GTF2F1

Summary

GTF2F1 (general transcription factor IIF subunit 1, HGNC:4652) is a protein-coding gene on chromosome 19p13.3, encoding General transcription factor IIF subunit 1 (P35269). TFIIF is a general transcription initiation factor that binds to RNA polymerase II and helps to recruit it to the initiation complex in collaboration with TFIIB. It is a selective cancer dependency (DepMap: 51.0% of cell lines).

Enables several functions, including RNA polymerase II general transcription initiation factor activity; phosphatase activator activity; and promoter-specific chromatin binding activity. Involved in positive regulation of transcription by RNA polymerase II; response to virus; and transcription by RNA polymerase II. Located in cell junction and nucleoplasm. Part of transcription factor TFIID complex and transcription factor TFIIF complex.

Source: NCBI Gene 2962 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 122 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 51.0% of screened cell lines
• MANE Select transcript: NM_002096

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4652
Approved symbol	GTF2F1
Name	general transcription factor IIF subunit 1
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	TFIIF, BTF4, RAP74, TF2F1
Ensembl gene	ENSG00000125651
Ensembl biotype	protein_coding
OMIM	189968
Entrez	2962

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 2 retained_intron

ENST00000394456, ENST00000593678, ENST00000594213, ENST00000594965, ENST00000595047, ENST00000598607, ENST00000869875, ENST00000933129, ENST00000933130

RefSeq mRNA: 1 — MANE Select: NM_002096 NM_002096

CCDS: CCDS12165

Canonical transcript exons

ENST00000394456 — 13 exons

Exon	Start	End
ENSE00000666056	6389444	6389637
ENSE00000666058	6387389	6387559
ENSE00000666060	6383311	6383495
ENSE00001060029	6381697	6381850
ENSE00001518517	6379572	6380485
ENSE00001720340	6391902	6391974
ENSE00003187061	6392984	6393164
ENSE00003461295	6381122	6381195
ENSE00003467792	6381554	6381615
ENSE00003618163	6380573	6380690
ENSE00003631791	6392857	6392903
ENSE00003636945	6380904	6381042
ENSE00003692659	6381359	6381478

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 81.4818 / max 354.2793, expressed in 1827 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178618	60.5618	1826
178619	11.1013	1806
178622	4.7029	1673
178620	2.0807	1372
178621	1.8796	931
178623	0.7816	566
178624	0.3110	114
178625	0.0546	14
178626	0.0082	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellum	UBERON:0002037	96.15	gold quality
cerebellar cortex	UBERON:0002129	96.12	gold quality
cerebellar hemisphere	UBERON:0002245	96.11	gold quality
left testis	UBERON:0004533	96.07	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.92	gold quality
right testis	UBERON:0004534	95.81	gold quality
cortical plate	UBERON:0005343	95.48	gold quality
left ovary	UBERON:0002119	95.22	gold quality
testis	UBERON:0000473	95.10	gold quality
ovary	UBERON:0000992	95.09	gold quality
prefrontal cortex	UBERON:0000451	95.02	gold quality
frontal cortex	UBERON:0001870	94.86	gold quality
adenohypophysis	UBERON:0002196	94.71	gold quality
superior frontal gyrus	UBERON:0002661	94.60	gold quality
pituitary gland	UBERON:0000007	94.55	gold quality
right frontal lobe	UBERON:0002810	94.53	gold quality
sural nerve	UBERON:0015488	94.46	gold quality
right ovary	UBERON:0002118	94.44	gold quality
anterior cingulate cortex	UBERON:0009835	94.35	gold quality
cerebral cortex	UBERON:0000956	94.33	gold quality
body of pancreas	UBERON:0001150	94.24	gold quality
ganglionic eminence	UBERON:0004023	94.20	gold quality
mucosa of transverse colon	UBERON:0004991	94.19	gold quality
brain	UBERON:0000955	94.17	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.16	gold quality
body of uterus	UBERON:0009853	94.14	gold quality
body of stomach	UBERON:0001161	94.03	gold quality
ventricular zone	UBERON:0003053	93.96	gold quality
gall bladder	UBERON:0002110	93.95	gold quality
nucleus accumbens	UBERON:0001882	93.86	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
BGLAP	Unknown

Upstream regulators (CollecTRI, top): AR, DNMT1, SSRP1, TBP

miRNA regulators (miRDB)

27 targeting GTF2F1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-7154-3P	97.65	65.02	985
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-3059-3P	96.71	67.08	606
HSA-MIR-500B-3P	96.49	65.40	1087
HSA-MIR-6879-3P	93.93	64.00	759

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 51.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 16)

• role of associated carboxyl-terminal domain phosphatase in dephosphorylating phosphoserines 2 and 5 of RNA polymerase II (PMID:12351650)
• The alpha 1 helix of human RAP74 has an important role in the initiation and elongation of RNA chains (PMID:12354769)
• The NMR solution structure of the C-terminal domain of RAP74 has been determined, and NMR methods have been used to map the binding sites of the C-terminus of CTD phosphatase/FCP1 on the RAP74 C-terminal fragment. (PMID:12578358)
• cocrystal structure of the winged-helix domain of human RNA polymerase II-associating protein 74 bound to the alpha-helical C terminus of human FCP1 (PMID:12591941)
• NMR structure of a complex containing this TFIIF subunit and the RNA polymerase II carboxyl-terminal domain phosphatase FCP1. (PMID:12732728)
• Interaction of TFIIF subunit RAP74 with recombinant androgen receptor N-terminal activation domain AF1 leads to imposition of helical structure on the AF1 domain. (PMID:15023052)
• TFIIF supports elongation and suppresses pausing by stabilizing the post-translocated elongation complex (PMID:15351637)
• alpha1-Helix of RAP74 is important for supporting NTP-driven translocation by RNAP II. (PMID:15831464)
• TFIIF and Rpb7 are involved in both early and late transcriptional stages (PMID:17848138)
• Mutated hydrophobic residues in RAP74 C-terminal structure disrupt secondary structure elements, showing that binding of the androgen receptor N-terminal domain depends upon helix 3 in the winged-helix domain of the RAP74 C-terminal domain polypeptide. (PMID:18284209)
• NMR and thermodynamic studies further elucidate the complex molecular mechanism by which TFIIF and FCP1 cooperate for RNAPII recycling. (PMID:19215094)
• Data show that TFIIF has an important role in stabilizing TFIIB within the PIC and after transcription initiates. (PMID:21896726)
• Gdown1 competes with TFIIF for binding to the RPB1 and RPB5 subunits of Pol II, thereby inhibiting an essential function of TFIIF in preinitiation complex assembly. (PMID:22244332)
• These results suggest that Mediator structural shifts induced by activator binding help stably orient pol II prior to transcription initiation within the human mediator-RNA polymerase II-TFIIF assembly. (PMID:22343046)
• An AR motif of the transactivation domain has been identified that contributes to transcriptional activity by recruiting the C-terminal domain of subunit 1 of the general transcription regulator TFIIF. (PMID:29225078)
• Leptin prevents aberrant targeting of tau to hippocampal synapses via PI 3 kinase driven inhibition of GSK3beta. (PMID:37822142)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gtf2f1	ENSDARG00000032129
mus_musculus	Gtf2f1	ENSMUSG00000002658
rattus_norvegicus	Gtf2f1	ENSRNOG00000047134
drosophila_melanogaster	TfIIFalpha	FBGN0010282
caenorhabditis_elegans		WBGENE00015296

Protein

Protein identifiers

General transcription factor IIF subunit 1 — P35269 (reviewed: P35269)

Alternative names: General transcription factor IIF 74 kDa subunit, Transcription initiation factor IIF subunit alpha, Transcription initiation factor RAP74

All UniProt accessions (4): P35269, M0QXD6, M0R0R9, M0R0Z3

UniProt curated annotations — full annotation on UniProt →

Function. TFIIF is a general transcription initiation factor that binds to RNA polymerase II and helps to recruit it to the initiation complex in collaboration with TFIIB. It promotes transcription elongation.

Subunit / interactions. Heterodimer of an alpha and a beta subunit. Interacts with GTF2F2, CTDP1, TAF6/TAFII80 and URI1. Interacts with GTF2B (via C-terminus and preferentially via acetylated form); this interaction prevents binding of GTF2B to GTF2F2. Part of TBP-based Pol II pre-initiation complex (PIC), in which Pol II core assembles with general transcription factors and other specific initiation factors including GTF2E1, GTF2E2, GTF2F1, GTF2F2, TCEA1, ERCC2, ERCC3, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2A1, GTF2A2, GTF2B and TBP; this large multi-subunit PIC complex mediates DNA unwinding and targets Pol II core to the transcription start site where the first phosphodiester bond forms.

Subcellular location. Nucleus.

Post-translational modifications. Phosphorylated on Ser and other residues by TAF1 and casein kinase II-like kinases.

Induction. Up-regulated in response to enterovirus 71 (EV71) infection.

Similarity. Belongs to the TFIIF alpha subunit family.

RefSeq proteins (1): NP_002087* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008851	TFIIF-alpha	Family
IPR011039	TFIIF_interaction	Homologous_superfamily
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily

Pfam: PF05793

UniProt features (61 total): modified residue 20, helix 12, strand 11, compositionally biased region 7, binding site 3, mutagenesis site 2, sequence conflict 2, initiator methionine 1, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

61 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
1I27	X-RAY DIFFRACTION	1.02
1F3U	X-RAY DIFFRACTION	1.7
1J2X	X-RAY DIFFRACTION	2
7NVU	ELECTRON MICROSCOPY	2.5
8WAV	ELECTRON MICROSCOPY	2.72
8WAX	ELECTRON MICROSCOPY	2.75
8WAZ	ELECTRON MICROSCOPY	2.76
8WAU	ELECTRON MICROSCOPY	2.78
7NVS	ELECTRON MICROSCOPY	2.8
8WAT	ELECTRON MICROSCOPY	2.82
8WAY	ELECTRON MICROSCOPY	2.85
7NVT	ELECTRON MICROSCOPY	2.9
8S52	ELECTRON MICROSCOPY	2.9
8WB0	ELECTRON MICROSCOPY	2.94
7ZWD	ELECTRON MICROSCOPY	3
7ZX8	ELECTRON MICROSCOPY	3
8WAW	ELECTRON MICROSCOPY	3.02
8S51	ELECTRON MICROSCOPY	3.1
7EGB	ELECTRON MICROSCOPY	3.3
7ZX7	ELECTRON MICROSCOPY	3.4
8S54	ELECTRON MICROSCOPY	3.4
8S55	ELECTRON MICROSCOPY	3.4
8S5N	ELECTRON MICROSCOPY	3.4
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

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35269-F1	63.20	0.21

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 (3): 503; 512; 517

Post-translational modifications (20): 2, 156, 217, 218, 221, 224, 331, 377, 380, 381, 385, 389, 391, 407, 431, 433, 436, 437, 446, 449

Mutagenesis-validated functional residues (2):

Position	Phenotype
385	eliminates putative kinase activity; when associated with a-389.
389	eliminates putative kinase activity; when associated with a-385.

Function

Pathways and Gene Ontology

Reactome pathways

59 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-113418	Formation of the Early Elongation Complex
R-HSA-167152	Formation of HIV elongation complex in the absence of HIV Tat
R-HSA-167158	Formation of the HIV-1 Early Elongation Complex
R-HSA-167160	RNA Pol II CTD phosphorylation and interaction with CE during HIV infection
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-167200	Formation of HIV-1 elongation complex containing HIV-1 Tat
R-HSA-167238	Pausing and recovery of Tat-mediated HIV elongation
R-HSA-167242	Abortive elongation of HIV-1 transcript in the absence of Tat
R-HSA-167243	Tat-mediated HIV elongation arrest and recovery
R-HSA-167246	Tat-mediated elongation of the HIV-1 transcript
R-HSA-167287	HIV elongation arrest and recovery
R-HSA-167290	Pausing and recovery of HIV elongation
R-HSA-168325	Viral Messenger RNA Synthesis
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes
R-HSA-6803529	FGFR2 alternative splicing
R-HSA-6807505	RNA polymerase II transcribes snRNA genes
R-HSA-72086	mRNA Capping
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72165	mRNA Splicing - Minor Pathway
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
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-75955	RNA Polymerase II Transcription Elongation
R-HSA-76042	RNA Polymerase II Transcription Initiation And Promoter Clearance
R-HSA-77075	RNA Pol II CTD phosphorylation and interaction with CE

MSigDB gene sets: 198 (showing top): GOBP_REGULATION_OF_PROTEIN_BINDING, REACTOME_VIRAL_MESSENGER_RNA_SYNTHESIS, REACTOME_SIGNALING_BY_FGFR, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_BINDING, REACTOME_HIV_INFECTION, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_NEGATIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, REACTOME_MRNA_SPLICING, GOCC_RNA_POLYMERASE_COMPLEX, MORF_PDPK1, ZAMORA_NOS2_TARGETS_UP, MORF_IKBKG

GO Biological Process (7): transcription by RNA polymerase II (GO:0006366), transcription initiation at RNA polymerase II promoter (GO:0006367), transcription elongation by RNA polymerase II (GO:0006368), response to virus (GO:0009615), negative regulation of protein binding (GO:0032091), positive regulation of transcription elongation by RNA polymerase II (GO:0032968), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (10): RNA polymerase II general transcription initiation factor binding (GO:0001091), TFIIF-class transcription factor complex binding (GO:0001096), DNA binding (GO:0003677), RNA binding (GO:0003723), RNA polymerase II general transcription initiation factor activity (GO:0016251), phosphatase activator activity (GO:0019211), protein phosphatase binding (GO:0019903), protein domain specific binding (GO:0019904), promoter-specific chromatin binding (GO:1990841), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription factor TFIID complex (GO:0005669), transcription factor TFIIF complex (GO:0005674), cell junction (GO:0030054), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Transcription of the HIV genome	8
HIV Transcription Elongation	3
RNA Polymerase II Transcription Elongation	2
RNA Polymerase II Transcription	2
Late Phase of HIV Life Cycle	1
Tat-mediated elongation of the HIV-1 transcript	1
Influenza Viral RNA Transcription and Replication	1
Transcriptional Regulation by TP53	1
Signaling by FGFR2	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	4
protein binding	2
nucleic acid binding	2
cellular anatomical structure	2
RNA polymerase II, holoenzyme	2
RNA polymerase II transcription regulator complex	2
DNA-templated transcription	1
DNA-templated transcription initiation	1
DNA-templated transcription elongation	1
response to other organism	1
regulation of protein binding	1
negative regulation of binding	1
transcription elongation by RNA polymerase II	1
positive regulation of DNA-templated transcription, elongation	1
regulation of transcription elongation by RNA polymerase II	1
positive regulation of transcription by RNA polymerase II	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
RNA polymerase II complex binding	1
general transcription initiation factor binding	1
RNA polymerase II general transcription initiation factor binding	1
general transcription initiation factor activity	1
enzyme activator activity	1
phosphatase activity	1
phosphatase regulator activity	1
phosphatase binding	1
chromatin binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular_component	1

Protein interactions and networks

STRING

2445 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GTF2F1	GTF2F2	P13984	999
GTF2F1	CTDP1	Q9Y5B0	996
GTF2F1	GTF2B	Q00403	977
GTF2F1	GTF2E1	P29083	937
GTF2F1	TBP	P20226	920
GTF2F1	TAF7	Q15545	857
GTF2F1	GTF2E2	P29084	838
GTF2F1	POLR2A	P24928	817
GTF2F1	POLR3K	Q9Y2Y1	814
GTF2F1	GTF2H1	P32780	733
GTF2F1	POLR2B	P30876	729
GTF2F1	GTF2A2	P52657	719
GTF2F1	TCEA1	P23193	696
GTF2F1	ZNF668	Q96K58	670
GTF2F1	POLR2I	P36954	666

IntAct

159 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
GTF2F1	GTF2F2	psi-mi:“MI:0407”(direct interaction)	0.870
GTF2F1	GTF2F2	psi-mi:“MI:0915”(physical association)	0.870
GTF2F1	GTF2F2	psi-mi:“MI:0914”(association)	0.870
GTF2F1	GTF2F2	psi-mi:“MI:2364”(proximity)	0.870
GTF2F2	GTF2F1	psi-mi:“MI:2364”(proximity)	0.870
GTF2F2	GTF2F1	psi-mi:“MI:0915”(physical association)	0.870
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850

BioGRID (333): ABL1 (Far Western), GTF2F1 (Affinity Capture-MS), GTF2F1 (Affinity Capture-MS), GTF2F1 (Affinity Capture-MS), GTF2F1 (Affinity Capture-MS), GTF2F1 (Affinity Capture-MS), GTF2F1 (Affinity Capture-MS), GTF2F1 (Affinity Capture-MS), GTF2F1 (Affinity Capture-MS), GTF2F1 (Affinity Capture-MS), GTF2F1 (Co-fractionation), GTF2F1 (Co-fractionation), GTF2F1 (Co-fractionation), GTF2F2 (Co-fractionation), HIRIP3 (Co-fractionation)

ESM2 similar proteins: A0JNI5, A2AJT4, A2AQ19, A4IFB1, B1H1X4, D3ZTQ1, O43290, P35269, Q05519, Q12872, Q13435, Q3THK3, Q3UJB0, Q3UQU0, Q3USH5, Q4V7C9, Q53F19, Q568R1, Q5EA53, Q5HZB6, Q5PQQ2, Q5R539, Q5RAD5, Q5XIW8, Q5ZM19, Q66I22, Q6AY96, Q6DDA4, Q6GLZ8, Q6INH5, Q6ZPZ3, Q8BZR9, Q8CFC7, Q8K194, Q8N2M8, Q8N5F7, Q8TF01, Q8VHI6, Q8WVK2, Q923D5

Diamond homologs: P35269, Q04870, Q05913, Q3THK3, Q5EA53, Q6AY96

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
GTF2F1	down-regulates	GTF2F1	phosphorylation
GTF2F2	“up-regulates activity”	GTF2F1	binding
GTF2F1	“form complex”	TFIIF	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 151 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	8	57.5×	6e-12
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	13	50.0×	9e-18
RNA Pol II CTD phosphorylation and interaction with CE	13	50.0×	9e-18
Abortive elongation of HIV-1 transcript in the absence of Tat	10	46.8×	1e-13
mRNA Capping	13	46.7×	1e-17
Signaling by FGFR2 IIIa TM	8	45.4×	5e-11
Formation of the Early Elongation Complex	14	44.4×	7e-18
Formation of the HIV-1 Early Elongation Complex	14	44.4×	7e-18

GO biological processes:

GO term	Partners	Fold	FDR
transcription initiation at RNA polymerase II promoter	9	24.6×	4e-08
transcription elongation by RNA polymerase II	6	19.4×	2e-04
RNA polymerase II preinitiation complex assembly	7	13.9×	2e-04
positive regulation of transcription initiation by RNA polymerase II	6	11.9×	2e-03
transcription by RNA polymerase II	18	9.3×	9e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	91
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1480 predictions. Top by Δscore:

Variant	Effect	Δscore
19:6380481:CGTCG:C	acceptor_gain	1.0000
19:6380482:GTCG:G	acceptor_gain	1.0000
19:6380483:TCG:T	acceptor_gain	1.0000
19:6380484:CG:C	acceptor_gain	1.0000
19:6380484:CGC:C	acceptor_gain	1.0000
19:6380486:C:CC	acceptor_gain	1.0000
19:6380492:A:AC	acceptor_gain	1.0000
19:6380492:A:C	acceptor_gain	1.0000
19:6380501:C:CT	acceptor_gain	1.0000
19:6380502:G:T	acceptor_gain	1.0000
19:6380569:TTA:T	donor_loss	1.0000
19:6380570:TACCC:T	donor_loss	1.0000
19:6380571:A:AC	donor_gain	1.0000
19:6380571:AC:A	donor_gain	1.0000
19:6380571:ACC:A	donor_gain	1.0000
19:6380571:ACCCG:A	donor_gain	1.0000
19:6380572:C:CT	donor_gain	1.0000
19:6380572:CC:C	donor_gain	1.0000
19:6380572:CCC:C	donor_gain	1.0000
19:6380572:CCCG:C	donor_gain	1.0000
19:6380572:CCCGC:C	donor_gain	1.0000
19:6380686:CTTCC:C	acceptor_gain	1.0000
19:6380687:TTCC:T	acceptor_gain	1.0000
19:6380688:TCC:T	acceptor_gain	1.0000
19:6380688:TCCC:T	acceptor_loss	1.0000
19:6380689:CC:C	acceptor_gain	1.0000
19:6380689:CCC:C	acceptor_gain	1.0000
19:6380689:CCCTG:C	acceptor_loss	1.0000
19:6380690:CCTG:C	acceptor_gain	1.0000
19:6380691:C:CC	acceptor_gain	1.0000

AlphaMissense

3446 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:6380297:A:G	F513S	1.000
19:6380330:G:T	P502H	1.000
19:6380331:G:A	P502S	1.000
19:6380336:A:G	L500P	1.000
19:6380345:A:G	L497P	1.000
19:6380345:A:T	L497H	1.000
19:6380354:G:T	A494D	1.000
19:6380357:A:G	L493S	1.000
19:6380405:A:G	F477S	1.000
19:6380409:T:C	K476E	1.000
19:6380414:A:G	L474P	1.000
19:6380417:A:G	L473P	1.000
19:6380417:A:T	L473Q	1.000
19:6380447:A:C	L463R	1.000
19:6380447:A:G	L463P	1.000
19:6380447:A:T	L463Q	1.000
19:6380451:A:C	Y462D	1.000
19:6380451:A:G	Y462H	1.000
19:6380456:C:G	R460P	1.000
19:6380459:A:T	V459E	1.000
19:6381750:G:C	S261R	1.000
19:6381750:G:T	S261R	1.000
19:6381752:T:G	S261R	1.000
19:6383471:G:C	F174L	1.000
19:6383471:G:T	F174L	1.000
19:6383472:A:G	F174S	1.000
19:6383473:A:G	F174L	1.000
19:6383492:C:A	R167S	1.000
19:6383492:C:G	R167S	1.000
19:6383493:C:A	R167M	1.000

dbSNP variants (sampled 300 via entrez): RS1000029043 (19:6380251 G>A,C,T), RS1000091228 (19:6381231 A>C,G), RS1000708854 (19:6383409 T>A), RS1001197030 (19:6387099 G>A), RS1001257736 (19:6389088 C>G), RS1001551416 (19:6392015 A>C), RS1001670772 (19:6386722 C>A,T), RS1001706327 (19:6382233 G>C), RS1001774858 (19:6394087 T>C,G), RS1001819631 (19:6384438 G>A,C,T), RS1002054491 (19:6392701 A>T), RS1002383265 (19:6391044 C>T), RS1002720420 (19:6394948 C>G,T), RS1002779599 (19:6390841 C>T), RS1002824331 (19:6394569 C>G,T)

Disease associations

OMIM: gene MIM:189968 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066158 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.50	Kd	32	nM	MOLIBRESIB
7.00	IC50	100	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 7 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179226: Binding affinity against GTF2F1 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0320	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Ozone	increases abundance, affects expression, decreases expression, affects cotreatment, increases oxidation	3
cobaltous chloride	increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Valproic Acid	increases expression, increases methylation	2
Particulate Matter	affects cotreatment, increases abundance, increases expression, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
sodium arsenite	increases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Vehicle Emissions	increases expression, increases abundance	1
Benztropine	affects cotreatment, decreases expression	1
Cannabidiol	affects cotreatment, decreases expression	1
Carmustine	decreases expression	1
Cuprizone	decreases expression, affects cotreatment	1
Diazinon	increases methylation	1
Gasoline	decreases expression, affects cotreatment, increases abundance, increases expression	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Mustard Gas	increases phosphorylation	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697633	Binding	Inhibition of GTF2F1 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A2I7	SEES3-1V human GTF2F1, clone1	Embryonic stem cell	Male
CVCL_A2I8	SEES3-1V human GTF2F1, clone2	Embryonic stem cell	Male
CVCL_A2I9	SEES3-1V human GTF2F1, clone3	Embryonic stem cell	Male
CVCL_B2YE	Abcam HEK293T GTF2F1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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