GTF2B

Summary

GTF2B (general transcription factor IIB, HGNC:4648) is a protein-coding gene on chromosome 1p22.2, encoding Transcription initiation factor IIB (Q00403). General transcription factor that plays a role in transcription initiation by RNA polymerase II (Pol II). It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

This gene encodes the general transcription factor IIB, one of the ubiquitous factors required for transcription initiation by RNA polymerase II. The protein localizes to the nucleus where it forms a complex (the DAB complex) with transcription factors IID and IIA. Transcription factor IIB serves as a bridge between IID, the factor which initially recognizes the promoter sequence, and RNA polymerase II.

Source: NCBI Gene 2959 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 25 total
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_001514

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4648
Approved symbol	GTF2B
Name	general transcription factor IIB
Location	1p22.2
Locus type	gene with protein product
Status	Approved
Aliases	TFIIB
Ensembl gene	ENSG00000137947
Ensembl biotype	protein_coding
OMIM	189963
Entrez	2959

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000370500, ENST00000418217, ENST00000448623, ENST00000471296, ENST00000471471, ENST00000486078, ENST00000494819, ENST00000862994, ENST00000964929

RefSeq mRNA: 1 — MANE Select: NM_001514 NM_001514

CCDS: CCDS715

Canonical transcript exons

ENST00000370500 — 7 exons

Exon	Start	End
ENSE00000932076	88857206	88857487
ENSE00001158811	88852633	88853346
ENSE00001452875	88891483	88891567
ENSE00003576350	88887261	88887367
ENSE00003585560	88860140	88860286
ENSE00003626024	88863981	88864114
ENSE00003663345	88859882	88860011

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 49.0535 / max 867.9454, expressed in 1819 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13122	49.0535	1819

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.46	gold quality
secondary oocyte	CL:0000655	99.05	gold quality
calcaneal tendon	UBERON:0003701	96.37	gold quality
gingival epithelium	UBERON:0001949	93.60	gold quality
epithelium of nasopharynx	UBERON:0001951	93.53	gold quality
bone marrow	UBERON:0002371	93.50	gold quality
esophagus squamous epithelium	UBERON:0006920	93.41	gold quality
islet of Langerhans	UBERON:0000006	93.36	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.35	gold quality
tongue squamous epithelium	UBERON:0006919	92.86	silver quality
gingiva	UBERON:0001828	92.65	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.62	gold quality
palpebral conjunctiva	UBERON:0001812	92.56	gold quality
colonic mucosa	UBERON:0000317	92.23	gold quality
squamous epithelium	UBERON:0006914	92.00	gold quality
monocyte	CL:0000576	91.94	gold quality
mononuclear cell	CL:0000842	91.94	gold quality
amniotic fluid	UBERON:0000173	91.94	gold quality
leukocyte	CL:0000738	91.93	gold quality
epithelium of esophagus	UBERON:0001976	91.62	gold quality
cortical plate	UBERON:0005343	91.37	gold quality
bone marrow cell	CL:0002092	91.12	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.99	gold quality
rectum	UBERON:0001052	90.97	gold quality
renal glomerulus	UBERON:0000074	90.86	gold quality
ganglionic eminence	UBERON:0004023	90.72	gold quality
cartilage tissue	UBERON:0002418	90.66	gold quality
gall bladder	UBERON:0002110	90.56	gold quality
upper leg skin	UBERON:0004262	90.55	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.51	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
BDKRB1	Unknown

Upstream regulators (CollecTRI, top): ESR1, HNF4A, JUN, NCOA1, NFKB, NR2F1, NR2F2, RELA, SP1, TBP, TBPL1, THRA, THRB, VDR

miRNA regulators (miRDB)

51 targeting GTF2B, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
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-22-3P	99.93	68.13	917
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-3685	99.62	68.83	1621

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 28)

• interaction with vitamin D receptor helix H10 residues (PMID:12529369)
• 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)
• The groove in the first cyclin repeat of TFIIB is identified as the FCP1-binding site of TFIIB core domain (TFIIBc), consisting of several hydrophobic and several basic amino acids. (PMID:12578358)
• lack of role in bending of TATA-binding protein simultaneously with promotoer DNA (PMID:12791683)
• TFIIB interacts with SP1/SP3 at the SP1 site, besides its association with EAR3 and the TATA-less core promoter region. (PMID:12972613)
• 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)
• The structural role of Zn2+ binding to the the zinc-ribbon domain of TFIIB was analysed. (PMID:14641108)
• Results identify a small nonconserved surface of the transcription factor TFIIB zinc ribbon that is required for RNA polymerase II (pol II) transcription in vivo and for different types of basal pol II transcription in vitro. (PMID:15024075)
• A TFIIB conformational change is critical for the formation of activator-dependent transcription complexes. (PMID:15037660)
• Collapse of the transcription bubble defines the RNA polymerase II promoter clearance transition. (PMID:15989968)
• high level of TFIIB can bypass the Mediator requirement for basal transcription and pol II recruitment in nuclear extract (PMID:16595664)
• Together, our results support a mode of preinitiation complex assembly in which TFIIB/RNA polymerase II recruitment to the promoter occurs in vivo. (PMID:16878124)
• TFIIB binding is required for the interferon antagonist effect exerted by Thogoto virus M protein. (PMID:18768974)
• slipping at juncture is induced by TATA-binding protein and transcription factor IIB and requires a TATA box but not a transcription factor IIB recognition sequence (PMID:19193635)
• TFIIF in HeLa cell nuclear extract helps to rescue the inactive mutations by interacting with either the B-finger or another component of the initiation complex that is influenced by the B-finger (PMID:19590095)
• phosphorylation of TFIIB at serine 65 is a critical event in transcription that links the gene promoter and terminator and triggers initiation by RNA pol II (PMID:20226668)
• a six-amino acid human TFIIB tip region is needed for appropriate levels of serine 5 C-terminal domain phosphorylation and mRNA capping and for retention of the required elongation factor TFIIF. (PMID:20880846)
• Data show that TFIIF has an important role in stabilizing TFIIB within the PIC and after transcription initiates. (PMID:21896726)
• TFIIB was involved in the proliferation and growth of HCC cells. (PMID:23055019)
• a mode of phospho-TFIIB-independent transcriptional regulation that prioritizes the transcription of p53-target genes during cellular stress. (PMID:23115335)
• these results establish a new paradigm for TFIIB functionality in human gene expression, which when downregulated has potent anti-viral effects. (PMID:24441171)
• Association of the winged helix motif of the TFIIEalpha subunit of TFIIE with either the TFIIEbeta subunit or TFIIB distinguishes its functions in transcription. (PMID:25492609)
• The role of zinc at Cys3His1 binding site in the absence of TFIIB protein folding (PMID:26016528)
• binding of specific DNA sequences changes the protein structure and dynamics, and TFIIB may exist in two conformational states (PMID:26284261)
• a hand-off model in which Ssu72 mediates a conformational transition in TFIIB, accounting for the role of Ssu72 in transcription reinitiation, gene looping, and promoter-terminator cross-talk. (PMID:29158257)
• Release of Human TFIIB from Actively Transcribing Complexes Is Triggered upon Synthesis of 7- and 9-nt RNAs. (PMID:32417370)
• Transcription factor GTF2B regulates AIP protein expression in growth hormone-secreting pituitary adenomas and influences tumor phenotypes. (PMID:34932801)
• Differential dependencies of human RNA polymerase II promoters on TBP, TAF1, TFIIB and XPB. (PMID:35947745)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gtf2b	ENSDARG00000103578
mus_musculus	Gtf2b	ENSMUSG00000028271
rattus_norvegicus	Gtf2b	ENSRNOG00000011135
drosophila_melanogaster	TfIIB	FBGN0004915
caenorhabditis_elegans		WBGENE00006648

Paralogs (2): BRF2 (ENSG00000104221), BRF1 (ENSG00000185024)

Protein

Protein identifiers

Transcription initiation factor IIB — Q00403 (reviewed: Q00403)

Alternative names: General transcription factor TFIIB, S300-II

All UniProt accessions (3): Q00403, B1APE1, B1APE2

UniProt curated annotations — full annotation on UniProt →

Function. General transcription factor that plays a role in transcription initiation by RNA polymerase II (Pol II). Involved in the pre-initiation complex (PIC) formation and Pol II recruitment at promoter DNA. Together with the TATA box-bound TBP forms the core initiation complex and provides a bridge between TBP and the Pol II-TFIIF complex. Released from the PIC early following the onset of transcription during the initiation and elongation transition and reassociates with TBP during the next transcription cycle. Associates with chromatin to core promoter-specific regions. Binds to two distinct DNA core promoter consensus sequence elements in a TBP-independent manner; these IIB-recognition elements (BREs) are localized immediately upstream (BREu), 5’-[GC][GC][GA]CGCC-3’, and downstream (BREd), 5’-[GA]T[TGA][TG][GT][TG][TG]-3’, of the TATA box element. Modulates transcription start site selection. Also exhibits autoacetyltransferase activity that contributes to the activated transcription.

Subunit / interactions. Found in a ternary complex with TATA box-bound TBP. Part of a TFIID-containing RNA polymerase II pre-initiation complex (PIC) 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. Associates with TFIID-TFIIA (DA complex) to form TFIID-TFIIA-TFIIB (DAB complex), which is then recognized by RNA polymerase II (Pol II). Found in a RNA polymerase II initiation complex. Interacts (via C-terminus) with TBP; this interaction with TATA box-bound TBP guides Pol II into the PIC. Interacts (via N-terminus) with Pol II. Interacts (via C-terminus) with SSU72; this interaction is inhibited by SYMPK. Interacts with NR2F1; this interaction is direct. Interacts with PGR. Interacts with ESR1. Interacts with GTF2F1 (via C-terminus and preferentially via acetylated form); this interaction prevents binding of GTF2B to GTF2F2. Interacts with GTF2F2 (via N-terminus); this interaction is inhibited in presence of GTF2F1. Interacts with the transcription elongation factor TCEA2. Interacts with HSF1 (via transactivation domain). Interacts with GPBP1. (Microbial infection) Interacts with HIV-1 Vpr. (Microbial infection) Interacts with Epstein-Barr virus EBNA2. (Microbial infection) Interacts with Herpes simplex virus 1 protein ICP4. (Microbial infection) Interacts (via C-terminus) with the Herpes simplex virus activator VP16; this interaction stimulates RNA Pol II transcription by increasing the extent of pre-initiation complex assembly.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Expressed in the inner cell mass forming the embryoblast. Not detected in cells from the outer thin layer trophoblast (at protein level).

Post-translational modifications. Acetylated. Autoacetylated; autoacetylation at Lys-238 stimulates transcription activation.

Domain organisation. The TFIIB-type zinc-binding domain is necessary for the interaction and recruitment of RNA polymerase II to the core promoter, the formation of a fully competent pre-initiation complex (PIC) assembly and basal transcription initiation. The C-terminus is necessary and sufficient for interaction with the TATA box-bound TBP complex and for the formation of PIC.

Similarity. Belongs to the TFIIB family.

RefSeq proteins (1): NP_001505* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000812	TFIIB	Family
IPR013137	Znf_TFIIB	Domain
IPR013150	TFIIB_cyclin	Domain
IPR013763	Cyclin-like_dom	Domain
IPR023486	TFIIB_CS	Conserved_site
IPR036915	Cyclin-like_sf	Homologous_superfamily

Pfam: PF00382, PF08271

Catalyzed reactions (Rhea), 1 shown:

• L-lysyl-[protein] + acetyl-CoA = N(6)-acetyl-L-lysyl-[protein] + CoA + H(+) (RHEA:45948)

UniProt features (84 total): mutagenesis site 26, binding site 16, helix 16, strand 9, modified residue 4, region of interest 4, turn 3, repeat 2, sequence variant 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

55 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7NVU	ELECTRON MICROSCOPY	2.5
1C9B	X-RAY DIFFRACTION	2.65
1VOL	X-RAY DIFFRACTION	2.7
7NVS	ELECTRON MICROSCOPY	2.8
7NVT	ELECTRON MICROSCOPY	2.9
8S52	ELECTRON MICROSCOPY	2.9
7ZWD	ELECTRON MICROSCOPY	3
7ZX8	ELECTRON MICROSCOPY	3
8S51	ELECTRON MICROSCOPY	3.1
7ZWC	ELECTRON MICROSCOPY	3.2
7EGB	ELECTRON MICROSCOPY	3.3
5WH1	X-RAY DIFFRACTION	3.39
7ZX7	ELECTRON MICROSCOPY	3.4
8S5N	ELECTRON MICROSCOPY	3.4
7ZXE	ELECTRON MICROSCOPY	3.5
7EG9	ELECTRON MICROSCOPY	3.7
8BZ1	ELECTRON MICROSCOPY	3.8
5IYB	ELECTRON MICROSCOPY	3.9
5IYC	ELECTRON MICROSCOPY	3.9
5IYD	ELECTRON MICROSCOPY	3.9
7EGC	ELECTRON MICROSCOPY	3.9
8BVW	ELECTRON MICROSCOPY	4
7ENA	ELECTRON MICROSCOPY	4.07
7EGA	ELECTRON MICROSCOPY	4.1
8BYQ	ELECTRON MICROSCOPY	4.1
7ENC	ELECTRON MICROSCOPY	4.13
8GXS	ELECTRON MICROSCOPY	4.16
7EDX	ELECTRON MICROSCOPY	4.5
7NVR	ELECTRON MICROSCOPY	4.5
7LBM	ELECTRON MICROSCOPY	4.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q00403-F1	87.30	0.67

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 (16): 34; 37; 53; 61; 152; 154; 189; 196; 248; 272; 281; 284 …

Post-translational modifications (4): 70, 76, 92, 238

Mutagenesis-validated functional residues (26):

Position	Phenotype
37	does not inhibit interaction with tbp. inhibits the recruitment of rna polymerase ii into the initiation complex.
51–56	partial loss of hiv-1 vpr binding.
51	defects in transcription start site selection. supports a level of transcription equivalent to wild-type.
52	partial loss of hiv-1 vpr binding.
53–54	partial loss of hiv-1 vpr binding.
55	partial loss of hiv-1 vpr binding.
66	defects in transcription start site selection. supports a level of transcription equivalent to wild-type.
153	decreases bred-dependent pre-initiation complex formation.
185	reduces interaction with ssu72; when associated with e-193 or e-200. inhibits interaction with vp16; when associated wit
185	reduces interaction with vp16; when associated with l-189.
189	inhibits interaction with ssu72; when associated with e-193. reduces interaction with ssu72; when associated with e-200.
189	reduces interaction with vp16; when associated with l-185.
193	inhibits interaction with ssu72; when associated with e-185 or e-189. inhibits interaction with vp16; when associated wi
196	reduces interaction with vp16; when associated with l-200.
200–208	reduces the formation of the tata box-bound tbp ternary complex.
200	reduces interaction with ssu72; when associated with e-185 or e-189. inhibits interaction with vp16; when associated wit
200	reduces the formation of the tata box-bound tbp ternary complex.
200	reduces interaction with vp16; when associated with l-196.
208	does not inhibit the formation of the tata box-bound tbp ternary complex.
238	abolishes autoacetylation, represses transcription activity, does not inhibit its association with chromatin to promoter
247	inhibits interaction with tbp.
283	reduces dna-binding.
286	reduces dna-binding.
286	inhibits interaction with rna polymerase ii; when associated with e-290 and e-295.
290	inhibits interaction with rna polymerase ii; when associated with e-286 and e-295.

Function

Pathways and Gene Ontology

Reactome pathways

17 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-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6807505	RNA polymerase II transcribes snRNA genes
R-HSA-73776	RNA Polymerase II Promoter Escape
R-HSA-73779	RNA Polymerase II Transcription Pre-Initiation And Promoter Opening
R-HSA-75953	RNA Polymerase II Transcription Initiation
R-HSA-76042	RNA Polymerase II Transcription Initiation And Promoter Clearance
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-5663205	Infectious disease
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 282 (showing top): GOBP_CHROMOSOME_ORGANIZATION, AP1_01, ENK_UV_RESPONSE_KERATINOCYTE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, BROWNE_HCMV_INFECTION_16HR_UP, FOXO1_01, PUJANA_CHEK2_PCC_NETWORK, GOBP_POSITIVE_REGULATION_OF_BINDING, CTAGGAA_MIR384, AP1_Q4_01, REACTOME_HIV_INFECTION, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN

GO Biological Process (15): transcriptional start site selection at RNA polymerase II promoter (GO:0001174), DNA-templated transcription initiation (GO:0006352), transcription by RNA polymerase II (GO:0006366), transcription initiation at RNA polymerase II promoter (GO:0006367), protein acetylation (GO:0006473), viral transcription (GO:0019083), RNA polymerase II preinitiation complex assembly (GO:0051123), meiotic sister chromatid cohesion (GO:0051177), spindle assembly (GO:0051225), positive regulation of core promoter binding (GO:1904798), RNA polymerase II core complex assembly (GO:1990114), chromatin remodeling (GO:0006338), gene expression (GO:0010467), chromosome organization (GO:0051276), transcription preinitiation complex assembly (GO:0070897)

GO Molecular Function (16): RNA polymerase II core promoter sequence-specific DNA binding (GO:0000979), RNA polymerase II complex binding (GO:0000993), zinc ion binding (GO:0008270), RNA polymerase II general transcription initiation factor activity (GO:0016251), acetyltransferase activity (GO:0016407), TBP-class protein binding (GO:0017025), nuclear thyroid hormone receptor binding (GO:0046966), protein-lysine-acetyltransferase activity (GO:0061733), DNA-binding transcription factor binding (GO:0140297), promoter-specific chromatin binding (GO:1990841), DNA binding (GO:0003677), histone acetyltransferase activity (GO:0004402), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), metal ion binding (GO:0046872)

GO Cellular Component (12): kinetochore (GO:0000776), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription factor TFIID complex (GO:0005669), chromosome (GO:0005694), nuclear body (GO:0016604), cell division site (GO:0032153), protein-DNA complex (GO:0032993), germinal vesicle (GO:0042585), RNA polymerase II transcription regulator complex (GO:0090575), transcription preinitiation complex (GO:0097550), condensed chromosome (GO:0000793)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
RNA Polymerase II Transcription	4
Transcription of the HIV genome	2
RNA Polymerase II Transcription Initiation And Promoter Clearance	2
Late Phase of HIV Life Cycle	1
HIV Infection	1
HIV Life Cycle	1
Viral Infection Pathways	1
Disease	1
Gene expression (Transcription)	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	3
transcription initiation at RNA polymerase II promoter	2
DNA-templated transcription	2
DNA-templated transcription initiation	2
transcription by RNA polymerase II	2
core promoter sequence-specific DNA binding	2
cellular anatomical structure	2
DNA-templated transcriptional start site selection	1
RNA biosynthetic process	1
protein acylation	1
viral process	1
viral gene expression	1
transcription preinitiation complex assembly	1
sister chromatid cohesion	1
spindle organization	1
chromosome segregation	1
membraneless organelle assembly	1
positive regulation of transcription regulatory region DNA binding	1
protein-containing complex assembly	1
chromatin organization	1
macromolecule biosynthetic process	1
organelle organization	1
protein-DNA complex assembly	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
RNA polymerase core enzyme binding	1
transition metal ion binding	1
general transcription initiation factor activity	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
general transcription initiation factor binding	1
nuclear receptor binding	1
protein N-acetyltransferase activity	1
transcription factor binding	1
chromatin binding	1
nucleic acid binding	1
protein-lysine-acetyltransferase activity	1
histone modifying activity	1
binding	1
catalytic activity	1
transferase activity	1
cation binding	1

Protein interactions and networks

STRING

2410 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GTF2B	TBP	P20226	999
GTF2B	GTF2F2	P13984	980
GTF2B	GTF2F1	P35269	977
GTF2B	GTF2E1	P29083	954
GTF2B	EP300	Q09472	950
GTF2B	ERCC3	P19447	950
GTF2B	TCEA2	Q15560	945
GTF2B	TCEA1	P23193	937
GTF2B	SSU72	Q9NP77	936
GTF2B	TAF1	P21675	934
GTF2B	GTF2E2	P29084	912
GTF2B	POLR2A	P24928	907
GTF2B	POLR2E	P19388	900
GTF2B	TCEA3	O75764	894
GTF2B	CFAP20	Q9Y6A4	880

IntAct

256 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
MED11	MED19	psi-mi:“MI:0914”(association)	0.840
POLR2E	POLR2D	psi-mi:“MI:0915”(physical association)	0.790
MED14	MED19	psi-mi:“MI:0914”(association)	0.790
MED9	MED19	psi-mi:“MI:0914”(association)	0.790
TNIP1	GTF2B	psi-mi:“MI:0915”(physical association)	0.780
GTF2B	TNIP1	psi-mi:“MI:0915”(physical association)	0.780
GTF2B	POLR2E	psi-mi:“MI:0915”(physical association)	0.740
MED21	POLR2D	psi-mi:“MI:0914”(association)	0.730
MED28	MED7	psi-mi:“MI:0914”(association)	0.730
POLR2A	POLR2D	psi-mi:“MI:0914”(association)	0.730
POLR2C	POLR2D	psi-mi:“MI:0914”(association)	0.730
POLR2D	POLR2C	psi-mi:“MI:0914”(association)	0.730
DRAP1	GTF2B	psi-mi:“MI:0915”(physical association)	0.720
GTF2B	DRAP1	psi-mi:“MI:0915”(physical association)	0.720
POLR2C	SUPT5H	psi-mi:“MI:0914”(association)	0.640
GTF2B	TBP	psi-mi:“MI:0915”(physical association)	0.590
GOLGA6L9	GTF2B	psi-mi:“MI:0915”(physical association)	0.560
GTF2B	ANXA8	psi-mi:“MI:0915”(physical association)	0.560
GTF2B	CBLB	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (203): TNIP1 (Two-hybrid), DRAP1 (Two-hybrid), IGKC (Affinity Capture-MS), SERPINB1 (Affinity Capture-MS), AMY1C (Affinity Capture-MS), CST4 (Affinity Capture-MS), CST1 (Affinity Capture-MS), CST2 (Affinity Capture-MS), PIGR (Affinity Capture-MS), NME2P1 (Affinity Capture-MS), ZG16B (Affinity Capture-MS), MUC7 (Affinity Capture-MS), IGHA1 (Affinity Capture-MS), PRB1 (Affinity Capture-MS), OXSM (Affinity Capture-MS)

ESM2 similar proteins: A7Y521, F1LMZ8, F1QGH9, F6P3G4, F6XBL2, O00231, O70133, O88544, P29052, P29054, P43246, P43247, P48444, P48512, P48513, P53619, P62915, P62916, P93394, Q00403, Q08211, Q13098, Q28141, Q2KI42, Q2KIN8, Q3MHE4, Q3SZA0, Q4R3J5, Q4R5E6, Q5R648, Q5R874, Q5R886, Q5R8Q7, Q5RA77, Q5XJY5, Q5XXB5, Q5ZL57, Q66H80, Q68FK8, Q68FS2

Diamond homologs: A0B5T8, A1RV37, A3CSQ6, A4G0F2, A4WMA6, A5UKA1, A6UW60, A6VI28, A7IAR4, A8AC96, A8MCX6, A9A8Q0, B1YCX0, B8GJQ9, O13749, O16991, O23215, O26971, O28970, O59151, P0CW14, P0CW15, P29052, P29054, P42198, P46221, P48512, P48513, P50387, P58109, P58110, P58111, P61998, P61999, P62915, P62916, Q00403, Q2KIN8, Q2NEL6, Q4R3J5

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
GTF2B	“up-regulates activity”	TFIIF	relocalization
TFIID	“up-regulates activity”	GTF2B	relocalization
GTF2B	“up-regulates activity”	FOXF2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 93 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
FGFR2 mutant receptor activation	6	83.0×	6e-10
Signaling by FGFR2 IIIa TM	7	76.5×	4e-11
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	10	74.2×	5e-15
RNA Pol II CTD phosphorylation and interaction with CE	10	74.2×	5e-15
Abortive elongation of HIV-1 transcript in the absence of Tat	8	72.2×	2e-12
mRNA Capping	10	69.2×	9e-15
Formation of the Early Elongation Complex	10	61.1×	3e-14
Formation of the HIV-1 Early Elongation Complex	10	61.1×	3e-14

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription initiation by RNA polymerase II	10	33.6×	2e-10
positive regulation of transcription elongation by RNA polymerase II	9	33.4×	2e-09
RNA polymerase II preinitiation complex assembly	9	30.2×	3e-09
transcription initiation at RNA polymerase II promoter	6	27.7×	1e-05
transcription by RNA polymerase II	13	11.3×	2e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1046 predictions. Top by Δscore:

Variant	Effect	Δscore
1:88853344:TTT:T	acceptor_gain	1.0000
1:88853346:TCTA:T	acceptor_loss	1.0000
1:88853347:C:A	acceptor_loss	1.0000
1:88853347:C:CC	acceptor_gain	1.0000
1:88853348:T:G	acceptor_loss	1.0000
1:88857483:TATTT:T	acceptor_gain	1.0000
1:88857485:TTT:T	acceptor_gain	1.0000
1:88857488:C:CC	acceptor_gain	1.0000
1:88860133:AACTT:A	donor_loss	1.0000
1:88860134:ACTTA:A	donor_loss	1.0000
1:88860135:CTTAC:C	donor_loss	1.0000
1:88860136:TTAC:T	donor_loss	1.0000
1:88860137:T:TG	donor_loss	1.0000
1:88860138:A:AC	donor_gain	1.0000
1:88860138:A:AG	donor_loss	1.0000
1:88860139:C:CG	donor_gain	1.0000
1:88860139:CA:C	donor_gain	1.0000
1:88860139:CAA:C	donor_gain	1.0000
1:88860139:CAACT:C	donor_gain	1.0000
1:88860282:GTGCC:G	acceptor_gain	1.0000
1:88860283:TGCC:T	acceptor_gain	1.0000
1:88860285:CC:C	acceptor_gain	1.0000
1:88860286:CC:C	acceptor_gain	1.0000
1:88860287:C:CC	acceptor_gain	1.0000
1:88860287:C:CG	acceptor_loss	1.0000
1:88860288:T:G	acceptor_loss	1.0000
1:88863975:TATTA:T	donor_loss	1.0000
1:88863976:ATTAC:A	donor_gain	1.0000
1:88863977:TTACC:T	donor_loss	1.0000
1:88863978:TAC:T	donor_loss	1.0000

AlphaMissense

2076 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:88853331:G:T	A278D	1.000
1:88857241:G:T	A261D	1.000
1:88857253:G:T	A257D	1.000
1:88857254:C:G	A257P	1.000
1:88857256:G:T	A256E	1.000
1:88857259:G:T	A255E	1.000
1:88857308:C:G	A239P	1.000
1:88857328:G:T	A232D	1.000
1:88857329:C:G	A232P	1.000
1:88857366:A:C	C219W	1.000
1:88857367:C:T	C219Y	1.000
1:88857369:G:C	F218L	1.000
1:88857369:G:T	F218L	1.000
1:88857371:A:G	F218L	1.000
1:88857372:C:A	R217S	1.000
1:88857372:C:G	R217S	1.000
1:88857373:C:A	R217M	1.000
1:88857373:C:G	R217T	1.000
1:88857438:A:C	F195L	1.000
1:88857438:A:T	F195L	1.000
1:88857440:A:G	F195L	1.000
1:88857448:C:T	G192D	1.000
1:88857484:A:T	I180K	1.000
1:88859892:C:A	R175S	1.000
1:88859892:C:G	R175S	1.000
1:88859893:C:A	R175M	1.000
1:88859893:C:G	R175T	1.000
1:88859910:T:A	R169S	1.000
1:88859910:T:G	R169S	1.000
1:88859913:A:C	C168W	1.000

dbSNP variants (sampled 300 via entrez): RS1000022599 (1:88862638 A>G), RS1000053928 (1:88872765 G>A), RS1000056187 (1:88867159 T>C), RS1000065667 (1:88866350 A>T), RS1000114413 (1:88873864 A>C), RS1000120829 (1:88890085 C>A), RS1000290265 (1:88891902 C>G,T), RS1000323988 (1:88892225 C>A), RS1000348205 (1:88861619 G>A,T), RS1000403762 (1:88872939 T>C), RS1000476878 (1:88853717 T>C), RS1000528897 (1:88877283 T>C), RS1000541874 (1:88876998 T>A,C), RS1000646366 (1:88886988 G>A), RS1000668655 (1:88866704 A>G)

Disease associations

OMIM: gene MIM:189963 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001762_221	Obesity-related traits	4.000000e-06
GCST004279_35	Systolic blood pressure	2.000000e-15
GCST005580_277	Intraocular pressure	9.000000e-10
GCST005790_80	Rosacea symptom severity	2.000000e-06
GCST007267_174	Systolic blood pressure	3.000000e-09
GCST007269_16	Pulse pressure	9.000000e-09
GCST007611_10	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	3.000000e-12
GCST90002383_329	Hematocrit	9.000000e-16

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004520	ICAM-1 measurement
EFO:0006335	systolic blood pressure
EFO:0004695	intraocular pressure measurement
EFO:0009180	rosacea severity measurement
EFO:0005763	pulse pressure measurement
EFO:0004348	hematocrit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

51 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Tobacco Smoke Pollution	increases expression	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
1,12-benzoperylene	increases expression	1
bisphenol A	increases expression	1
geraniol	increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
butyraldehyde	increases expression	1
zinc chromate	increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
4-hydroxy-2-nonenal	decreases expression	1
nickel sulfate	increases expression	1
cupric oxide	increases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
chromium hexavalent ion	increases expression, increases abundance	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
cladribine monophosphate	affects binding, affects reaction	1
Resveratrol	increases expression, decreases expression	1
Temozolomide	increases expression	1
Acetaminophen	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Copper	affects binding, decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Dinitrochlorobenzene	increases expression	1
Disulfiram	affects binding, decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A2I4	SEES3-1V human GTF2B, clone1	Embryonic stem cell	Male
CVCL_A2I5	SEES3-1V human GTF2B, clone2	Embryonic stem cell	Male
CVCL_A2I6	SEES3-1V human GTF2B, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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