IKZF1 (DNA-binding protein Ikaros) variants and mutations
IKZF1 (also known as DNA-binding protein Ikaros) is a human protein-coding gene encoding a DNA-binding protein Ikaros protein. It establishes transcriptional programs required for lymphoid development, especially B-cell differentiation. Somatic deletion or mutation is common in high-risk B-cell acute lymphoblastic leukemia, while germline variants can cause immunodeficiency and leukemia predisposition. This analysis covers 1,702 IKZF1 variants and mutations. Of these, 38% have computational variant effect predictions. Disease context includes pancytopenia due to IKZF1 mutations, acute lymphoblastic leukemia, and immunodeficiency disease. Example IKZF1 variants include M1?, D2N, and D2Y.
Variant analysis overview
- Gene: IKZF1
- Protein: DNA-binding protein Ikaros
- UniProt accession: Q13422
- Organism: Homo sapiens
- Variants analyzed: 1702
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 1,530 unspecified-consequence records; 73 missense variants; 73 synonymous variants; 3 splice-region variants; 10 frameshift variants; 2 stop-gained variants; 2 stop lost; 1 stop retained variant; 8 substitution
- Prediction scores: 653 variants have prediction scores (38% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: pancytopenia due to IKZF1 mutations, acute lymphoblastic leukemia, immunodeficiency disease, B-cell acute lymphoblastic leukemia, acute myeloid leukemia, cutaneous melanoma, systemic lupus erythematosus, Crohn disease, melanoma, lung carcinoma, lymphoid neoplasm, pancreatic ductal adenocarcinoma.
Protein structure and variant hotspots
- Protein features: 23 post-translational modification sites.
- PTM context: 69 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, ClinGen, MaveDB, LitVar.
Notable IKZF1 variants
Examples include M1?, D2N, D2Y, D2H, D2G, A3P, A3T, A3V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA Cosmic COSV5878, cosmic curated COSV58789, cosmic curated COSV10521, Variant assessed as somatic; high impact.
- D2N (p.Asp2Asn), cosmic curated COSV58781, TOPMed rs1256598973, gnomAD rs1256598973
- D2Y (p.Asp2Tyr), TOPMed rs1256598973, gnomAD rs1256598973, REVEL 0.13, CADD 25.60
- D2H (p.Asp2His), gnomAD 7-50319065-G-C, REVEL 0.09, CADD 24.90
- D2G (p.Asp2Gly), gnomAD 7-50319066-A-G, REVEL 0.15, CADD 24.50
- A3P (p.Ala3Pro), Ensembl rs1584438980, Uncertain significance
- A3T (p.Ala3Thr), rs1584438980, ClinGen CA367568835, ClinVar RCV000788725, Ensembl rs1584438980, REVEL 0.04, CADD 14.20, Uncertain significance
- A3V (p.Ala3Val), Ensembl rs2153363337
- A3S (p.Ala3Ser), gnomAD 7-50319068-G-T, REVEL 0.06, CADD 15.40
- D4Y (p.Asp4Tyr), cosmic curated COSV58786, TOPMed rs1792377766, REVEL 0.33, CADD 31.00
- D4V (p.Asp4Val), gnomAD 7-50319072-A-T, REVEL 0.34, CADD 28.10
- E5D (p.Glu5Asp), ESP rs374267123, ExAC rs374267123, TOPMed rs374267123, gnomAD rs374267123, REVEL 0.08, CADD 16.60, Benign
- E5G (p.Glu5Gly), TOPMed rs1335984507, gnomAD rs1335984507, REVEL 0.09, CADD 24.60
- E5K (p.Glu5Lys), cosmic curated COSV58780
- E5A (p.Glu5Ala), gnomAD 7-50319075-A-C, REVEL 0.11, CADD 23.60
- E5E (p.Glu5Glu), rs374267123, gnomAD 7-50319076-G-A, CADD 7.50
- G6S (p.Gly6Ser), TOPMed rs1024766283, REVEL 0.07, CADD 16.10
- G6V (p.Gly6Val), NCI-TCGA Cosmic COSV1004, cosmic curated COSV10049, Variant assessed as somatic; moderate impact.
- Q7E (p.Gln7Glu), gnomAD rs1325476367, Uncertain significance
- Q7K (p.Gln7Lys), gnomAD rs1325476367, REVEL 0.24, CADD 23.80, Uncertain significance
- D8G (p.Asp8Gly), NCI-TCGA Cosmic COSV1004, cosmic curated COSV10049, Variant assessed as somatic; moderate impact.
- D8N (p.Asp8Asn), gnomAD 7-50319083-G-A, REVEL 0.17, CADD 26.00
- D8D (p.Asp8Asp), rs763123993, gnomAD 7-50319085-C-T, CADD 8.89
- M9I (p.Met9Ile), ExAC rs774453089, gnomAD rs774453089, REVEL 0.06, CADD 21.00
- M9T (p.Met9Thr), rs964046541, ClinGen CA158660149, ClinVar RCV002736733, ClinVar RCV003444113, REVEL 0.16, CADD 23.50, Uncertain significance
- M9V (p.Met9Val), ExAC rs766502771, gnomAD rs766502771, REVEL 0.12, CADD 15.50
- S10F (p.Ser10Phe), NCI-TCGA Cosmic COSV5878, cosmic curated COSV58782, REVEL 0.18, CADD 22.30, Variant assessed as somatic; moderate impact.
- Q11* (p.Gln11Ter), cosmic curated COSV10521, CADD 37.00
- Q11H (p.Gln11His), rs1480100906, cosmic curated COSV10589, TOPMed rs1480100906, gnomAD rs1480100906, REVEL 0.11, CADD 18.00, Likely benign
- Q11R (p.Gln11Arg), gnomAD 7-50319093-A-G, REVEL 0.05, CADD 19.60
- Q11Q (p.Gln11Gln), rs1480100906, gnomAD 7-50319094-A-G, CADD 8.43
- V12A (p.Val12Ala), gnomAD 7-50319096-T-C, REVEL 0.08, CADD 22.40
- S13* (p.Ser13Ter), NCI-TCGA Cosmic COSV1004, cosmic curated COSV10049, Variant assessed as somatic; high impact.
- S13L (p.Ser13Leu), cosmic curated COSV10963
- S13T (p.Ser13Thr), NCI-TCGA Cosmic COSV1004, cosmic curated COSV10049, Variant assessed as somatic; moderate impact.
- G14E (p.Gly14Glu), cosmic curated COSV58782, REVEL 0.25, CADD 29.50
- G14G (p.Gly14Gly), rs1379261020, gnomAD 7-50327639-G-C, CADD 10.20
- K15N (p.Lys15Asn), cosmic curated COSV10049, cosmic curated COSV10963, REVEL 0.06, CADD 16.60
- K15R (p.Lys15Arg), Ensembl rs2153384545
- E16* (p.Glu16Ter), cosmic curated COSV10049
- E16K (p.Glu16Lys), cosmic curated COSV58788, Ensembl rs1045233686
- S17C (p.Ser17Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S17G (p.Ser17Gly), ExAC rs751054964, gnomAD rs751054964, REVEL 0.28, CADD 23.80
- S17N (p.Ser17Asn), NCI-TCGA Cosmic COSV1004, cosmic curated COSV10049, REVEL 0.19, CADD 24.90, Variant assessed as somatic; moderate impact.
- S17R (p.Ser17Arg), Ensembl rs1795393376, REVEL 0.20, CADD 22.40
- S17T (p.Ser17Thr), Ensembl rs1562748776, REVEL 0.18, CADD 23.40
- P18H (p.Pro18His), rs1397682553, NCI-TCGA Cosmic COSV1004, cosmic curated COSV10049, TOPMed rs1397682553, REVEL 0.22, CADD 24.50, Variant assessed as somatic; moderate impact.
- P18L (p.Pro18Leu), cosmic curated COSV10521, TOPMed rs1397682553, gnomAD rs1397682553, REVEL 0.24, CADD 23.30
- P18S (p.Pro18Ser), cosmic curated COSV10521
- P18T (p.Pro18Thr), rs754640737, ClinGen CA4261194, ClinVar RCV002750257, ExAC rs754640737, REVEL 0.20, CADD 22.30, Uncertain significance
- P18P (p.Pro18Pro), rs780897370, gnomAD 7-50327651-C-A, CADD 1.93
- P19A (p.Pro19Ala), rs931548912, ClinGen CA367569308, ClinVar RCV003708383, TOPMed rs931548912, REVEL 0.04, CADD 14.80, Uncertain significance
- P19H (p.Pro19His), rs752227855, ClinGen CA367569309, cosmic curated COSV58788, ClinVar RCV002857230, AlphaMissense 0.10, MetaLR 0.02, Uncertain significance
- P19L (p.Pro19Leu), rs752227855, ClinGen CA4261196, cosmic curated COSV58786, ClinVar RCV003715517, REVEL 0.04, AlphaMissense 0.10, Uncertain significance
- P19S (p.Pro19Ser), cosmic curated COSV10644
- P19T (p.Pro19Thr), rs931548912, ClinGen CA158661180, ClinVar RCV003046176, TOPMed rs931548912, REVEL 0.08, CADD 15.60, Uncertain significance
- P19R (p.Pro19Arg), gnomAD 7-50327653-C-G, REVEL 0.09, CADD 22.30
- P19P (p.Pro19Pro), rs755989663, gnomAD 7-50327654-T-C, CADD 0.40
- V20E (p.Val20Glu), Ensembl rs2153384614
- V20I (p.Val20Ile), Ensembl rs2153384609
- V20C (p.Val20Cys), rs1795394160, gnomAD 7-50327647-G-GC, CADD 27.70
- V20V (p.Val20Val), gnomAD 7-50327657-A-G, CADD 4.39
- S21I (p.Ser21Ile), gnomAD rs1795401260, REVEL 0.10, CADD 25.20
- S21R (p.Ser21Arg), ExAC rs777664112, TOPMed rs777664112, gnomAD rs777664112, Uncertain significance
- S21S (p.Ser21Ser), rs777664112, gnomAD 7-50327660-C-T, CADD 2.06
- D22H (p.Asp22His), gnomAD rs1245618829, REVEL 0.26, CADD 26.80, Likely pathogenic
- D22N (p.Asp22Asn), rs1245618829, ClinGen CA367569325, NCI-TCGA Cosmic COSV1004, NCI-TCGA Cosmic COSV5878, REVEL 0.20, CADD 27.50, Likely pathogenic
- D22Y (p.Asp22Tyr), NCI-TCGA Cosmic COSV1004, cosmic curated COSV10049, NCI-TCGA Cosmic COSV5878, Variant assessed as somatic; moderate impact.
- D22D (p.Asp22Asp), gnomAD 7-50327663-T-C, CADD 8.77
- T23N (p.Thr23Asn), Ensembl rs2153384635
- T23A (p.Thr23Ala), gnomAD 7-50327664-A-G, REVEL 0.05, CADD 18.10
- P24A (p.Pro24Ala), gnomAD rs1293971596, REVEL 0.08, CADD 18.90
- P24L (p.Pro24Leu), cosmic curated COSV58792
- P24S (p.Pro24Ser), cosmic curated COSV10644, REVEL 0.10, CADD 16.20
- P24T (p.Pro24Thr), gnomAD 7-50327667-C-A, REVEL 0.09, CADD 16.90
- P24Q (p.Pro24Gln), gnomAD 7-50327668-C-A, REVEL 0.09, CADD 24.00
- D25V (p.Asp25Val), rs919149752, ClinGen CA158661181, ClinVar RCV003715737, gnomAD rs919149752, REVEL 0.18, CADD 24.90, Uncertain significance
- D25N (p.Asp25Asn), gnomAD 7-50327670-G-A, REVEL 0.14, CADD 25.10
- E26D (p.Glu26Asp), TOPMed rs1284126054, gnomAD rs1284126054, REVEL 0.10, CADD 0.19, Uncertain significance
- E26K (p.Glu26Lys), TOPMed rs938596544, REVEL 0.09, CADD 25.30
- E26E (p.Glu26Glu), rs1284126054, gnomAD 7-50327675-G-A, CADD 2.19
- G27C (p.Gly27Cys), cosmic curated COSV10049
- G27S (p.Gly27Ser), rs749271573, ClinGen CA4261199, ClinVar RCV003659454, ExAC rs749271573, REVEL 0.05, CADD 13.20, Uncertain significance
- G27G (p.Gly27Gly), rs369941285, gnomAD 7-50327678-C-T, CADD 3.62
- D28A (p.Asp28Ala), Ensembl rs2153384668
- D28E (p.Asp28Glu), ESP rs371713365, ExAC rs371713365, TOPMed rs371713365, gnomAD rs371713365
- D28G (p.Asp28Gly), Ensembl rs2153384668
- D28H (p.Asp28His), ExAC rs778910457, TOPMed rs778910457, gnomAD rs778910457, Uncertain significance
- D28N (p.Asp28Asn), rs778910457, ClinGen CA4261201, NCI-TCGA Cosmic COSV5878, cosmic curated COSV58784, REVEL 0.21, CADD 29.90, Uncertain significance
- D28V (p.Asp28Val), Ensembl rs2153384668
- D28D (p.Asp28Asp), rs371713365, gnomAD 7-50327681-T-C, CADD 7.42
- E29* (p.Glu29Ter), cosmic curated COSV10609
- E29D (p.Glu29Asp), cosmic curated COSV58791
- E29G (p.Glu29Gly), Ensembl rs2153384683
- E29K (p.Glu29Lys), cosmic curated COSV58789
- E29E (p.Glu29Glu), rs1256104315, gnomAD 7-50327684-G-A, CADD 6.57
- P30H (p.Pro30His), gnomAD rs1424834532, REVEL 0.26, CADD 26.20
- P30S (p.Pro30Ser), Ensembl rs2153384690
- P30T (p.Pro30Thr), Ensembl rs2153384690
- M31I (p.Met31Ile), Ensembl rs2153384719
- M31L (p.Met31Leu), ESP rs375037109, ExAC rs375037109, TOPMed rs375037109, gnomAD rs375037109, Uncertain significance
- M31V (p.Met31Val), rs375037109, ClinGen CA4261203, ClinVar RCV003074935, ESP rs375037109, REVEL 0.28, CADD 23.70, Uncertain significance
- M31R (p.Met31Arg), gnomAD 7-50327689-T-G, REVEL 0.27, CADD 24.80
- P32A (p.Pro32Ala), Ensembl rs866731167
- P32L (p.Pro32Leu), rs775793261, ClinGen CA4261204, NCI-TCGA Cosmic COSV5878, cosmic curated COSV58789, REVEL 0.19, CADD 26.30, Uncertain significance
- P32Q (p.Pro32Gln), ExAC rs775793261, TOPMed rs775793261, gnomAD rs775793261, Uncertain significance
- P32R (p.Pro32Arg), cosmic curated COSV10963
- P32S (p.Pro32Ser), Ensembl rs866731167
- P32T (p.Pro32Thr), Ensembl rs866731167
- P32P (p.Pro32Pro), rs760835849, gnomAD 7-50327693-G-A, CADD 5.27
- I33F (p.Ile33Phe), gnomAD rs1482011693, REVEL 0.07, CADD 22.80
- I33I (p.Ile33Ile), rs61732861, gnomAD 7-50327696-C-A, CADD 10.70
- I33V (p.Ile33Val), gnomAD 7-50368044-A-G, CADD 17.50
- P34H (p.Pro34His), Ensembl rs2153384763
- P34L (p.Pro34Leu), cosmic curated COSV58786, Ensembl rs2153384763
- P34R (p.Pro34Arg), cosmic curated COSV10963, Ensembl rs2153384763, REVEL 0.19, CADD 25.70
- P34S (p.Pro34Ser), cosmic curated COSV58780
- P34T (p.Pro34Thr), cosmic curated COSV10963
- P34P (p.Pro34Pro), rs776947333, gnomAD 7-50327699-C-G, CADD 1.21
- E35D (p.Glu35Asp), gnomAD rs757321486
- E35K (p.Glu35Lys), cosmic curated COSV58785, TOPMed rs1432663785, gnomAD rs1432663785, REVEL 0.34, CADD 31.00
- E35V (p.Glu35Val), Ensembl rs2153384783
- E35E (p.Glu35Glu), rs757321486, gnomAD 7-50327702-G-A, CADD 6.30
- D36H (p.Asp36His), Ensembl rs2153384793
- D36N (p.Asp36Asn), Ensembl rs2153384793
- L37L (p.Leu37Leu), rs762352967, gnomAD 7-50327708-C-T, CADD 1.01
- S38F (p.Ser38Phe), NCI-TCGA Cosmic COSV1004, cosmic curated COSV10049, REVEL 0.29, CADD 27.30, Variant assessed as somatic; moderate impact.
- S38T (p.Ser38Thr), TOPMed rs1453359888, gnomAD rs1453359888, REVEL 0.18, CADD 24.40
- S38Y (p.Ser38Tyr), Ensembl rs2153384809
- S38S (p.Ser38Ser), rs765758367, gnomAD 7-50327711-C-T, CADD 12.40
- T39A (p.Thr39Ala), cosmic curated COSV10589
- T39I (p.Thr39Ile), cosmic curated COSV10816, gnomAD rs1351654980, REVEL 0.13, CADD 25.80
- T40S (p.Thr40Ser), Ensembl rs2153384827
- T40I (p.Thr40Ile), gnomAD 7-50327716-C-T, REVEL 0.07, CADD 23.00
- S41* (p.Ser41Ter), ExAC rs751092583, TOPMed rs751092583, gnomAD rs751092583, Uncertain significance
- S41L (p.Ser41Leu), rs751092583, ClinGen CA4261210, cosmic curated COSV58783, ClinVar RCV001768040, REVEL 0.13, CADD 24.20, Uncertain significance
- S41W (p.Ser41Trp), ExAC rs751092583, TOPMed rs751092583, gnomAD rs751092583, Uncertain significance
- S41S (p.Ser41Ser), rs373934387, gnomAD 7-50327720-G-T, CADD 3.78
- G42E (p.Gly42Glu), cosmic curated COSV10049
- G42R (p.Gly42Arg), NCI-TCGA Cosmic COSV5879, cosmic curated COSV58790, Variant assessed as somatic; moderate impact.
- G42V (p.Gly42Val), cosmic curated COSV58782, REVEL 0.10, CADD 24.80
- G43A (p.Gly43Ala), cosmic curated COSV58790
- G43E (p.Gly43Glu), NCI-TCGA Cosmic COSV5878, cosmic curated COSV58783, NCI-TCGA Cosmic COSV5879, Variant assessed as somatic; moderate impact.
- G43R (p.Gly43Arg), cosmic curated COSV58784, Ensembl rs1795425315
- G43V (p.Gly43Val), rs1378576386, ClinGen CA367569466, ClinVar RCV002811484, TOPMed rs1378576386, REVEL 0.06, CADD 19.00, Uncertain significance
- Q44* (p.Gln44Ter), Ensembl rs2153384852
- Q44H (p.Gln44His), cosmic curated COSV58781
- Q44L (p.Gln44Leu), cosmic curated COSV10589
- Q45* (p.Gln45Ter), Ensembl rs2153384862
- Q45P (p.Gln45Pro), gnomAD 7-50327731-A-C, REVEL 0.15, CADD 23.80
- Q45Q (p.Gln45Gln), rs1198525472, gnomAD 7-50327732-A-G, CADD 10.50
- S46G (p.Ser46Gly), gnomAD rs1318919672, REVEL 0.06, CADD 23.20
- S46N (p.Ser46Asn), Ensembl rs2153384884
- S46S (p.Ser46Ser), rs1431967137, gnomAD 7-50327735-C-T, CADD 8.01
- S47F (p.Ser47Phe), cosmic curated COSV58783
- S47P (p.Ser47Pro), Ensembl rs2153384899
- S47A (p.Ser47Ala), gnomAD 7-50327736-T-G, REVEL 0.01, CADD 16.10
- S47S (p.Ser47Ser), gnomAD 7-50327738-C-A, CADD 8.48
- K48G (p.Lys48Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- K48T (p.Lys48Thr), cosmic curated COSV58789
- K48R (p.Lys48Arg), gnomAD 7-50327740-A-G, REVEL 0.08, CADD 22.70
- K48K (p.Lys48Lys), rs377643064, gnomAD 7-50327741-G-A, CADD 11.10
- S49N (p.Ser49Asn), rs1255711584, ClinGen CA367569508, ClinVar RCV003674650, gnomAD rs1255711584, REVEL 0.04, CADD 13.20, Uncertain significance
- S49R (p.Ser49Arg), gnomAD rs1483773472
- D50H (p.Asp50His), cosmic curated COSV10816
- D50G (p.Asp50Gly), gnomAD 7-50327746-A-G, REVEL 0.16, CADD 23.30
- R51G (p.Arg51Gly), cosmic curated COSV58790, TOPMed rs1264440159, REVEL 0.17, CADD 19.90
- R51K (p.Arg51Lys), cosmic curated COSV58783, REVEL 0.13, CADD 20.60
- R51P (p.Arg51Pro), NCI-TCGA Cosmic COSV5879, Variant assessed as somatic; high impact.
- R51Q (p.Arg51Gln), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- V52A (p.Val52Ala), ExAC rs752423552, gnomAD rs752423552, REVEL 0.01, CADD 20.00
- V52I (p.Val52Ile), cosmic curated COSV58788
- V52L (p.Val52Leu), Ensembl rs1795433938
- V52V (p.Val52Val), rs200992647, gnomAD 7-50327753-C-T, CADD 0.53
- V53G (p.Val53Gly), NCI-TCGA Cosmic COSV1004, cosmic curated COSV10049, Variant assessed as somatic; moderate impact.
- V53L (p.Val53Leu), ESP rs369417059, ExAC rs369417059, TOPMed rs369417059, gnomAD rs369417059, REVEL 0.03, CADD 2.89, Uncertain significance
- V53M (p.Val53Met), rs369417059, ClinGen CA4261215, cosmic curated COSV58783, ClinVar RCV001819257, REVEL 0.03, CADD 7.67, Uncertain significance
- V53V (p.Val53Val), gnomAD 7-50327756-G-A, CADD 9.59
- A54D (p.Ala54Asp), Ensembl rs2153468488
- A54G (p.Ala54Gly), Ensembl rs2153468488
Public IKZF1 analysis runs
- IKZF1 analysis run — IKZF1 (1,702 variants) — completed 2026-08-18