IL18RAP

protein-coding

interleukin 18 receptor accessory protein, the group of CD molecules|Interleukin receptors|Immunoglobulin like domain containing|TIR domain containing|MicroRNA protein coding host genes

Gene summary

The protein encoded by this gene is an accessory subunit of the heterodimeric receptor for interleukin 18 (IL18), a proinflammatory cytokine involved in inducing cell-mediated immunity. This protein enhances the IL18-binding activity of the IL18 receptor and plays a role in signaling by IL18. Mutations in this gene are associated with Crohn's disease and inflammatory bowel disease, and susceptibility to celiac disease and leprosy. Alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2014]

MANE transcript

NM_001393487.1

Inheritance

—

ClinVar variants

U:66B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr2:102,418,689-102,452,565

External References & Databases

Ensembl (ENSG00000115607)

Transcript & Mutation Effects

hg38 • Region Span ~33.9 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 IL18RAP variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 73

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001393487.1. 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			65 clinvar	9 clinvar	1 clinvar	75
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	66	10	1	77

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001393487.1	RefSeq	NP_001380416.1	10	MANE Select
ENST00000687160.1	Ensembl	ENSP00000510345.1	10	MANE Select
NM_001393486.1	RefSeq	NP_001380415.1	10	Standard
NM_001393488.1	RefSeq	NP_001380417.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Inflammatory bowel disease (IBD) - Homo sapiens (human)
Cytokine-cytokine receptor interaction - Homo sapiens (human)
Signaling by Interleukins
Cytokine Signaling in Immune system
IL12 signaling mediated by STAT4

Biological Process

inflammatory response
immune response
cell population proliferation
interferon-gamma production
interleukin-6 production

Molecular Function

interleukin-18 receptor activity

Cellular Component

plasma membrane
interleukin-18 receptor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000264260
Coding exons: 10
Length: 33877
Individuals with no LoFs: 125718
Homozygous LoFs: 0
Heterozygous LoFs: 30
Defined: 125748
p: 0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.699	283	318	0.890	0.0000160	3915
Missense (PolyPhen)		52	83.281	0.62439		1152
Synonymous	-0.592	131	123	1.07	0.00000667	1132
Loss of Function	3.30	10	29.3	0.342	0.00000155	343

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000064	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00074	0.00074	rare
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.000065	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Within the IL18 receptor complex, does not mediate IL18- binding, but involved in IL18-dependent signal transduction, leading to NF-kappa-B and JNK activation (PubMed:9792649, PubMed:14528293, PubMed:25500532). May play a role in IL18- mediated IFNG synthesis from T-helper 1 (Th1) cells (Probable). {ECO:0000269|PubMed:14528293, ECO:0000269|PubMed:25500532, ECO:0000269|PubMed:9792649, ECO:0000305|PubMed:10653850}.;

Recessive Scores

pRec: 0.178

Intolerance Scores

LoFtool: 0.624
RVIS EVS: 0.02
RVIS percentile EVS: 55.61

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0357

Gene Damage Prediction

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