IL23R

protein-coding

interleukin 23 receptor

Gene summary

The protein encoded by this gene is a subunit of the receptor for IL23A/IL23. This protein pairs with the receptor molecule IL12RB1/IL12Rbeta1, and both are required for IL23A signaling. This protein associates constitutively with Janus kinase 2 (JAK2), and also binds to transcription activator STAT3 in a ligand-dependent manner. [provided by RefSeq, Jul 2008]

MANE transcript

NM_144701.3

Inheritance

ClinVar variants

U:240B:120

Top phenotype

immunodeficiency disease

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr1:67,138,907-67,259,979

External References & Databases

Ensembl (ENSG00000162594)

Transcript & Mutation Effects

hg38 • Region Span ~121.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

immunodeficiency diseaseSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0021094

Submitter: PanelApp Australia

inherited susceptibility to mycobacterial diseasesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0019146

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IL23R variants in ClinVar

5 Conditions Cataloged

not providedTotal: 401

not specifiedTotal: 81

IL23R-related disorderTotal: 7

Psoriasis 7, susceptibility toTotal: 2

Inflammatory bowel disease 17Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_144701.3. 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			6 clinvar	98 clinvar	2 clinvar	106
missense			221 clinvar	17 clinvar	2 clinvar	240
nonsense			5 clinvar			5
start loss						0
frameshift			6 clinvar			6
splice donor/acceptor (+/-2bp)			2 clinvar		1 clinvar	3
Total	0	0	240	115	5	360

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 40 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_144701.3	RefSeq	NP_653302.2	10	MANE Select
ENST00000347310.10	Ensembl	ENSP00000321345.5	10	MANE Select
ENST00000425614.3	Ensembl	ENSP00000387640.2	6	Standard
ENST00000425614.4	Ensembl	ENSP00000387640.2	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Jak-STAT signaling pathway - Homo sapiens (human)
Inflammatory bowel disease (IBD) - Homo sapiens (human)
Th17 cell differentiation - Homo sapiens (human)
Pathways in cancer - Homo sapiens (human)
Cytokine-cytokine receptor interaction - Homo sapiens (human)

Biological Process

positive regulation of T cell mediated cytotoxicity
positive regulation of defense response to virus by host
positive regulation of T-helper 1 type immune response
inflammatory response
positive regulation of activation of Janus kinase activity

Molecular Function

cytokine receptor activity
interleukin-12 receptor binding
protein binding
cytokine binding
interleukin-23 binding

Cellular Component

plasma membrane
external side of plasma membrane
receptor complex
interleukin-23 receptor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000347310
Coding exons: 10
Length: 93580
Individuals with no LoFs: 125727
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 125748
p: 0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.08	264	318	0.829	0.0000145	4173
Missense (PolyPhen)		48	79.053	0.60718		928
Synonymous	-0.0174	114	114	1.00	0.00000579	1141
Loss of Function	3.22	11	30.0	0.366	0.00000136	377

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.000098	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Associates with IL12RB1 to form the interleukin-23 receptor. Binds IL23 and mediates T-cells, NK cells and possibly certain macrophage/myeloid cells stimulation probably through activation of the Jak-Stat signaling cascade. IL23 functions in innate and adaptive immunity and may participate in acute response to infection in peripheral tissues. IL23 may be responsible for autoimmune inflammatory diseases and be important for tumorigenesis. {ECO:0000269|PubMed:12023369}.;
Disease: DISEASE: Inflammatory bowel disease 17 (IBD17) [MIM:612261]: A chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints. {ECO:0000269|PubMed:17068223, ECO:0000269|PubMed:17804789}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.331

Intolerance Scores

LoFtool: 0.367
RVIS EVS: 0.8
RVIS percentile EVS: 87.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.969

Gene Damage Prediction

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