IL21R

interleukin 21 receptor, the group of CD molecules|Interleukin receptors

Basic information

Region (hg38): 16:27402173-27452042

Links

ENSG00000103522 ∙ NCBI:50615 ∙ OMIM:605383 ∙ HGNC:6006 ∙ Uniprot:Q9HBE5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cryptosporidiosis-chronic cholangitis-liver disease syndrome (Moderate), mode of inheritance: AR
• cryptosporidiosis-chronic cholangitis-liver disease syndrome (Supportive), mode of inheritance: AR
• cryptosporidiosis-chronic cholangitis-liver disease syndrome (Strong), mode of inheritance: AR
• immunodeficiency disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency, primary, autosomal recessive, IL21R-related	AR	Allergy/Immunology/Infectious	Individuals may manifest with immunodeficiency, and prophylactic measures, as well as early and aggressive treatment of infections may be beneficial; HSCT has been described	Allergy/Immunology/Infectious	23440042; 25398835

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IL21R gene.

• Cryptosporidiosis-chronic cholangitis-liver disease syndrome (294 variants)
• not provided (38 variants)
• Inborn genetic diseases (25 variants)
• not specified (6 variants)
• IgE responsiveness, atopic;Cryptosporidiosis-chronic cholangitis-liver disease syndrome (4 variants)
• IL21R-related condition (2 variants)
• Cryptosporidiosis-chronic cholangitis-liver disease syndrome;IgE responsiveness, atopic (2 variants)
• Increased circulating IgE level (1 variants)
• Autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IL21R 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	86	6	93
missense			163	3	2	168
nonsense	2		1			3
start loss			1			1
frameshift	1	2				3
inframe indel						0
splice donor/acceptor (+/-2bp)		2				2
splice region			3	6		9
non coding			2	28	15	45
Total	3	4	168	117	23

Variants in IL21R

This is a list of pathogenic ClinVar variants found in the IL21R region.

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

Position	Type	Phenotype	Significance	ClinVar
16-27403018-T-C		Increased circulating IgE level	Benign (Nov 12, 2018)
16-27403057-T-G		not specified	Benign (Nov 12, 2023)
16-27403181-G-A		Cryptosporidiosis-chronic cholangitis-liver disease syndrome;IgE responsiveness, atopic	Conflicting classifications of pathogenicity (Jan 01, 2024)
16-27403184-G-A		Inborn genetic diseases	Uncertain significance (Dec 19, 2022)
16-27403203-C-T			Likely benign (Jun 05, 2020)
16-27429962-A-G		not specified	Benign (Jan 24, 2024)
16-27430074-GC-AA		Cryptosporidiosis-chronic cholangitis-liver disease syndrome	Uncertain significance (May 18, 2018)
16-27430078-C-T		Cryptosporidiosis-chronic cholangitis-liver disease syndrome	Uncertain significance (Feb 10, 2022)
16-27430079-G-A		Cryptosporidiosis-chronic cholangitis-liver disease syndrome	Uncertain significance (Mar 19, 2022)
16-27430081-G-A		Cryptosporidiosis-chronic cholangitis-liver disease syndrome	Uncertain significance (May 08, 2022)
16-27430088-C-T		Cryptosporidiosis-chronic cholangitis-liver disease syndrome	Uncertain significance (Aug 03, 2022)
16-27430089-C-T		Cryptosporidiosis-chronic cholangitis-liver disease syndrome	Likely benign (Dec 31, 2022)
16-27430090-G-A		Cryptosporidiosis-chronic cholangitis-liver disease syndrome	Likely benign (Oct 09, 2023)
16-27430091-C-G		Cryptosporidiosis-chronic cholangitis-liver disease syndrome • Inborn genetic diseases	Uncertain significance (Dec 08, 2023)
16-27430095-C-T		Cryptosporidiosis-chronic cholangitis-liver disease syndrome	Likely benign (Jul 12, 2022)
16-27430097-T-TG		Cryptosporidiosis-chronic cholangitis-liver disease syndrome	Pathogenic (Mar 01, 2022)
16-27430098-G-T		Cryptosporidiosis-chronic cholangitis-liver disease syndrome	Uncertain significance (Sep 24, 2021)
16-27430110-G-A		Cryptosporidiosis-chronic cholangitis-liver disease syndrome	Likely benign (Dec 31, 2019)
16-27430119-A-G		Cryptosporidiosis-chronic cholangitis-liver disease syndrome	Uncertain significance (Oct 21, 2021)
16-27430135-C-T		Cryptosporidiosis-chronic cholangitis-liver disease syndrome	Likely benign (Aug 09, 2023)
16-27430136-G-A		Cryptosporidiosis-chronic cholangitis-liver disease syndrome	Likely benign (Jun 18, 2022)
16-27434039-G-C			Benign (Nov 12, 2018)
16-27434329-T-C		Cryptosporidiosis-chronic cholangitis-liver disease syndrome	Likely benign (Jul 28, 2023)
16-27434331-C-A		Cryptosporidiosis-chronic cholangitis-liver disease syndrome	Uncertain significance (Apr 12, 2022)
16-27434331-C-T		Cryptosporidiosis-chronic cholangitis-liver disease syndrome	Likely benign (Aug 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IL21R	protein_coding	protein_coding	ENST00000337929	8	48633

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00165	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.749	272	309	0.880	0.0000174	3455
Missense in Polyphen		48	74.311	0.64593		893
Synonymous	0.924	124	138	0.900	0.00000869	1105
Loss of Function	4.26	1	23.1	0.0433	9.84e-7	269

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000162	0.000159
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000274	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This is a receptor for interleukin-21.
• Disease: DISEASE: Immunodeficiency 56 (IMD56) [MIM:615207]: An autosomal recessive primary immunodeficiency characterized by B- and T-cell defects and variable dysfunction of NK cells. Patients tend to have normal numbers of lymphocytes, but show defective class- switched B-cells, low IgG, defective antibody response, and defective T-cell responses to certain antigens. {ECO:0000269|PubMed:23440042}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Chromosomal aberrations involving IL21R is a cause of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation t(3;16)(q27;p11), with BCL6.
• 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 (Consensus)

Recessive Scores

• pRec: 0.211

Intolerance Scores

• loftool: 0.168
• rvis_EVS: 0.64
• rvis_percentile_EVS: 84.05

Haploinsufficiency Scores

• pHI: 0.0897
• hipred: Y
• hipred_score: 0.594
• ghis: 0.504

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Il21r
• Phenotype: hematopoietic system phenotype; immune system phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: natural killer cell activation;interleukin-21-mediated signaling pathway
• Cellular component: plasma membrane;integral component of membrane
• Molecular function: interleukin-21 receptor activity;transmembrane signaling receptor activity;cytokine receptor activity