IL1RAP

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

Basic information

Region (hg38): 3:190514050-190659750

Links

ENSG00000196083 ∙ NCBI:3556 ∙ OMIM:602626 ∙ HGNC:5995 ∙ Uniprot:Q9NPH3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IL1RAP gene.

• Inborn genetic diseases (10 variants)
• not provided (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IL1RAP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	4	5
missense			10		1	11
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	10	1	5

Variants in IL1RAP

This is a list of pathogenic ClinVar variants found in the IL1RAP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-190604213-T-C			Benign (Jul 10, 2018)
3-190604281-C-T		not specified	Uncertain significance (Feb 14, 2024)
3-190604284-G-T		not specified	Uncertain significance (Jan 08, 2024)
3-190604288-G-A			Likely benign (Jun 28, 2018)
3-190604334-C-T		not specified	Uncertain significance (Jul 20, 2022)
3-190604401-C-A		not specified	Uncertain significance (Jan 05, 2022)
3-190620279-G-A		not specified	Uncertain significance (Dec 31, 2023)
3-190620339-T-A		not specified	Uncertain significance (Apr 11, 2023)
3-190620374-G-A		not specified	Uncertain significance (May 25, 2022)
3-190627377-G-T		not specified	Uncertain significance (Jan 03, 2024)
3-190627396-C-T			Benign (Jul 25, 2017)
3-190629435-T-C		not specified	Uncertain significance (Jan 09, 2023)
3-190629458-C-A			Benign (Apr 23, 2018)
3-190644248-T-C		not specified	Uncertain significance (Aug 23, 2021)
3-190644319-A-G		not specified	Uncertain significance (Apr 22, 2022)
3-190644353-T-C		not specified	Uncertain significance (Sep 22, 2023)
3-190648599-G-C		High myopia	Uncertain significance (Dec 17, 2018)
3-190656067-G-A			Benign (May 18, 2018)
3-190656092-G-A		not specified	Uncertain significance (Sep 16, 2021)
3-190656169-G-T		not specified	Uncertain significance (Jul 09, 2021)
3-190656425-C-T		not specified	Uncertain significance (Jun 22, 2021)
3-190656441-A-G			Benign (May 18, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IL1RAP	protein_coding	protein_coding	ENST00000317757	10	144004

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.258	0.742	125706	0	42	125748	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.82	277	377	0.735	0.0000200	4535
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000382	0.000366
Ashkenazi Jewish	0.000250	0.000198
East Asian	0.0000629	0.0000544
Finnish	0.000147	0.000139
European (Non-Finnish)	0.000200	0.000185
Middle Eastern	0.0000629	0.0000544
South Asian	0.000245	0.000196
Other	0.000367	0.000326

dbNSFP

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}.
• Pathway: 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;IL-1 signaling pathway;Structural Pathway of Interleukin 1 (IL-1);TLR NFkB;Signal Transduction;Signaling by Interleukins;signal transduction through il1r;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;Interleukin-1 signaling;Immune System;p73 transcription factor network;Neuronal System;IL-1 NFkB;IL-1 p38;IL-1 JNK;IL1;JAK STAT MolecularVariation 2;PIP3 activates AKT signaling;JAK STAT pathway and regulation;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;Receptor-type tyrosine-protein phosphatases;TLR ECSIT MEKK1 JNK;Protein-protein interactions at synapses;Intracellular signaling by second messengers;Interleukin-33 signaling;IL1-mediated signaling events;Interleukin-36 pathway;Interleukin-1 family signaling (Consensus)

Recessive Scores

• pRec: 0.223

Intolerance Scores

• loftool: 0.621
• rvis_EVS: -0.64
• rvis_percentile_EVS: 16.53

Haploinsufficiency Scores

• pHI: 0.794
• hipred: Y
• hipred_score: 0.689
• ghis: 0.554

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Il1rap
• Phenotype: immune system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: inflammatory response;immune response;cytokine-mediated signaling pathway;positive regulation of interleukin-13 production;positive regulation of interleukin-5 production;interleukin-33-mediated signaling pathway;interleukin-2 biosynthetic process;innate immune response;positive regulation of NF-kappaB transcription factor activity;positive regulation of synapse assembly;protein-containing complex assembly;interleukin-1-mediated signaling pathway;interleukin-4 secretion;regulation of postsynaptic density assembly;trans-synaptic signaling by trans-synaptic complex;synaptic membrane adhesion;regulation of presynapse assembly;positive regulation of interleukin-6 secretion
• Cellular component: extracellular region;plasma membrane;integral component of plasma membrane;membrane;glutamatergic synapse
• Molecular function: interleukin-33 receptor activity;interleukin-1 receptor activity