FBXW7 (Q969H0) variants and mutations
FBXW7 (also known as Q969H0) is a human protein-coding gene encoding a f-box/WD repeat-containing protein 7 protein. Its annotated function is substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. It is annotated at the nucleus, nucleoplasm. This analysis covers 3,191 FBXW7 variants and mutations. Of these, 25% have computational variant effect predictions. Disease context includes developmental delay, hypotonia, and impaired language, colorectal adenocarcinoma, and cervical squamous cell carcinoma. Example FBXW7 variants include N2D, N2K, and N2Y.
Variant analysis overview
- Gene: FBXW7
- Protein: Q969H0
- UniProt accession: Q969H0
- Organism: Homo sapiens
- Variants analyzed: 3191
- Variant scope: all variants
- Completed: 2026-08-28
Variant and mutation evidence
- Variant composition: 3,023 unspecified-consequence records; 132 synonymous variants; 27 missense variants; 5 frameshift variants; 3 splice-region variants; 5 substitution
- Prediction scores: 805 variants have prediction scores (25% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: developmental delay, hypotonia, and impaired language, colorectal adenocarcinoma, cervical squamous cell carcinoma, endometrial cancer, colon adenocarcinoma, urinary bladder cancer, type 2 diabetes mellitus, esophageal cancer, uterine carcinosarcoma, head and neck squamous cell carcinoma, cancer, anal squamous cell carcinoma.
Protein structure and variant hotspots
- Protein features: 1 domains; 3 post-translational modification sites.
- Structural context: 181 variants have structural context.
- PTM context: 14 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 FBXW7 variants
Examples include N2D, N2K, N2Y, Q3*, Q3E, Q3H, Q3R, E4*. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- N2D (p.Asn2Asp), Ensembl rs2126883194
- N2K (p.Asn2Lys), Ensembl rs2126883175
- N2Y (p.Asn2Tyr), Ensembl rs2126883194
- Q3* (p.Gln3Ter), Ensembl rs2126883163
- Q3E (p.Gln3Glu), cosmic curated COSV99029, Ensembl rs2126883163, REVEL 0.26, CADD 24.80
- Q3H (p.Gln3His), TOPMed rs1462131711, gnomAD rs1462131711
- Q3R (p.Gln3Arg), TOPMed rs1737993515, gnomAD rs1737993515, REVEL 0.27, CADD 25.70
- E4* (p.Glu4Ter), cosmic curated COSV55954, Ensembl rs2126883133
- E4D (p.Glu4Asp), ESP rs371527630, ExAC rs371527630, TOPMed rs371527630, gnomAD rs371527630
- E4K (p.Glu4Lys), cosmic curated COSV10460, Ensembl rs2126883133
- E4Q (p.Glu4Gln), Ensembl rs2126883133
- E4V (p.Glu4Val), Ensembl rs2126883124
- L5P (p.Leu5Pro), Ensembl rs2126883076, REVEL 0.42, CADD 27.50
- L5Q (p.Leu5Gln), Ensembl rs2126883076
- L5V (p.Leu5Val), Ensembl rs2126883096
- L6F (p.Leu6Phe), cosmic curated COSV55905
- L6H (p.Leu6His), ESP rs139074724, ExAC rs139074724, TOPMed rs139074724, gnomAD rs139074724, Uncertain significance
- L6P (p.Leu6Pro), rs139074724, ClinGen CA3106584, ClinVar RCV002821353, ClinVar RCV005099680, REVEL 0.47, CADD 27.70, Uncertain significance, Inborn genetic diseases; not provided
- L6V (p.Leu6Val), cosmic curated COSV10586, REVEL 0.25, CADD 25.50, Uncertain significance, Inborn genetic diseases
- S7C (p.Ser7Cys), Ensembl rs2126883009
- S7F (p.Ser7Phe), cosmic curated COSV55900
- S7T (p.Ser7Thr), Ensembl rs2126883023
- S7Y (p.Ser7Tyr), cosmic curated COSV55969
- V8A (p.Val8Ala), Ensembl rs2126882981
- V8E (p.Val8Glu), Ensembl rs2126882981
- V8L (p.Val8Leu), Ensembl rs1737992105, NCI-TCGA Cosmic COSV9989, NCI-TCGA Cosmic COSV9990, cosmic curated COSV99900, REVEL 0.13, CADD 21.40, Variant assessed as somatic; moderate impact.
- V8M (p.Val8Met), NCI-TCGA Cosmic COSV9989, cosmic curated COSV99898, NCI-TCGA Cosmic COSV9990, Variant assessed as somatic; moderate impact.
- G9A (p.Gly9Ala), Ensembl rs1737991343
- G9C (p.Gly9Cys), Ensembl rs1560865017
- G9D (p.Gly9Asp), Ensembl rs1737991343
- G9R (p.Gly9Arg), Ensembl rs1560865017
- G9S (p.Gly9Ser), rs1560865017, NCI-TCGA Cosmic COSV9990, cosmic curated COSV99900, Ensembl rs1560865017, REVEL 0.31, CADD 25.70, Variant assessed as somatic; moderate impact.
- G9V (p.Gly9Val), Ensembl rs1737991343
- S10C (p.Ser10Cys), Ensembl rs2126882906
- S10N (p.Ser10Asn), Ensembl rs2126882888, Uncertain significance, Inborn genetic diseases
- S10R (p.Ser10Arg), gnomAD rs1456547174, REVEL 0.26, CADD 26.30
- S10T (p.Ser10Thr), Ensembl rs2126882888
- K11E (p.Lys11Glu), rs1737990894, ClinGen CA358620849, ClinVar RCV003404806, TOPMed rs1737990894, REVEL 0.10, CADD 23.80, Uncertain significance, not specified
- K11I (p.Lys11Ile), Ensembl rs2126882849
- K11N (p.Lys11Asn), Ensembl rs2126882840
- K11R (p.Lys11Arg), cosmic curated COSV55968
- R12* (p.Arg12Ter), Ensembl rs2126882821
- R12G (p.Arg12Gly), Ensembl rs2126882821
- R12I (p.Arg12Ile), cosmic curated COSV10438
- R12S (p.Arg12Ser), TOPMed rs1182094162, gnomAD rs1182094162
- R13* (p.Arg13Ter), rs781123562, ClinGen CA108595474, NCI-TCGA Cosmic COSV5591, cosmic curated COSV55916, CADD 36.00, Uncertain significance
- R13G (p.Arg13Gly), gnomAD rs781123562, Uncertain significance
- R13L (p.Arg13Leu), cosmic curated COSV55938, TOPMed rs1471232420, gnomAD rs1471232420, REVEL 0.30, CADD 26.80
- R13P (p.Arg13Pro), TOPMed rs1471232420, gnomAD rs1471232420
- R13Q (p.Arg13Gln), TOPMed rs1471232420, gnomAD rs1471232420, REVEL 0.25, CADD 27.00, Uncertain significance, Inborn genetic diseases
- R14* (p.Arg14Ter), rs1362274408, NCI-TCGA Cosmic COSV5592, cosmic curated COSV55920, gnomAD rs1362274408, CADD 36.00, Variant assessed as somatic; high impact.
- R14G (p.Arg14Gly), gnomAD rs1362274408
- R14P (p.Arg14Pro), ESP rs200698994, ExAC rs200698994, TOPMed rs200698994, gnomAD rs200698994
- R14Q (p.Arg14Gln), rs200698994, cosmic curated COSV55903, ESP rs200698994, ExAC rs200698994, REVEL 0.08, CADD 23.70, Variant assessed as somatic; moderate impact.
- T15I (p.Thr15Ile), Ensembl rs1737989109
- T15P (p.Thr15Pro), Ensembl rs2126882726
- T15S (p.Thr15Ser), Ensembl rs1737989109
- G16* (p.Gly16Ter), Ensembl rs2126882672
- G16A (p.Gly16Ala), Ensembl rs2126882652
- G16E (p.Gly16Glu), Ensembl rs2126882652
- G16R (p.Gly16Arg), Ensembl rs2126882672
- G16V (p.Gly16Val), Ensembl rs2126882652
- G17A (p.Gly17Ala), Ensembl rs2126882616
- G17C (p.Gly17Cys), Ensembl rs2126882637
- G17D (p.Gly17Asp), cosmic curated COSV10874, Ensembl rs2126882616
- G17R (p.Gly17Arg), Ensembl rs2126882637
- G17V (p.Gly17Val), Ensembl rs2126882616
- S18C (p.Ser18Cys), ExAC rs778748560, TOPMed rs778748560, gnomAD rs778748560, REVEL 0.13, CADD 24.20
- S18F (p.Ser18Phe), ExAC rs778748560, TOPMed rs778748560, gnomAD rs778748560, REVEL 0.18, CADD 24.40
- S18T (p.Ser18Thr), Ensembl rs2126882583
- S18Y (p.Ser18Tyr), ExAC rs778748560, TOPMed rs778748560, gnomAD rs778748560
- L19M (p.Leu19Met), Ensembl rs2126882530
- L19Q (p.Leu19Gln), Ensembl rs2126882506
- L19V (p.Leu19Val), Ensembl rs2126882530
- R20* (p.Arg20Ter), 1000Genomes rs115679616, ESP rs115679616, ExAC rs115679616, TOPMed rs115679616
- R20G (p.Arg20Gly), rs115679616, ClinGen CA159656, ClinVar RCV000121057, ClinVar RCV006612226, REVEL 0.30, CADD 23.10, Likely benign, not provided
- R20I (p.Arg20Ile), cosmic curated COSV99905
- R20S (p.Arg20Ser), Ensembl rs2126882460, REVEL 0.32, CADD 24.00
- G21C (p.Gly21Cys), cosmic curated COSV10940, Ensembl rs2126882443, REVEL 0.27, CADD 24.00
- G21D (p.Gly21Asp), 1000Genomes rs548137658, ExAC rs548137658, TOPMed rs548137658, gnomAD rs548137658, REVEL 0.23, CADD 23.30
- G21R (p.Gly21Arg), Ensembl rs2126882443
- G21S (p.Gly21Ser), Ensembl rs2126882443, REVEL 0.19, CADD 23.40
- N22D (p.Asn22Asp), Ensembl rs2126882395
- N22I (p.Asn22Ile), Ensembl rs2126882378
- N22S (p.Asn22Ser), Ensembl rs2126882378
- N22Y (p.Asn22Tyr), Ensembl rs2126882395
- P23A (p.Pro23Ala), Ensembl rs2126882353
- P23H (p.Pro23His), cosmic curated COSV10957, Ensembl rs2126882336
- P23L (p.Pro23Leu), Ensembl rs2126882336, REVEL 0.06, CADD 23.80
- P23R (p.Pro23Arg), Ensembl rs2126882336
- P23S (p.Pro23Ser), cosmic curated COSV99906, Ensembl rs2126882353
- P23T (p.Pro23Thr), Ensembl rs2126882353
- S24F (p.Ser24Phe), cosmic curated COSV10460
- S25* (p.Ser25Ter), cosmic curated COSV10460, cosmic curated COSV55899
- S25P (p.Ser25Pro), Ensembl rs2126882290
- S25T (p.Ser25Thr), Ensembl rs2126882290
- S26C (p.Ser26Cys), Ensembl rs2126882259
- S26G (p.Ser26Gly), Ensembl rs2126882259
- S26I (p.Ser26Ile), Ensembl rs2126882240, REVEL 0.18, CADD 23.30
- S26N (p.Ser26Asn), Ensembl rs2126882240
- S26R (p.Ser26Arg), ESP rs376591844, TOPMed rs376591844, gnomAD rs376591844, REVEL 0.13, CADD 23.50
- S26T (p.Ser26Thr), Ensembl rs2126882240
- Q27* (p.Gln27Ter), cosmic curated COSV10515, Ensembl rs2126882204
- Q27E (p.Gln27Glu), Ensembl rs2126882204
- Q27H (p.Gln27His), Ensembl rs2126882184
- Q27R (p.Gln27Arg), rs1019191519, ClinGen CA108595471, ClinVar RCV003367541, gnomAD rs1019191519, REVEL 0.12, CADD 22.90, Uncertain significance, Inborn genetic diseases
- V28A (p.Val28Ala), Ensembl rs2126882165
- V28E (p.Val28Glu), NCI-TCGA TCGA novel, Ensembl rs2126882165, Variant assessed as somatic; moderate impact.
- V28G (p.Val28Gly), Ensembl rs2126882165
- V28I (p.Val28Ile), Ensembl rs2126882174, REVEL 0.11, CADD 9.11
- V28L (p.Val28Leu), Ensembl rs2126882174
- D29E (p.Asp29Glu), gnomAD rs1357003997
- D29H (p.Asp29His), Ensembl rs2126882144
- D29N (p.Asp29Asn), Ensembl rs2126882144, REVEL 0.13, CADD 23.60
- D29V (p.Asp29Val), Ensembl rs2126882134
- E30* (p.Glu30Ter), 1000Genomes rs535906025, ExAC rs535906025, gnomAD rs535906025
- E30K (p.Glu30Lys), 1000Genomes rs535906025, ExAC rs535906025, gnomAD rs535906025, REVEL 0.14, CADD 24.00
- E30Q (p.Glu30Gln), 1000Genomes rs535906025, ExAC rs535906025, gnomAD rs535906025
- E30V (p.Glu30Val), Ensembl rs2126882089
- E31* (p.Glu31Ter), Ensembl rs2126882047
- E31D (p.Glu31Asp), Ensembl rs1009097309
- E31K (p.Glu31Lys), Ensembl rs2126882047
- E31Q (p.Glu31Gln), Ensembl rs2126882047
- Q32* (p.Gln32Ter), TOPMed rs1737985356
- Q32E (p.Gln32Glu), TOPMed rs1737985356
- Q32H (p.Gln32His), Ensembl rs2126881987, REVEL 0.05, CADD 19.80
- Q32K (p.Gln32Lys), TOPMed rs1737985356, Uncertain significance, not provided
- Q32R (p.Gln32Arg), TOPMed rs1737985112
- M33I (p.Met33Ile), Ensembl rs2126881955, NCI-TCGA Cosmic COSV5597, cosmic curated COSV55975, Variant assessed as somatic; moderate impact.
- M33K (p.Met33Lys), Ensembl rs2126881967
- M33L (p.Met33Leu), Ensembl rs2126881975
- M33R (p.Met33Arg), Ensembl rs2126881967
- M33V (p.Met33Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- N34D (p.Asn34Asp), Ensembl rs2126881945
- N34I (p.Asn34Ile), Ensembl rs2126881925
- N34K (p.Asn34Lys), 1000Genomes rs192773704, ESP rs192773704, ExAC rs192773704, TOPMed rs192773704
- N34S (p.Asn34Ser), Ensembl rs2126881925
- N34T (p.Asn34Thr), Ensembl rs2126881925
- N34Y (p.Asn34Tyr), Ensembl rs2126881945, REVEL 0.20, CADD 25.40
- R35C (p.Arg35Cys), rs751626529, NCI-TCGA Cosmic COSV5592, cosmic curated COSV55929, ExAC rs751626529, REVEL 0.20, CADD 27.90, Variant assessed as somatic; moderate impact.
- R35G (p.Arg35Gly), ExAC rs751626529, TOPMed rs751626529, gnomAD rs751626529
- R35H (p.Arg35His), cosmic curated COSV55903, 1000Genomes rs199629238, ExAC rs199629238, TOPMed rs199629238, REVEL 0.16, CADD 24.10, Uncertain significance, not provided
- R35L (p.Arg35Leu), NCI-TCGA Cosmic COSV5590, NCI-TCGA Cosmic COSV9990, cosmic curated COSV99906, 1000Genomes rs199629238, Variant assessed as somatic; moderate impact.
- R35P (p.Arg35Pro), 1000Genomes rs199629238, ExAC rs199629238, TOPMed rs199629238, gnomAD rs199629238, REVEL 0.29, CADD 24.10
- R35S (p.Arg35Ser), ExAC rs751626529, TOPMed rs751626529, gnomAD rs751626529
- V36A (p.Val36Ala), Ensembl rs2126881819
- V36E (p.Val36Glu), Ensembl rs2126881819
- V36G (p.Val36Gly), Ensembl rs2126881819
- V36L (p.Val36Leu), Ensembl rs2126881840, REVEL 0.22, CADD 24.90
- V36M (p.Val36Met), Ensembl rs2126881840
- E38* (p.Glu38Ter), cosmic curated COSV10726, Ensembl rs2126881789
- E38A (p.Glu38Ala), ExAC rs758603153, TOPMed rs758603153, gnomAD rs758603153, REVEL 0.22, CADD 23.80
- E38D (p.Glu38Asp), TOPMed rs1026105131
- E38G (p.Glu38Gly), ExAC rs758603153, TOPMed rs758603153, gnomAD rs758603153, REVEL 0.25, CADD 24.80
- E38K (p.Glu38Lys), Ensembl rs2126881789
- E38Q (p.Glu38Gln), Ensembl rs2126881789
- E39* (p.Glu39Ter), cosmic curated COSV55919, gnomAD rs1382805117
- E39D (p.Glu39Asp), ExAC rs750669133, TOPMed rs750669133, gnomAD rs750669133, cosmic curated COSV10940
- E39G (p.Glu39Gly), TOPMed rs1036262056, gnomAD rs1036262056, REVEL 0.16, CADD 24.50
- E39K (p.Glu39Lys), gnomAD rs1382805117, REVEL 0.19, CADD 23.80
- E39Q (p.Glu39Gln), gnomAD rs1382805117
- E40* (p.Glu40Ter), gnomAD rs1462136302
- E40A (p.Glu40Ala), Ensembl rs2126881680, CADD 21.40
- E40D (p.Glu40Asp), Ensembl rs1737982766, CADD 20.90
- E40G (p.Glu40Gly), Ensembl rs2126881680
- E40K (p.Glu40Lys), gnomAD rs1462136302, CADD 20.50
- E40Q (p.Glu40Gln), gnomAD rs1462136302, CADD 20.10
- E40V (p.Glu40Val), Ensembl rs2126881680
- Q41* (p.Gln41Ter), Ensembl rs2126881635, CADD 19.70
- Q41E (p.Gln41Glu), Ensembl rs2126881635
- Q41H (p.Gln41His), Ensembl rs2126881576, CADD 17.30
- Q41L (p.Gln41Leu), Ensembl rs2126881615
- Q41R (p.Gln41Arg), Ensembl rs2126881615, CADD 20.60
- Q42* (p.Gln42Ter), ExAC rs765487207, gnomAD rs765487207
- Q42E (p.Gln42Glu), ExAC rs765487207, gnomAD rs765487207, REVEL 0.10, CADD 23.30
- Q42H (p.Gln42His), Ensembl rs2126881525
- Q42K (p.Gln42Lys), ExAC rs765487207, gnomAD rs765487207
- Q42P (p.Gln42Pro), Ensembl rs2126881555
- Q42R (p.Gln42Arg), Ensembl rs2126881555
- Q43* (p.Gln43Ter), cosmic curated COSV55912, Ensembl rs2126881508
Public FBXW7 analysis runs
- FBXW7 analysis run — FBXW7 (3,191 variants) — completed 2026-08-28