TBP

TATA-box binding protein, the group of General transcription factors|General transcription factor IID complex subunits |General transcription factor IIIB complex subunits

Basic information

Region (hg38): 6:170554301-170572870

Previous symbols: [ "GTF2D1", "SCA17" ]

Links

ENSG00000112592 ∙ NCBI:6908 ∙ OMIM:600075 ∙ HGNC:11588 ∙ Uniprot:P20226 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spinocerebellar ataxia type 17 (Definitive), mode of inheritance: AD
• spinocerebellar ataxia type 17 (Supportive), mode of inheritance: AD
• spinocerebellar ataxia type 17 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia 17	AD/AR/Digenic	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	10484774; 11448935; 11313753; 11914409; 11939898; 12805114; 15521976; 14985389; 15313853; 15365789; 20587494; 21108634; 21710129; 34906452

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TBP gene.

• not provided (20 variants)
• Inborn genetic diseases (9 variants)
• not specified (6 variants)
• Spinocerebellar ataxia type 17 (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				6	1	7
missense			9			9
nonsense						0
start loss						0
frameshift			1		2	3
inframe indel	1			2	7	10
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding					4	4
Total	1	0	10	8	14

Highest pathogenic variant AF is 0.000181

Variants in TBP

This is a list of pathogenic ClinVar variants found in the TBP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-170561488-T-G			Benign (Jun 19, 2021)
6-170561925-A-ACAG			Benign (Jun 09, 2021)
6-170561936-A-G		Inborn genetic diseases	Uncertain significance (Nov 10, 2022)
6-170561943-GCAGCAGCAACAGCAA-G			Likely benign (Jan 01, 2024)
6-170561949-GCAA-G		Spinocerebellar ataxia type 17	Benign (Jun 09, 2021)
6-170561950-CA-C		not specified	Benign (-)
6-170561952-A-G		not specified • Spinocerebellar ataxia type 17 • Inborn genetic diseases	Benign/Likely benign (Nov 09, 2023)
6-170561955-GCAA-G		not specified	Benign (-)
6-170561958-A-G		Inborn genetic diseases	Likely benign (Aug 02, 2023)
6-170561957-A-AGC		Spinocerebellar ataxia type 17	Uncertain significance (Jan 01, 2019)
6-170561958-ACAG-A		not specified	Benign (Mar 20, 2017)
6-170561958-ACAGCAGCAG-A		not specified	Benign (Mar 20, 2017)
6-170561958-ACAGCAGCAGCAGCAGCAGCAGCAG-A			Benign (May 01, 2022)
6-170561958-ACAGCAGCAGCAGCAGCAGCAGCAGCAG-A			Benign (Oct 01, 2022)
6-170561958-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-A			Benign (Mar 01, 2022)
6-170561958-A-ACAGCAG			Likely benign (Jun 05, 2017)
6-170561958-A-ACAGCAGCAGCAGCAGCAG		Spinocerebellar ataxia type 17	Pathogenic (May 24, 2023)
6-170561962-C-CCAA		not specified	Benign/Likely benign (-)
6-170561963-AGC-A		not specified	Benign (Jun 09, 2021)
6-170561964-G-A			Conflicting classifications of pathogenicity (Jun 09, 2021)
6-170561966-AG-A			Likely benign (Mar 26, 2024)
6-170561966-AGCAGCAGCAG-A		not specified	Benign (-)
6-170561966-AGCAGCAGCAGCAG-A		not specified	Benign/Likely benign (-)
6-170561966-AGCAGCAGCAGCAGCAG-A		Hepatocellular carcinoma	Pathogenic (Jun 15, 2021)
6-170561966-AGCAGCAGCAGCAGCAGCAGCAGCAG-A		Hepatocellular carcinoma	Pathogenic (Jun 15, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBP	protein_coding	protein_coding	ENST00000392092	7	18569

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0150	0.984	125720	7	21	125748	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.61	82	181	0.454	0.00000946	2202
Missense in Polyphen		14	60.765	0.2304		734
Synonymous	-1.31	85	70.9	1.20	0.00000433	650
Loss of Function	2.86	7	21.2	0.330	0.00000111	206

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000472	0.000360
Ashkenazi Jewish	0.00	0.00
East Asian	0.000273	0.000163
Finnish	0.0000929	0.0000924
European (Non-Finnish)	0.000232	0.000123
Middle Eastern	0.000273	0.000163
South Asian	0.000137	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: General transcription factor that functions at the core of the DNA-binding multiprotein factor TFIID (PubMed:2374612, PubMed:2363050, PubMed:2194289, PubMed:9836642, PubMed:27193682). Binding of TFIID to the TATA box is the initial transcriptional step of the pre-initiation complex (PIC), playing a role in the activation of eukaryotic genes transcribed by RNA polymerase II (PubMed:2374612, PubMed:2363050, PubMed:2194289, PubMed:9836642, PubMed:27193682). Component of a BRF2-containing transcription factor complex that regulates transcription mediated by RNA polymerase III (PubMed:26638071). Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (pre-initiation complex) during RNA polymerase I-dependent transcription (PubMed:15970593). 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. {ECO:0000269|PubMed:15970593, ECO:0000269|PubMed:2194289, ECO:0000269|PubMed:2363050, ECO:0000269|PubMed:2374612, ECO:0000269|PubMed:26638071, ECO:0000269|PubMed:27193682, ECO:0000269|PubMed:9836642, ECO:0000305}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:11313753, ECO:0000269|PubMed:11448935, ECO:0000269|PubMed:11939898}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Huntington,s disease - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Basal transcription factors - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Glucocorticoid Pathway (Peripheral Tissue), Pharmacodynamics;Prion disease pathway;Eukaryotic Transcription Initiation;B-WICH complex positively regulates rRNA expression;Positive epigenetic regulation of rRNA expression;SIRT1 negatively regulates rRNA expression;Disease;NoRC negatively regulates rRNA expression;Negative epigenetic regulation of rRNA expression;Signal Transduction;Epigenetic regulation of gene expression;Gene expression (Transcription);Generic Transcription Pathway;Transcription of the HIV genome;Late Phase of HIV Life Cycle;HIV Life Cycle;HIV Infection;RNA Polymerase II HIV Promoter Escape;RNA Polymerase II Pre-transcription Events;RNA Polymerase II Transcription Initiation;RNA Polymerase II Transcription Initiation And Promoter Clearance;RNA Polymerase I Promoter Clearance;HIV Transcription Initiation;RNA polymerase II transcribes snRNA genes;RNA Polymerase II Transcription;Infectious disease;RNA Polymerase I Transcription Termination;RNA Polymerase I Transcription;RNA Polymerase I Transcription Initiation;RNA Polymerase I Promoter Escape;RNA Polymerase II Promoter Escape;RNA Polymerase I Chain Elongation;RNA Polymerase II Transcription Pre-Initiation And Promoter Opening;Glucocorticoid receptor regulatory network;Regulation of TP53 Activity through Phosphorylation;Signaling by Nuclear Receptors;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Estrogen-dependent gene expression;RNA Polymerase III Abortive And Retractive Initiation;RNA Polymerase III Transcription Initiation From Type 1 Promoter;RNA Polymerase III Transcription Initiation From Type 2 Promoter;ESR-mediated signaling;RNA Polymerase III Transcription Initiation From Type 3 Promoter;RNA Polymerase III Transcription Initiation;RNA Polymerase III Transcription;Validated targets of C-MYC transcriptional repression;Regulation of retinoblastoma protein (Consensus)

Recessive Scores

• pRec: 0.688

Intolerance Scores

• loftool: 0.573
• rvis_EVS: -0.23
• rvis_percentile_EVS: 36.86

Haploinsufficiency Scores

• pHI: 0.999
• hipred: Y
• hipred_score: 0.783
• ghis: 0.642

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tbp
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: tbp
• Affected structure: axis
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;transcription initiation from RNA polymerase I promoter;termination of RNA polymerase I transcription;transcription by RNA polymerase II;transcription initiation from RNA polymerase II promoter;transcription by RNA polymerase III;spermatogenesis;viral process;snRNA transcription by RNA polymerase II;positive regulation of gene expression, epigenetic;positive regulation of transcription, DNA-templated;RNA polymerase II preinitiation complex assembly;RNA polymerase III preinitiation complex assembly;regulation of signal transduction by p53 class mediator
• Cellular component: transcription factor TFIIIB complex;nuclear chromatin;female pronucleus;male pronucleus;nucleus;nucleoplasm;transcription factor complex;transcription factor TFIID complex;transcription factor TFIIA complex;nuclear euchromatin;cytoplasm;protein-containing complex;transcriptional preinitiation complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II core promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;proximal promoter sequence-specific DNA binding;RNA polymerase III general transcription initiation factor activity;RNA polymerase III regulatory region DNA binding;core promoter binding;TFIIB-class transcription factor binding;RNA polymerase II repressing transcription factor binding;DNA-binding transcription factor activity;protein binding;transcription factor binding;RNA polymerase II general transcription initiation factor activity;aryl hydrocarbon receptor binding;enzyme binding;transcription regulatory region DNA binding;repressing transcription factor binding