IL33

protein-coding

interleukin 33, the group of Interleukins

Gene summary

The protein encoded by this gene is a cytokine that binds to the IL1RL1/ST2 receptor. The encoded protein is involved in the maturation of Th2 cells and the activation of mast cells, basophils, eosinophils and natural killer cells. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

Previous symbols:

C9orf26

MANE transcript

NM_033439.4

Inheritance

—

ClinVar variants

U:43B:9

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 1.15

Max pathogenic AF

—

Genomic locus

chr9:6,215,786-6,257,983

External References & Databases

Ensembl (ENSG00000137033)

Transcript & Mutation Effects

hg38 • Region Span ~42.2 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 IL33 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 44

not providedTotal: 6

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033439.4. 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					2 clinvar	2
missense			42 clinvar	3 clinvar	3 clinvar	48
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar	1 clinvar		2
Total	0	0	43	4	5	52

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 61 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033439.4	RefSeq	NP_254274.1	7	MANE Select
ENST00000682010.1	Ensembl	ENSP00000507310.1	7	MANE Select
NM_001199640.2	RefSeq	NP_001186569.1	6	Standard
NM_001199641.2	RefSeq	NP_001186570.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Influenza A - Homo sapiens (human)
Cytosolic DNA-sensing pathway - Homo sapiens (human)
Necroptosis - Homo sapiens (human)
Development and heterogeneity of the ILC family
Signal Transduction

Biological Process

microglial cell activation involved in immune response
negative regulation of leukocyte migration
negative regulation of T-helper 1 type immune response
positive regulation of type 2 immune response
regulation of signaling receptor activity

Molecular Function

cytokine activity
protein binding

Cellular Component

extracellular region
extracellular space
nucleoplasm
chromosome
transport vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000381434
Coding exons: 7
Length: 42179
Individuals with no LoFs: 125083
Homozygous LoFs: 1
Heterozygous LoFs: 628
Defined: 125712
p: 0.00250

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.03	168	134	1.25	0.00000601	1785
Missense (PolyPhen)		44	35.653	1.2341		504
Synonymous	-0.755	52	45.5	1.14	0.00000212	462
Loss of Function	-0.454	13	11.3	1.15	4.73e-7	168

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00062	0.00062	rare
Latino/Admixed American	0.0010	0.0010	notable
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0	0.0	absent
Finnish	0.0019	0.0018	notable
European (Non-Finnish)	0.0044	0.0044	notable
South Asian	0.0011	0.0011	notable
Other	0.0020	0.0020	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cytokine that binds to and signals through the IL1RL1/ST2 receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells (PubMed:16286016). Involved in the maturation of Th2 cells inducing the secretion of T-helper type 2-associated cytokines. Also involved in activation of mast cells, basophils, eosinophils and natural killer cells. Acts as a chemoattractant for Th2 cells, and may function as an "alarmin", that amplifies immune responses during tissue injury (PubMed:17853410, PubMed:18836528). {ECO:0000269|PubMed:16286016, ECO:0000269|PubMed:17853410, ECO:0000269|PubMed:18836528}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.866
RVIS EVS: 0.42
RVIS percentile EVS: 76.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0638

Gene Damage Prediction

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