IL18R1 (Interleukin-18 receptor 1) variants and mutations
IL18R1 (also known as Interleukin-18 receptor 1) is a human protein-coding gene encoding an interleukin-18 receptor 1 protein. It binds IL-18 and, together with IL18RAP, initiates signaling that promotes IFN-gamma production and cellular immune activation. Variation in this pathway can influence inflammatory and allergic disease susceptibility, although severe monogenic deficiency is uncommon. This analysis covers 913 IL18R1 variants and mutations. Of these, 87% have computational variant effect predictions. Disease context includes Ascending aortic dissection, Wheezing, and Behcet disease. Example IL18R1 variants include M1?, N2D, and N2N.
Variant analysis overview
- Gene: IL18R1
- Protein: Interleukin-18 receptor 1
- UniProt accession: Q13478
- Organism: Homo sapiens
- Variants analyzed: 913
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 712 unspecified-consequence records; 102 missense variants; 17 frameshift variants; 69 synonymous variants; 11 stop-gained variants; 1 splice-region variants; 1 in-frame insertions
- Prediction scores: 790 variants have prediction scores (87% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Ascending aortic dissection, Wheezing, Behcet disease, asthma, Eczematoid dermatitis, atopic eczema, ulcerative colitis, Crohn disease, dermatitis, inflammatory bowel disease, chronic obstructive pulmonary disease, celiac disease.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 4 domains; 8 post-translational modification sites.
- Structural context: 703 variants have structural context.
- PTM context: 14 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable IL18R1 variants
Examples include M1?, N2D, N2N, C3F, C3G, C3R, C3V, C3Y. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV52127
- N2D (p.Asn2Asp), gnomAD 2-102362664-A-G, REVEL 0.03, MetaLR 0.01
- N2N (p.Asn2Asn), rs1426846562, gnomAD 2-102362666-T-C, CADD 3.49
- C3F (p.Cys3Phe), cosmic curated COSV52124
- C3G (p.Cys3Gly), TOPMed rs1678645488, REVEL 0.02, CADD 0.05
- C3R (p.Cys3Arg), TOPMed rs1678645488, MetaLR 0.01, MetaSVM -0.91
- C3V (p.Cys3Val), rs1260873221, gnomAD 2-102362665-AT-A, CADD 18.10
- C3Y (p.Cys3Tyr), gnomAD 2-102362668-G-A, REVEL 0.01, MetaLR 0.00
- C3* (p.Cys3Ter), gnomAD 2-102362669-T-A, CADD 24.20
- C3C (p.Cys3Cys), rs1166975948, gnomAD 2-102362669-T-C, CADD 0.88
- L6L (p.Leu6Leu), rs760548790, gnomAD 2-102362676-T-C, CADD 0.51
- L6* (p.Leu6Ter), gnomAD 2-102362677-T-G, CADD 32.00
- L6S (p.Leu6Ser), gnomAD 2-102362677-T-C, REVEL 0.23, MetaLR 0.02
- L6F (p.Leu6Phe), gnomAD 2-102362678-A-C, REVEL 0.06, MetaLR 0.01
- P7H (p.Pro7His), cosmic curated COSV10586
- P7L (p.Pro7Leu), NCI-TCGA Cosmic COSV5212, cosmic curated COSV52125, Variant assessed as somatic; moderate impact.
- P7S (p.Pro7Ser), cosmic curated COSV52125, MetaLR 0.00, MetaSVM -0.94
- P7P (p.Pro7Pro), rs11465569, gnomAD 2-102362681-C-A, CADD 0.52
- L8M (p.Leu8Met), ExAC rs754624008, TOPMed rs754624008, gnomAD rs754624008, REVEL 0.08, CADD 5.69
- L8* (p.Leu8Ter), gnomAD 2-102362683-T-A, CADD 33.00
- L8L (p.Leu8Leu), gnomAD 2-102362684-G-A, CADD 3.26
- T9I (p.Thr9Ile), rs1391311212, NCI-TCGA Cosmic COSV5212, cosmic curated COSV52127, TOPMed rs1391311212, REVEL 0.04, CADD 0.10, Variant assessed as somatic; moderate impact.
- T9P (p.Thr9Pro), NCI-TCGA Cosmic COSV5212, cosmic curated COSV52124, MetaLR 0.02, MetaSVM -1.00, Variant assessed as somatic; moderate impact.
- T9N (p.Thr9Asn), gnomAD 2-102362686-C-A, REVEL 0.07, MetaLR 0.02
- T9T (p.Thr9Thr), gnomAD 2-102362687-C-T, CADD 0.05
- L10P (p.Leu10Pro), gnomAD 2-102362676-T-TTA, CADD 17.70
- L10I (p.Leu10Ile), gnomAD 2-102362688-C-A, REVEL 0.02, MetaLR 0.01
- L10H (p.Leu10His), gnomAD 2-102362689-T-A, REVEL 0.20, MetaLR 0.03
- L10L (p.Leu10Leu), gnomAD 2-102362690-T-G, CADD 1.74
- W11L (p.Trp11Leu), cosmic curated COSV52123, MetaLR 0.01, MetaSVM -0.92
- W11G (p.Trp11Gly), gnomAD 2-102362688-CT-C, CADD 19.90
- W11C (p.Trp11Cys), gnomAD 2-102362693-G-T, REVEL 0.06, MetaLR 0.00
- W11* (p.Trp11Ter), gnomAD 2-102362693-G-A, CADD 26.10
- V12A (p.Val12Ala), Ensembl rs758610627, MetaLR 0.01, MetaSVM -0.92
- V12L (p.Val12Leu), rs778597504, ClinGen CA1809755, ClinVar RCV004405069, ExAC rs778597504, REVEL 0.07, CADD 0.30, Uncertain significance, not specified
- V12M (p.Val12Met), ExAC rs778597504, TOPMed rs778597504, gnomAD rs778597504, REVEL 0.09, CADD 1.45, Uncertain significance
- L13I (p.Leu13Ile), gnomAD 2-102362697-C-A, REVEL 0.08, MetaLR 0.02
- L13L (p.Leu13Leu), gnomAD 2-102362699-T-C, CADD 1.03
- I14M (p.Ile14Met), rs757943982, ClinGen CA1809757, ClinVar RCV004186219, ExAC rs757943982, REVEL 0.02, CADD 0.05, Likely benign, not specified
- I14T (p.Ile14Thr), gnomAD 2-102362699-T-TAC, CADD 15.50
- I14V (p.Ile14Val), gnomAD 2-102362700-A-G, REVEL 0.02, MetaLR 0.00
- S15P (p.Ser15Pro), TOPMed rs1678648011, MetaLR 0.00, MetaSVM -0.95
- S15* (p.Ser15Ter), gnomAD 2-102362702-ATCTG, CADD 17.00
- S15Y (p.Ser15Tyr), gnomAD 2-102362704-C-A, REVEL 0.07, MetaLR 0.00
- V16I (p.Val16Ile), gnomAD 2-102362706-G-A, REVEL 0.01, MetaLR 0.01
- V16V (p.Val16Val), rs1678648394, gnomAD 2-102362708-A-G, CADD 0.81
- S17G (p.Ser17Gly), NCI-TCGA TCGA novel, REVEL 0.02, CADD 3.30, Variant assessed as somatic; moderate impact.
- S17K (p.Ser17Lys), rs775454652, gnomAD 2-102362706-G-GT, CADD 14.30
- S17A (p.Ser17Ala), gnomAD 2-102362707-TA-T, CADD 13.50
- S17N (p.Ser17Asn), gnomAD 2-102362710-G-A, REVEL 0.01, MetaLR 0.01
- S17R (p.Ser17Arg), gnomAD 2-102362711-C-A, REVEL 0.00, MetaLR 0.01
- T18N (p.Thr18Asn), gnomAD rs1314205511, REVEL 0.03, CADD 9.95
- T18P (p.Thr18Pro), ExAC rs777296794, TOPMed rs777296794, gnomAD rs777296794, REVEL 0.07, CADD 17.40
- T18S (p.Thr18Ser), ExAC rs777296794, TOPMed rs777296794, gnomAD rs777296794, MetaLR 0.01, MetaSVM -0.90
- T18T (p.Thr18Thr), rs746338663, gnomAD 2-102362714-T-A, CADD 0.34
- A19S (p.Ala19Ser), ExAC rs770217181, TOPMed rs770217181, gnomAD rs770217181, REVEL 0.01, CADD 0.02
- A19V (p.Ala19Val), ExAC rs780460211, gnomAD rs780460211, REVEL 0.04, CADD 19.90
- A19E (p.Ala19Glu), gnomAD 2-102362716-C-A, REVEL 0.04, MetaLR 0.01
- A19A (p.Ala19Ala), rs1359392744, gnomAD 2-102362717-A-G, CADD 4.54
- E20K (p.Glu20Lys), ExAC rs749670362, gnomAD rs749670362, REVEL 0.02, CADD 23.10
- S21A (p.Ser21Ala), cosmic curated COSV52125, MetaLR 0.00, MetaSVM -0.89
- S21Y (p.Ser21Tyr), TOPMed rs1442467116, gnomAD rs1442467116, REVEL 0.02, CADD 0.14
- S21C (p.Ser21Cys), gnomAD 2-102367828-C-G, REVEL 0.05, MetaLR 0.01
- S21S (p.Ser21Ser), gnomAD 2-102367829-T-G, CADD 1.34
- C22Y (p.Cys22Tyr), gnomAD rs763304570, REVEL 0.30, CADD 23.80
- C22R (p.Cys22Arg), gnomAD 2-102367830-T-C, REVEL 0.34, MetaLR 0.02
- T23A (p.Thr23Ala), TOPMed rs1678996936, REVEL 0.05, CADD 6.00
- T23S (p.Thr23Ser), gnomAD 2-102367833-A-T, REVEL 0.05, MetaLR 0.01
- S24L (p.Ser24Leu), cosmic curated COSV10509, REVEL 0.01, CADD 6.58
- S24* (p.Ser24Ter), gnomAD 2-102367837-C-A, CADD 33.00
- R25C (p.Arg25Cys), rs764548979, NCI-TCGA Cosmic COSV9929, cosmic curated COSV99294, ExAC rs764548979, REVEL 0.22, CADD 24.50, Variant assessed as somatic; moderate impact.
- R25H (p.Arg25His), cosmic curated COSV52122, ExAC rs764661915, gnomAD rs764661915, REVEL 0.19, CADD 24.20
- P26H (p.Pro26His), 1000Genomes rs993433276, TOPMed rs993433276, gnomAD rs993433276, REVEL 0.20, CADD 0.01
- P26L (p.Pro26Leu), 1000Genomes rs993433276, TOPMed rs993433276, gnomAD rs993433276, REVEL 0.17, CADD 0.01
- P26R (p.Pro26Arg), cosmic curated COSV99295, MetaLR 0.06, MetaSVM -0.88
- H27Q (p.His27Gln), gnomAD rs1678998110, REVEL 0.02, CADD 0.54
- H27R (p.His27Arg), cosmic curated COSV10802, gnomAD rs1304101284, REVEL 0.02, CADD 0.43, Uncertain significance, not specified
- H27T (p.His27Thr), NCI-TCGA TCGA novel, MetaLR 0.05, MetaSVM -1.02, Variant assessed as somatic; high impact.
- H27Y (p.His27Tyr), gnomAD 2-102367845-C-T, REVEL 0.03, MetaLR 0.06
- H27P (p.His27Pro), gnomAD 2-102367846-A-C, REVEL 0.08, MetaLR 0.09
- I28F (p.Ile28Phe), ExAC rs759505022, TOPMed rs759505022, gnomAD rs759505022, REVEL 0.14, CADD 17.50
- I28V (p.Ile28Val), ExAC rs759505022, TOPMed rs759505022, gnomAD rs759505022, REVEL 0.01, CADD 3.98
- T29A (p.Thr29Ala), TOPMed rs1273693542, gnomAD rs1273693542, REVEL 0.07, CADD 13.30
- T29I (p.Thr29Ile), TOPMed rs1232230818, gnomAD rs1232230818
- T29N (p.Thr29Asn), TOPMed rs1232230818, gnomAD rs1232230818
- T29S (p.Thr29Ser), cosmic curated COSV52124, MetaLR 0.09, MetaSVM -1.01
- V31L (p.Val31Leu), gnomAD rs1276855314, REVEL 0.04, CADD 0.52
- V31F (p.Val31Phe), gnomAD 2-102367857-G-T, REVEL 0.14, MetaLR 0.16
- E32D (p.Glu32Asp), gnomAD 2-102367862-A-T, REVEL 0.07, MetaLR 0.21
- G33R (p.Gly33Arg), Ensembl rs1573191317
- G33V (p.Gly33Val), cosmic curated COSV99295, MetaLR 0.37, MetaSVM -0.32
- G33E (p.Gly33Glu), gnomAD 2-102367864-G-A, REVEL 0.38, MetaLR 0.32
- E34D (p.Glu34Asp), gnomAD rs1438663084, REVEL 0.21, CADD 22.80
- E34K (p.Glu34Lys), rs1223706178, cosmic curated COSV10723, TOPMed rs1223706178, gnomAD rs1223706178, REVEL 0.22, CADD 26.80, Variant assessed as somatic; moderate impact.
- E34E (p.Glu34Glu), gnomAD 2-102367868-A-G, CADD 8.03
- P35H (p.Pro35His), TOPMed rs774529728, gnomAD rs774529728, REVEL 0.10, CADD 18.20
- P35L (p.Pro35Leu), TOPMed rs774529728, gnomAD rs774529728, REVEL 0.22, CADD 22.00
- P35R (p.Pro35Arg), TOPMed rs774529728, gnomAD rs774529728, REVEL 0.30, CADD 22.40
- P35S (p.Pro35Ser), TOPMed rs1319638276, gnomAD rs1319638276, REVEL 0.18, CADD 20.90
- P35T (p.Pro35Thr), cosmic curated COSV10437, MetaLR 0.20, MetaSVM -0.91
- P35A (p.Pro35Ala), gnomAD 2-102367869-C-G, REVEL 0.18, MetaLR 0.17
- P35P (p.Pro35Pro), gnomAD 2-102367871-T-G, CADD 9.77
- F36V (p.Phe36Val), ExAC rs775279396, gnomAD rs775279396, MetaLR 0.17, MetaSVM -0.90
- Y37C (p.Tyr37Cys), TOPMed rs1215014352, MetaLR 0.15, MetaSVM -0.82
- Y37H (p.Tyr37His), gnomAD rs1679000624, REVEL 0.06, CADD 21.30
- Y37S (p.Tyr37Ser), gnomAD 2-102367876-A-C, REVEL 0.24, MetaLR 0.15
- Y37Y (p.Tyr37Tyr), rs1679001023, gnomAD 2-102367877-T-C, CADD 8.96
- Y37* (p.Tyr37Ter), gnomAD 2-102367877-T-A, CADD 36.00
- L38Q (p.Leu38Gln), Ensembl rs1559619775, MetaLR 0.40, MetaSVM -0.16
- L38V (p.Leu38Val), ExAC rs762528444, TOPMed rs762528444, gnomAD rs762528444, REVEL 0.31, CADD 23.30, Uncertain significance, not specified
- L38M (p.Leu38Met), gnomAD 2-102367878-C-A, REVEL 0.35, MetaLR 0.33
- K39E (p.Lys39Glu), TOPMed rs1679001989
- K39Q (p.Lys39Gln), TOPMed rs1679001989, MetaLR 0.02, MetaSVM -1.00
- K39N (p.Lys39Asn), gnomAD 2-102367883-A-T, REVEL 0.07, MetaLR 0.01
- K39K (p.Lys39Lys), rs1295739636, gnomAD 2-102367883-A-G, CADD 5.53
- H40Y (p.His40Tyr), ExAC rs763710435, gnomAD rs763710435, REVEL 0.08, CADD 0.16
- H40D (p.His40Asp), gnomAD 2-102367884-C-G, REVEL 0.05, MetaLR 0.00
- H40H (p.His40His), rs751057067, gnomAD 2-102367886-T-C, CADD 1.93
- C41F (p.Cys41Phe), Ensembl rs1679002897, MetaLR 0.02, MetaSVM -1.11
- C41R (p.Cys41Arg), Ensembl rs760423365, REVEL 0.32, CADD 23.40
- C41C (p.Cys41Cys), gnomAD 2-102367889-C-T, CADD 2.35
- S42L (p.Ser42Leu), rs917316315, TOPMed rs917316315, gnomAD rs917316315, REVEL 0.03, CADD 4.56, Variant assessed as somatic; moderate impact.
- S42S (p.Ser42Ser), rs56183212, gnomAD 2-102367892-G-A, CADD 0.07
- C43Y (p.Cys43Tyr), TOPMed rs951497108, gnomAD rs951497108, REVEL 0.10, CADD 0.02
- C43F (p.Cys43Phe), gnomAD 2-102367894-G-T, REVEL 0.08, MetaLR 0.14
- C43S (p.Cys43Ser), gnomAD 2-102367894-G-C, REVEL 0.12, MetaLR 0.08
- A46S (p.Ala46Ser), gnomAD 2-102367902-G-T, REVEL 0.01, MetaLR 0.06
- A46A (p.Ala46Ala), rs375398936, gnomAD 2-102367904-A-G, CADD 3.57
- H47Q (p.His47Gln), Ensembl rs1679004213, REVEL 0.06, CADD 2.49
- H47R (p.His47Arg), Ensembl rs1679004012, MetaLR 0.08, MetaSVM -0.93
- H47L (p.His47Leu), gnomAD 2-102367906-A-T, REVEL 0.08, MetaLR 0.09
- E48D (p.Glu48Asp), TOPMed rs1171545140, cosmic curated COSV99295, REVEL 0.01, CADD 3.30, Uncertain significance, not specified
- E48K (p.Glu48Lys), cosmic curated COSV10457
- E48Q (p.Glu48Gln), TOPMed rs1349597131, MetaLR 0.07, MetaSVM -1.04
- I49M (p.Ile49Met), gnomAD 2-102367913-T-G, REVEL 0.02, MetaLR 0.08
- E50* (p.Glu50Ter), cosmic curated COSV52124
- E50K (p.Glu50Lys), NCI-TCGA Cosmic COSV5212, cosmic curated COSV52126, MetaLR 0.06, MetaSVM -1.07, Variant assessed as somatic; moderate impact.
- E50E (p.Glu50Glu), gnomAD 2-102367916-A-G, CADD 2.41
- T51A (p.Thr51Ala), ExAC rs779351136, gnomAD rs779351136, REVEL 0.03, CADD 0.03
- T51T (p.Thr51Thr), rs368716787, gnomAD 2-102367919-A-C, CADD 0.76
- T52N (p.Thr52Asn), gnomAD rs1559619837, REVEL 0.02, CADD 0.00
- T53I (p.Thr53Ile), 1000Genomes rs535384643, ExAC rs535384643, gnomAD rs535384643, REVEL 0.04, CADD 13.10
- T53S (p.Thr53Ser), 1000Genomes rs535384643, ExAC rs535384643, gnomAD rs535384643, MetaLR 0.07, MetaSVM -1.00
- T53N (p.Thr53Asn), gnomAD 2-102367924-C-A, REVEL 0.06, MetaLR 0.09
- T53T (p.Thr53Thr), rs777908870, gnomAD 2-102367925-C-T, CADD 1.58
- K54E (p.Lys54Glu), gnomAD rs1326301745, REVEL 0.03, CADD 5.10
- K54T (p.Lys54Thr), gnomAD 2-102367927-A-C, REVEL 0.02, MetaLR 0.05
- K54K (p.Lys54Lys), rs1679007546, gnomAD 2-102367928-A-G, CADD 1.01
- S55I (p.Ser55Ile), NCI-TCGA Cosmic COSV5212, cosmic curated COSV52123, Ensembl rs1412043981, Variant assessed as somatic; moderate impact.
- S55N (p.Ser55Asn), NCI-TCGA Cosmic COSV5212, cosmic curated COSV52125, Variant assessed as somatic; moderate impact.
- S55R (p.Ser55Arg), Ensembl rs909864674, Likely benign, not specified
- S55T (p.Ser55Thr), Ensembl rs1412043981, MetaLR 0.04, MetaSVM -0.99
- W56* (p.Trp56Ter), NCI-TCGA Cosmic COSV5212, cosmic curated COSV52126, CADD 35.00, Variant assessed as somatic; high impact.
- W56C (p.Trp56Cys), NCI-TCGA Cosmic COSV5212, cosmic curated COSV52122, Variant assessed as somatic; moderate impact.
- W56G (p.Trp56Gly), NCI-TCGA Cosmic COSV5212, cosmic curated COSV52123, MetaLR 0.73, MetaSVM 0.03, Variant assessed as somatic; moderate impact.
- Y57* (p.Tyr57Ter), cosmic curated COSV10634
- Y57C (p.Tyr57Cys), gnomAD 2-102367936-A-G, REVEL 0.10, MetaLR 0.12
- K58R (p.Lys58Arg), gnomAD 2-102367939-A-G, REVEL 0.02, MetaLR 0.11
- S59G (p.Ser59Gly), gnomAD rs1370238586, REVEL 0.01, CADD 2.90
- S59I (p.Ser59Ile), NCI-TCGA TCGA novel, REVEL 0.02, CADD 6.99, Variant assessed as somatic; moderate impact.
- S59S (p.Ser59Ser), gnomAD 2-102367943-C-T, CADD 4.25
- S60N (p.Ser60Asn), Ensembl rs1679008446, REVEL 0.02, CADD 0.00
- G61R (p.Gly61Arg), Ensembl rs752359007, MetaLR 0.14, MetaSVM -1.00
- G61* (p.Gly61Ter), gnomAD 2-102367947-G-T, CADD 32.00
- G61G (p.Gly61Gly), gnomAD 2-102367949-A-G, CADD 0.41
- S62* (p.Ser62Ter), ExAC rs770879570, gnomAD rs770879570, CADD 33.00
- S62L (p.Ser62Leu), NCI-TCGA Cosmic COSV5212, cosmic curated COSV52125, MetaLR 0.09, MetaSVM -1.07, Variant assessed as somatic; moderate impact.
- S62P (p.Ser62Pro), gnomAD 2-102367950-T-C, REVEL 0.02, MetaLR 0.09
- Q63H (p.Gln63His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Q63R (p.Gln63Arg), cosmic curated COSV10957, MetaLR 0.06, MetaSVM -1.03
- Q63Q (p.Gln63Gln), rs370305765, gnomAD 2-102367955-G-A, CADD 0.21
- E64* (p.Glu64Ter), ExAC rs776795173, gnomAD rs776795173, CADD 32.00
- E64K (p.Glu64Lys), ExAC rs776795173, gnomAD rs776795173, REVEL 0.04, CADD 4.23
- E64Q (p.Glu64Gln), ExAC rs776795173, gnomAD rs776795173, REVEL 0.04, CADD 2.67
- E64E (p.Glu64Glu), rs1340155321, gnomAD 2-102367958-A-G, CADD 0.46
- H65R (p.His65Arg), ESP rs139816270, MetaLR 0.03, MetaSVM -1.05
- H65M (p.His65Met), gnomAD 2-102367958-AC-A, CADD 15.90
- H65Y (p.His65Tyr), gnomAD 2-102367959-C-T, REVEL 0.10, MetaLR 0.03
- V66E (p.Val66Glu), gnomAD 2-102367963-T-A, REVEL 0.17, MetaLR 0.06
- V66A (p.Val66Ala), gnomAD 2-102367963-T-C, REVEL 0.09, MetaLR 0.06
Public IL18R1 analysis runs
- IL18R1 analysis run — IL18R1 (913 variants) — completed 2026-08-20