IL18BP

protein-coding

interleukin 18 binding protein, the group of Immunoglobulin like domain containing

Gene summary

The protein encoded by this gene functions as an inhibitor of the proinflammatory cytokine, IL18. It binds IL18, prevents the binding of IL18 to its receptor, and thus inhibits IL18-induced IFN-gamma production, resulting in reduced T-helper type 1 immune responses. This protein is constitutively expressed and secreted in mononuclear cells. Elevated level of this protein is detected in the intestinal tissues of patients with Crohn's disease. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

MANE transcript

NM_001039660.2

Inheritance

ClinVar variants

U:118B:38

Top phenotype

Hepatitis, fulminant viral, suspectibility to

gnomAD constraint

pLI —, LoF o/e 1.19

Max pathogenic AF

—

Genomic locus

chr11:71,998,613-72,007,315

External References & Databases

Ensembl (ENSG00000137496)

Transcript & Mutation Effects

hg38 • Region Span ~8.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hepatitis, fulminant viral, susceptibility toLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032809

Submitter: PanelApp Australia

hepatitis, fulminant viral, susceptibility toLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0032809

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Hepatitis, fulminant viral, suspectibility toAR

Manifestation: Allergy/Immunology/Infectious

Intervention: Allergy/Immunology/Infectious

Rationale: The condition has been described as involving susceptibilty to fulminant viral hepatitis as well as other autoimmune manifestations, and awareness may allow prompt and aggressive management of infectious and related sequelae

Refs: 31213488

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IL18BP variants in ClinVar

3 Conditions Cataloged

not providedTotal: 186

not specifiedTotal: 44

Hepatitis, fulminant viral, susceptibility toTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001039660.2. 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			12 clinvar	29 clinvar	1 clinvar	42
missense			89 clinvar	5 clinvar	3 clinvar	97
nonsense			2 clinvar			2
start loss						0
frameshift			5 clinvar			5
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	0	0	118	34	4	156

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 65 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001039660.2	RefSeq	NP_001034749.1	5	MANE Select
ENST00000393703.9	Ensembl	ENSP00000377306.4	5	MANE Select
NM_001039659.2	RefSeq	NP_001034748.1	5	Standard
NM_001145055.1	RefSeq	NP_001138527.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by Interleukins
Cytokine Signaling in Immune system
Interleukin-18 signaling
Purine metabolism
Immune System

Biological Process

response to lipopolysaccharide
interleukin-18-mediated signaling pathway
T-helper 1 type immune response
cellular response to hydrogen peroxide
cellular response to cytokine stimulus

Molecular Function

interleukin-18 binding
receptor antagonist activity

Cellular Component

extracellular region
extracellular space
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000404792
Coding exons: 5
Length: 7175
Individuals with no LoFs: 124749
Homozygous LoFs: 0
Heterozygous LoFs: 56
Defined: 124805
p: 0.000224

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.554	126	110	1.15	0.00000626	1229
Missense (PolyPhen)		31	22.579	1.373		293
Synonymous	-0.749	54	47.4	1.14	0.00000272	414
Loss of Function	-0.541	11	9.23	1.19	4.79e-7	95

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0010	0.0010	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.00060	0.00056	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Isoform A binds to IL-18 and inhibits its activity. Functions as an inhibitor of the early TH1 cytokine response. {ECO:0000269|PubMed:10023777, ECO:0000269|PubMed:10655506}.;

Recessive Scores

pRec: 0.0732

Intolerance Scores

LoFtool: 0.645
RVIS EVS: 0.26
RVIS percentile EVS: 70.26

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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