IL1RAPL2 (X-linked interleukin-1 receptor accessory protein-like 2) variants and mutations
IL1RAPL2 (also known as X-linked interleukin-1 receptor accessory protein-like 2) is a human protein-coding gene encoding a x-linked interleukin-1 receptor accessory protein-like 2 protein. A single-pass cell-surface protein in the interleukin-1 receptor accessory-protein family. Its precise molecular function remains incompletely characterized, but its membrane localization and receptor-like architecture suggest a role in cell-surface signaling. This analysis covers 785 IL1RAPL2 variants and mutations. Of these, 61% have computational variant effect predictions. Disease context includes osteoarthritis, hip, central nervous system cancer, and non-small cell lung carcinoma. Example IL1RAPL2 variants include M1?, P3A, and P3L.
Variant analysis overview
- Gene: IL1RAPL2
- Protein: X-linked interleukin-1 receptor accessory protein-like 2
- UniProt accession: Q9NP60
- Organism: Homo sapiens
- Variants analyzed: 785
- Variant scope: all variants
- Completed: 2026-09-02
Variant and mutation evidence
- Variant composition: 585 unspecified-consequence records; 112 missense variants; 75 synonymous variants; 10 frameshift variants; 1 in-frame insertions; 1 in-frame deletions; 1 stop-gained variants
- Prediction scores: 478 variants have prediction scores (61% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: osteoarthritis, hip, central nervous system cancer, non-small cell lung carcinoma, Duchenne muscular dystrophy, autism, autism spectrum disorder, primary biliary cholangitis, migraine disorder, hepatocellular carcinoma, bipolar disorder, psychiatric disorder, Global developmental delay.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 4 domains; 5 post-translational modification sites.
- Structural context: 577 variants have structural context.
- PTM context: 7 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 IL1RAPL2 variants
Examples include M1?, P3A, P3L, P3T, P4S, F5L, F5C, L6F. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- P3A (p.Pro3Ala), Ensembl rs1602666383
- P3L (p.Pro3Leu), ExAC rs200115938, TOPMed rs200115938, gnomAD rs200115938, REVEL 0.01, MetaLR 0.01
- P3T (p.Pro3Thr), gnomAD X-104658920-C-A, REVEL 0.03, MetaLR 0.01
- P4S (p.Pro4Ser), NCI-TCGA Cosmic COSV6115, Ensembl rs1930332249, REVEL 0.05, MetaLR 0.01, Variant assessed as somatic; moderate impact.
- F5L (p.Phe5Leu), TOPMed rs1930332321
- F5C (p.Phe5Cys), gnomAD X-104658927-T-G, REVEL 0.12, MetaLR 0.01
- L6F (p.Leu6Phe), rs148390300, ClinGen CA10480233, ClinVar RCV003434596, ClinVar RCV004076727, REVEL 0.08, MetaLR 0.00, Conflicting interpretations, not provided; not specified
- L7S (p.Leu7Ser), gnomAD X-104658933-T-C, REVEL 0.26, MetaLR 0.02
- A8T (p.Ala8Thr), ExAC rs768588754, gnomAD rs768588754, REVEL 0.05, MetaLR 0.01, Uncertain significance, not specified
- A8V (p.Ala8Val), gnomAD X-104658936-C-T, REVEL 0.06, MetaLR 0.01
- A8A (p.Ala8Ala), rs201558481, gnomAD X-104658937-C-T, CADD 3.80
- L9F (p.Leu9Phe), TOPMed rs1930332736, REVEL 0.09, MetaLR 0.01
- L9I (p.Leu9Ile), gnomAD X-104658938-C-A, REVEL 0.12, MetaLR 0.01
- L9P (p.Leu9Pro), gnomAD X-104658939-T-C, REVEL 0.26, MetaLR 0.02
- V10M (p.Val10Met), gnomAD X-104658941-G-A, REVEL 0.14, MetaLR 0.01
- V10V (p.Val10Val), rs1930332852, gnomAD X-104658943-G-A, CADD 7.84
- V11G (p.Val11Gly), ESP rs142515452, ExAC rs142515452, TOPMed rs142515452, gnomAD rs142515452, REVEL 0.14, MetaLR 0.01, Uncertain significance, not specified
- V11I (p.Val11Ile), gnomAD X-104658944-G-A, REVEL 0.04, MetaLR 0.00
- C12Y (p.Cys12Tyr), TOPMed rs1930333113, REVEL 0.06, MetaLR 0.01
- C12C (p.Cys12Cys), gnomAD X-104658949-T-C, CADD 9.33
- S13F (p.Ser13Phe), TOPMed rs968682444, gnomAD rs968682444
- S13Y (p.Ser13Tyr), TOPMed rs968682444, gnomAD rs968682444
- S13S (p.Ser13Ser), gnomAD X-104658952-T-C, CADD 10.80
- V14A (p.Val14Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V14V (p.Val14Val), gnomAD X-104658955-A-G, CADD 7.72
- V15A (p.Val15Ala), gnomAD rs1203023158, REVEL 0.09, MetaLR 0.01
- V15I (p.Val15Ile), gnomAD X-104658956-G-A, REVEL 0.04, MetaLR 0.01
- S16G (p.Ser16Gly), NCI-TCGA TCGA novel, REVEL 0.09, MetaLR 0.01, Variant assessed as somatic; moderate impact.
- S16R (p.Ser16Arg), gnomAD X-104658959-A-C, REVEL 0.20, MetaLR 0.01
- S16S (p.Ser16Ser), gnomAD X-104658961-C-T, CADD 10.30
- T17K (p.Thr17Lys), ExAC rs771962632, TOPMed rs771962632, gnomAD rs771962632, Uncertain significance
- T17R (p.Thr17Arg), rs771962632, ClinGen CA10480237, ClinVar RCV004303118, ExAC rs771962632, REVEL 0.15, MetaLR 0.01, Uncertain significance, not specified
- L19P (p.Leu19Pro), gnomAD X-104658969-T-C, REVEL 0.27, MetaLR 0.02
- K20N (p.Lys20Asn), ExAC rs772757942, gnomAD rs772757942, REVEL 0.06, MetaLR 0.02
- K20T (p.Lys20Thr), TOPMed rs1230121004, gnomAD rs1230121004, REVEL 0.17, MetaLR 0.01
- K20R (p.Lys20Arg), gnomAD X-104658972-A-G, REVEL 0.07, MetaLR 0.01
- M21T (p.Met21Thr), NCI-TCGA TCGA novel, gnomAD rs1930334023, REVEL 0.18, MetaLR 0.01, Variant assessed as somatic; moderate impact.
- M21I (p.Met21Ile), gnomAD X-104658976-G-T, REVEL 0.07, MetaLR 0.01
- V22A (p.Val22Ala), rs139525400, ClinGen CA10480239, ClinVar RCV004235989, 1000Genomes rs139525400, REVEL 0.15, MetaLR 0.03, Uncertain significance, not specified
- S23A (p.Ser23Ala), gnomAD X-104658980-T-G, REVEL 0.13, MetaLR 0.02
- K24K (p.Lys24Lys), rs1328888029, gnomAD X-104658985-G-A, CADD 7.95
- N26I (p.Asn26Ile), gnomAD X-104658990-A-T, REVEL 0.22, MetaLR 0.02
- N26N (p.Asn26Asn), gnomAD X-104658991-T-C, CADD 8.23
- N26K (p.Asn26Lys), gnomAD X-104658991-T-G, REVEL 0.14, MetaLR 0.02
- S27T (p.Ser27Thr), gnomAD X-104658992-T-A, REVEL 0.15, MetaLR 0.02
- S27Y (p.Ser27Tyr), gnomAD X-104658993-C-A, REVEL 0.20, MetaLR 0.04
- V28=, NCI-TCGA TCGA novel, Variant assessed as somatic; low impact.
- V28M (p.Val28Met), TOPMed rs1930334224, gnomAD rs1930334224, REVEL 0.19, MetaLR 0.02
- D29G (p.Asp29Gly), gnomAD rs1556140305, REVEL 0.27, MetaLR 0.04
- G30R (p.Gly30Arg), Ensembl rs1603002054
- S35P (p.Ser35Pro), NCI-TCGA Cosmic COSV1007, Variant assessed as somatic; moderate impact.
- S35S (p.Ser35Ser), rs782810617, gnomAD X-105195497-A-C, CADD 8.91
- V36E (p.Val36Glu), TOPMed rs1413068763
- V36L (p.Val36Leu), gnomAD X-105195498-G-C, REVEL 0.30, MetaLR 0.03
- V36V (p.Val36Val), gnomAD X-105195500-G-A, CADD 9.68
- K39N (p.Lys39Asn), gnomAD X-105195509-G-T, REVEL 0.43, MetaLR 0.50
- T40T (p.Thr40Thr), rs1556140329, gnomAD X-105195512-A-G, CADD 9.88
- Y41H (p.Tyr41His), NCI-TCGA Cosmic COSV6117, Variant assessed as somatic; moderate impact.
- M42I (p.Met42Ile), NCI-TCGA Cosmic COSV1007, Variant assessed as somatic; moderate impact.
- M42T (p.Met42Thr), TOPMed rs1354930281, REVEL 0.19, MetaLR 0.24
- M42K (p.Met42Lys), gnomAD X-105195517-T-A, REVEL 0.17, MetaLR 0.25
- A43V (p.Ala43Val), rs1556140350, TOPMed rs1556140350, gnomAD rs1556140350, REVEL 0.20, MetaLR 0.10, Variant assessed as somatic; moderate impact.
- A45S (p.Ala45Ser), gnomAD X-105195525-G-T, REVEL 0.31, MetaLR 0.35
- A45A (p.Ala45Ala), rs1556140362, gnomAD X-105195527-A-T, CADD 8.72
- G46S (p.Gly46Ser), gnomAD X-105195528-G-A, REVEL 0.80, MetaLR 0.79
- E47* (p.Glu47Ter), NCI-TCGA Cosmic COSV6117, Variant assessed as somatic; high impact.
- E47D (p.Glu47Asp), gnomAD X-105195533-A-T, REVEL 0.73, MetaLR 0.62
- P48L (p.Pro48Leu), 1000Genomes rs782144125, ExAC rs782144125, gnomAD rs782144125, REVEL 0.85, MetaLR 0.68
- P48R (p.Pro48Arg), gnomAD X-105195535-C-G, REVEL 0.88, MetaLR 0.68
- V49I (p.Val49Ile), Ensembl rs1569401350, REVEL 0.32, MetaLR 0.48
- V49V (p.Val49Val), rs782817415, gnomAD X-105195539-C-G, CADD 7.56
- R50* (p.Arg50Ter), TOPMed rs1308678266, gnomAD rs1308678266, CADD 34.00
- R50Q (p.Arg50Gln), NCI-TCGA Cosmic COSV6115, REVEL 0.59, MetaLR 0.61, Variant assessed as somatic; moderate impact.
- R50L (p.Arg50Leu), gnomAD X-105195541-G-T, REVEL 0.63, MetaLR 0.59
- R50R (p.Arg50Arg), rs2033666075, gnomAD X-105195542-A-T, CADD 9.65
- V51E (p.Val51Glu), NCI-TCGA Cosmic COSV6115, Variant assessed as somatic; moderate impact.
- V51V (p.Val51Val), rs782591779, gnomAD X-105195545-G-A, CADD 9.10
- K52N (p.Lys52Asn), gnomAD X-105195548-A-T, REVEL 0.59, MetaLR 0.55
- K52K (p.Lys52Lys), gnomAD X-105195548-A-G, CADD 10.00
- C53R (p.Cys53Arg), NCI-TCGA Cosmic COSV1007, Variant assessed as somatic; moderate impact.
- A54S (p.Ala54Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L55I (p.Leu55Ile), ExAC rs782196098, gnomAD rs782196098, REVEL 0.40, MetaLR 0.66
- Y57F (p.Tyr57Phe), NCI-TCGA Cosmic COSV6117, Variant assessed as somatic; moderate impact.
- Y57S (p.Tyr57Ser), gnomAD rs1556140422, REVEL 0.60, MetaLR 0.51
- S58I (p.Ser58Ile), TOPMed rs1352629300, gnomAD rs1352629300, REVEL 0.59, MetaLR 0.54
- Y59H (p.Tyr59His), gnomAD X-105195567-T-C, REVEL 0.59, MetaLR 0.60
- Y59Y (p.Tyr59Tyr), rs1030143428, gnomAD X-105195569-T-C, CADD 1.42
- I60L (p.Ile60Leu), gnomAD X-105195570-A-C, REVEL 0.39, MetaLR 0.40
- R61C (p.Arg61Cys), NCI-TCGA Cosmic COSV6114, TOPMed rs2033666360, Variant assessed as somatic; moderate impact.
- R61H (p.Arg61His), rs782435701, NCI-TCGA Cosmic COSV1007, ExAC rs782435701, TOPMed rs782435701, REVEL 0.59, MetaLR 0.63, Variant assessed as somatic; moderate impact.
- T62T (p.Thr62Thr), rs1405732856, gnomAD X-105195578-C-T, CADD 9.56
- N63D (p.Asn63Asp), ESP rs149712731, ExAC rs149712731, TOPMed rs149712731, gnomAD rs149712731, REVEL 0.62, MetaLR 0.64
- N63N (p.Asn63Asn), rs1556140475, gnomAD X-105195581-C-T, CADD 8.40
- Y64C (p.Tyr64Cys), TOPMed rs2033666512, REVEL 0.73, MetaLR 0.62, Uncertain significance, not specified
- T66K (p.Thr66Lys), NCI-TCGA Cosmic COSV6115, Variant assessed as somatic; moderate impact.
- T66M (p.Thr66Met), 1000Genomes rs146735893, ESP rs146735893, ExAC rs146735893, TOPMed rs146735893, REVEL 0.21, MetaLR 0.24
- T66T (p.Thr66Thr), gnomAD X-105195590-G-A, CADD 7.82
- Q68K (p.Gln68Lys), gnomAD X-105195594-C-A, REVEL 0.29, MetaLR 0.41
- Q68Q (p.Gln68Gln), rs782379476, gnomAD X-105195596-G-A, CADD 7.19
- S69N (p.Ser69Asn), Ensembl rs2033666681, REVEL 0.12, MetaLR 0.02
- S69T (p.Ser69Thr), gnomAD X-105195598-G-C, REVEL 0.10, MetaLR 0.04
- G71A (p.Gly71Ala), TOPMed rs1474647997, gnomAD rs1474647997, REVEL 0.12, MetaLR 0.07
- G71E (p.Gly71Glu), gnomAD X-105195604-G-A, REVEL 0.17, MetaLR 0.08
- G71G (p.Gly71Gly), rs2033666759, gnomAD X-105195605-G-T, CADD 5.78
- L72P (p.Leu72Pro), NCI-TCGA Cosmic COSV6116, Variant assessed as somatic; moderate impact.
- L72L (p.Leu72Leu), rs782637436, gnomAD X-105195608-C-T, CADD 8.43
- R73G (p.Arg73Gly), TOPMed rs112921669, gnomAD rs112921669
- R73K (p.Arg73Lys), ExAC rs782229964, gnomAD rs782229964, REVEL 0.19, MetaLR 0.03
- R73W (p.Arg73Trp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R73R (p.Arg73Arg), rs112921669, gnomAD X-105195609-A-C, CADD 10.60
- M75I (p.Met75Ile), ESP rs377453704, ExAC rs377453704, gnomAD rs377453704, REVEL 0.08, MetaLR 0.02
- M75K (p.Met75Lys), Ensembl rs2147612377
- M75V (p.Met75Val), ExAC rs782346881, gnomAD rs782346881, REVEL 0.21, MetaLR 0.03
- K78I (p.Lys78Ile), ExAC rs782059851, gnomAD rs782059851
- K78R (p.Lys78Arg), ExAC rs782059851, gnomAD rs782059851, REVEL 0.06, MetaLR 0.03
- N79H (p.Asn79His), NCI-TCGA Cosmic COSV6115, Variant assessed as somatic; moderate impact.
- N79T (p.Asn79Thr), NCI-TCGA Cosmic COSV1007, REVEL 0.20, MetaLR 0.32, Variant assessed as somatic; moderate impact.
- N79N (p.Asn79Asn), rs140392861, gnomAD X-105195629-C-T, CADD 7.53
- K80N (p.Lys80Asn), gnomAD rs1556140571
- K80K (p.Lys80Lys), rs1556140571, gnomAD X-105195632-A-G, CADD 9.10
- G81R (p.Gly81Arg), gnomAD X-105195633-G-C, REVEL 0.40, MetaLR 0.07
- D82E (p.Asp82Glu), ExAC rs782021145
- D82N (p.Asp82Asn), NCI-TCGA Cosmic COSV6116, Variant assessed as somatic; moderate impact.
- D82Y (p.Asp82Tyr), gnomAD X-105195636-G-T, REVEL 0.26, MetaLR 0.10
- E84K (p.Glu84Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- P86P (p.Pro86Pro), gnomAD X-105195650-C-T, CADD 7.98
- I87F (p.Ile87Phe), gnomAD rs1556140582, REVEL 0.28, MetaLR 0.05
- I87V (p.Ile87Val), gnomAD rs1556140582, REVEL 0.15, MetaLR 0.04
- I87S (p.Ile87Ser), gnomAD X-105195647-GC-G, CADD 26.80
- I88M (p.Ile88Met), Ensembl rs782809809
- I88V (p.Ile88Val), gnomAD X-105195654-A-G, REVEL 0.12, MetaLR 0.02
- S90* (p.Ser90Ter), gnomAD rs1556140601, CADD 35.00
- S90P (p.Ser90Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E91G (p.Glu91Gly), ExAC rs782136535, gnomAD rs782136535, REVEL 0.24, MetaLR 0.14
- E91K (p.Glu91Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R93S (p.Arg93Ser), NCI-TCGA Cosmic COSV6115, REVEL 0.65, MetaLR 0.55, Variant assessed as somatic; moderate impact.
- M94V (p.Met94Val), gnomAD X-105195672-A-G, REVEL 0.25, MetaLR 0.30
- S95N (p.Ser95Asn), gnomAD X-105195676-G-A, REVEL 0.36, MetaLR 0.61
- S95S (p.Ser95Ser), gnomAD X-105195677-C-T, CADD 7.80
- K96N (p.Lys96Asn), TOPMed rs1481941261, gnomAD rs1481941261, NCI-TCGA TCGA novel, REVEL 0.13, MetaLR 0.08, Variant assessed as somatic; moderate impact.
- K96R (p.Lys96Arg), gnomAD X-105195677-CAA-C, CADD 27.70
- K96K (p.Lys96Lys), rs1481941261, gnomAD X-105195680-A-G, CADD 9.85
- E97G (p.Glu97Gly), Ensembl rs2033667496, REVEL 0.47, MetaLR 0.42
- E97K (p.Glu97Lys), NCI-TCGA Cosmic COSV6115, Variant assessed as somatic; moderate impact.
- E97Q (p.Glu97Gln), NCI-TCGA Cosmic COSV6115, Variant assessed as somatic; moderate impact.
- E98K (p.Glu98Lys), TOPMed rs1231669382, gnomAD rs1231669382, REVEL 0.35, MetaLR 0.26
- E98G (p.Glu98Gly), gnomAD X-105195685-A-G, REVEL 0.14, MetaLR 0.21
- D99Y (p.Asp99Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I101V (p.Ile101Val), gnomAD X-105195693-A-G, REVEL 0.58, MetaLR 0.60
- W102L (p.Trp102Leu), gnomAD X-105195697-G-T, REVEL 0.51, MetaLR 0.07
- F103V (p.Phe103Val), gnomAD X-105195699-T-G, REVEL 0.66, MetaLR 0.40
- F103L (p.Phe103Leu), gnomAD X-105195701-T-G, REVEL 0.47, MetaLR 0.34
- H104R (p.His104Arg), gnomAD X-105195703-A-G, REVEL 0.12, MetaLR 0.01
- S105T (p.Ser105Thr), NCI-TCGA Cosmic COSV1007, Variant assessed as somatic; moderate impact.
- S105L (p.Ser105Leu), gnomAD X-105195706-C-T, REVEL 0.54, MetaLR 0.41
- A106V (p.Ala106Val), rs144175494, ClinGen CA10480272, ClinVar RCV000900861, 1000Genomes rs144175494, REVEL 0.10, MetaLR 0.03, Likely benign, not provided
- E107K (p.Glu107Lys), Ensembl rs2033667681, REVEL 0.19, MetaLR 0.03
- A108T (p.Ala108Thr), rs781818591, ExAC rs781818591, AlphaMissense 0.07, MetaLR 0.02, Variant assessed as somatic; moderate impact.
- Q109Q (p.Gln109Gln), gnomAD X-105195719-A-G, CADD 7.69
- D110D (p.Asp110Asp), rs2033667784, gnomAD X-105195722-C-T, CADD 8.46
- S111T (p.Ser111Thr), gnomAD X-105195724-G-C, REVEL 0.07, MetaLR 0.04
- G112R (p.Gly112Arg), NCI-TCGA Cosmic COSV1007, Variant assessed as somatic; moderate impact.
- V117D (p.Val117Asp), NCI-TCGA Cosmic COSV1007, Variant assessed as somatic; moderate impact.
- V117V (p.Val117Val), gnomAD X-105195743-T-C, CADD 9.09
- L118L (p.Leu118Leu), gnomAD X-105195744-T-C, CADD 8.18
- N120S (p.Asn120Ser), gnomAD X-105233820-A-G, REVEL 0.76, MetaLR 0.69
- N120K (p.Asn120Lys), gnomAD X-105233821-C-A, REVEL 0.78, MetaLR 0.72
- S121* (p.Ser121Ter), NCI-TCGA Cosmic COSV6116, Variant assessed as somatic; high impact.
- T122A (p.Thr122Ala), gnomAD X-105233825-A-G, REVEL 0.42, MetaLR 0.11
- T122T (p.Thr122Thr), rs782709147, gnomAD X-105233827-A-G, CADD 6.54
- Y123N (p.Tyr123Asn), gnomAD X-105233828-T-A, REVEL 0.77, MetaLR 0.63
- Y123Y (p.Tyr123Tyr), gnomAD X-105233830-T-C, CADD 6.74
- M125V (p.Met125Val), gnomAD rs1556198556, REVEL 0.58, MetaLR 0.51
- M125L (p.Met125Leu), gnomAD X-105233834-A-C, REVEL 0.49, MetaLR 0.38
- V127V (p.Val127Val), gnomAD X-105233842-G-T, CADD 8.16
- S128P (p.Ser128Pro), Ensembl rs868929868
- M129T (p.Met129Thr), gnomAD X-105233847-T-C, REVEL 0.46, MetaLR 0.05
- L131F (p.Leu131Phe), NCI-TCGA Cosmic COSV6116, Variant assessed as somatic; moderate impact.
- T132S (p.Thr132Ser), Ensembl rs2034095916
Public IL1RAPL2 analysis runs
- IL1RAPL2 analysis run — IL1RAPL2 (785 variants) — completed 2026-09-02
- IL1RAPL2 analysis run — IL1RAPL2 (785 variants) — completed 2026-07-07
- IL1RAPL2 analysis run — IL1RAPL2 (768 variants) — completed 2026-06-04
- IL1RAPL2 analysis run — IL1RAPL2 (768 variants) — completed 2026-05-31