IL1R1 (Interleukin-1 receptor type 1) variants and mutations
IL1R1 (also known as Interleukin-1 receptor type 1) is a human protein-coding gene encoding an interleukin-1 receptor type 1 protein. It transmits signals from IL-1alpha and IL-1beta to NF-kappaB and MAPK pathways, coordinating fever and inflammatory gene expression. Excess activation contributes to autoinflammatory and rheumatic disease, while receptor blockade can suppress IL-1-driven pathology. This analysis covers 753 IL1R1 variants and mutations. Of these, 76% have computational variant effect predictions. Disease context includes rheumatoid arthritis, Ascending aortic dissection, and asthma. Example IL1R1 variants include V3E, V3A, and L4F.
Variant analysis overview
- Gene: IL1R1
- Protein: Interleukin-1 receptor type 1
- UniProt accession: P14778
- Organism: Homo sapiens
- Variants analyzed: 753
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 508 unspecified-consequence records; 121 missense variants; 97 synonymous variants; 3 in-frame deletions; 3 splice-region variants; 13 frameshift variants; 5 stop-gained variants; 2 in-frame insertions; 1 substitution
- Prediction scores: 575 variants have prediction scores (76% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: rheumatoid arthritis, Ascending aortic dissection, asthma, inflammatory bowel disease, COVID-19, CINCA syndrome, immune system disorder, neurodegenerative disease, gout, chronic recurrent multifocal osteomyelitis 3, adult-onset Still disease, systemic-onset juvenile idiopathic arthritis.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 4 domains; 7 post-translational modification sites.
- Structural context: 613 variants have structural context.
- PTM context: 8 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 IL1R1 variants
Examples include V3E, V3A, L4F, L4L, L5I, L5L, R6G, R6R. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- V3E (p.Val3Glu), ExAC rs779905023, TOPMed rs779905023, gnomAD rs779905023, REVEL 0.20, CADD 19.80, Uncertain significance, not specified
- V3A (p.Val3Ala), gnomAD 2-102157732-T-C, REVEL 0.07, CADD 18.90
- L4F (p.Leu4Phe), gnomAD 2-102157736-A-C, REVEL 0.07, CADD 16.80
- L4L (p.Leu4Leu), rs201289347, gnomAD 2-102157736-A-G, CADD 7.93
- L5I (p.Leu5Ile), gnomAD 2-102157737-C-A, REVEL 0.09, CADD 22.80
- L5L (p.Leu5Leu), gnomAD 2-102157739-C-A, CADD 6.06
- R6G (p.Arg6Gly), gnomAD 2-102157740-A-G, REVEL 0.14, CADD 7.53
- R6R (p.Arg6Arg), gnomAD 2-102157742-A-G, CADD 6.14
- L7F (p.Leu7Phe), 1000Genomes rs200131321, ExAC rs200131321, gnomAD rs200131321, REVEL 0.10, CADD 10.70
- L7R (p.Leu7Arg), TOPMed rs1376344625, gnomAD rs1376344625, REVEL 0.26, CADD 22.50
- L7V (p.Leu7Val), 1000Genomes rs200131321, ExAC rs200131321, gnomAD rs200131321, REVEL 0.10, CADD 7.45
- L7I (p.Leu7Ile), gnomAD 2-102157743-C-A, REVEL 0.12, CADD 8.76
- I8T (p.Ile8Thr), ExAC rs761384702, TOPMed rs761384702, gnomAD rs761384702, REVEL 0.03, CADD 6.92
- C9Y (p.Cys9Tyr), ExAC rs771763567, TOPMed rs771763567, gnomAD rs771763567, REVEL 0.16, CADD 24.00, Uncertain significance, not specified
- C9C (p.Cys9Cys), gnomAD 2-102157751-T-C, CADD 9.22
- F10C (p.Phe10Cys), gnomAD 2-102157753-T-G, REVEL 0.04, CADD 19.30
- I11L (p.Ile11Leu), TOPMed rs1559495992
- I11M (p.Ile11Met), ESP rs144810374, TOPMed rs144810374, gnomAD rs144810374
- A12S (p.Ala12Ser), TOPMed rs1359694887, REVEL 0.04, CADD 16.80
- A12V (p.Ala12Val), TOPMed rs1684328291
- A12D (p.Ala12Asp), gnomAD 2-102157759-C-A, REVEL 0.19, CADD 16.10
- A12A (p.Ala12Ala), gnomAD 2-102157760-T-C, CADD 7.90
- L13P (p.Leu13Pro), Ensembl rs998308685, REVEL 0.17, CADD 17.90
- L13L (p.Leu13Leu), rs777273469, gnomAD 2-102157761-C-T, CADD 7.29
- L14P (p.Leu14Pro), ExAC rs760125077, gnomAD rs760125077, REVEL 0.28, CADD 25.90
- L14del (p.Leu14del), rs758552852, gnomAD 2-102157760-TCTA-, CADD 13.80
- S16Y (p.Ser16Tyr), gnomAD 2-102157771-C-A, REVEL 0.09, CADD 22.80
- S17Y (p.Ser17Tyr), NCI-TCGA TCGA novel, REVEL 0.12, CADD 15.70, Variant assessed as somatic; moderate impact.
- L18L (p.Leu18Leu), gnomAD 2-102157776-C-T, CADD 7.12
- L18M (p.Leu18Met), gnomAD 2-102157776-C-A, REVEL 0.08, CADD 22.60
- E19G (p.Glu19Gly), gnomAD 2-102157780-A-G, REVEL 0.04, CADD 24.00
- E19E (p.Glu19Glu), rs1684329685, gnomAD 2-102157781-G-A, CADD 8.38
- A20T (p.Ala20Thr), rs2528448973, ClinGen CA347924116, ClinVar RCV004109289, Uncertain significance, not specified
- A20P (p.Ala20Pro), gnomAD 2-102157782-G-C, REVEL 0.11, CADD 24.40
- A20D (p.Ala20Asp), gnomAD 2-102157783-C-A, REVEL 0.13, CADD 23.20
- D21G (p.Asp21Gly), TOPMed rs1685026814, REVEL 0.08, CADD 23.10
- D21Y (p.Asp21Tyr), gnomAD 2-102157785-G-T, REVEL 0.20, CADD 35.00
- D21N (p.Asp21Asn), gnomAD 2-102157785-G-A, REVEL 0.07, CADD 34.00
- D21V (p.Asp21Val), gnomAD 2-102164774-A-T, REVEL 0.15, CADD 23.70
- D21D (p.Asp21Asp), rs202008017, gnomAD 2-102164775-T-C, CADD 12.40
- C23W (p.Cys23Trp), gnomAD 2-102164781-C-G, REVEL 0.29, CADD 22.00
- K24T (p.Lys24Thr), ExAC rs750296992, gnomAD rs750296992, REVEL 0.04, CADD 8.40
- K24K (p.Lys24Lys), rs1479282608, gnomAD 2-102164784-G-A, CADD 3.82
- E25Q (p.Glu25Gln), TOPMed rs1205738901, gnomAD rs1205738901, REVEL 0.06, CADD 17.60
- E25K (p.Glu25Lys), gnomAD 2-102164785-G-A, REVEL 0.12, CADD 19.30
- R26C (p.Arg26Cys), rs56337419, ExAC rs56337419, TOPMed rs56337419, gnomAD rs56337419, REVEL 0.08, CADD 14.30, Variant assessed as somatic; moderate impact.
- R26H (p.Arg26His), ExAC rs779664597, TOPMed rs779664597, gnomAD rs779664597, REVEL 0.07, CADD 9.38
- R26L (p.Arg26Leu), ExAC rs779664597, TOPMed rs779664597, gnomAD rs779664597
- R26P (p.Arg26Pro), ExAC rs779664597, TOPMed rs779664597, gnomAD rs779664597, REVEL 0.12, CADD 16.60
- R26S (p.Arg26Ser), gnomAD 2-102164788-C-A, REVEL 0.05, CADD 9.58
- E27D (p.Glu27Asp), rs113620360, ClinGen CA1808113, ClinVar RCV004253981, ESP rs113620360, REVEL 0.02, CADD 14.30, Uncertain significance, not specified
- E28* (p.Glu28Ter), NCI-TCGA Cosmic COSV5210, Variant assessed as somatic; high impact.
- E28K (p.Glu28Lys), NCI-TCGA Cosmic COSV5210, cosmic curated COSV52105, REVEL 0.13, CADD 13.40, Variant assessed as somatic; moderate impact.
- E28V (p.Glu28Val), ExAC rs754771479, gnomAD rs754771479, REVEL 0.07, CADD 11.50
- I30* (p.Ile30Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- I30M (p.Ile30Met), gnomAD rs1401939230, REVEL 0.02, CADD 1.81
- L32L (p.Leu32Leu), gnomAD 2-102164806-T-C, CADD 2.19
- L32I (p.Leu32Ile), gnomAD 2-102164806-T-A, REVEL 0.07, CADD 1.77
- V33L (p.Val33Leu), TOPMed rs1309826161
- V33M (p.Val33Met), TOPMed rs1309826161
- V33V (p.Val33Val), gnomAD 2-102164811-G-C, CADD 6.69
- S34L (p.Ser34Leu), TOPMed rs1374298333, gnomAD rs1374298333, REVEL 0.04, CADD 13.40
- S34S (p.Ser34Ser), gnomAD 2-102164814-A-G, CADD 1.58
- S35C (p.Ser35Cys), ExAC rs201587813, gnomAD rs201587813, REVEL 0.07, CADD 20.30
- S35S (p.Ser35Ser), gnomAD 2-102164817-T-C, CADD 9.01
- A36S (p.Ala36Ser), ExAC rs747874532, gnomAD rs747874532, REVEL 0.18, CADD 19.30
- A36T (p.Ala36Thr), gnomAD 2-102164818-G-A, REVEL 0.18, CADD 21.10
- N37D (p.Asn37Asp), ExAC rs771640827, gnomAD rs771640827, REVEL 0.08, CADD 15.10
- N37Y (p.Asn37Tyr), gnomAD 2-102164821-A-T, REVEL 0.07, CADD 9.21
- N37K (p.Asn37Lys), gnomAD 2-102164823-T-G, REVEL 0.09, CADD 16.80
- E38A (p.Glu38Ala), ExAC rs772861436, TOPMed rs772861436, gnomAD rs772861436, REVEL 0.16, CADD 24.40
- E38K (p.Glu38Lys), NCI-TCGA Cosmic COSV5210, cosmic curated COSV52104, Variant assessed as somatic; moderate impact.
- I39M (p.Ile39Met), gnomAD 2-102164827-AT-A, CADD 26.40
- D40G (p.Asp40Gly), ExAC rs746323923, gnomAD rs746323923, REVEL 0.13, CADD 10.80
- D40N (p.Asp40Asn), TOPMed rs1685031848
- V41G (p.Val41Gly), ExAC rs770360631, gnomAD rs770360631, REVEL 0.24, CADD 21.70
- V41V (p.Val41Val), gnomAD 2-102164835-T-C, CADD 6.89
- R42C (p.Arg42Cys), rs867221636, NCI-TCGA Cosmic COSV5210, cosmic curated COSV52104, TOPMed rs867221636, REVEL 0.15, CADD 23.90, Variant assessed as somatic; moderate impact.
- R42H (p.Arg42His), cosmic curated COSV52107, gnomAD rs1221699681, REVEL 0.11, CADD 15.60
- R42S (p.Arg42Ser), gnomAD 2-102164836-C-A, REVEL 0.14, CADD 16.50
- R42R (p.Arg42Arg), gnomAD 2-102164838-T-C, CADD 6.75
- P43L (p.Pro43Leu), rs188550005, NCI-TCGA Cosmic COSV5210, cosmic curated COSV52108, 1000Genomes rs188550005, REVEL 0.17, CADD 13.30, Variant assessed as somatic; moderate impact.
- P43S (p.Pro43Ser), gnomAD 2-102164839-C-T, REVEL 0.13, CADD 0.00
- P43P (p.Pro43Pro), rs763351267, gnomAD 2-102164841-C-T, CADD 1.42
- C44R (p.Cys44Arg), rs1198478724, gnomAD rs1198478724, AlphaMissense 0.79, MetaLR 0.30, Variant assessed as somatic; moderate impact.
- C44V (p.Cys44Val), gnomAD 2-102164838-TC-T, CADD 5.64
- C44C (p.Cys44Cys), rs1271295422, gnomAD 2-102164844-T-C, CADD 10.40
- P45S (p.Pro45Ser), TOPMed rs1685034267
- P45T (p.Pro45Thr), gnomAD 2-102164845-C-A, REVEL 0.08, CADD 7.75
- P45L (p.Pro45Leu), gnomAD 2-102164846-C-T, REVEL 0.09, CADD 13.60
- L46L (p.Leu46Leu), rs1453880320, gnomAD 2-102164850-T-G, CADD 6.45
- N47N (p.Asn47Asn), rs137958518, gnomAD 2-102164853-C-T, CADD 5.96
- P48L (p.Pro48Leu), TOPMed rs1685035386, REVEL 0.08, CADD 2.96
- P48T (p.Pro48Thr), gnomAD rs1246589793, REVEL 0.08, CADD 0.29
- P48P (p.Pro48Pro), rs1490044452, gnomAD 2-102164856-A-G, CADD 7.61
- N49N (p.Asn49Asn), rs1685035918, gnomAD 2-102164859-T-C, CADD 4.21
- E50V (p.Glu50Val), gnomAD 2-102164861-A-T, REVEL 0.04, CADD 15.40
- H51Y (p.His51Tyr), gnomAD 2-102164863-C-T, REVEL 0.03, CADD 0.03
- H51R (p.His51Arg), gnomAD 2-102164864-A-G, REVEL 0.06, CADD 3.21
- H51Q (p.His51Gln), gnomAD 2-102164865-C-G, REVEL 0.02, CADD 0.18
- G53D (p.Gly53Asp), rs774553627, ClinGen CA1808124, ClinVar RCV004122871, ExAC rs774553627, REVEL 0.24, CADD 5.14, Uncertain significance, not specified
- G53G (p.Gly53Gly), rs1454942118, gnomAD 2-102164871-C-T, CADD 3.20
- T54L (p.Thr54Leu), rs1559501396, gnomAD 2-102164870-GC-G, CADD 13.40
- T54I (p.Thr54Ile), gnomAD 2-102164873-C-T, REVEL 0.21, CADD 7.86
- I55V (p.Ile55Val), gnomAD rs1196641679, REVEL 0.08, CADD 2.54
- I55M (p.Ile55Met), gnomAD 2-102164877-A-G, REVEL 0.38, CADD 17.90
- I55I (p.Ile55Ile), rs762031293, gnomAD 2-102164877-A-T, CADD 3.75
- T56S (p.Thr56Ser), gnomAD 2-102164879-C-G, REVEL 0.09, CADD 0.08
- W57* (p.Trp57Ter), NCI-TCGA Cosmic COSV9929, cosmic curated COSV99292, CADD 36.00, Variant assessed as somatic; high impact.
- W57C (p.Trp57Cys), Ensembl rs1345298159, REVEL 0.86, CADD 26.90
- W57L (p.Trp57Leu), Ensembl rs1685037542
- Y58H (p.Tyr58His), Ensembl rs201100543, REVEL 0.44, CADD 25.30
- D60E (p.Asp60Glu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D60V (p.Asp60Val), gnomAD 2-102164891-A-T, REVEL 0.27, CADD 18.70
- D61E (p.Asp61Glu), gnomAD 2-102164895-C-A, REVEL 0.05, CADD 4.74
- S62G (p.Ser62Gly), rs202061965, ClinGen CA1808126, ClinVar RCV004078391, ExAC rs202061965, REVEL 0.04, CADD 10.30, Uncertain significance, not specified
- S62N (p.Ser62Asn), gnomAD 2-102164897-G-A, REVEL 0.12, CADD 8.42
- T64I (p.Thr64Ile), cosmic curated COSV52108, ExAC rs760945361, gnomAD rs760945361, REVEL 0.08, CADD 9.53
- T64R (p.Thr64Arg), ExAC rs760945361, gnomAD rs760945361, REVEL 0.29, CADD 14.60
- P65A (p.Pro65Ala), TOPMed rs1378836045, REVEL 0.12, CADD 2.61
- P65H (p.Pro65His), cosmic curated COSV99292, TOPMed rs1185879650, gnomAD rs1185879650, REVEL 0.12, CADD 20.30
- P65T (p.Pro65Thr), gnomAD 2-102164905-C-A, REVEL 0.15, CADD 16.40
- P65S (p.Pro65Ser), gnomAD 2-102164905-C-T, REVEL 0.12, CADD 7.77
- P65P (p.Pro65Pro), gnomAD 2-102164907-T-A, CADD 3.19
- V66A (p.Val66Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V66L (p.Val66Leu), TOPMed rs905031467, REVEL 0.16, CADD 1.67
- V66I (p.Val66Ile), gnomAD 2-102164908-G-A, REVEL 0.08, CADD 0.01
- S67C (p.Ser67Cys), NCI-TCGA Cosmic COSV5210, cosmic curated COSV52106, REVEL 0.16, CADD 14.70, Variant assessed as somatic; moderate impact.
- S67S (p.Ser67Ser), rs1417165988, gnomAD 2-102164913-T-C, CADD 7.06
- T68I (p.Thr68Ile), gnomAD 2-102164915-C-T, REVEL 0.11, CADD 0.29
- A71V (p.Ala71Val), TOPMed rs1255796907
- A71D (p.Ala71Asp), gnomAD 2-102164924-C-A, REVEL 0.17, CADD 0.01
- A71A (p.Ala71Ala), gnomAD 2-102164925-C-T, CADD 3.41
- S72C (p.Ser72Cys), Ensembl rs1685040941, REVEL 0.26, CADD 12.60
- S72F (p.Ser72Phe), gnomAD 2-102164927-C-T, REVEL 0.18, CADD 21.90
- R73G (p.Arg73Gly), 1000Genomes rs138930592, ExAC rs138930592, gnomAD rs138930592, REVEL 0.48, CADD 24.30
- R73K (p.Arg73Lys), NCI-TCGA Cosmic COSV9929, cosmic curated COSV99292, Variant assessed as somatic; moderate impact.
- R73T (p.Arg73Thr), gnomAD 2-102164930-G-C, REVEL 0.43, CADD 24.10
- H75N (p.His75Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- H75R (p.His75Arg), TOPMed rs1198971096
- H75Y (p.His75Tyr), Ensembl rs867513855
- Q76* (p.Gln76Ter), NCI-TCGA Cosmic COSV9929, cosmic curated COSV99292, Variant assessed as somatic; high impact.
- Q76Q (p.Gln76Gln), rs1685041946, gnomAD 2-102164940-A-G, CADD 4.93
- H77D (p.His77Asp), cosmic curated COSV52107, ESP rs373700866, ExAC rs373700866, gnomAD rs373700866
- H77Q (p.His77Gln), NCI-TCGA Cosmic COSV5210, cosmic curated COSV52106, Variant assessed as somatic; moderate impact.
- H77Y (p.His77Tyr), gnomAD 2-102164941-C-T, REVEL 0.06, CADD 1.17
- K78* (p.Lys78Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- K78E (p.Lys78Glu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E79* (p.Glu79Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- E79D (p.Glu79Asp), NCI-TCGA Cosmic COSV9929, cosmic curated COSV99292, Variant assessed as somatic; moderate impact.
- E79K (p.Glu79Lys), 1000Genomes rs200321568, ExAC rs200321568, TOPMed rs200321568, gnomAD rs200321568, REVEL 0.24, CADD 14.90
- K80Q (p.Lys80Gln), ExAC rs778577313, gnomAD rs778577313, REVEL 0.05, CADD 7.72
- K80K (p.Lys80Lys), gnomAD 2-102164952-A-G, CADD 2.42
- W82L (p.Trp82Leu), ExAC rs748718957, TOPMed rs748718957, gnomAD rs748718957, REVEL 0.56, CADD 26.90
- F83C (p.Phe83Cys), gnomAD rs1360449099, REVEL 0.63, CADD 27.10
- F83L (p.Phe83Leu), gnomAD 2-102164959-T-C, REVEL 0.41, CADD 24.70
- V84G (p.Val84Gly), ExAC rs758142695, gnomAD rs758142695, REVEL 0.31, CADD 25.10
- V84L (p.Val84Leu), gnomAD 2-102164962-G-C, REVEL 0.13, CADD 17.80
- V84I (p.Val84Ile), gnomAD 2-102164962-G-A, REVEL 0.03, CADD 17.70
- V84V (p.Val84Val), rs1286832817, gnomAD 2-102164964-T-C, CADD 9.60
- P85L (p.Pro85Leu), Ensembl rs201278803, REVEL 0.45, CADD 26.00
- P85S (p.Pro85Ser), NCI-TCGA Cosmic COSV5210, cosmic curated COSV52106, Variant assessed as somatic; moderate impact.
- A86V (p.Ala86Val), TOPMed rs1452888518, gnomAD rs1452888518, REVEL 0.17, CADD 23.00
- A86T (p.Ala86Thr), gnomAD 2-102164968-G-A, REVEL 0.34, CADD 23.00
- K87G (p.Lys87Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- K87N (p.Lys87Asn), TOPMed rs1001921691, gnomAD rs1001921691, REVEL 0.09, CADD 13.70
- K87R (p.Lys87Arg), gnomAD 2-102164972-A-G, REVEL 0.02, CADD 15.80
- K87K (p.Lys87Lys), rs1001921691, gnomAD 2-102164973-G-A, CADD 7.04
- V88L (p.Val88Leu), gnomAD 2-102164974-G-T, REVEL 0.05, CADD 5.68
- V88V (p.Val88Val), rs202222726, gnomAD 2-102164976-G-A, CADD 2.29
- E89V (p.Glu89Val), gnomAD 2-102164976-G-GGT, CADD 28.40
- E89E (p.Glu89Glu), rs1685045176, gnomAD 2-102164979-G-A, CADD 8.10
- D90N (p.Asp90Asn), NCI-TCGA Cosmic COSV5210, cosmic curated COSV52106, Variant assessed as somatic; moderate impact.
- D90D (p.Asp90Asp), gnomAD 2-102164982-T-C, CADD 5.01
- S91L (p.Ser91Leu), TOPMed rs1685045396
- S91S (p.Ser91Ser), rs1358937255, gnomAD 2-102164985-A-G, CADD 8.10
- G92E (p.Gly92Glu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G92G (p.Gly92Gly), gnomAD 2-102164988-A-G, CADD 9.41
- H93R (p.His93Arg), TOPMed rs1245300387, REVEL 0.13, CADD 8.58
- H93H (p.His93His), rs938230267, gnomAD 2-102164991-T-C, CADD 8.77
Public IL1R1 analysis runs
- IL1R1 analysis run — IL1R1 (753 variants) — completed 2026-08-20