IL4R (P24394) variants and mutations
IL4R (also known as P24394) is a human protein-coding gene encoding an interleukin-4 receptor subunit alpha protein. It transmits IL-4 and IL-13 signals that promote type 2 immunity, immunoglobulin class switching, and allergic inflammation. Gain-of-function or common regulatory variation can influence atopy, while therapeutic blockade is effective in diseases such as atopic dermatitis and asthma. This analysis covers 1,304 IL4R variants and mutations. Of these, 69% have computational variant effect predictions. Disease context includes asthma, atopic eczema, and Nasal polyposis. Example IL4R variants include M1?, G2R, and G2W.
Variant analysis overview
- Gene: IL4R
- Protein: P24394
- UniProt accession: P24394
- Organism: Homo sapiens
- Variants analyzed: 1304
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 1,124 unspecified-consequence records; 95 missense variants; 64 synonymous variants; 8 frameshift variants; 4 splice-region variants; 5 stop-gained variants; 2 in-frame deletions; 1 incomplete terminal codon variant; 1 substitution
- Prediction scores: 902 variants have prediction scores (69% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: asthma, atopic eczema, Nasal polyposis, childhood onset asthma, respiratory system disorder, Eczematoid dermatitis, Wheezing, chronic rhinosinusitis, lower respiratory tract disorder, sinusitis, allergic asthma, allergic rhinitis.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 1 domains; 10 post-translational modification sites.
- Structural context: 164 variants have structural context.
- PTM context: 20 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 IL4R variants
Examples include M1?, G2R, G2W, G2E, G2G, W3C, L4I, C5R. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV99405
- G2R (p.Gly2Arg), ExAC rs768492688, gnomAD rs768492688, REVEL 0.29, CADD 26.30
- G2W (p.Gly2Trp), ExAC rs768492688, gnomAD rs768492688, REVEL 0.31, CADD 27.40
- G2E (p.Gly2Glu), gnomAD 16-27340208-G-A, REVEL 0.31, CADD 25.60
- G2G (p.Gly2Gly), gnomAD 16-27340209-G-A, CADD 12.10
- W3C (p.Trp3Cys), gnomAD 16-27340212-G-T, REVEL 0.08, CADD 17.30
- L4I (p.Leu4Ile), cosmic curated COSV50166
- C5R (p.Cys5Arg), Ensembl rs914663466, REVEL 0.11, CADD 8.43
- S6C (p.Ser6Cys), ESP rs151179009, ExAC rs151179009, TOPMed rs151179009, gnomAD rs151179009, REVEL 0.10, CADD 17.00
- S6F (p.Ser6Phe), rs151179009, ESP rs151179009, ExAC rs151179009, TOPMed rs151179009, REVEL 0.08, CADD 21.70, Variant assessed as somatic; moderate impact.
- S6P (p.Ser6Pro), TOPMed rs1404481261, gnomAD rs1404481261, REVEL 0.09, CADD 13.30, Uncertain significance, not specified
- G7R (p.Gly7Arg), TOPMed rs2085396864
- G7W (p.Gly7Trp), gnomAD 16-27341313-G-T, CADD 24.00
- L8V (p.Leu8Val), TOPMed rs1397246428, gnomAD rs1397246428
- L8F (p.Leu8Phe), gnomAD 16-27340225-C-T, REVEL 0.03, CADD 13.40
- L8I (p.Leu8Ile), gnomAD 16-27340225-C-A, REVEL 0.06, CADD 16.60
- L8L (p.Leu8Leu), rs2085397025, gnomAD 16-27340227-C-T, CADD 8.69
- L9P (p.Leu9Pro), ExAC rs771200748, TOPMed rs771200748, gnomAD rs771200748, REVEL 0.19, CADD 20.30
- L9R (p.Leu9Arg), ExAC rs771200748, TOPMed rs771200748, gnomAD rs771200748
- L9V (p.Leu9Val), gnomAD 16-27340228-C-G, REVEL 0.02, CADD 9.36
- L9L (p.Leu9Leu), rs1236757696, gnomAD 16-27340230-G-A, CADD 7.27
- F10I (p.Phe10Ile), ESP rs140214944, TOPMed rs140214944, gnomAD rs140214944, REVEL 0.03, CADD 8.20, Uncertain significance, not specified
- F10L (p.Phe10Leu), ESP rs375986399, ExAC rs375986399, TOPMed rs375986399, gnomAD rs375986399, REVEL 0.03, CADD 14.90
- F10F (p.Phe10Phe), rs375986399, gnomAD 16-27340233-C-T, CADD 9.21
- P11A (p.Pro11Ala), gnomAD rs1218358034, REVEL 0.05, CADD 10.60
- P11L (p.Pro11Leu), rs1414703751, gnomAD 16-27340232-TC-T, CADD 22.50
- P11S (p.Pro11Ser), gnomAD 16-27340234-C-T, REVEL 0.05, CADD 10.80
- P11P (p.Pro11Pro), gnomAD 16-27340236-T-C, CADD 4.99
- V12A (p.Val12Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V12E (p.Val12Glu), gnomAD 16-27340238-T-A, REVEL 0.23, CADD 25.90
- S13R (p.Ser13Arg), TOPMed rs1266243839, gnomAD rs1266243839, REVEL 0.19, CADD 23.00, Uncertain significance, not specified
- C14F (p.Cys14Phe), TOPMed rs1316439220, gnomAD rs1316439220, REVEL 0.14, CADD 14.50
- L15V (p.Leu15Val), cosmic curated COSV99405
- L15L (p.Leu15Leu), rs1307128794, gnomAD 16-27340248-G-A, CADD 11.20
- V16F (p.Val16Phe), Ensembl rs2085397874
- V16I (p.Val16Ile), gnomAD 16-27340249-G-A, REVEL 0.03, CADD 0.74
- V16V (p.Val16Val), rs1490083700, gnomAD 16-27340251-C-T, CADD 5.80
- L17L (p.Leu17Leu), rs2085398024, gnomAD 16-27340254-G-T, CADD 8.68
- L18M (p.Leu18Met), gnomAD 16-27340255-C-A, REVEL 0.04, CADD 5.25
- L18L (p.Leu18Leu), gnomAD 16-27340257-G-A, CADD 7.87
- Q19R (p.Gln19Arg), gnomAD 16-27340259-A-G, REVEL 0.07, CADD 23.10
- Q19* (p.Gln19Ter), gnomAD 16-27341292-C-T, CADD 13.40
- Q19K (p.Gln19Lys), gnomAD 16-27341292-C-A, CADD 5.31
- V20A (p.Val20Ala), TOPMed rs1242372941, gnomAD rs1242372941, REVEL 0.03, CADD 4.12, Likely benign, not specified
- V20E (p.Val20Glu), TOPMed rs1242372941, gnomAD rs1242372941, REVEL 0.23, CADD 16.00
- V20G (p.Val20Gly), TOPMed rs1242372941, gnomAD rs1242372941
- V20L (p.Val20Leu), TOPMed rs1191330149, gnomAD rs1191330149, REVEL 0.06, CADD 20.80
- V20M (p.Val20Met), TOPMed rs1191330149, gnomAD rs1191330149, REVEL 0.09, CADD 24.50
- V20V (p.Val20Val), rs1356931972, gnomAD 16-27340263-G-A, CADD 4.83
- A21G (p.Ala21Gly), ExAC rs753306538, gnomAD rs753306538, REVEL 0.05, CADD 22.00
- A21T (p.Ala21Thr), ESP rs150316902, ExAC rs150316902, TOPMed rs150316902, gnomAD rs150316902, REVEL 0.06, CADD 13.70
- A21V (p.Ala21Val), gnomAD 16-27340265-C-T, REVEL 0.06, CADD 22.50
- A21S (p.Ala21Ser), gnomAD 16-27341111-G-T, CADD 2.38
- A21P (p.Ala21Pro), gnomAD 16-27341111-G-C, CADD 3.04
- A21D (p.Ala21Asp), gnomAD 16-27341302-C-A, CADD 1.00
- A21A (p.Ala21Ala), gnomAD 16-27341303-C-A, CADD 1.06
- S22I (p.Ser22Ile), cosmic curated COSV50155
- S22R (p.Ser22Arg), cosmic curated COSV99405, REVEL 0.08, CADD 21.70
- S22N (p.Ser22Asn), gnomAD 16-27340268-G-A, REVEL 0.04, CADD 22.20
- S23C (p.Ser23Cys), cosmic curated COSV10724
- S23S (p.Ser23Ser), rs371559384, gnomAD 16-27340272-T-A, CADD 15.40
- G24W (p.Gly24Trp), cosmic curated COSV99405
- G24V (p.Gly24Val), gnomAD 16-27341070-G-T, CADD 7.38
- G24R (p.Gly24Arg), rs1423496052, gnomAD 16-27341090-G-A, CADD 2.82
- G24G (p.Gly24Gly), rs2085462078, gnomAD 16-27342122-G-A, CADD 8.15
- N25N (p.Asn25Asn), rs1437821551, gnomAD 16-27342125-C-T, CADD 0.39
- M26I (p.Met26Ile), ExAC rs762532424, gnomAD rs762532424, REVEL 0.02, CADD 0.10
- M26V (p.Met26Val), 1000Genomes rs553282601, ExAC rs553282601, TOPMed rs553282601, gnomAD rs553282601, REVEL 0.01, CADD 0.04
- M26T (p.Met26Thr), gnomAD 16-27342127-T-C, REVEL 0.04, MetaLR 0.04
- K27Q (p.Lys27Gln), rs1165695489, gnomAD 16-27341099-A-C, CADD 1.80
- K27* (p.Lys27Ter), rs1165695489, gnomAD 16-27341099-A-T, CADD 4.46
- K27K (p.Lys27Lys), rs1351705077, gnomAD 16-27341101-G-A, CADD 0.15
- K3del (p.Lys3del), gnomAD 16-27341292-CAGA-, CADD 4.67
- K27R (p.Lys27Arg), gnomAD 16-27341296-A-G, CADD 15.40
- K27N (p.Lys27Asn), gnomAD 16-27341297-G-T, CADD 7.05
- V28I (p.Val28Ile), gnomAD 16-27342132-G-A, REVEL 0.07, MetaLR 0.13
- V28F (p.Val28Phe), gnomAD 16-27342132-G-T, REVEL 0.14, MetaLR 0.13
- V28V (p.Val28Val), rs766039972, gnomAD 16-27342134-C-T, CADD 0.74
- L29L (p.Leu29Leu), rs759670811, gnomAD 16-27341074-C-G, CADD 5.61
- L29C (p.Leu29Cys), gnomAD 16-27342133-TC-T, CADD 13.40
- L29S (p.Leu29Ser), gnomAD 16-27342136-T-C, REVEL 0.22, MetaLR 0.16
- Q30E (p.Gln30Glu), Ensembl rs2085462557
- E31A (p.Glu31Ala), TOPMed rs908910299, REVEL 0.12, CADD 8.45
- E31K (p.Glu31Lys), gnomAD rs2085462641, REVEL 0.11, CADD 0.32
- E31V (p.Glu31Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E31* (p.Glu31Ter), gnomAD 16-27341093-G-T, CADD 4.62
- E31G (p.Glu31Gly), gnomAD 16-27341109-A-G, CADD 4.82
- E31E (p.Glu31Glu), rs751032016, gnomAD 16-27342143-G-A, CADD 1.53
- P32T (p.Pro32Thr), gnomAD rs1356167742, REVEL 0.12, CADD 17.50
- P32S (p.Pro32Ser), gnomAD 16-27341084-C-T, CADD 1.81
- P32L (p.Pro32Leu), rs910286128, gnomAD 16-27341085-C-T, CADD 2.71
- P32P (p.Pro32Pro), gnomAD 16-27341086-G-C, CADD 0.41
- T33A (p.Thr33Ala), NCI-TCGA Cosmic COSV9940, cosmic curated COSV99404, Variant assessed as somatic; moderate impact.
- T33P (p.Thr33Pro), gnomAD rs1596814378
- T33S (p.Thr33Ser), gnomAD rs1596814378, REVEL 0.06, CADD 10.40
- T33T (p.Thr33Thr), rs1275529879, gnomAD 16-27342149-C-T, CADD 7.79
- C34F (p.Cys34Phe), cosmic curated COSV50138
- C34R (p.Cys34Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- C34G (p.Cys34Gly), gnomAD 16-27341087-T-G, CADD 0.94
- C34Y (p.Cys34Tyr), gnomAD 16-27342151-G-A, REVEL 0.66, MetaLR 0.43
- C34C (p.Cys34Cys), rs55671142, gnomAD 16-27342152-C-T, CADD 9.82
- V35I (p.Val35Ile), rs372988882, cosmic curated COSV10455, ExAC rs372988882, TOPMed rs372988882, REVEL 0.02, CADD 1.41, Variant assessed as somatic; moderate impact.
- V35A (p.Val35Ala), rs1460471582, gnomAD 16-27341106-T-C, CADD 0.41
- V35M (p.Val35Met), rs1310530968, gnomAD 16-27341138-G-A, CADD 1.88
- V35G (p.Val35Gly), gnomAD 16-27341139-T-G, CADD 3.25
- V35E (p.Val35Glu), rs1314345314, gnomAD 16-27341139-T-A, CADD 0.68
- V35V (p.Val35Val), gnomAD 16-27342155-C-T, CADD 2.00
- S36S (p.Ser36Ser), rs17548704, gnomAD 16-27342158-C-T, CADD 0.77
- D37N (p.Asp37Asn), cosmic curated COSV50138, ExAC rs776677335, TOPMed rs776677335, gnomAD rs776677335, REVEL 0.17, CADD 22.40
- D37H (p.Asp37His), rs2085434692, gnomAD 16-27341298-G-C, CADD 11.10
- D37Y (p.Asp37Tyr), gnomAD 16-27341298-G-T, CADD 10.80
- D37D (p.Asp37Asp), gnomAD 16-27341300-T-C, CADD 2.25
- Y38C (p.Tyr38Cys), NCI-TCGA Cosmic COSV9940, cosmic curated COSV99405, TOPMed rs1775077711, REVEL 0.19, CADD 22.70, Variant assessed as somatic; moderate impact.
- Y38S (p.Tyr38Ser), gnomAD 16-27342163-A-C, REVEL 0.23, MetaLR 0.21
- M39I (p.Met39Ile), cosmic curated COSV50139
- M39L (p.Met39Leu), ExAC rs777645418, TOPMed rs777645418, gnomAD rs777645418
- M39V (p.Met39Val), ExAC rs777645418, TOPMed rs777645418, gnomAD rs777645418, REVEL 0.03, CADD 0.00
- M39R (p.Met39Arg), gnomAD 16-27342166-T-G, REVEL 0.24, MetaLR 0.02
- S40N (p.Ser40Asn), Ensembl rs2141133465, REVEL 0.04, CADD 2.60
- S40R (p.Ser40Arg), TOPMed rs2085463781
- I41T (p.Ile41Thr), cosmic curated COSV99405
- I41V (p.Ile41Val), gnomAD 16-27342171-A-G, REVEL 0.01, MetaLR 0.03
- I41I (p.Ile41Ile), gnomAD 16-27342173-C-T, CADD 3.31
- S42C (p.Ser42Cys), cosmic curated COSV50138
- S42F (p.Ser42Phe), gnomAD 16-27341133-C-T, CADD 1.96
- S42S (p.Ser42Ser), gnomAD 16-27342176-T-G, CADD 5.28
- T43A (p.Thr43Ala), ExAC rs749110570, TOPMed rs749110570, gnomAD rs749110570, REVEL 0.14, CADD 18.10
- T43I (p.Thr43Ile), cosmic curated COSV10503, REVEL 0.17, CADD 17.90
- C44* (p.Cys44Ter), TOPMed rs930075388, gnomAD rs930075388, CADD 27.10
- C44W (p.Cys44Trp), TOPMed rs930075388, gnomAD rs930075388
- C44C (p.Cys44Cys), rs930075388, gnomAD 16-27342182-C-T, CADD 2.02
- E45* (p.Glu45Ter), NCI-TCGA Cosmic COSV9940, cosmic curated COSV99404, Variant assessed as somatic; high impact.
- E45G (p.Glu45Gly), rs2506949151, ClinGen CA395304036, ClinVar RCV003148460, Uncertain significance, IgE responsiveness, atopic
- E45K (p.Glu45Lys), rs1051167644, ClinGen CA279698895, NCI-TCGA Cosmic COSV9940, cosmic curated COSV99404, REVEL 0.25, CADD 22.80, Uncertain significance, not specified
- E45E (p.Glu45Glu), rs2085428176, gnomAD 16-27341143-G-A, CADD 0.76
- W46S (p.Trp46Ser), rs1241712642, gnomAD 16-27341169-G-C, CADD 5.79
- W46L (p.Trp46Leu), gnomAD 16-27341193-G-T, CADD 12.80
- W46C (p.Trp46Cys), rs2085429600, gnomAD 16-27341194-G-C, CADD 8.36
- W46* (p.Trp46Ter), gnomAD 16-27341194-G-A, CADD 8.38
- W46V (p.Trp46Val), gnomAD 16-27342184-A-AG, CADD 23.30
- K47E (p.Lys47Glu), Ensembl rs1596814485
- M48I (p.Met48Ile), cosmic curated COSV50147, REVEL 0.11, CADD 22.60
- M48T (p.Met48Thr), Ensembl rs1596814514
- M48V (p.Met48Val), ExAC rs780462972, gnomAD rs780462972, REVEL 0.11, CADD 15.60
- M48L (p.Met48Leu), gnomAD 16-27342192-A-T, REVEL 0.05, MetaLR 0.04
- N49D (p.Asn49Asp), gnomAD rs1390829715, REVEL 0.03, CADD 2.74
- N49H (p.Asn49His), gnomAD rs1390829715, REVEL 0.12, CADD 14.40
- N49S (p.Asn49Ser), rs747063458, NCI-TCGA Cosmic COSV5018, cosmic curated COSV50183, ExAC rs747063458, REVEL 0.05, CADD 0.42, Variant assessed as somatic; moderate impact.
- N49N (p.Asn49Asn), gnomAD 16-27342197-T-C, CADD 0.20
- G50A (p.Gly50Ala), rs772337577, gnomAD 16-27341124-G-C, CADD 2.07
- G50R (p.Gly50Arg), gnomAD 16-27341126-G-A, CADD 2.16
- G50E (p.Gly50Glu), rs1378108730, gnomAD 16-27341127-G-A, CADD 4.75
- G50G (p.Gly50Gly), gnomAD 16-27341128-G-T, CADD 3.83
- G50* (p.Gly50Ter), gnomAD 16-27341159-G-T, CADD 4.60
- G50V (p.Gly50Val), gnomAD 16-27341160-G-T, CADD 5.00
- P51S (p.Pro51Ser), NCI-TCGA Cosmic COSV5014, cosmic curated COSV50148, Variant assessed as somatic; moderate impact.
- P51T (p.Pro51Thr), Ensembl rs2085464900
- P51L (p.Pro51Leu), gnomAD 16-27342202-C-T, REVEL 0.07, MetaLR 0.06
- T52A (p.Thr52Ala), cosmic curated COSV50138, TOPMed rs1326264155, gnomAD rs1326264155, REVEL 0.02, CADD 4.03
- N53I (p.Asn53Ile), ESP rs201852059, ExAC rs201852059, TOPMed rs201852059, gnomAD rs201852059
- N53S (p.Asn53Ser), ESP rs201852059, ExAC rs201852059, TOPMed rs201852059, gnomAD rs201852059, REVEL 0.11, CADD 21.30
- N53N (p.Asn53Asn), gnomAD 16-27342209-T-C, CADD 4.40
- C54F (p.Cys54Phe), gnomAD 16-27342211-G-T, REVEL 0.55, MetaLR 0.42
- C54Y (p.Cys54Tyr), gnomAD 16-27342211-G-A, REVEL 0.57, MetaLR 0.42
- S55P (p.Ser55Pro), gnomAD 16-27341156-T-C, CADD 11.00
- S55S (p.Ser55Ser), rs776137353, gnomAD 16-27341158-C-T, CADD 0.19
- S55F (p.Ser55Phe), rs1201034539, gnomAD 16-27341163-C-T, CADD 7.77
- S55Y (p.Ser55Tyr), rs1201034539, gnomAD 16-27341163-C-A, CADD 7.19
- S55I (p.Ser55Ile), gnomAD 16-27342214-G-T, REVEL 0.28, MetaLR 0.19
- T56I (p.Thr56Ile), TOPMed rs1481750037, gnomAD rs1481750037, REVEL 0.09, CADD 15.30
- T56T (p.Thr56Thr), rs927581850, gnomAD 16-27342218-C-T, CADD 0.10
- E57K (p.Glu57Lys), rs200293983, ClinGen CA7974148, cosmic curated COSV50151, ClinVar RCV004254502, REVEL 0.17, CADD 9.57, Uncertain significance, not specified
- E57Q (p.Glu57Gln), gnomAD 16-27342219-G-C, REVEL 0.17, MetaLR 0.05
- E57E (p.Glu57Glu), gnomAD 16-27342221-G-A, CADD 2.02
- L58R (p.Leu58Arg), TOPMed rs1357356695
- L58F (p.Leu58Phe), gnomAD 16-27341165-C-T, CADD 0.17
- L58V (p.Leu58Val), gnomAD 16-27341165-C-G, CADD 0.14
- L58L (p.Leu58Leu), gnomAD 16-27341167-C-G, CADD 6.99
- R59C (p.Arg59Cys), rs191774649, ClinGen CA7974149, cosmic curated COSV50144, ClinVar RCV004205806, REVEL 0.11, CADD 14.30, Uncertain significance, not specified
- R59H (p.Arg59His), ExAC rs770213018, TOPMed rs770213018, gnomAD rs770213018, REVEL 0.13, CADD 0.08, Uncertain significance, not specified
Public IL4R analysis runs
- IL4R analysis run — IL4R (1,304 variants) — completed 2026-08-19