IL23R

Chr 1

interleukin 23 receptor

Also known as: PSORS7

NCBI Gene: 149233 ENSG00000162594 UniProt: Q5VWK5 OMIM: 607562

This protein associates with IL12RB1 to form the interleukin-23 receptor, which binds IL-23 and mediates stimulation of T-cells, NK cells, and certain macrophage/myeloid cells through the Jak-Stat signaling cascade. Mutations in this gene are associated with protection against inflammatory bowel disease and psoriasis rather than causing disease. The gene is not highly constrained against loss-of-function variants, consistent with protective rather than pathogenic effects of certain mutations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Inflammatory bowel disease 17, protection against}MIM #612261

{Psoriasis, protection against}MIM #605606

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.61

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.61LOEUF

pLI 0.001

Z-score 3.22

OE 0.37 (0.23–0.61)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.08Z-score

OE missense 0.83 (0.75–0.92)

264 obs / 318.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.37 (0.23–0.61)

0≤0.351.4

Missense OE?0.83 (0.75–0.92)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 11 / 30.0Missense obs/exp: 264 / 318.4Syn Z: -0.02

Background carrier burden — how many people carry a rare variant somewhere in IL23R?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

688 rare PASS variants

Rare truncating (LoF)

1 in 1,500

85 rare PASS variants

Rare synonymous (reference)

1 in 130

248 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IL23R. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 1,700
South Asian	~43k	1 in 68	1 in 600
Remaining (unassigned)	~30k	1 in 93	1 in 2,500
European (Finnish)	~27k	1 in 520	1 in 2,700
Admixed American	~22k	1 in 120	1 in 1,400
African / African American	~21k	1 in 82	1 in 2,100
East Asian	~20k	1 in 170	1 in 1,400
Ashkenazi Jewish	~13k	1 in 250	1 in 2,300
Middle Eastern	~2,884	1 in 71	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 10 coding exons well covered in gnomAD exomes; exon 10 marginal. Genomes: 9 of 10 (exon 6 below).? see exons ↓