IRF4 (Interferon regulatory factor 4) variants and mutations
IRF4 (also known as Interferon regulatory factor 4) is a human protein-coding gene encoding an interferon regulatory factor 4 protein. It controls differentiation and function of B cells, plasma cells, T cells, and other immune lineages in a context-dependent manner. Germline variants can cause immunodeficiency, while rearrangements or abnormal expression drive several lymphoid malignancies. This analysis covers 915 IRF4 variants and mutations. Of these, 64% have computational variant effect predictions. Disease context includes B-cell chronic lymphocytic leukemia, melanoma, and plasma cell myeloma. Example IRF4 variants include M1R, N2S, and N2K.
Variant analysis overview
- Gene: IRF4
- Protein: Interferon regulatory factor 4
- UniProt accession: Q15306
- Organism: Homo sapiens
- Variants analyzed: 915
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 625 unspecified-consequence records; 157 missense variants; 108 synonymous variants; 12 stop-gained variants; 10 frameshift variants; 1 in-frame deletions; 2 splice-region variants
- Prediction scores: 585 variants have prediction scores (64% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: B-cell chronic lymphocytic leukemia, melanoma, plasma cell myeloma, cutaneous melanoma, neurodegenerative disease, skin cancer, skin neoplasm, hair color, skin disorder, neoplasm, hypothyroidism, basal cell carcinoma.
Protein structure and variant hotspots
- Protein features: 2 post-translational modification sites.
- PTM context: 3 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable IRF4 variants
Examples include M1R, N2S, N2K, L3V, L3M, L3L, E4*, E4G. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1R (p.Met1Arg), rs1384614373, ClinGen CA362546210, ClinVar RCV003695817, MutPred 0.97, Likely benign, not provided
- N2S (p.Asn2Ser), Ensembl rs891224445, REVEL 0.41, CADD 24.30
- N2K (p.Asn2Lys), gnomAD 6-393158-C-A, REVEL 0.47, CADD 23.90
- L3V (p.Leu3Val), NCI-TCGA Cosmic COSV1011, REVEL 0.38, CADD 20.00, Variant assessed as somatic; moderate impact.
- L3M (p.Leu3Met), gnomAD 6-393159-C-A, REVEL 0.36, CADD 23.10
- L3L (p.Leu3Leu), rs970412899, gnomAD 6-393159-C-T, CADD 12.40
- E4* (p.Glu4Ter), gnomAD rs1452883883, CADD 39.00
- E4G (p.Glu4Gly), Ensembl rs1581220805
- E4K (p.Glu4Lys), gnomAD 6-393162-G-A, REVEL 0.54, CADD 26.10
- E4D (p.Glu4Asp), gnomAD 6-393164-G-T, REVEL 0.29, CADD 17.50
- G5D (p.Gly5Asp), rs564941413, ClinGen CA133329000, ClinVar RCV003665517, Ensembl rs564941413, REVEL 0.24, CADD 21.90, Uncertain significance, not provided
- G5C (p.Gly5Cys), gnomAD 6-393165-G-T, REVEL 0.26, CADD 23.50
- G5A (p.Gly5Ala), gnomAD 6-393166-G-C, REVEL 0.25, CADD 20.50
- G5G (p.Gly5Gly), gnomAD 6-393167-C-A, CADD 10.50
- G6R (p.Gly6Arg), rs1296646377, ClinGen CA362546242, ClinVar RCV003821169, gnomAD rs1296646377, REVEL 0.35, CADD 9.79, Uncertain significance, not provided
- G6S (p.Gly6Ser), NCI-TCGA Cosmic COSV6670, Variant assessed as somatic; moderate impact.
- G6C (p.Gly6Cys), gnomAD 6-393168-G-T, REVEL 0.38, CADD 19.10
- G6D (p.Gly6Asp), gnomAD 6-393169-G-A, REVEL 0.25, CADD 22.60
- G6G (p.Gly6Gly), rs1339754619, gnomAD 6-393170-C-A, CADD 12.10
- G7D (p.Gly7Asp), rs769695946, ClinGen CA3612604, ClinVar RCV001901182, ExAC rs769695946, REVEL 0.28, CADD 23.00, Uncertain significance, not provided
- G7S (p.Gly7Ser), NCI-TCGA Cosmic COSV1011, REVEL 0.26, CADD 18.20, Uncertain significance, not provided
- G7C (p.Gly7Cys), gnomAD 6-393171-G-T, REVEL 0.34, CADD 21.90
- G7A (p.Gly7Ala), gnomAD 6-393172-G-C, REVEL 0.28, CADD 22.00
- G7G (p.Gly7Gly), gnomAD 6-393173-C-T, CADD 15.10
- R8G (p.Arg8Gly), gnomAD rs1251757585, REVEL 0.33, CADD 23.30
- R8L (p.Arg8Leu), rs139884486, ClinGen CA3612606, ClinVar RCV001889492, 1000Genomes rs139884486, REVEL 0.35, CADD 23.60, Uncertain significance, not provided
- R8Q (p.Arg8Gln), rs139884486, ClinGen CA3612605, ClinVar RCV001945320, ClinVar RCV004043440, REVEL 0.29, CADD 23.40, Conflicting interpretations, not specified; not provided
- R8* (p.Arg8Ter), gnomAD 6-393174-C-T, CADD 38.00
- R8R (p.Arg8Arg), gnomAD 6-393174-C-A, CADD 16.00
- G9D (p.Gly9Asp), Ensembl rs1581220840, REVEL 0.38, CADD 21.50
- G9S (p.Gly9Ser), rs1285362149, TOPMed rs1285362149, REVEL 0.24, CADD 22.30, Variant assessed as somatic; moderate impact.
- G9C (p.Gly9Cys), gnomAD 6-393177-G-T, REVEL 0.46, CADD 26.60
- G9V (p.Gly9Val), gnomAD 6-393178-G-T, REVEL 0.44, CADD 22.70
- G9G (p.Gly9Gly), gnomAD 6-393179-C-A, CADD 13.70
- G10R (p.Gly10Arg), TOPMed rs1403333371, gnomAD rs1403333371, REVEL 0.26, CADD 23.00
- G10* (p.Gly10Ter), gnomAD 6-393180-G-T, CADD 35.00
- G10A (p.Gly10Ala), gnomAD 6-393181-G-C, REVEL 0.34, CADD 15.90
- G10G (p.Gly10Gly), gnomAD 6-393182-A-G, CADD 13.70
- E11D (p.Glu11Asp), TOPMed rs1761163199, REVEL 0.27, CADD 21.50
- E11* (p.Glu11Ter), gnomAD 6-393183-G-T, CADD 39.00
- E11E (p.Glu11Glu), gnomAD 6-393185-G-A, CADD 14.80
- F12L (p.Phe12Leu), rs546956488, ClinGen CA133329015, ClinVar RCV002047135, ClinVar RCV006424823, REVEL 0.31, CADD 23.10, Uncertain significance, not specified; not provided
- F12V (p.Phe12Val), gnomAD 6-393186-T-G, REVEL 0.33, CADD 23.10
- F12F (p.Phe12Phe), gnomAD 6-393188-C-T, CADD 16.90
- G13R (p.Gly13Arg), gnomAD 6-393189-G-C, REVEL 0.67, CADD 32.00
- G13C (p.Gly13Cys), gnomAD 6-393189-G-T, REVEL 0.71, CADD 32.00
- G13D (p.Gly13Asp), gnomAD 6-393190-G-A, REVEL 0.61, CADD 24.60
- G13G (p.Gly13Gly), gnomAD 6-393191-C-A, CADD 15.60
- M14R (p.Met14Arg), gnomAD rs1265068205
- M14T (p.Met14Thr), rs1265068205, ClinGen CA362546291, ClinVar RCV003035920, MutPred 0.60, Uncertain significance, not provided
- M14V (p.Met14Val), gnomAD 6-393192-A-G, REVEL 0.53, CADD 24.10
- S15G (p.Ser15Gly), gnomAD 6-393195-A-G, REVEL 0.33, CADD 24.70
- S15N (p.Ser15Asn), gnomAD 6-393196-G-A, REVEL 0.25, CADD 22.80
- S15I (p.Ser15Ile), gnomAD 6-393196-G-T, REVEL 0.35, CADD 24.30
- S15R (p.Ser15Arg), gnomAD 6-393197-C-A, REVEL 0.34, CADD 23.60
- S15S (p.Ser15Ser), rs1461973609, gnomAD 6-393197-C-T, CADD 15.90
- A16T (p.Ala16Thr), Ensembl rs2127436076, REVEL 0.21, CADD 22.60
- A16V (p.Ala16Val), NCI-TCGA Cosmic COSV6670, Variant assessed as somatic; moderate impact.
- A16S (p.Ala16Ser), gnomAD 6-393198-G-T, REVEL 0.21, CADD 17.70
- A16A (p.Ala16Ala), rs915113320, gnomAD 6-393200-G-T, CADD 13.00
- V17L (p.Val17Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V17M (p.Val17Met), gnomAD 6-393201-G-A, REVEL 0.42, CADD 23.50
- V17V (p.Val17Val), gnomAD 6-393203-G-T, CADD 15.60
- S18G (p.Ser18Gly), TOPMed rs1343907006, gnomAD rs1343907006, REVEL 0.72, CADD 26.40
- S18I (p.Ser18Ile), TOPMed rs1000698747, gnomAD rs1000698747, REVEL 0.74, CADD 32.00, Uncertain significance
- S18N (p.Ser18Asn), rs1000698747, ClinGen CA133329066, ClinVar RCV003826813, TOPMed rs1000698747, REVEL 0.42, CADD 23.70, Uncertain significance, not provided
- S18R (p.Ser18Arg), NCI-TCGA Cosmic COSV6670, Variant assessed as somatic; moderate impact.
- S18T (p.Ser18Thr), rs1000698747, ClinGen CA362546320, ClinVar RCV003730844, TOPMed rs1000698747, REVEL 0.57, CADD 25.70, Uncertain significance, not provided
- S18S (p.Ser18Ser), gnomAD 6-393206-C-T, CADD 18.80
- C19S (p.Cys19Ser), gnomAD 6-393207-T-A, REVEL 0.33, CADD 23.10
- C19* (p.Cys19Ter), gnomAD 6-393209-C-A, CADD 36.00
- C19C (p.Cys19Cys), rs1761164251, gnomAD 6-393209-C-T, CADD 15.60
- G20D (p.Gly20Asp), Ensembl rs1761164408, REVEL 0.82, CADD 32.00
- G20S (p.Gly20Ser), Ensembl rs1761164334, REVEL 0.69, CADD 32.00
- G20A (p.Gly20Ala), gnomAD 6-393209-CG-C, CADD 32.00
- G20R (p.Gly20Arg), gnomAD 6-393210-G-C, REVEL 0.77, CADD 32.00
- G20C (p.Gly20Cys), gnomAD 6-393210-G-T, REVEL 0.86, CADD 32.00
- G20V (p.Gly20Val), gnomAD 6-393211-G-T, REVEL 0.84, CADD 32.00
- G20G (p.Gly20Gly), rs375593254, gnomAD 6-393212-C-A, CADD 15.60
- N21S (p.Asn21Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- N21N (p.Asn21Asn), gnomAD 6-393215-C-T, CADD 14.60
- N21K (p.Asn21Lys), gnomAD 6-393215-C-A, REVEL 0.48, CADD 23.30
- G22R (p.Gly22Arg), gnomAD 6-393216-G-A, REVEL 0.68, CADD 26.60
- G22G (p.Gly22Gly), rs945235716, gnomAD 6-393218-G-C, CADD 15.70
- K23E (p.Lys23Glu), gnomAD 6-393219-A-G, REVEL 0.95, CADD 32.00
- L24I (p.Leu24Ile), gnomAD 6-393222-C-A, REVEL 0.76, CADD 27.00
- L24L (p.Leu24Leu), gnomAD 6-393224-C-A, CADD 13.10
- R25C (p.Arg25Cys), NCI-TCGA TCGA novel, REVEL 0.97, CADD 31.00, Variant assessed as somatic; moderate impact.
- R25G (p.Arg25Gly), rs2127436091, ClinGen CA362546367, ClinVar RCV001924668, Ensembl rs2127436091, MutPred 0.89, Uncertain significance, not provided
- R25S (p.Arg25Ser), gnomAD 6-393225-C-A, REVEL 0.93, CADD 27.30
- R25R (p.Arg25Arg), gnomAD 6-393227-C-G, CADD 16.10
- Q26R (p.Gln26Arg), Ensembl rs1761164866, REVEL 0.84, CADD 30.00
- Q26* (p.Gln26Ter), gnomAD 6-393228-C-T, CADD 38.00
- Q26H (p.Gln26His), gnomAD 6-393230-G-T, REVEL 0.76, CADD 26.20
- W27L (p.Trp27Leu), gnomAD 6-393232-G-T, REVEL 0.96, CADD 33.00
- L28M (p.Leu28Met), gnomAD 6-393234-C-A, REVEL 0.83, CADD 25.10
- L28P (p.Leu28Pro), gnomAD 6-393235-T-C, REVEL 0.98, CADD 32.00
- L28L (p.Leu28Leu), gnomAD 6-393236-G-T, CADD 13.70
- I29S (p.Ile29Ser), rs1761165092, ClinGen CA362546397, ClinVar RCV001968221, TOPMed rs1761165092, REVEL 0.94, CADD 32.00, Uncertain significance, not provided
- I29V (p.Ile29Val), gnomAD 6-393237-A-G, REVEL 0.53, CADD 23.20
- I29M (p.Ile29Met), gnomAD 6-393239-C-G, REVEL 0.79, CADD 24.80
- I29I (p.Ile29Ile), gnomAD 6-393239-C-T, CADD 15.90
- D30Y (p.Asp30Tyr), gnomAD 6-393240-G-T, REVEL 0.78, CADD 32.00
- D30N (p.Asp30Asn), gnomAD 6-393240-G-A, REVEL 0.35, CADD 24.50
- D30H (p.Asp30His), gnomAD 6-393240-G-C, REVEL 0.71, CADD 28.30
- D30V (p.Asp30Val), gnomAD 6-393241-A-T, REVEL 0.73, CADD 26.60
- D30E (p.Asp30Glu), gnomAD 6-393242-C-A, REVEL 0.28, CADD 18.20
- D30D (p.Asp30Asp), rs1407610583, gnomAD 6-393242-C-T, CADD 15.80
- Q31E (p.Gln31Glu), rs2480806143, ClinGen CA362546410, ClinVar RCV002304811, Uncertain significance, not provided
- Q31H (p.Gln31His), NCI-TCGA TCGA novel, REVEL 0.88, CADD 29.00, Variant assessed as somatic; moderate impact.
- Q31K (p.Gln31Lys), gnomAD 6-393243-C-A, REVEL 0.94, CADD 28.40
- Q31R (p.Gln31Arg), gnomAD 6-393244-A-G, REVEL 0.96, CADD 32.00
- Q31Q (p.Gln31Gln), rs2127436102, gnomAD 6-393245-G-A, CADD 14.90
- I32F (p.Ile32Phe), TOPMed rs1761165279
- I32V (p.Ile32Val), gnomAD 6-393246-A-G, REVEL 0.53, CADD 23.20
- I32N (p.Ile32Asn), gnomAD 6-393247-T-A, REVEL 0.92, CADD 32.00
- I32M (p.Ile32Met), gnomAD 6-393248-C-G, REVEL 0.78, CADD 25.40
- I32I (p.Ile32Ile), rs1761165352, gnomAD 6-393248-C-A, CADD 16.00
- D33N (p.Asp33Asn), NCI-TCGA Cosmic COSV6670, REVEL 0.60, CADD 32.00, Variant assessed as somatic; moderate impact.
- D33G (p.Asp33Gly), gnomAD 6-393250-A-G, REVEL 0.95, CADD 32.00
- D33D (p.Asp33Asp), rs1470021018, gnomAD 6-393251-C-T, CADD 16.30
- S34G (p.Ser34Gly), gnomAD 6-393252-A-G, REVEL 0.91, CADD 30.00
- S34I (p.Ser34Ile), gnomAD 6-393253-G-T, REVEL 0.89, CADD 32.00
- S34R (p.Ser34Arg), gnomAD 6-393254-C-A, REVEL 0.82, CADD 25.70
- S34S (p.Ser34Ser), rs1319408734, gnomAD 6-393254-C-T, CADD 15.20
- G35A (p.Gly35Ala), 1000Genomes rs538907751, ExAC rs538907751, gnomAD rs538907751, REVEL 0.82, CADD 25.00
- G35C (p.Gly35Cys), NCI-TCGA Cosmic COSV1011, NCI-TCGA Cosmic COSV6670, REVEL 0.88, CADD 32.00, Variant assessed as somatic; moderate impact.
- G35D (p.Gly35Asp), NCI-TCGA Cosmic COSV1011, REVEL 0.84, CADD 31.00, Variant assessed as somatic; moderate impact.
- G35S (p.Gly35Ser), NCI-TCGA Cosmic COSV1011, NCI-TCGA Cosmic COSV6670, TOPMed rs1761165556, REVEL 0.70, CADD 25.40, Variant assessed as somatic; moderate impact.
- G35V (p.Gly35Val), gnomAD 6-393256-G-T, REVEL 0.92, CADD 31.00
- K36T (p.Lys36Thr), Ensembl rs1581220917, REVEL 0.74, CADD 28.90
- K36E (p.Lys36Glu), gnomAD 6-393258-A-G, REVEL 0.62, CADD 25.90
- K36Q (p.Lys36Gln), gnomAD 6-393258-A-C, REVEL 0.46, CADD 25.40
- K36K (p.Lys36Lys), gnomAD 6-393260-G-A, CADD 15.40
- K36N (p.Lys36Asn), gnomAD 6-393260-G-T, REVEL 0.46, CADD 25.30
- Y37H (p.Tyr37His), gnomAD 6-393261-T-C, REVEL 0.97, CADD 32.00
- Y37N (p.Tyr37Asn), gnomAD 6-393261-T-A, REVEL 0.96, CADD 32.00
- Y37S (p.Tyr37Ser), gnomAD 6-393262-A-C, REVEL 0.98, CADD 32.00
- Y37C (p.Tyr37Cys), gnomAD 6-393262-A-G, REVEL 0.94, CADD 32.00
- Y37* (p.Tyr37Ter), gnomAD 6-393263-C-A, CADD 36.00
- Y37Y (p.Tyr37Tyr), rs1383638158, gnomAD 6-393263-C-T, CADD 14.60
- P38L (p.Pro38Leu), ExAC rs755738102, REVEL 0.89, CADD 29.70
- P38S (p.Pro38Ser), rs369688140, ClinGen CA3612612, ClinVar RCV002595110, ESP rs369688140, REVEL 0.78, CADD 24.50, Likely benign, not provided
- P38A (p.Pro38Ala), gnomAD 6-393264-C-G, REVEL 0.76, CADD 22.60
- P38P (p.Pro38Pro), rs1330509350, gnomAD 6-393266-C-A, CADD 7.22
- G39E (p.Gly39Glu), gnomAD rs1230948269
- G39R (p.Gly39Arg), gnomAD 6-393267-G-A, REVEL 0.98, CADD 32.00
- G39G (p.Gly39Gly), rs1210737562, gnomAD 6-393269-G-C, CADD 15.10
- L40M (p.Leu40Met), TOPMed rs1761166230, gnomAD rs1761166230, REVEL 0.86, CADD 25.10
- L40W (p.Leu40Trp), gnomAD 6-393262-AC-A, CADD 27.10
- L40L (p.Leu40Leu), gnomAD 6-393272-G-T, CADD 11.10
- V41L (p.Val41Leu), ExAC rs751037944, gnomAD rs751037944, REVEL 0.57, CADD 23.20, Uncertain significance, not provided
- V41C (p.Val41Cys), gnomAD 6-393271-TG-T, CADD 23.40
- V41V (p.Val41Val), gnomAD 6-393275-G-A, CADD 15.30
- W42* (p.Trp42Ter), gnomAD rs1208372867, CADD 40.00
- W42C (p.Trp42Cys), gnomAD 6-393278-G-T, REVEL 0.97, CADD 33.00
- E43Q (p.Glu43Gln), NCI-TCGA Cosmic COSV1011, Variant assessed as somatic; moderate impact.
- E43* (p.Glu43Ter), gnomAD 6-393279-G-T, CADD 42.00
- E43K (p.Glu43Lys), gnomAD 6-393279-G-A, REVEL 0.86, CADD 32.00
- E43E (p.Glu43Glu), rs764159153, gnomAD 6-393281-G-A, CADD 15.30
- E43D (p.Glu43Asp), gnomAD 6-393281-G-T, REVEL 0.72, CADD 31.00
- N44K (p.Asn44Lys), gnomAD 6-393284-C-G, REVEL 0.86, CADD 27.50
- N44N (p.Asn44Asn), gnomAD 6-393284-C-T, CADD 15.90
- E45Q (p.Glu45Gln), rs934099606, ClinGen CA133329147, ClinVar RCV003811967, TOPMed rs934099606, REVEL 0.49, CADD 25.70, Uncertain significance, not provided
- E45V (p.Glu45Val), gnomAD 6-393286-A-T, REVEL 0.69, CADD 26.30
- E45E (p.Glu45Glu), rs1261009207, gnomAD 6-393287-G-A, CADD 14.40
- E45D (p.Glu45Asp), gnomAD 6-393287-G-C, REVEL 0.35, CADD 18.90
- E46D (p.Glu46Asp), gnomAD rs1267078147, REVEL 0.36, CADD 22.30
- E46K (p.Glu46Lys), ExAC rs780297970, gnomAD rs780297970, REVEL 0.71, CADD 28.50
- E46del (p.Glu46del), rs753781892, gnomAD 6-393284-CGAG-C, CADD 22.80
- E46E (p.Glu46Glu), rs1267078147, gnomAD 6-393290-G-A, CADD 15.30
- K47N (p.Lys47Asn), NCI-TCGA TCGA novel, REVEL 0.87, CADD 29.80, Variant assessed as somatic; moderate impact.
- K47R (p.Lys47Arg), TOPMed rs1431984073, gnomAD rs1431984073, REVEL 0.54, CADD 23.70, Uncertain significance, not provided; not specified
- K47E (p.Lys47Glu), gnomAD 6-393291-A-G, REVEL 0.90, CADD 32.00
- K47K (p.Lys47Lys), rs1202171815, gnomAD 6-393293-G-A, CADD 15.50
- S48I (p.Ser48Ile), gnomAD 6-393295-G-T, REVEL 0.81, CADD 29.00
- S48T (p.Ser48Thr), gnomAD 6-393295-G-C, REVEL 0.45, CADD 20.40
- S48S (p.Ser48Ser), rs1323052445, gnomAD 6-393296-C-T, CADD 16.50
- I49V (p.Ile49Val), gnomAD 6-393297-A-G, REVEL 0.32, CADD 20.60
- I49F (p.Ile49Phe), gnomAD 6-393297-A-T, REVEL 0.67, CADD 23.80
Public IRF4 analysis runs
- IRF4 analysis run — IRF4 (915 variants) — completed 2026-08-19