TBP

Summary

TBP (TATA-box binding protein, HGNC:11588) is a protein-coding gene on chromosome 6q27, encoding TATA-box-binding protein (P20226). The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription. It is a selective cancer dependency (DepMap: 78.6% of cell lines).

Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes TBP, the TATA-binding protein. A distinctive feature of TBP is a long string of glutamines in the N-terminus. This region of the protein modulates the DNA binding activity of the C terminus, and modulation of DNA binding affects the rate of transcription complex formation and initiation of transcription. The number of CAG repeats encoding the polyglutamine tract is usually 25-42, and expansion of the number of repeats to 45-66 increases the length of the polyglutamine string and is associated with spinocerebellar ataxia 17, a neurodegenerative disorder classified as a polyglutamine disease. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6908 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinocerebellar ataxia type 17 (Definitive, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 53 total — 2 pathogenic
• Phenotypes (HPO): 68
• Cancer dependency (DepMap): dependent in 78.6% of screened cell lines
• Transcription factor: yes — 223 downstream targets (CollecTRI)
• MANE Select transcript: NM_003194

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11588
Approved symbol	TBP
Name	TATA-box binding protein
Location	6q27
Locus type	gene with protein product
Status	Approved
Aliases	TFIID, TBP1
Ensembl gene	ENSG00000112592
Ensembl biotype	protein_coding
OMIM	600075
Entrez	6908

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 nonsense_mediated_decay

ENST00000230354, ENST00000392092, ENST00000421512, ENST00000423353, ENST00000446829, ENST00000540980, ENST00000636632, ENST00000944453, ENST00000944454

RefSeq mRNA: 2 — MANE Select: NM_003194 NM_001172085, NM_003194

CCDS: CCDS5315, CCDS55077

Canonical transcript exons

ENST00000392092 — 8 exons

Exon	Start	End
ENSE00001593404	170569612	170569779
ENSE00001773146	170571410	170571504
ENSE00003842256	170554369	170554463
ENSE00003843281	170572186	170572859
ENSE00003889293	170556882	170557083
ENSE00003889315	170566918	170567009
ENSE00003889953	170564545	170564632
ENSE00003893949	170561791	170562233

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 90.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.3959 / max 217.0966, expressed in 1818 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71303	20.3859	1813
71302	1.3384	793
71304	1.1386	716
71307	0.2931	116
71301	0.1687	84
71306	0.0367	7
71305	0.0346	5

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	90.31	gold quality
right testis	UBERON:0004534	90.10	gold quality
testis	UBERON:0000473	89.66	gold quality
oocyte	CL:0000023	89.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.68	gold quality
granulocyte	CL:0000094	86.80	gold quality
sperm	CL:0000019	86.60	silver quality
secondary oocyte	CL:0000655	86.28	gold quality
adult organism	UBERON:0007023	86.15	gold quality
mucosa of transverse colon	UBERON:0004991	86.01	gold quality
middle temporal gyrus	UBERON:0002771	85.88	gold quality
cortical plate	UBERON:0005343	85.69	gold quality
sural nerve	UBERON:0015488	85.68	gold quality
spleen	UBERON:0002106	85.65	gold quality
right uterine tube	UBERON:0001302	85.18	gold quality
ovary	UBERON:0000992	85.02	gold quality
male germ cell	CL:0000015	85.00	silver quality
cerebellar hemisphere	UBERON:0002245	84.98	gold quality
left ovary	UBERON:0002119	84.97	gold quality
muscle layer of sigmoid colon	UBERON:0035805	84.91	gold quality
cerebellar cortex	UBERON:0002129	84.90	gold quality
body of pancreas	UBERON:0001150	84.75	gold quality
tibia	UBERON:0000979	84.74	gold quality
mucosa of stomach	UBERON:0001199	84.73	gold quality
right ovary	UBERON:0002118	84.68	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.56	gold quality
body of uterus	UBERON:0009853	84.51	gold quality
left uterine tube	UBERON:0001303	84.48	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.46	gold quality
ganglionic eminence	UBERON:0004023	84.44	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.60

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

223 targets.

Target	Regulation
ABCB1
ACHE
ACTA1
ACTB
ACTC1
ADAM2
ADH1A
ADH1B
ADH1C
ADH4
ADRA1D
AFM
AFP
AGTR2
AKT1
ANK1
APP	Unknown
AURKA
BCL2	Repression
BDKRB1	Unknown
BDP1
BGLAP
BRF1
BRF2
BTAF1
BTK
C4B
CAMK4
CCNA2
CCNB1	Unknown

JASPAR motifs

Motif	Name	Family
MA0108.2	TBP	TBP-related factors
MA0108.3	TBP	TBP-related factors

JASPAR matrix evidence (PMIDs): PMID:2329577

Upstream regulators (CollecTRI, top): AP1, AR, ARID3B, BTAF1, CDX1, CREM, DR1, DRAP1, ELK1, GTF2A1, HNF4A, MAFB, NFKB1, ONECUT1, RELA, TAF1, TBP, TBPL2, TP53, ZBED1, ZNF76

miRNA regulators (miRDB)

69 targeting TBP, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 78.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• constitutive association of TBP with mitotic chromosomes (PMID:11809839)
• TBP can bind the TATA box through a regulated two-step mechanism, involving a transition from unbent complex to bent complex (PMID:11893333)
• Developmental specificity of recruitment of TBP to the TATA box of the human gamma-globin gene (PMID:11960008)
• Human papillomavirus-16 E7 protein inhibits the DNA interaction of the TATA binding transcription factor. (PMID:11968006)
• Data show that TATA-binding protein labelling was relatively more abundant than huntingtin labelling in the brains of Huntington disease patients, and increased with the grade of the disease. (PMID:12531510)
• Data show that human TATA box binding protein (TBP) can use a shared surface to interact with two different transcription factor IIB (TFIIB) family members to initiate transcription by different RNA polymerases. (PMID:12535529)
• spatial positioning of the DNA-bound activation domain is important for efficient activation, possibly by maximizing its interactions with the transcriptional machinery including the TBP-TFIIA-TFIIB-promoter quaternary complex (PMID:12538582)
• TBP expression is elevated in human colon carcinomas relative to normal colon epithelium. Both Ras-dependent and Ras-independent mechanisms mediate increases in TBP expression in colon carcinoma cell lines. (PMID:12697807)
• Sequence-dependent solution structure and motions of TBP complexes were studied. (PMID:12767124)
• simultaneously binds and bends promoter DNA without a slow isomerization step or TFIIB requirement (PMID:12791683)
• Our data provides biochemical evidence that Mediator functions by facilitating activator-mediated recruitment of pol II and also promoter recognition by TBP, both of which can occur in the absence of TBP-associated factors in TFIID (PMID:12917344)
• p300 plays a role in formation of the TBP-TFIIA-containing basal transcription complex, TAC. (PMID:12941701)
• Results present the X-ray structures of human and yeast TATA box-binding protein /transcription factor IIA/DNA complexes at 2.1A and 1.9A resolution, respectively. (PMID:12972251)
• in addition to its role in regulating TBP binding to a TATA box, the TBP surface is unexpectedly involved in TBP association with all three TFIIB family members (PMID:14585974)
• abnormal expansions of an allele in SCA8 and SCA17 genes were detected in patients with both Parkinson’s disease and spinocerebellar ataxia (PMID:14756671)
• Analysis of Spinocerebellar ataxia type 17 (SCA17) locus in a group of ataxic patients excluded on other known SCAs. (PMID:14763955)
• We report on the clinical manifestation of spinocerebellar ataxia 17 (SCA17) in 3 members of a German family, in whom the pathological repeat expansion in the TATA-binding protein gene ranged from 53 to 55 repeats (PMID:14978680)
• genotype-phenotype correlations in white patients with Huntington’s disease-like phenotype (PMID:14985389)
• Data suggest that the accumulation or misfolding of the polyQ-containing TATA binding protein may be a contributing factor in Alzheimer’s disease. (PMID:15193429)
• TBP binds to ZNF76, allowing it to function as a transcriptional repressor (PMID:15280358)
• the function of NRL-MTD is to activate transcription by recruiting or stabilizing TBP (and consequently other components of the general transcription complex) at the promoter of target genes (PMID:15328344)
• physical cooperation between BTAF1 and NC2alpha in TBP regulation (PMID:15509807)
• an induced-fit mechanism gives structure to the glucocorticoid receptor AF1 domain when it encounters TATA box binding protein (PMID:15545613)
• NC2 controls TBP binding and maintenance on DNA that is largely independent of a canonical TATA sequence (PMID:15574413)
• results show that HSV-1 infection has no influence on the protein levels of TFIID components and leads to a redistribution of TBP and TBP-associated factors to prereplicative sites that enlarge to viral DNA replication compartments (PMID:16271277)
• TBP-GR interaction is functionally significant (PMID:16469772)
• A pathological CAG/CAA expansion in the TATA-binding protein gene (SCA17) is indicative of spinocerebellar ataxia. (PMID:16532453)
• The most common TBP allele in humans (37 repeats) is close to the threshold value upon which neurodegenerative changes can occur and may act as a repository for expanded, pathogenic alleles (PMID:17033685)
• JNK1 and JNK2 differentially regulate TBP through Elk-1, controlling c-Jun expression and cell proliferation (PMID:17074809)
• Case of spinocerebellar ataxia type 17 (SCA17) associated with only 41 repeats of the TATA-binding protein (TBP) gene. (PMID:17149738)
• We identified three SCA17 families with expansion of uninterrupted alleles. We found that uninterrupted SCA17 alleles are unstable, associated with anticipation, and show a paternal expansion bias that increases with age. (PMID:17474109)
• Changes in Maf1 expression affect Pol I- and Pol III-dependent transcription. These effects are mediated, in part, through the ability of Maf1 to repress transcription of the TATA binding protein, TBP. (PMID:17499043)
• TFIIA induces a conformational change within the TBP/TATA complex that enhances its stability under both in vitro and physiological salt conditions. (PMID:17681538)
• Several oculomotor deficits of spinocerebellar ataxia type 17 (SCA17) mutation carriers are compatible with cerebellar degeneration. (PMID:17846415)
• The autosomal dominantly inherited progressive neurodegenerative disorder is caused by an expanded CAA/CAG repeat in the TATA-box binding protein (PMID:17853080)
• The cell cycle regulation by vaccinia virus is correlated with the inactivation of p53 and Rb, which are associated with the RNA polymerase III transcription factor B (TFIIIB) subunits, TBP and Brf1 respectively. (PMID:17877750)
• The study of this clinical data confirm the large variability in SCA17 phenotypic presentation, and indicate that a peculiar combination of neuroradiological, electrophysiological and oculomotor findings is recognizable in SCA17. (PMID:17934876)
• findings suggest that the polyQ tract affects the binding of TBP to promoter DNA and that polyQ-expanded TBP can induce neuronal toxicity independent of its interaction with DNA (PMID:18218637)
• TAF7 interacts with the transcription factors, TFIIH and P-TEFb, resulting in the inhibition of their Pol II CTD kinase activities (PMID:18391197)
• Tata box bindin protein mutation in Spinocerebellar ataxia 17 is found in spinocerebellar ataxis 17 and in other polyglutamine-related diseases, suggesting transcription down regulation. (PMID:18418687)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbp	ENSDARG00000014994
mus_musculus	Tbp	ENSMUSG00000014767
rattus_norvegicus	Tbp	ENSRNOG00000001489

Paralogs (2): TBPL1 (ENSG00000028839), TBPL2 (ENSG00000182521)

Protein

Protein identifiers

TATA-box-binding protein — P20226 (reviewed: P20226)

Alternative names: TATA sequence-binding protein, TATA-binding factor, TATA-box factor, Transcription initiation factor TFIID TBP subunit

All UniProt accessions (5): A0A1B0GVC6, P20226, H0Y6D8, Q7Z6S4, Q7Z6S5

UniProt curated annotations — full annotation on UniProt →

Function. The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription. TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. The TFIID complex structure can be divided into 3 modules TFIID-A, TFIID-B, and TFIID-C. TBP forms the TFIID-A module together with TAF3 and TAF5. TBP is a general transcription factor that functions at the core of the TFIID complex. During assembly of the core PIC on the promoter, as part of TFIID, TBP binds to and also bends promoter DNA, irrespective of whether the promoter contains a TATA box. Component of a BRF2-containing transcription factor complex that regulates transcription mediated by RNA polymerase III. Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1 with the rDNA promoter. SL1 is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA.

Subunit / interactions. Binds DNA as monomer. Component of the TFIID basal transcription factor complex, composed of TATA-box-binding protein TBP, and a number of TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. Part of a TFIID-containing RNA polymerase II pre-initiation complex that is composed of TBP and at least GTF2A1, GTF2A2, GTF2E1, GTF2E2, GTF2F1, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2B, TCEA1, ERCC2, ERCC3, TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. Component of the transcription factor SL1/TIF-IB complex, composed of TBP and at least TAF1A, TAF1B, TAF1C and TAF1D. Association of TBP to form either TFIID or SL1/TIF-IB appears to be mutually exclusive. Interacts with TAF1A, TAF1B and TAF1C. Interacts with TFIIB, NCOA6, DRAP1, DR1 and ELF3. Interacts with SPIB, SNAPC1, SNAPC2 and SNAPC4. Interacts with UTF1. Interacts with BRF2; this interaction promotes recruitment of BRF2 to TATA box-containing promoters. Interacts with UBTFD. Interacts with GPBP1D. Interacts with CITED2. Interacts with ATF7IP. Interacts with LLPH. Interacts with HSF1 (via transactivation domain). Interacts with GTF2B (via C-terminus); this interaction with promoter-bound TBP guides RNA polymerase II into the pre-initiation complex (PIC). Interacts with PAX5. Interacts with MSX1; the interaction may inhibit MSX1 autoinactivation. Interacts with ZNF76; inhibiting TBP activity. (Microbial infection) Interacts with HIV-1 Tat. (Microbial infection) Interacts with herpes simplex virus 1 ICP4. (Microbial infection) Interacts with herpes simplex virus 2 ICP4. (Microbial infection) Interacts with human adenovirus E1A protein; this interaction probably disrupts the TBP-TATA complex.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed, with levels highest in the testis and ovary.

Disease relevance. Spinocerebellar ataxia 17 (SCA17) [MIM:607136] Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA17 is an autosomal dominant cerebellar ataxia (ADCA) characterized by widespread cerebral and cerebellar atrophy, dementia and extrapyramidal signs. The molecular defect in SCA17 is the expansion of a CAG repeat in the coding region of TBP. Longer expansions result in earlier onset and more severe clinical manifestations of the disease. The disease is caused by variants affecting the gene represented in this entry.

Polymorphism. The poly-Gln region of TBP is highly polymorphic (25 to 42 repeats) in normal individuals and is expanded to about 47-63 repeats in spinocerebellar ataxia 17 (SCA17) patients.

Similarity. Belongs to the TBP family.

Isoforms (2)

UniProt ID	Names	Canonical?
P20226-1	1	yes
P20226-2	2

RefSeq proteins (2): NP_001165556, NP_003185* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000814	TBP	Family
IPR012295	TBP_dom_sf	Homologous_superfamily
IPR030491	TBP_CS	Conserved_site
IPR033710	TBP_eukaryotic	Family

Pfam: PF00352

UniProt features (40 total): strand 11, binding site 5, turn 5, helix 4, compositionally biased region 4, sequence conflict 3, region of interest 3, repeat 2, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

77 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
1CDW	X-RAY DIFFRACTION	1.9
4ROC	X-RAY DIFFRACTION	1.9
1NVP	X-RAY DIFFRACTION	2.1
4ROE	X-RAY DIFFRACTION	2.2
7NVU	ELECTRON MICROSCOPY	2.5
1JFI	X-RAY DIFFRACTION	2.62
1C9B	X-RAY DIFFRACTION	2.65
4ROD	X-RAY DIFFRACTION	2.7
5N9G	X-RAY DIFFRACTION	2.7
7NVS	ELECTRON MICROSCOPY	2.8
1TGH	X-RAY DIFFRACTION	2.9
7NVT	ELECTRON MICROSCOPY	2.9
8S52	ELECTRON MICROSCOPY	2.9
7ZWD	ELECTRON MICROSCOPY	3
7ZX8	ELECTRON MICROSCOPY	3
9K3U	ELECTRON MICROSCOPY	3
8S51	ELECTRON MICROSCOPY	3.1
7EGF	ELECTRON MICROSCOPY	3.16
7ZWC	ELECTRON MICROSCOPY	3.2
9FSO	ELECTRON MICROSCOPY	3.28
7EGB	ELECTRON MICROSCOPY	3.3
9LXN	ELECTRON MICROSCOPY	3.3
9FSP	ELECTRON MICROSCOPY	3.39
7ZX7	ELECTRON MICROSCOPY	3.4
8IUH	ELECTRON MICROSCOPY	3.4
8S5N	ELECTRON MICROSCOPY	3.4
7ZXE	ELECTRON MICROSCOPY	3.5
9K3V	ELECTRON MICROSCOPY	3.5
9FSQ	ELECTRON MICROSCOPY	3.51
7EG9	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20226-F1	78.28	0.53

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 167; 203; 218; 257; 294

Function

Pathways and Gene Ontology

Reactome pathways

42 pathways

ID	Pathway
R-HSA-167161	HIV Transcription Initiation
R-HSA-167162	RNA Polymerase II HIV Promoter Escape
R-HSA-167172	Transcription of the HIV genome
R-HSA-427359	SIRT1 negatively regulates rRNA expression
R-HSA-427413	NoRC negatively regulates rRNA expression
R-HSA-5250924	B-WICH complex positively regulates rRNA expression
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-6807505	RNA polymerase II transcribes snRNA genes
R-HSA-73762	RNA Polymerase I Transcription Initiation
R-HSA-73772	RNA Polymerase I Promoter Escape
R-HSA-73776	RNA Polymerase II Promoter Escape
R-HSA-73779	RNA Polymerase II Transcription Pre-Initiation And Promoter Opening
R-HSA-73863	RNA Polymerase I Transcription Termination
R-HSA-749476	RNA Polymerase III Abortive And Retractive Initiation
R-HSA-75953	RNA Polymerase II Transcription Initiation
R-HSA-76042	RNA Polymerase II Transcription Initiation And Promoter Clearance
R-HSA-76061	RNA Polymerase III Transcription Initiation From Type 1 Promoter
R-HSA-76066	RNA Polymerase III Transcription Initiation From Type 2 Promoter
R-HSA-76071	RNA Polymerase III Transcription Initiation From Type 3 Promoter
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-162582	Signal Transduction
R-HSA-162587	HIV Life Cycle
R-HSA-162599	Late Phase of HIV Life Cycle
R-HSA-162906	HIV Infection
R-HSA-1643685	Disease
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-5250913	Positive epigenetic regulation of rRNA expression

MSigDB gene sets: 337 (showing top): REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_INITIATION_FROM_TYPE_3_PROMOTER, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, XU_GH1_AUTOCRINE_TARGETS_UP, HOFMANN_CELL_LYMPHOMA_UP, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, PID_REG_GR_PATHWAY, PUJANA_CHEK2_PCC_NETWORK, REACTOME_HIV_INFECTION, GOBP_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, KEGG_HUNTINGTONS_DISEASE, ACATTCC_MIR1_MIR206, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER

GO Biological Process (10): DNA-templated transcription initiation (GO:0006352), transcription by RNA polymerase II (GO:0006366), transcription initiation at RNA polymerase II promoter (GO:0006367), transcription by RNA polymerase III (GO:0006383), spermatogenesis (GO:0007283), mRNA transcription by RNA polymerase II (GO:0042789), RNA polymerase II preinitiation complex assembly (GO:0051123), positive regulation of transcription initiation by RNA polymerase II (GO:0060261), RNA polymerase I preinitiation complex assembly (GO:0001188), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (15): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), RNA polymerase II core promoter sequence-specific DNA binding (GO:0000979), RNA polymerase III general transcription initiation factor activity (GO:0000995), core promoter sequence-specific DNA binding (GO:0001046), RNA polymerase II general transcription initiation factor binding (GO:0001091), TFIIB-class transcription factor binding (GO:0001093), RNA polymerase I core promoter sequence-specific DNA binding (GO:0001164), RNA polymerase II general transcription initiation factor activity (GO:0016251), aryl hydrocarbon receptor binding (GO:0017162), enzyme binding (GO:0019899), DNA-binding transcription factor binding (GO:0140297), DNA binding (GO:0003677), protein binding (GO:0005515), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629)

GO Cellular Component (15): chromatin (GO:0000785), euchromatin (GO:0000791), male germ cell nucleus (GO:0001673), female germ cell nucleus (GO:0001674), female pronucleus (GO:0001939), male pronucleus (GO:0001940), nucleus (GO:0005634), nucleoplasm (GO:0005654), RNA polymerase transcription factor SL1 complex (GO:0005668), transcription factor TFIID complex (GO:0005669), transcription factor TFIIA complex (GO:0005672), cytosol (GO:0005829), protein-containing complex (GO:0032991), cytoplasm (GO:0005737), pronucleus (GO:0045120)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
RNA Polymerase II Transcription	4
RNA Polymerase III Transcription Initiation	3
Transcription of the HIV genome	2
Negative epigenetic regulation of rRNA expression	2
RNA Polymerase I Promoter Clearance	2
RNA Polymerase II Transcription Initiation And Promoter Clearance	2
Late Phase of HIV Life Cycle	1
Positive epigenetic regulation of rRNA expression	1
Regulation of TP53 Activity	1
RNA Polymerase I Transcription	1
RNA Polymerase III Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	4
cellular anatomical structure	4
transcription by RNA polymerase II	3
transcription initiation at RNA polymerase II promoter	2
transcription preinitiation complex assembly	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
core promoter sequence-specific DNA binding	2
general transcription initiation factor activity	2
germ cell nucleus	2
pronucleus	2
RNA polymerase II, holoenzyme	2
RNA polymerase II transcription regulator complex	2
RNA biosynthetic process	1
DNA-templated transcription initiation	1
developmental process involved in reproduction	1
male gamete generation	1
mRNA transcription	1
positive regulation of transcription by RNA polymerase II	1
regulation of transcription initiation by RNA polymerase II	1
positive regulation of DNA-templated transcription initiation	1
transcription initiation at RNA polymerase I promoter	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
transcription by RNA polymerase III	1
transcription cis-regulatory region binding	1
RNA polymerase II complex binding	1
general transcription initiation factor binding	1
RNA polymerase II general transcription initiation factor binding	1
RNA polymerase I transcription regulatory region sequence-specific DNA binding	1
RNA polymerase I preinitiation complex assembly	1
signaling receptor binding	1
RNA polymerase II-specific DNA-binding transcription factor binding	1
protein binding	1
transcription factor binding	1
nucleic acid binding	1
binding	1
DNA-binding transcription factor binding	1

Protein interactions and networks

STRING

6036 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBP	TAF1	P21675	999
TBP	GTF2B	Q00403	999
TBP	BDP1	A6H8Y1	994
TBP	BTAF1	O14981	982
TBP	TP53	P04637	972
TBP	TAF1A	Q15573	969
TBP	GTF2F2	P13984	962
TBP	LGALS4	P56470	962
TBP	TAF4	O00268	959
TBP	DR1	Q01658	953
TBP	TAF9	Q16594	950
TBP	TAF5	Q15542	948
TBP	POLR2A	P24928	946
TBP	TAF6	P49848	946
TBP	TAF10	Q12962	935

IntAct

218 interactions, top by confidence:

A	B	Type	Score
TBP	TAF1	psi-mi:“MI:0914”(association)	0.890
TAF1	TBP	psi-mi:“MI:0915”(physical association)	0.890
TBP	TAF1	psi-mi:“MI:0915”(physical association)	0.890
TBP	TAF1	psi-mi:“MI:0407”(direct interaction)	0.890
TAF10	TBP	psi-mi:“MI:0914”(association)	0.840
NFKBIB	NFKB1	psi-mi:“MI:0914”(association)	0.820
TBP		psi-mi:“MI:0914”(association)	0.820
GTF2A2	TBP	psi-mi:“MI:0407”(direct interaction)	0.800
TAF12	TBP	psi-mi:“MI:0915”(physical association)	0.800
POLR2E	POLR2D	psi-mi:“MI:0915”(physical association)	0.790
TAF12	TAF4	psi-mi:“MI:0914”(association)	0.760
TAF1B	TBP	psi-mi:“MI:0915”(physical association)	0.760
TBP	TAF1B	psi-mi:“MI:0915”(physical association)	0.760
TBP	GTF2A1	psi-mi:“MI:0915”(physical association)	0.740
GTF2A1	TBP	psi-mi:“MI:0914”(association)	0.740
TAF1A	TBP	psi-mi:“MI:0914”(association)	0.740
TBP	TAF1A	psi-mi:“MI:0915”(physical association)	0.740
TBP	TAF4	psi-mi:“MI:0914”(association)	0.730
AAGAB	AP2A2	psi-mi:“MI:0914”(association)	0.670
TAF1C	TBP	psi-mi:“MI:0915”(physical association)	0.660
TBP	TAF1C	psi-mi:“MI:0915”(physical association)	0.660

BioGRID (971): TBP (Two-hybrid), TBP (Two-hybrid), SSX2IP (Two-hybrid), GTF2A1 (Affinity Capture-Western), TBP (Affinity Capture-Western), TBP (Protein-peptide), TBP (Affinity Capture-MS), TBP (Affinity Capture-MS), TBP (Affinity Capture-MS), TBP (Affinity Capture-MS), TBP (Co-fractionation), TBP (Phenotypic Enhancement), TBP (Affinity Capture-Western), TBP (Affinity Capture-Western), TBP (Reconstituted Complex)

ESM2 similar proteins: A0A086T5L8, A0A0D2Y4S0, A0A0J9U3L6, A0A9P4XWM4, A1CW67, A8NYG2, B0D4E7, B2CQK1, B8MYL0, C8VTS4, G0RL42, G0S0Y3, G2X740, G4MRQ6, G4MUB2, G5EDF0, G9NAW2, I1RCN9, I1S0A8, I1S537, I1S5P3, J9N5P9, L0PQS5, M2SQ20, M2TF54, N1PZ58, O42632, O74252, P0C5H8, P0CR60, P20226, P28159, P38093, P51140, P53361, Q0V0I4, Q1EA11, Q1K5S5, Q2GNT4, Q2HJ52

Diamond homologs: A0B5H8, A1RSQ1, A3MV36, A5UL47, A6H907, A6H909, A6URP5, A6UTF6, A6VIP7, A7UFC2, A9A840, B1Y949, B6YXI6, C4M7H7, C6A0R1, D4GZA2, D4H071, O13270, O17488, O27664, O29874, O43133, O45211, O52004, O52018, O58737, P13393, P17871, P20226, P20227, P26354, P26355, P26356, P26357, P27633, P28147, P28148, P29037, P32085, P32086

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
ZNF76	“down-regulates activity”	TBP	binding
TBP	“up-regulates quantity by expression”	LIN28B	“transcriptional regulation”
TBP	“form complex”	TFIID	binding
TBP	“form complex”	“SL1 complex”	binding
HUWE1	“down-regulates quantity”	TBP	ubiquitination
FOXF2	“up-regulates activity”	TBP	binding
MSX1	“down-regulates activity”	TBP	binding
GTF2A2	“up-regulates activity”	TBP	binding
YWHAE	“up-regulates activity”	TBP	binding
BTAF1	“up-regulates activity”	TBP	binding
TBP	“form complex”	TFIIIB	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 150 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
HIV Transcription Initiation	15	35.0×	5e-18
RNA Polymerase II HIV Promoter Escape	15	35.0×	5e-18
RNA Polymerase II Promoter Escape	15	35.0×	5e-18
RNA Polymerase II Transcription Pre-Initiation And Promoter Opening	15	35.0×	5e-18
RNA Polymerase II Transcription Initiation	15	35.0×	5e-18
RNA Polymerase II Transcription Initiation And Promoter Clearance	15	35.0×	5e-18
Transcription of the HIV genome	17	29.4×	3e-18
Late Phase of HIV Life Cycle	15	25.2×	1e-15

GO biological processes:

GO term	Partners	Fold	FDR
DNA-templated transcription initiation	6	44.6×	5e-07
transcription initiation at RNA polymerase II promoter	12	35.7×	2e-13
RNA polymerase II preinitiation complex assembly	15	32.4×	4e-16
positive regulation of transcription initiation by RNA polymerase II	11	23.7×	4e-10
mRNA transcription by RNA polymerase II	6	15.7×	3e-04
regulation of DNA repair	5	11.0×	9e-03
transcription by RNA polymerase II	17	9.5×	7e-10
negative regulation of gene expression	9	4.9×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

53 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	26
Likely benign	5
Benign	7

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1711652	GRCh37/hg19 6q26-27(chr6:163836226-170893669)x1	Pathogenic
2583044	GRCh37/hg19 6q25.3-27(chr6:160952761-170892276)x1	Pathogenic

SpliceAI

1453 predictions. Top by Δscore:

Variant	Effect	Δscore
6:170556689:T:A	acceptor_gain	1.0000
6:170556692:C:CA	acceptor_gain	1.0000
6:170561787:A:AG	acceptor_gain	1.0000
6:170561787:ACAG:A	acceptor_gain	1.0000
6:170561789:A:AG	acceptor_gain	1.0000
6:170561789:AG:A	acceptor_gain	1.0000
6:170561790:G:GG	acceptor_gain	1.0000
6:170561790:G:T	acceptor_loss	1.0000
6:170561790:GG:G	acceptor_gain	1.0000
6:170562231:GCA:G	donor_gain	1.0000
6:170562234:G:GG	donor_gain	1.0000
6:170564544:GAAAT:G	acceptor_gain	1.0000
6:170566916:A:AG	acceptor_gain	1.0000
6:170566916:AGC:A	acceptor_gain	1.0000
6:170566917:G:GG	acceptor_gain	1.0000
6:170566917:GCG:G	acceptor_gain	1.0000
6:170567016:G:GG	donor_gain	1.0000
6:170568115:G:GT	donor_gain	1.0000
6:170569607:CCTAG:C	acceptor_loss	1.0000
6:170569608:CTAG:C	acceptor_loss	1.0000
6:170569609:TA:T	acceptor_loss	1.0000
6:170569610:A:AG	acceptor_gain	1.0000
6:170569610:AGT:A	acceptor_gain	1.0000
6:170569610:AGTG:A	acceptor_loss	1.0000
6:170569611:G:GA	acceptor_gain	1.0000
6:170569611:GT:G	acceptor_gain	1.0000
6:170569611:GTG:G	acceptor_gain	1.0000
6:170569611:GTGA:G	acceptor_gain	1.0000
6:170569611:GTGAA:G	acceptor_gain	1.0000
6:170569775:AGTAG:A	donor_loss	1.0000

AlphaMissense

2215 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:170562223:C:T	P163S	1.000
6:170562224:C:A	P163Q	1.000
6:170562224:C:G	P163R	1.000
6:170562230:T:A	L165Q	1.000
6:170562230:T:C	L165P	1.000
6:170562233:A:C	Q166P	1.000
6:170564546:A:C	N167H	1.000
6:170564546:A:G	N167D	1.000
6:170564547:A:C	N167T	1.000
6:170564547:A:G	N167S	1.000
6:170564547:A:T	N167I	1.000
6:170564548:T:A	N167K	1.000
6:170564548:T:G	N167K	1.000
6:170564549:A:T	I168F	1.000
6:170564550:T:A	I168N	1.000
6:170564550:T:G	I168S	1.000
6:170564552:G:C	V169L	1.000
6:170564552:G:T	V169L	1.000
6:170564553:T:A	V169E	1.000
6:170564553:T:C	V169A	1.000
6:170564553:T:G	V169G	1.000
6:170564555:T:C	S170P	1.000
6:170564556:C:A	S170Y	1.000
6:170564556:C:T	S170F	1.000
6:170564559:C:A	T171K	1.000
6:170564559:C:G	T171R	1.000
6:170564559:C:T	T171I	1.000
6:170564562:T:A	V172E	1.000
6:170564568:T:A	L174H	1.000
6:170564568:T:C	L174P	1.000

dbSNP variants (sampled 300 via entrez): RS1000406378 (6:170565767 A>G), RS1000460239 (6:170566074 C>G), RS1000619544 (6:170552925 T>A), RS1000678322 (6:170553122 G>A), RS1000753231 (6:170570215 A>T), RS1000929423 (6:170564723 A>G), RS1001023828 (6:170571930 A>G), RS1001355516 (6:170568490 C>G,T), RS1001476245 (6:170571566 C>T), RS1001527153 (6:170561479 GTATTATAGT>G), RS1001578639 (6:170572716 T>C), RS1001826962 (6:170554842 T>C), RS1001832705 (6:170568743 G>A), RS1001885750 (6:170552844 A>G), RS1001924378 (6:170573155 G>T)

Disease associations

OMIM: gene MIM:600075 | disease phenotypes: MIM:164700, MIM:213100, MIM:607136

GenCC curated gene-disease

Disease	Classification	Inheritance
spinocerebellar ataxia type 17	Definitive	Autosomal dominant

Mondo (1): spinocerebellar ataxia type 17 (MONDO:0011781)

Orphanet (1): Spinocerebellar ataxia type 17 (Orphanet:98759)

HPO phenotypes

68 total (30 of 68 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000012	Urinary urgency
HP:0000020	Urinary incontinence
HP:0000298	Mask-like facies
HP:0000473	Torticollis
HP:0000640	Gaze-evoked nystagmus
HP:0000643	Blepharospasm
HP:0000708	Atypical behavior
HP:0000716	Depression
HP:0000718	Aggressive behavior
HP:0000726	Dementia
HP:0000727	Frontal lobe dementia
HP:0000738	Hallucinations
HP:0000743	Frontal release signs
HP:0000751	Personality changes
HP:0000757	Lack of insight
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001268	Mental deterioration
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001289	Confusion
HP:0001300	Parkinsonism
HP:0001310	Dysmetria
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001621	Weak voice

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001255_3	Type 1 diabetes	8.000000e-09

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C563505	Olivopontocerebellar Atrophy V (supp.)
C564616	Spinocerebellar Ataxia 17 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
1,12-benzoperylene	increases expression	1
deoxynivalenol	increases expression	1
cladribine monophosphate	affects activity, affects binding, affects reaction	1
abrine	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	affects methylation	1
Doxorubicin	decreases expression	1
Ozone	increases expression	1
Rotenone	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	affects expression	1
Cyclosporine	increases methylation	1
Aflatoxin B1	decreases methylation	1

Cellosaurus cell lines

7 cell lines: 3 embryonic stem cell, 3 cancer cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A7A2	SEES3-1V human TBP, clone1	Embryonic stem cell	Male
CVCL_A7A3	SEES3-1V human TBP, clone2	Embryonic stem cell	Male
CVCL_A7A4	SEES3-1V human TBP, clone3	Embryonic stem cell	Male
CVCL_A8NA	RCPCMi008-A	Induced pluripotent stem cell	Male
CVCL_B7ZU	Abcam Raji TBP KO	Cancer cell line	Male
CVCL_C0AM	Abcam THP-1 TBP KO	Cancer cell line	Male
CVCL_C7CA	Abcam PC-3 TBP KO	Cancer cell line	Male

Clinical trials (associated diseases)

2 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04301284	PHASE2	WITHDRAWN	Study of CAD-1883 for Spinocerebellar Ataxia
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford