TBP (TATA-box-binding protein) variants and mutations
TBP (also known as TATA-box-binding protein) is a human protein-coding gene encoding a TATA-box-binding protein. It binds TATA and related promoter elements as a core component of transcription-initiation complexes used by all three nuclear RNA polymerases. Expansion of its polyglutamine tract causes spinocerebellar ataxia type 17 with progressive ataxia, cognitive and psychiatric symptoms, and movement abnormalities. This analysis covers 602 TBP variants and mutations. Of these, 73% have computational variant effect predictions. Disease context includes spinocerebellar ataxia type 17, HIV infectious disease, and neurodegenerative disease. Example TBP variants include M1?, D2E, and D2N.
Variant analysis overview
- Gene: TBP
- Protein: TATA-box-binding protein
- UniProt accession: P20226
- Organism: Homo sapiens
- Variants analyzed: 602
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 315 unspecified-consequence records; 73 missense variants; 112 synonymous variants; 54 frameshift variants; 5 stop-gained variants; 31 in-frame deletions; 11 in-frame insertions; 1 substitution
- Prediction scores: 442 variants have prediction scores (73% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: spinocerebellar ataxia type 17, HIV infectious disease, neurodegenerative disease, alcohol drinking, Parkinson disease, late-onset Parkinson disease, Hereditary late-onset Parkinson disease, hereditary disease, neoplasm, hepatocellular carcinoma, genetic developmental and epileptic encephalopathy, depressive disorder.
Protein structure and variant hotspots
- Protein features: 5 binding 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 TBP variants
Examples include M1?, D2E, D2N, Q3P, Q3R, N5D, N5S, S6C. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV10002
- D2E (p.Asp2Glu), ExAC rs751702127, gnomAD rs751702127, REVEL 0.20, CADD 17.50
- D2N (p.Asp2Asn), cosmic curated COSV10456
- Q3P (p.Gln3Pro), Ensembl rs1779043167, REVEL 0.22, CADD 24.20
- Q3R (p.Gln3Arg), gnomAD 6-170557037-A-G, REVEL 0.21, CADD 23.90
- N5D (p.Asn5Asp), ExAC rs757450205, gnomAD rs757450205, REVEL 0.08, CADD 22.50
- N5S (p.Asn5Ser), gnomAD 6-170557043-A-G, REVEL 0.23, CADD 13.70
- S6C (p.Ser6Cys), cosmic curated COSV10436
- S6R (p.Ser6Arg), ExAC rs766191843, gnomAD rs766191843, REVEL 0.21, CADD 26.30
- S6N (p.Ser6Asn), gnomAD 6-170557046-G-A, REVEL 0.27, CADD 23.90
- L7L (p.Leu7Leu), rs1779043305, gnomAD 6-170557048-C-T, CADD 9.66
- P8L (p.Pro8Leu), TOPMed rs1009942407, gnomAD rs1009942407, REVEL 0.04, CADD 22.50
- Y10* (p.Tyr10Ter), cosmic curated COSV10002, CADD 24.20
- Y10Y (p.Tyr10Tyr), rs369276648, gnomAD 6-170557059-C-T, CADD 0.93
- A11T (p.Ala11Thr), ExAC rs764142412, TOPMed rs764142412, gnomAD rs764142412, REVEL 0.18, CADD 23.60, Uncertain significance, Inborn genetic diseases
- A11S (p.Ala11Ser), gnomAD 6-170557060-G-T, REVEL 0.20, CADD 22.90
- A11A (p.Ala11Ala), gnomAD 6-170557062-T-C, CADD 7.83
- Q12K (p.Gln12Lys), cosmic curated COSV51530
- Q12P (p.Gln12Pro), Ensembl rs1779043475
- Q12E (p.Gln12Glu), gnomAD 6-170557063-C-G, REVEL 0.10, CADD 17.30
- G13V (p.Gly13Val), gnomAD 6-170557067-G-T, REVEL 0.16, CADD 24.00
- G13G (p.Gly13Gly), gnomAD 6-170557068-C-G, CADD 10.90
- A15T (p.Ala15Thr), cosmic curated COSV10002, REVEL 0.25, CADD 22.20
- A15V (p.Ala15Val), cosmic curated COSV10436
- A15P (p.Ala15Pro), gnomAD 6-170557072-G-C, REVEL 0.15, CADD 23.50
- A15A (p.Ala15Ala), rs778805694, gnomAD 6-170557074-C-A, CADD 9.55
- P17A (p.Pro17Ala), TOPMed rs949315152
- P17H (p.Pro17His), gnomAD 6-170557050-G-GCC, CADD 24.90
- P17P (p.Pro17Pro), rs1186816386, gnomAD 6-170557080-T-C, CADD 8.99
- G19V (p.Gly19Val), gnomAD rs1390001535, REVEL 0.19, CADD 24.10
- G19C (p.Gly19Cys), gnomAD 6-170561791-G-T, REVEL 0.14, CADD 28.00
- A20V (p.Ala20Val), ExAC rs758309293, gnomAD rs758309293, REVEL 0.07, CADD 21.20
- A20G (p.Ala20Gly), gnomAD 6-170561795-C-G, REVEL 0.07, CADD 19.80
- T22I (p.Thr22Ile), cosmic curated COSV57830
- T22T (p.Thr22Thr), rs1165296018, gnomAD 6-170561802-T-C, CADD 9.17
- P23T (p.Pro23Thr), Ensembl rs2114993781
- P23P (p.Pro23Pro), rs777182875, gnomAD 6-170561805-C-G, CADD 7.37
- G24R (p.Gly24Arg), cosmic curated COSV10507, TOPMed rs970666552, gnomAD rs970666552, REVEL 0.10, CADD 22.80
- I25N (p.Ile25Asn), cosmic curated COSV57832
- I25I (p.Ile25Ile), gnomAD 6-170561811-C-T, CADD 8.25
- P26A (p.Pro26Ala), 1000Genomes rs558863660, ExAC rs558863660, gnomAD rs558863660, REVEL 0.04, CADD 21.60
- I27F (p.Ile27Phe), ESP rs150312586, ExAC rs150312586, TOPMed rs150312586, gnomAD rs150312586, REVEL 0.12, CADD 22.90
- I27V (p.Ile27Val), ESP rs150312586, ExAC rs150312586, TOPMed rs150312586, gnomAD rs150312586, REVEL 0.08, CADD 18.40
- I27I (p.Ile27Ile), gnomAD 6-170561817-C-T, CADD 11.30
- F28L (p.Phe28Leu), gnomAD 6-170561820-T-G, REVEL 0.49, CADD 18.90
- F28F (p.Phe28Phe), gnomAD 6-170561820-T-C, CADD 8.18
- M31I (p.Met31Ile), 1000Genomes rs577070091, ExAC rs577070091, TOPMed rs577070091, gnomAD rs577070091, REVEL 0.17, CADD 22.50
- M31V (p.Met31Val), ExAC rs746303115, TOPMed rs746303115, gnomAD rs746303115, REVEL 0.21, CADD 18.10
- M32R (p.Met32Arg), 1000Genomes rs776116052, ExAC rs776116052, REVEL 0.41, CADD 24.10
- M32S (p.Met32Ser), gnomAD 6-170561830-AT-A, CADD 27.50
- M32V (p.Met32Val), gnomAD 6-170561830-A-G, REVEL 0.34, CADD 21.20
- P33L (p.Pro33Leu), cosmic curated COSV57831, REVEL 0.38, CADD 26.00
- P33T (p.Pro33Thr), gnomAD 6-170561833-C-A, REVEL 0.30, CADD 24.60
- P33P (p.Pro33Pro), rs138026963, gnomAD 6-170561835-T-A, CADD 8.31
- Y34C (p.Tyr34Cys), NCI-TCGA Cosmic COSV1000, cosmic curated COSV10002, Variant assessed as somatic; moderate impact.
- Y34F (p.Tyr34Phe), TOPMed rs1394976596, REVEL 0.21, CADD 23.50
- Y34M (p.Tyr34Met), rs749938009, gnomAD 6-170561834-CT-C, CADD 21.20
- Y34Y (p.Tyr34Tyr), gnomAD 6-170561838-T-C, CADD 1.32
- G35V (p.Gly35Val), ExAC rs749788903, gnomAD rs749788903, REVEL 0.72, CADD 27.10
- T36T (p.Thr36Thr), gnomAD 6-170561844-T-A, CADD 2.10
- L38L (p.Leu38Leu), rs191076110, gnomAD 6-170561850-G-A, CADD 9.47
- T39P (p.Thr39Pro), Ensembl rs1583127364
- T39I (p.Thr39Ile), gnomAD 6-170561852-C-T, REVEL 0.47, CADD 23.10
- P40A (p.Pro40Ala), ESP rs375575792, ExAC rs375575792, gnomAD rs375575792
- P40P (p.Pro40Pro), rs1228893947, gnomAD 6-170561856-A-C, CADD 4.21
- I43V (p.Ile43Val), Ensembl rs1779143555, REVEL 0.14, CADD 10.90
- I43I (p.Ile43Ile), gnomAD 6-170561865-T-A, CADD 9.24
- Q44H (p.Gln44His), Ensembl rs1779143652
- Q44P (p.Gln44Pro), ExAC rs761867883, gnomAD rs761867883, REVEL 0.48, CADD 24.10
- Q44R (p.Gln44Arg), cosmic curated COSV57834
- Q44* (p.Gln44Ter), gnomAD 6-170561866-C-T, CADD 36.00
- Q44Q (p.Gln44Gln), gnomAD 6-170561868-G-A, CADD 9.34
- N45S (p.Asn45Ser), cosmic curated COSV10801
- N45N (p.Asn45Asn), rs1459652616, gnomAD 6-170561871-C-T, CADD 10.60
- T46P (p.Thr46Pro), Ensembl rs1779143735
- T46A (p.Thr46Ala), gnomAD 6-170561872-A-G, REVEL 0.09, CADD 19.40
- T46S (p.Thr46Ser), gnomAD 6-170561873-C-G, REVEL 0.07, CADD 16.40
- N47S (p.Asn47Ser), ExAC rs772344160, TOPMed rs772344160, gnomAD rs772344160, REVEL 0.26, CADD 14.30
- N47N (p.Asn47Asn), rs554594365, gnomAD 6-170561877-T-C, CADD 7.37
- S48N (p.Ser48Asn), NCI-TCGA Cosmic COSV1000, cosmic curated COSV10002, TOPMed rs1779143915, gnomAD rs1779143915, REVEL 0.07, CADD 21.90, Variant assessed as somatic; moderate impact.
- S48I (p.Ser48Ile), gnomAD 6-170561879-G-T, REVEL 0.28, CADD 22.80
- L49L (p.Leu49Leu), rs1207784627, gnomAD 6-170561881-C-T, CADD 10.10
- L49R (p.Leu49Arg), gnomAD 6-170561882-T-G, REVEL 0.35, CADD 26.50
- S50F (p.Ser50Phe), gnomAD 6-170561878-AGTCT, CADD 28.90
- S50V (p.Ser50Val), gnomAD 6-170561881-C-CT, CADD 27.80
- S50P (p.Ser50Pro), gnomAD 6-170561884-T-C, REVEL 0.15, CADD 25.30
- I51L (p.Ile51Leu), ExAC rs773389193, TOPMed rs773389193, gnomAD rs773389193, REVEL 0.06, CADD 13.30
- I51V (p.Ile51Val), ExAC rs773389193, TOPMed rs773389193, gnomAD rs773389193, REVEL 0.05, CADD 10.40
- I51I (p.Ile51Ile), rs759374115, gnomAD 6-170561889-T-C, CADD 5.59
- L52L (p.Leu52Leu), gnomAD 6-170561892-G-A, CADD 10.90
- E54K (p.Glu54Lys), rs1190072930, NCI-TCGA Cosmic COSV1000, cosmic curated COSV10002, NCI-TCGA Cosmic COSV5783, REVEL 0.40, CADD 23.50, Variant assessed as somatic; moderate impact.
- E54Q (p.Glu54Gln), cosmic curated COSV57833
- E54E (p.Glu54Glu), rs1178590548, gnomAD 6-170561898-G-A, CADD 1.89
- Q55* (p.Gln55Ter), NCI-TCGA TCGA novel, CADD 34.00, Variant assessed as somatic; high impact.
- R57S (p.Arg57Ser), gnomAD 6-170561901-A-ACA, CADD 23.20
- R57K (p.Arg57Lys), gnomAD 6-170561906-G-A, REVEL 0.17, CADD 17.30
- Q58L (p.Gln58Leu), ExAC rs764966099, TOPMed rs764966099, gnomAD rs764966099, REVEL 0.04, CADD 22.20
- Q58R (p.Gln58Arg), ExAC rs764966099, TOPMed rs764966099, gnomAD rs764966099, REVEL 0.04, CADD 20.80
- Q59* (p.Gln59Ter), gnomAD 6-170561911-C-T, CADD 35.00
- Q59R (p.Gln59Arg), gnomAD 6-170561911-CA-C, CADD 25.20
- Q59P (p.Gln59Pro), gnomAD 6-170561912-A-C, REVEL 0.12, CADD 22.90
- Q59Q (p.Gln59Gln), gnomAD 6-170561913-G-A, CADD 8.23
- Q59H (p.Gln59His), gnomAD 6-170561913-G-T, REVEL 0.14, CADD 22.90
- Q60H (p.Gln60His), ExAC rs752498284
- Q60Q (p.Gln60Gln), rs752498284, gnomAD 6-170561916-G-A, CADD 7.24
- Q61H (p.Gln61His), cosmic curated COSV57833
- Q61Q (p.Gln61Gln), rs541359952, gnomAD 6-170561919-A-G, CADD 2.28
- Q62H (p.Gln62His), 1000Genomes rs559386285, gnomAD rs559386285, REVEL 0.14, CADD 17.20, Uncertain significance, Inborn genetic diseases
- Q62R (p.Gln62Arg), gnomAD 6-170561915-A-AGC, CADD 24.90
- Q62A (p.Gln62Ala), gnomAD 6-170561919-A-AG, CADD 23.30
- Q62Q (p.Gln62Gln), rs559386285, gnomAD 6-170561922-A-G, CADD 4.11
- Q63* (p.Gln63Ter), gnomAD rs1215217094, CADD 32.00
- Q63Q (p.Gln63Gln), rs574714675, gnomAD 6-170561925-A-G, CADD 0.73
- Q64H (p.Gln64His), cosmic curated COSV57832
- Q64K (p.Gln64Lys), Ensembl rs1779146023
- Q64R (p.Gln64Arg), Ensembl rs1779146689
- Q64A (p.Gln64Ala), rs1562359375, gnomAD 6-170561925-A-AG, CADD 22.80
- Q64Q (p.Gln64Gln), rs542031948, gnomAD 6-170561928-G-A, CADD 1.95
- Q65Q (p.Gln65Gln), rs935523115, gnomAD 6-170561931-G-A, CADD 1.79
- Q66R (p.Gln66Arg), Ensembl rs1779147170
- Q66Q (p.Gln66Gln), rs1779147219, gnomAD 6-170561934-G-A, CADD 0.83
- Q67H (p.Gln67His), 1000Genomes rs563388884, gnomAD rs563388884, REVEL 0.28, CADD 8.67
- Q67R (p.Gln67Arg), rs762804204, ClinGen CA4108280, ClinVar RCV002697998, ExAC rs762804204, REVEL 0.21, CADD 13.70, Uncertain significance, Inborn genetic diseases
- Q67Q (p.Gln67Gln), rs563388884, gnomAD 6-170561937-G-A, CADD 0.85
- p.Gln68 Gln95del, gnomAD 6-170561906-GGCAG, CADD 16.30
- Q69A (p.Gln69Ala), rs1491092074, gnomAD 6-170561939-AGC-A, CADD 18.50
- Q69H (p.Gln69His), gnomAD 6-170561942-AGCAG, CADD 25.70
- Q69Q (p.Gln69Gln), rs1383672526, gnomAD 6-170561943-G-A, CADD 1.62
- Q70A (p.Gln70Ala), gnomAD 6-170561942-AGC-A, CADD 18.40
- p.Gln70 Gln71insLeu, rs1416336210, gnomAD 6-170561945-A-AGC, CADD 5.12
- Q70H (p.Gln70His), gnomAD 6-170561945-AG-A, CADD 14.10
- Q70Q (p.Gln70Gln), rs878924202, gnomAD 6-170561946-G-A, CADD 1.14
- Q71P (p.Gln71Pro), gnomAD rs1331989064
- p.Gln71 Gln95del, gnomAD 6-170561925-ACAGC, CADD 15.40
- Q71A (p.Gln71Ala), rs1491456401, gnomAD 6-170561945-AGC-A, CADD 19.40
- Q71H (p.Gln71His), rs1419176062, gnomAD 6-170561948-AGCAA, CADD 25.80
- Q71Q (p.Gln71Gln), rs915011520, gnomAD 6-170561949-G-A, CADD 1.88
- Q72H (p.Gln72His), Ensembl rs55736770, Uncertain significance, Inborn genetic diseases
- p.Gln72 Gln95del, gnomAD 6-170561925-ACAGC, CADD 15.40
- p.Gln72 Gln73insTer, gnomAD 6-170561950-C-CAG, CADD 22.90
- Q72Q (p.Gln72Gln), rs55736770, gnomAD 6-170561952-A-G, CADD 3.52
- Q73* (p.Gln73Ter), gnomAD rs1410409146
- Q73E (p.Gln73Glu), gnomAD rs1410409146
- Q73H (p.Gln73His), ExAC rs764035011, gnomAD rs764035011, REVEL 0.05, CADD 8.96
- Q73R (p.Gln73Arg), Ensembl rs1229412131
- p.Gln73 Gln95del, gnomAD 6-170561925-ACAGC, CADD 15.40
- Q73A (p.Gln73Ala), gnomAD 6-170561952-A-AGC, CADD 19.50
- Q73S (p.Gln73Ser), rs1562359486, gnomAD 6-170561952-A-AT, CADD 19.90
- Q73T (p.Gln73Thr), rs1562359486, gnomAD 6-170561952-A-AAC, CADD 19.80
- Q73Q (p.Gln73Gln), rs764035011, gnomAD 6-170561955-G-A, CADD 2.40
- Q74* (p.Gln74Ter), Ensembl rs1779150136, CADD 32.00
- Q74H (p.Gln74His), gnomAD rs62430309, REVEL 0.10, CADD 10.90, Likely benign
- Q74R (p.Gln74Arg), Ensembl rs1779150300
- p.Gln74 Gln95del, rs1562359336, gnomAD 6-170561906-GGCAG, CADD 16.00
- Q74Q (p.Gln74Gln), rs62430309, gnomAD 6-170561958-A-G, CADD 3.89
- Q75H (p.Gln75His), ExAC rs56241301, gnomAD rs56241301
- Q75L (p.Gln75Leu), Ensembl rs1197414368
- p.Gln75 Gln95del, rs1779144969, gnomAD 6-170561906-GGCAG, CADD 16.00
- Q75A (p.Gln75Ala), rs1779150506, gnomAD 6-170561958-A-AGC, CADD 20.60
- Q75T (p.Gln75Thr), gnomAD 6-170561958-A-AAC, CADD 20.90
- Q75R (p.Gln75Arg), rs1348161234, gnomAD 6-170561959-CA-C, CADD 21.20
- Q75Q (p.Gln75Gln), rs56241301, gnomAD 6-170561961-G-A, CADD 2.85
- p.Gln75 Gln76insLys, gnomAD 6-170561961-G-GAA, CADD 7.87
- Q76H (p.Gln76His), ExAC rs112083427, gnomAD rs112083427, REVEL 0.09, CADD 10.40, Uncertain significance
- Q76R (p.Gln76Arg), Ensembl rs1336548568
- p.Gln76 Gln95del, rs1779146639, gnomAD 6-170561925-ACAGC, CADD 15.40
- Q76A (p.Gln76Ala), rs1491171766, gnomAD 6-170561960-AGC-A, CADD 21.30
- p.Gln76 Gln77insTer, gnomAD 6-170561962-C-CAA, CADD 23.20
- Q76P (p.Gln76Pro), gnomAD 6-170561962-CAG-C, CADD 21.60
- Q76Q (p.Gln76Gln), rs112083427, gnomAD 6-170561964-G-A, CADD 3.06
- Q77* (p.Gln77Ter), gnomAD rs1346721481
- Q77K (p.Gln77Lys), gnomAD rs1346721481
- p.Gln77 Gln95del, gnomAD 6-170561906-GGCAG, CADD 15.20
- Q77A (p.Gln77Ala), rs1491487452, gnomAD 6-170561963-AGC-A, CADD 24.50
- Q77S (p.Gln77Ser), gnomAD 6-170561964-GC-G, CADD 24.50
- Q77R (p.Gln77Arg), gnomAD 6-170561965-CA-C, CADD 26.00
- Q77H (p.Gln77His), rs1779153082, gnomAD 6-170561966-AGCAG, CADD 26.00
- p.Gln77 Gln78insTrp, gnomAD 6-170561966-A-AGT, CADD 16.70
- Q77Q (p.Gln77Gln), rs112928724, gnomAD 6-170561967-G-A, CADD 7.46
- Q78* (p.Gln78Ter), gnomAD rs1198340310
Public TBP analysis runs
- TBP analysis run — TBP (602 variants) — completed 2026-08-22