IL22RA2

protein-coding

interleukin 22 receptor subunit alpha 2, the group of Interleukin receptors

Gene summary

This gene encodes a member of the class II cytokine receptor family. The encoded soluble protein specifically binds to and inhibits interleukin 22 activity by blocking the interaction of interleukin 22 with its cell surface receptor. The encoded protein may be important in the regulation of inflammatory response, and has been implicated in the regulation of tumorigenesis in the colon. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2013]

MANE transcript

NM_052962.3

Inheritance

—

ClinVar variants

U:30B:2

Top phenotype

Multisystem inflammatory syndrome in children

gnomAD constraint

pLI —, LoF o/e 1.38

Max pathogenic AF

—

Genomic locus

chr6:137,143,820-137,173,648

External References & Databases

Ensembl (ENSG00000164485)

Transcript & Mutation Effects

hg38 • Region Span ~29.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IL22RA2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 30

Multisystem inflammatory syndrome in childrenTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_052962.3. 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			1 clinvar			1
missense			28 clinvar	2 clinvar		30
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	30	2	0	32

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_052962.3	RefSeq	NP_443194.1	6	MANE Select
ENST00000296980.7	Ensembl	ENSP00000296980.2	6	MANE Select
NM_181309.2	RefSeq	NP_851826.1	5	Standard
NM_181310.2	RefSeq	NP_851827.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Jak-STAT signaling pathway - Homo sapiens (human)
Cytokine-cytokine receptor interaction - Homo sapiens (human)
JAK-STAT-Ncore
Signaling by Interleukins
il22 soluble receptor signaling pathway

Biological Process

cytokine-mediated signaling pathway
regulation of tyrosine phosphorylation of STAT protein
negative regulation of inflammatory response

Molecular Function

cytokine receptor activity
interleukin-22 binding
interleukin-22 receptor activity

Cellular Component

extracellular region
extracellular space
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000296980
Coding exons: 6
Length: 29818
Individuals with no LoFs: 125668
Homozygous LoFs: 0
Heterozygous LoFs: 72
Defined: 125740
p: 0.000286

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.136	145	140	1.03	0.00000685	1731
Missense (PolyPhen)		55	42.155	1.3047		516
Synonymous	1.10	39	48.7	0.800	0.00000260	458
Loss of Function	-1.36	21	15.3	1.38	8.20e-7	161

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00099	0.00098	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00044	0.00044	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00032	0.00032	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Isoform 2 is a receptor for IL22. Binds to IL22, prevents interaction with the functional IL-22R complex and blocks the activity of IL22 (in vitro). May play an important role as an IL22 antagonist in the regulation of inflammatory responses.;

Recessive Scores

pRec: 0.0815

Intolerance Scores

LoFtool: 0.612
RVIS EVS: -0.25
RVIS percentile EVS: 35.99

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.970

Gene Damage Prediction

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