IL1RAP

protein-coding

interleukin 1 receptor accessory protein, the group of Interleukin receptors|Immunoglobulin like domain containing|TIR domain containing

Gene summary

This gene encodes a component of the interleukin 1 receptor complex, which initiates signalling events that result in the activation of interleukin 1-responsive genes. Alternative splicing of this gene results in membrane-bound and soluble isoforms differing in their C-terminus. The ratio of soluble to membrane-bound forms increases during acute-phase induction or stress. [provided by RefSeq, Jul 2018]

MANE transcript

NM_002182.4

Inheritance

ClinVar variants

U:33B:6

Top phenotype

High myopia

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr3:190,514,051-190,659,750

External References & Databases

Ensembl (ENSG00000196083)

Transcript & Mutation Effects

hg38 • Region Span ~145.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

nephrotic syndrome of childhood - steroid sensitiveLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0044781

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IL1RAP variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 29

not providedTotal: 6

High myopiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002182.4. 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 clinvar	3 clinvar	7
missense			31 clinvar	1 clinvar		32
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	33	3	3	39

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 62 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002182.4	RefSeq	NP_002173.1	10	MANE Select
ENST00000447382.6	Ensembl	ENSP00000390541.1	10	MANE Select
NM_001167928.2	RefSeq	NP_001161400.1	10	Standard
NM_001167929.2	RefSeq	NP_001161401.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Inflammatory mediator regulation of TRP channels - Homo sapiens (human)
Th17 cell differentiation - Homo sapiens (human)
MAPK signaling pathway - Homo sapiens (human)
Cytokine-cytokine receptor interaction - Homo sapiens (human)
JAK-STAT-Core

Biological Process

inflammatory response
immune response
cytokine-mediated signaling pathway
positive regulation of interleukin-13 production
positive regulation of interleukin-5 production

Molecular Function

interleukin-33 receptor activity
interleukin-1 receptor activity

Cellular Component

extracellular region
plasma membrane
integral component of plasma membrane
membrane
glutamatergic synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000317757
Coding exons: 10
Length: 144004
Individuals with no LoFs: 125706
Homozygous LoFs: 0
Heterozygous LoFs: 42
Defined: 125748
p: 0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.82	277	377	0.735	0.0000200	4535
Missense (PolyPhen)		86	133.66	0.64341		1628
Synonymous	1.05	118	133	0.885	0.00000687	1296
Loss of Function	3.85	7	29.6	0.236	0.00000142	374

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00032	0.00031	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00025	0.00020	rare
East Asian	0.000063	0.000054	rare
Finnish	0.00015	0.00014	rare
European (Non-Finnish)	0.00020	0.00018	rare
South Asian	0.00024	0.00020	rare
Other	0.00037	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Coreceptor for IL1RL2 in the IL-36 signaling system (By similarity). Coreceptor with IL1R1 in the IL-1 signaling system. Associates with IL1R1 bound to IL1B to form the high affinity interleukin-1 receptor complex which mediates interleukin-1- dependent activation of NF-kappa-B and other pathways. Signaling involves the recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR domains of the receptor/coreceptor subunits. Recruits TOLLIP to the signaling complex. Does not bind to interleukin-1 alone; binding of IL1RN to IL1R1, prevents its association with IL1R1 to form a signaling complex. The cellular response is modulated through a non- signaling association with the membrane IL1R2 decoy receptor. Coreceptor for IL1RL1 in the IL-33 signaling system. Can bidirectionally induce pre- and postsynaptic differentiation of neurons by trans-synaptically binding to PTPRD (By similarity). May play a role in IL1B-mediated costimulation of IFNG production from T-helper 1 (Th1) cells (Probable). {ECO:0000250|UniProtKB:Q61730, ECO:0000269|PubMed:10799889, ECO:0000269|PubMed:9371760, ECO:0000305|PubMed:10653850, ECO:0000305|PubMed:19836339}.; FUNCTION: Isoform 4: Unable to mediate canonical IL-1 signaling (PubMed:19481478). Required for Src phosphorylation by IL1B. May be involved in IL1B-potentiated NMDA-induced calcium influx in neurons (By similarity). {ECO:0000250|UniProtKB:Q61730, ECO:0000269|PubMed:19481478}.;

Recessive Scores

pRec: 0.223

Intolerance Scores

LoFtool: 0.621
RVIS EVS: -0.64
RVIS percentile EVS: 16.53

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.994

Gene Damage Prediction

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