IL21R

Protein identityUniProt · HPA

UniProt accession

Q9HBE5

Gene

IL21R

Ensembl

ENSG00000103522

Chromosome

16

Canonical length

538 aa

Protein class

Cancer-related genes, CD markers, Disease related genes, Human disease related genes, Predicted membrane proteins

Subcellular location

Plasma membrane,Cytosol

OverviewNCBI Gene

The protein encoded by this gene is a cytokine receptor for interleukin 21 (IL21). It belongs to the type I cytokine receptors, and has been shown to form a heterodimeric receptor complex with the common gamma-chain, a receptor subunit also shared by the receptors for interleukin 2, 4, 7, 9, and 15. This receptor transduces the growth promoting signal of IL21, and is important for the proliferation and differentiation of T cells, B cells, and natural killer (NK) cells. The ligand binding of this receptor leads to the activation of multiple downstream signaling molecules, including JAK1, JAK3, STAT1, and STAT3. Knockout studies of a similar gene in mouse suggest a role for this gene in regulating immunoglobulin production. Three alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2010]

Canonical amino-acid sequenceUniProt

538 residues, UniProt reviewed canonical sequence.

>Q9HBE5|IL21R
     1  MPRGWAAPLL LLLLQGGWGC PDLVCYTDYL QTVICILEMW NLHPSTLTLT WQDQYEELKD
    61  EATSCSLHRS AHNATHATYT CHMDVFHFMA DDIFSVNITD QSGNYSQECG SFLLAESIKP
   121  APPFNVTVTF SGQYNISWRS DYEDPAFYML KGKLQYELQY RNRGDPWAVS PRRKLISVDS
   181  RSVSLLPLEF RKDSSYELQV RAGPMPGSSY QGTWSEWSDP VIFQTQSEEL KEGWNPHLLL
   241  LLLLVIVFIP AFWSLKTHPL WRLWKKIWAV PSPERFFMPL YKGCSGDFKK WVGAPFTGSS
   301  LELGPWSPEV PSTLEVYSCH PPRSPAKRLQ LTELQEPAEL VESDGVPKPS FWPTAQNSGG
   361  SAYSEERDRP YGLVSIDTVT VLDAEGPCTW PCSCEDDGYP ALDLDAGLEP SPGLEDPLLD
   421  AGTTVLSCGC VSAGSPGLGG PLGSLLDRLK PPLADGEDWA GGLPWGGRSP GGVSESEAGS
   481  PLAGLDMDTF DSGFVGSDCS SPVECDFTSP GDEGPPRSYL RQWVVIPPPL SSPGPQAS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IL21R can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.53

Highest tissue expression

23 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about IL21R.

Disease | AllUniProt

Conditions IL21R is implicated in, by any mechanism.

• Immunodeficiency 56 (IMD56) MIM:615207

Disease | GeneticClinVar

11 pathogenic / likely-pathogenic of 445 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Cryptosporidiosis-chronic cholangitis-liver disease syndrome

ReferencesPubMed · IEDB

Publications for IL21R from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.21

gnomAD pLI

1

gnomAD missense Z

0.75

DepMap mean gene effect

0.07

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cytokine-mediated signaling pathway
• natural killer cell activation

Molecular functions

• cytokine receptor activity
• transmembrane signaling receptor activity
• interleukin-21 receptor activity

Cellular components

• external side of plasma membrane
• membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Short hematopoietin receptor, family 1, conserved site
• Fibronectin type III
• Immunoglobulin-like fold
• Fibronectin type III superfamily

KeywordsUniProt

• Chromosomal rearrangement
• Disulfide bond
• Glycoprotein
• Membrane
• Receptor
• Repeat
• Signal
• Transmembrane
• Transmembrane helix