IL18 (Interleukin-18) variants and mutations
IL18 (also known as Interleukin-18) is a human protein-coding gene encoding an interleukin-18 protein. After inflammasome-dependent processing, it promotes IFN-gamma production and strengthens natural-killer and T-cell responses, particularly together with IL-12. Excessive IL-18 activity contributes to macrophage-activation syndromes and other hyperinflammatory states. This analysis covers 453 IL18 variants and mutations. Of these, 98% have computational variant effect predictions. Disease context includes hemophagocytic syndrome, adult-onset Still disease, and type 2 diabetes mellitus. Example IL18 variants include P5A, E7D, and D8N.
Variant analysis overview
- Gene: IL18
- Protein: Interleukin-18
- UniProt accession: Q14116
- Organism: Homo sapiens
- Variants analyzed: 453
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 161 unspecified-consequence records; 2 stop lost; 170 missense variants; 87 synonymous variants; 3 in-frame deletions; 18 frameshift variants; 8 stop-gained variants; 2 splice-region variants; 2 substitution
- Prediction scores: 443 variants have prediction scores (98% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: hemophagocytic syndrome, adult-onset Still disease, type 2 diabetes mellitus, smoking initiation, systemic lupus erythematosus, rheumatoid arthritis, chronic obstructive pulmonary disease, neoplasm, acute kidney injury, infection, asthma, colitis.
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 IL18 variants
Examples include P5A, E7D, D8N, I11V, V14A, V14L, V14I, A15P. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- P5A (p.Pro5Ala), ExAC rs774621216, gnomAD rs774621216, REVEL 0.05, MetaLR 0.09
- E7D (p.Glu7Asp), Ensembl rs1866509618, REVEL 0.05, MetaLR 0.12
- D8N (p.Asp8Asn), Ensembl rs1866509544, MetaLR 0.06, MetaSVM -1.06
- I11V (p.Ile11Val), gnomAD rs1261098651, REVEL 0.01, MetaLR 0.08
- V14A (p.Val14Ala), TOPMed rs1866509214, MetaLR 0.10, MetaSVM -1.02
- V14L (p.Val14Leu), TOPMed rs1354475224, REVEL 0.05, MetaLR 0.09
- V14I (p.Val14Ile), rs766654584, []
- A15P (p.Ala15Pro), TOPMed rs1866509148, gnomAD rs1866509148, REVEL 0.15, MetaLR 0.04
- M16I (p.Met16Ile), cosmic curated COSV54781, MetaLR 0.12, MetaSVM -0.91
- K17Q (p.Lys17Gln), gnomAD rs1317762487, REVEL 0.07, MetaLR 0.12
- F18C (p.Phe18Cys), NCI-TCGA Cosmic COSV9973, cosmic curated COSV99737, MetaLR 0.30, MetaSVM -0.18, Variant assessed as somatic; moderate impact.
- I19F (p.Ile19Phe), ExAC rs766654584, gnomAD rs766654584, REVEL 0.32, MetaLR 0.15
- I19V (p.Ile19Val), ExAC rs766654584, gnomAD rs766654584, REVEL 0.03, MetaLR 0.07
- T22M (p.Thr22Met), cosmic curated COSV54781, 1000Genomes rs61734549, ESP rs61734549, ExAC rs61734549, REVEL 0.07, MetaLR 0.15
- T22R (p.Thr22Arg), 1000Genomes rs61734549, ESP rs61734549, ExAC rs61734549, TOPMed rs61734549, REVEL 0.17, MetaLR 0.16
- Y24H (p.Tyr24His), gnomAD rs1455115453, REVEL 0.41, MetaLR 0.36
- F25C (p.Phe25Cys), rs1271061057, ClinGen CA382615489, ClinVar RCV004405066, TOPMed rs1271061057, REVEL 0.40, MetaLR 0.31, Uncertain significance, not specified
- I26M (p.Ile26Met), gnomAD rs1381138292, REVEL 0.05, MetaLR 0.08
- I26T (p.Ile26Thr), TOPMed rs1866508198, REVEL 0.03, MetaLR 0.08
- E28K (p.Glu28Lys), cosmic curated COSV54781
- D29E (p.Asp29Glu), Ensembl rs1866484206
- D30G (p.Asp30Gly), TOPMed rs972965703, gnomAD rs972965703, REVEL 0.24, MetaLR 0.13
- D30N (p.Asp30Asn), Ensembl rs1866484147, MetaLR 0.08, MetaSVM -1.01
- E31G (p.Glu31Gly), gnomAD 11-112150206-T-C, REVEL 0.03, MetaLR 0.08
- N32K (p.Asn32Lys), gnomAD 11-112150202-G-T, REVEL 0.04, MetaLR 0.10
- N32N (p.Asn32Asn), gnomAD 11-112150202-G-A, CADD 7.76
- N32D (p.Asn32Asp), gnomAD 11-112150204-T-C, REVEL 0.02, MetaLR 0.05
- L33L (p.Leu33Leu), rs1866414192, gnomAD 11-112150199-C-T, CADD 13.30
- L33P (p.Leu33Pro), gnomAD 11-112150200-A-G, REVEL 0.62, MetaLR 0.41
- L33M (p.Leu33Met), gnomAD 11-112150201-G-T, REVEL 0.24, MetaLR 0.25
- E34A (p.Glu34Ala), Ensembl rs2135313616, MetaLR 0.42, MetaSVM -0.03
- E34D (p.Glu34Asp), gnomAD 11-112150196-T-A, REVEL 0.65, MetaLR 0.29
- E34G (p.Glu34Gly), gnomAD 11-112150197-T-C, REVEL 0.44, MetaLR 0.41
- E34N (p.Glu34Asn), gnomAD 11-112150197-TC-T, CADD 27.20
- S35S (p.Ser35Ser), rs549908, gnomAD 11-112150193-T-A, CADD 5.95
- S35* (p.Ser35Ter), gnomAD 11-112150194-G-T, CADD 36.00
- S35P (p.Ser35Pro), gnomAD 11-112150195-A-G, REVEL 0.16, MetaLR 0.14
- D36G (p.Asp36Gly), gnomAD 11-112150191-T-C, REVEL 0.43, MetaLR 0.41
- D36N (p.Asp36Asn), gnomAD 11-112150192-C-T, REVEL 0.50, MetaLR 0.42
- D36Y (p.Asp36Tyr), gnomAD 11-112150192-C-A, REVEL 0.46, MetaLR 0.42
- Y37* (p.Tyr37Ter), ExAC rs764067517, gnomAD rs764067517, CADD 35.00
- Y37F (p.Tyr37Phe), gnomAD 11-112150188-T-A, REVEL 0.06, MetaLR 0.11
- Y37H (p.Tyr37His), gnomAD 11-112150189-A-G, REVEL 0.04, MetaLR 0.06
- Y37N (p.Tyr37Asn), gnomAD 11-112150189-A-T, REVEL 0.07, MetaLR 0.06
- F38I (p.Phe38Ile), cosmic curated COSV99737, MetaLR 0.14, MetaSVM -0.89
- F38V (p.Phe38Val), ExAC rs760493708, gnomAD rs760493708, REVEL 0.33, MetaLR 0.38
- F38F (p.Phe38Phe), rs775577498, gnomAD 11-112150184-A-G, CADD 4.46
- F38L (p.Phe38Leu), gnomAD 11-112150186-A-G, REVEL 0.33, MetaLR 0.26
- G39G (p.Gly39Gly), gnomAD 11-112150181-G-T, CADD 2.12
- G39V (p.Gly39Val), gnomAD 11-112150182-C-A, REVEL 0.16, MetaLR 0.17
- G39D (p.Gly39Asp), gnomAD 11-112150182-C-T, REVEL 0.14, MetaLR 0.22
- G39C (p.Gly39Cys), gnomAD 11-112150183-C-A, REVEL 0.11, MetaLR 0.17
- K40K (p.Lys40Lys), gnomAD 11-112150178-C-T, CADD 0.87
- K40T (p.Lys40Thr), gnomAD 11-112150179-T-G, REVEL 0.14, MetaLR 0.19
- K40E (p.Lys40Glu), gnomAD 11-112150180-T-C, REVEL 0.07, MetaLR 0.11
- L41L (p.Leu41Leu), rs2135313583, gnomAD 11-112150175-A-G, CADD 1.37
- L41F (p.Leu41Phe), gnomAD 11-112150177-G-A, REVEL 0.07, MetaLR 0.13
- L41I (p.Leu41Ile), gnomAD 11-112150177-G-T, REVEL 0.03, MetaLR 0.08
- E42E (p.Glu42Glu), rs1465017742, gnomAD 11-112150172-T-C, CADD 1.75
- E42G (p.Glu42Gly), gnomAD 11-112150173-T-C, REVEL 0.03, MetaLR 0.09
- S43Y (p.Ser43Tyr), gnomAD 11-112150170-G-T, REVEL 0.04, MetaLR 0.07
- S43C (p.Ser43Cys), gnomAD 11-112150170-G-C, REVEL 0.02, MetaLR 0.07
- S43T (p.Ser43Thr), gnomAD 11-112150171-A-T, REVEL 0.04, MetaLR 0.05
- K44N (p.Lys44Asn), gnomAD 11-112150165-AT-A, CADD 21.50
- S46* (p.Ser46Ter), NCI-TCGA Cosmic COSV5478, cosmic curated COSV54782, CADD 34.00, Variant assessed as somatic; high impact.
- S46L (p.Ser46Leu), gnomAD 11-112150161-G-A, REVEL 0.14, MetaLR 0.25
- V47I (p.Val47Ile), 1000Genomes rs567330603, ExAC rs567330603, TOPMed rs567330603, gnomAD rs567330603, REVEL 0.05, MetaLR 0.02
- V47V (p.Val47Val), gnomAD 11-112150157-G-T, CADD 4.03
- I48T (p.Ile48Thr), gnomAD 11-112150155-A-G, REVEL 0.70, MetaLR 0.24
- I48V (p.Ile48Val), gnomAD 11-112150156-T-C, REVEL 0.14, MetaLR 0.12
- R49T (p.Arg49Thr), NCI-TCGA Cosmic COSV5478, cosmic curated COSV54780, MetaLR 0.42, MetaSVM -0.13, Variant assessed as somatic; moderate impact.
- L51F (p.Leu51Phe), NCI-TCGA TCGA novel, REVEL 0.06, MetaLR 0.14, Variant assessed as somatic; moderate impact.
- L51L (p.Leu51Leu), rs201671698, gnomAD 11-112150147-A-G, CADD 1.23
- N52S (p.Asn52Ser), Ensembl rs2135313563, MetaLR 0.12, MetaSVM -0.96
- N52N (p.Asn52Asn), gnomAD 11-112150142-A-G, CADD 2.07
- D53Y (p.Asp53Tyr), gnomAD 11-112150141-C-A, REVEL 0.16, MetaLR 0.21
- Q54H (p.Gln54His), NCI-TCGA Cosmic COSV5478, cosmic curated COSV54780, REVEL 0.29, MetaLR 0.31, Variant assessed as somatic; moderate impact.
- Q54Q (p.Gln54Gln), rs200824874, gnomAD 11-112150136-T-C, CADD 10.10
- V55I (p.Val55Ile), TOPMed rs1438010700, REVEL 0.18, MetaLR 0.27
- V55V (p.Val55Val), gnomAD 11-112150133-A-G, CADD 9.53
- L56F (p.Leu56Phe), NCI-TCGA Cosmic COSV5478, Variant assessed as somatic; moderate impact.
- L56I (p.Leu56Ile), cosmic curated COSV54782, gnomAD rs1182649992, REVEL 0.25, MetaLR 0.43
- L56L (p.Leu56Leu), gnomAD 11-112150130-G-A, CADD 8.69
- F57L (p.Phe57Leu), cosmic curated COSV54781, MetaLR 0.08, MetaSVM -0.98
- F57F (p.Phe57Phe), gnomAD 11-112150127-G-A, CADD 8.61
- D59E (p.Asp59Glu), gnomAD 11-112150121-G-T, REVEL 0.02, MetaLR 0.11
- D59Y (p.Asp59Tyr), gnomAD 11-112150123-C-A, REVEL 0.01, MetaLR 0.08
- Q60E (p.Gln60Glu), ExAC rs770531763, gnomAD rs770531763, REVEL 0.06, MetaLR 0.07
- Q60R (p.Gln60Arg), ExAC rs748523570, gnomAD rs748523570, REVEL 0.02, MetaLR 0.07
- G61E (p.Gly61Glu), rs1266223590, gnomAD rs1266223590, REVEL 0.03, MetaLR 0.10, Variant assessed as somatic; moderate impact.
- G61R (p.Gly61Arg), cosmic curated COSV10514
- G61G (p.Gly61Gly), gnomAD 11-112150115-T-A, CADD 18.00
- N62S (p.Asn62Ser), gnomAD 11-112150113-T-C, REVEL 0.04, MetaLR 0.07
- R63G (p.Arg63Gly), ESP rs199733090, ExAC rs199733090, TOPMed rs199733090, gnomAD rs199733090, REVEL 0.15, MetaLR 0.06
- R63Q (p.Arg63Gln), 1000Genomes rs183932139, ExAC rs183932139, TOPMed rs183932139, gnomAD rs183932139, REVEL 0.00, MetaLR 0.01, Likely benign, not specified
- R63W (p.Arg63Trp), ESP rs199733090, ExAC rs199733090, TOPMed rs199733090, gnomAD rs199733090, REVEL 0.16, MetaLR 0.06
- R63R (p.Arg63Arg), gnomAD 11-112150109-C-T, CADD 0.46
- P64S (p.Pro64Ser), gnomAD rs1329702763, REVEL 0.05, MetaLR 0.24
- P64L (p.Pro64Leu), gnomAD 11-112150107-G-A, REVEL 0.20, MetaLR 0.26
- L65L (p.Leu65Leu), rs747448658, gnomAD 11-112150103-T-C, CADD 3.44
- L65P (p.Leu65Pro), gnomAD 11-112150104-A-G, REVEL 0.24, MetaLR 0.27
- F66C (p.Phe66Cys), TOPMed rs1184810403, REVEL 0.45, MetaLR 0.42, Uncertain significance, not specified
- F66S (p.Phe66Ser), TOPMed rs1184810403, REVEL 0.71, MetaLR 0.42, Uncertain significance
- E67D (p.Glu67Asp), TOPMed rs1866412499
- E67K (p.Glu67Lys), NCI-TCGA Cosmic COSV9973, cosmic curated COSV99737, Variant assessed as somatic; moderate impact.
- D68Y (p.Asp68Tyr), cosmic curated COSV99737
- T70S (p.Thr70Ser), gnomAD rs1199026248, REVEL 0.06, MetaLR 0.08
- T70T (p.Thr70Thr), gnomAD 11-112150088-A-G, CADD 3.06
- D71G (p.Asp71Gly), Ensembl rs1866412377
- D71V (p.Asp71Val), NCI-TCGA Cosmic COSV5478, cosmic curated COSV54782, MetaLR 0.36, MetaSVM -0.04, Variant assessed as somatic; moderate impact.
- D71D (p.Asp71Asp), gnomAD 11-112150085-A-G, CADD 5.50
- S72F (p.Ser72Phe), Ensembl rs2135313477, REVEL 0.03, MetaLR 0.21
- S72S (p.Ser72Ser), rs780550512, gnomAD 11-112150082-A-C, CADD 5.45
- S72C (p.Ser72Cys), gnomAD 11-112150083-G-C, REVEL 0.04, MetaLR 0.21
- D73D (p.Asp73Asp), gnomAD 11-112150079-G-A, CADD 1.63
- D76A (p.Asp76Ala), TOPMed rs1866383862, REVEL 0.02, MetaLR 0.02
- D76E (p.Asp76Glu), gnomAD rs1285841242, REVEL 0.03, MetaLR 0.02
- D76G (p.Asp76Gly), TOPMed rs1866383862
- D76D (p.Asp76Asp), gnomAD 11-112148735-A-G, CADD 0.04
- N77N (p.Asn77Asn), rs1866383742, gnomAD 11-112148732-A-G, CADD 2.92
- N77M (p.Asn77Met), gnomAD 11-112148732-AT-A, CADD 23.40
- N77S (p.Asn77Ser), gnomAD 11-112148733-T-C, REVEL 0.11, MetaLR 0.06
- N77I (p.Asn77Ile), gnomAD 11-112148733-T-A, REVEL 0.13, MetaLR 0.10
- A78V (p.Ala78Val), gnomAD rs1242480821, REVEL 0.07, MetaLR 0.08
- A78A (p.Ala78Ala), gnomAD 11-112148729-T-C, CADD 6.83
- A78E (p.Ala78Glu), gnomAD 11-112148730-G-T, REVEL 0.02, MetaLR 0.03
- A78P (p.Ala78Pro), gnomAD 11-112148731-C-G, REVEL 0.12, MetaLR 0.11
- A78S (p.Ala78Ser), gnomAD 11-112148731-C-A, REVEL 0.04, MetaLR 0.07
- A78T (p.Ala78Thr), gnomAD 11-112148731-C-T, REVEL 0.06, MetaLR 0.08
- P79L (p.Pro79Leu), gnomAD rs1174079432, REVEL 0.07, MetaLR 0.07
- P79P (p.Pro79Pro), gnomAD 11-112148726-G-C, CADD 1.62
- P79H (p.Pro79His), gnomAD 11-112148727-G-T, REVEL 0.08, MetaLR 0.09
- P79S (p.Pro79Ser), gnomAD 11-112148728-G-A, REVEL 0.02, MetaLR 0.02
- P79A (p.Pro79Ala), gnomAD 11-112148728-G-C, REVEL 0.03, MetaLR 0.03
- P79T (p.Pro79Thr), gnomAD 11-112148728-G-T, REVEL 0.05, MetaLR 0.06
- R80Q (p.Arg80Gln), rs768843343, NCI-TCGA Cosmic COSV1043, cosmic curated COSV10438, ExAC rs768843343, REVEL 0.02, MetaLR 0.01, Variant assessed as somatic; moderate impact.
- R80W (p.Arg80Trp), TOPMed rs201058918, gnomAD rs201058918, REVEL 0.08, MetaLR 0.06
- R80R (p.Arg80Arg), gnomAD 11-112148723-C-G, CADD 1.14
- R80L (p.Arg80Leu), gnomAD 11-112148724-C-A, REVEL 0.02, MetaLR 0.03
- R80P (p.Arg80Pro), gnomAD 11-112148724-C-G, REVEL 0.10, MetaLR 0.04
- R80G (p.Arg80Gly), gnomAD 11-112148724-CG-C, CADD 21.70
- T81N (p.Thr81Asn), cosmic curated COSV54781, REVEL 0.08, MetaLR 0.12
- T81T (p.Thr81Thr), gnomAD 11-112148720-G-T, CADD 0.32
- T81I (p.Thr81Ile), gnomAD 11-112148721-G-A, REVEL 0.12, MetaLR 0.10
- T81S (p.Thr81Ser), gnomAD 11-112148722-T-A, REVEL 0.16, MetaLR 0.11
- T81A (p.Thr81Ala), gnomAD 11-112148722-T-C, REVEL 0.13, MetaLR 0.11
- I82T (p.Ile82Thr), gnomAD rs1866383356, REVEL 0.02, MetaLR 0.03
- I82M (p.Ile82Met), gnomAD 11-112148717-T-C, REVEL 0.05, MetaLR 0.09
- I82I (p.Ile82Ile), rs747430123, gnomAD 11-112148717-T-A, CADD 1.19
- I82K (p.Ile82Lys), gnomAD 11-112148718-A-T, REVEL 0.02, MetaLR 0.03
- I82L (p.Ile82Leu), gnomAD 11-112148719-T-G, REVEL 0.03, MetaLR 0.04
- I82V (p.Ile82Val), gnomAD 11-112148719-T-C, REVEL 0.01, MetaLR 0.03
- F83L (p.Phe83Leu), gnomAD 11-112148714-A-T, REVEL 0.07, MetaLR 0.05
- F83F (p.Phe83Phe), gnomAD 11-112148714-A-G, CADD 3.16
- F83S (p.Phe83Ser), gnomAD 11-112148715-A-G, REVEL 0.29, MetaLR 0.18
- F83I (p.Phe83Ile), gnomAD 11-112148716-A-T, REVEL 0.11, MetaLR 0.10
- F83V (p.Phe83Val), gnomAD 11-112148716-A-C, REVEL 0.12, MetaLR 0.13
- I84N (p.Ile84Asn), gnomAD 11-112148712-A-T, REVEL 0.16, MetaLR 0.03
- I84T (p.Ile84Thr), gnomAD 11-112148712-A-G, REVEL 0.29, MetaLR 0.07
- I84V (p.Ile84Val), gnomAD 11-112148713-T-C, REVEL 0.04, MetaLR 0.03
- I85T (p.Ile85Thr), TOPMed rs1866383237, REVEL 0.26, MetaLR 0.16
- I85V (p.Ile85Val), NCI-TCGA TCGA novel, REVEL 0.19, MetaLR 0.12, Variant assessed as somatic; moderate impact.
- I85M (p.Ile85Met), gnomAD 11-112148708-T-C, REVEL 0.17, MetaLR 0.09
- I85* (p.Ile85Ter), gnomAD 11-112148710-TA-T, CADD 9.29
- S86N (p.Ser86Asn), ExAC rs780531931, TOPMed rs780531931, gnomAD rs780531931, REVEL 0.04, MetaLR 0.03
- S86T (p.Ser86Thr), ExAC rs780531931, TOPMed rs780531931, gnomAD rs780531931, REVEL 0.02, MetaLR 0.03
- S86S (p.Ser86Ser), gnomAD 11-112148705-A-G, CADD 2.14
- S86R (p.Ser86Arg), gnomAD 11-112148705-A-T, REVEL 0.12, MetaLR 0.03
- S86I (p.Ser86Ile), gnomAD 11-112148706-C-A, REVEL 0.03, MetaLR 0.04
- S86V (p.Ser86Val), gnomAD 11-112148706-CT-C, CADD 7.02
- S86C (p.Ser86Cys), gnomAD 11-112148707-T-A, REVEL 0.06, MetaLR 0.02
- S86G (p.Ser86Gly), gnomAD 11-112148707-T-C, REVEL 0.03, MetaLR 0.02
- M87V (p.Met87Val), gnomAD rs1297677125, REVEL 0.05, MetaLR 0.03
- M87I (p.Met87Ile), gnomAD 11-112148702-C-G, REVEL 0.04, MetaLR 0.06
- M87T (p.Met87Thr), gnomAD 11-112148703-A-G, REVEL 0.12, MetaLR 0.04
- M87L (p.Met87Leu), gnomAD 11-112148704-T-A, REVEL 0.03, MetaLR 0.06
- Y88K (p.Tyr88Lys), gnomAD 11-112148697-TTAT, CADD 24.70
- Y88Y (p.Tyr88Tyr), rs1195717698, gnomAD 11-112148699-A-G, CADD 2.13
- Y88* (p.Tyr88Ter), gnomAD 11-112148699-A-T, CADD 34.00
- Y88C (p.Tyr88Cys), gnomAD 11-112148700-T-C, REVEL 0.47, MetaLR 0.16
Public IL18 analysis runs
- IL18 analysis run — IL18 (453 variants) — completed 2026-08-20