IL21

interleukin 21, the group of Interleukins

Basic information

Region (hg38): 4:122610108-122621066

Links

ENSG00000138684 ∙ NCBI:59067 ∙ OMIM:605384 ∙ HGNC:6005 ∙ Uniprot:Q9HBE4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• IL21-related infantile inflammatory bowel disease (Supportive), mode of inheritance: AR
• IL21-related infantile inflammatory bowel disease (Limited), mode of inheritance: Unknown
• common variable immunodeficiency (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency, common variable, 11	AR	Allergy/Immunology/Infectious	Individuals have been described as manifesting with primary immunodeficiency (with sequelae including severe inflammatory bowel disease, as well as recurrent/severe respiratory infections) and recognition may allow prophylactic measures and early and aggressive treatment of infections	Allergy/Immunology/Infectious	24746753

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IL21 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IL21 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			1	9	2	12
missense			41	1		42
nonsense						0
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	4		5
non coding				16	6	22
Total	0	0	43	26	8

Variants in IL21

This is a list of pathogenic ClinVar variants found in the IL21 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-122612665-C-T			Benign (Jun 20, 2021)
4-122612679-G-A			Benign (Jun 20, 2021)
4-122612707-T-G		IL21-related disorder	Benign (Sep 30, 2019)
4-122612712-A-G			Uncertain significance (Sep 25, 2022)
4-122612714-G-C			Uncertain significance (Jan 03, 2022)
4-122612724-T-G			Uncertain significance (Nov 27, 2019)
4-122612727-C-T			Uncertain significance (Oct 05, 2023)
4-122612728-G-A			Benign (Jan 10, 2024)
4-122612729-T-A			Uncertain significance (Aug 26, 2019)
4-122612748-G-A			Uncertain significance (Dec 03, 2018)
4-122612755-A-G			Likely benign (Aug 04, 2023)
4-122612778-C-T			Likely benign (Dec 04, 2022)
4-122612779-G-A			Likely benign (Dec 28, 2023)
4-122612808-GTAAAGATAAAGCAGAAAATCAAATGAAACTTAAGGTAGATAC-G			Uncertain significance (Nov 20, 2020)
4-122612835-A-T			Likely benign (Aug 17, 2023)
4-122612845-A-G			Uncertain significance (Jan 26, 2021)
4-122612851-C-A			Uncertain significance (Nov 20, 2020)
4-122612864-G-A			Uncertain significance (Jan 10, 2024)
4-122612884-T-A			Uncertain significance (Nov 01, 2022)
4-122612895-G-A			Uncertain significance (Oct 13, 2022)
4-122612895-G-T			Uncertain significance (Dec 08, 2023)
4-122612935-A-G			Likely benign (Jan 06, 2021)
4-122612945-AAGTAAC-A			Likely benign (Jun 03, 2023)
4-122612946-A-C			Likely benign (Oct 07, 2022)
4-122612947-G-A			Likely benign (Mar 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IL21	protein_coding	protein_coding	ENST00000264497	5	8442

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.625	0.368	125410	0	1	125411	0.00000399

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.54	44	83.6	0.527	0.00000395	1066
Missense in Polyphen		5	22.159	0.22564		294
Synonymous	2.56	11	28.3	0.388	0.00000131	292
Loss of Function	2.18	1	7.38	0.136	3.10e-7	100

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)	0.00000881	0.00000881
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cytokine with immunoregulatory activity. May promote the transition between innate and adaptive immunity. Induces the production of IgG(1) and IgG(3) in B-cells (By similarity). May play a role in proliferation and maturation of natural killer (NK) cells in synergy with IL15. May regulate proliferation of mature B- and T-cells in response to activating stimuli. In synergy with IL15 and IL18 stimulates interferon gamma production in T-cells and NK cells. During T-cell mediated immune response may inhibit dendritic cells (DC) activation and maturation. {ECO:0000250, ECO:0000269|PubMed:11081504, ECO:0000269|PubMed:15178704}.
• Pathway: Jak-STAT signaling pathway - Homo sapiens (human);Inflammatory bowel disease (IBD) - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);JAK-STAT-Core;Allograft Rejection (Consensus)

Recessive Scores

• pRec: 0.158

Intolerance Scores

• loftool: 0.310
• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.2

Haploinsufficiency Scores

• pHI: 0.0621
• hipred: N
• hipred_score: 0.299
• ghis: 0.437

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.949

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Il21
• Phenotype: hematopoietic system phenotype; normal phenotype; immune system phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: positive regulation of cytokine production;immune response;signal transduction;tyrosine phosphorylation of STAT protein;positive regulation of cell population proliferation;regulation of signaling receptor activity;positive regulation of B cell proliferation;positive regulation of interleukin-17 production;positive regulation of tissue remodeling;interleukin-21-mediated signaling pathway;positive regulation of T cell proliferation;positive regulation of tyrosine phosphorylation of STAT protein;positive regulation of interferon-gamma biosynthetic process;positive regulation of natural killer cell mediated cytotoxicity;cell maturation;positive regulation of inflammatory response
• Cellular component: extracellular region;extracellular space
• Molecular function: cytokine activity;cytokine receptor binding;interleukin-2 receptor binding