loss of Function	2.04	2	8.36	0.239	4.24e-7	99

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig- secreting cells Involved in lymphocyte and monocyte differentiation. Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. Required for the generation of T(H)17 cells. Also acts as a myokine. It is discharged into the bloodstream after muscle contraction and acts to increase the breakdown of fats and to improve insulin resistance. It induces myeloma and plasmacytoma growth and induces nerve cells differentiation.;
Disease: DISEASE: Rheumatoid arthritis systemic juvenile (RASJ) [MIM:604302]: An inflammatory articular disorder with systemic- onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis. {ECO:0000269|PubMed:9769329}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Note=A IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in HIV-infected men. {ECO:0000269|PubMed:11001912}.;

Recessive Scores

pRec: 0.997

Intolerance Scores

LoFtool: 0.541
RVIS EVS: 0.73
RVIS percentile EVS: 85.98

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.848

Gene Damage Prediction

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