TBP

protein-coding

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

Gene summary

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. [provided by RefSeq, Jul 2016]

Previous symbols:

GTF2D1
SCA17

MANE transcript

NM_003194.5

Inheritance

AD, AR, Digenic

ClinVar variants

P:2U:36B:20

Top phenotype

Spinocerebellar ataxia 17

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr6:170,554,302-170,572,870

External References & Databases

Ensembl (ENSG00000112592)

Transcript & Mutation Effects

hg38 • Region Span ~18.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spinocerebellar ataxia type 17DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011781

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

spinocerebellar ataxia type 17STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011781

Submitter: Labcorp Genetics (formerly Invitae)

spinocerebellar ataxia type 17STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011781

Submitter: Ambry Genetics

spinocerebellar ataxia type 17SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011781

Submitter: Orphanet

Clinical Genomic Database (CGD)

Spinocerebellar ataxia 17AD/AR/Digenic

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 10484774; 11448935; 11313753; 11914409; 11939898; 12805114; 15521976; 14985389; 15313853; 15365789; 20587494; 21108634; 21710129; 34906452

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TBP variants in ClinVar

6 Conditions Cataloged

Inborn genetic diseasesTotal: 30

not providedTotal: 25

not specifiedTotal: 12

Spinocerebellar ataxia type 17Total: 6

Parkinson disease, late-onsetTotal: 1

TBP-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003194.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar		13 clinvar		14
missense			31 clinvar	1 clinvar		32
nonsense						0
start loss						0
frameshift		1 clinvar	2 clinvar	3 clinvar	3 clinvar	9
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	2	36	17	3	58

Highest pathogenic variant AF is 0.00008682186

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003194.5	RefSeq	NP_003185.1	7	MANE Select
ENST00000392092.7	Ensembl	ENSP00000375942.2	7	MANE Select
NM_001172085.2	RefSeq	NP_001165556.1	6	Standard
ENST00000230354.10	Ensembl	ENSP00000230354.5	7	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
tbp	Danio rerio	Structure: axis Quality: decreased length abnormal

Gene / Model

Organism

Observed Phenotype

tbp

Danio rerio

Structure: axis

Quality: decreased length

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

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

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

Cellular Component

transcription factor TFIIIB complex
nuclear chromatin
female pronucleus
male pronucleus
nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000392092
Coding exons: 7
Length: 18569
Individuals with no LoFs: 125720
Homozygous LoFs: 7
Heterozygous LoFs: 21
Defined: 125748
p: 0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.61	82	181	0.454	0.00000946	2202
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00024	0.00012	rare
Latino/Admixed American	0.00024	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00016	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00023	0.00012	rare
South Asian	0.00014	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.688

Intolerance Scores

LoFtool: 0.573
RVIS EVS: -0.23
RVIS percentile EVS: 36.86

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

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