GTF2E2

Summary

GTF2E2 (general transcription factor IIE subunit 2, HGNC:4651) is a protein-coding gene on chromosome 8p12, encoding Transcription initiation factor IIE subunit beta (P29084). Recruits TFIIH to the initiation complex and stimulates the RNA polymerase II C-terminal domain kinase and DNA-dependent ATPase activities of TFIIH. It is a common-essential gene (DepMap: required in 99.3% of cancer cell lines).

The general transcription factor IIE (TFIIE) is part of the RNA polymerase II transcription initiation complex, recruiting TFIIH and being essential for promoter clearance by RNA polymerase II. TFIIE is a heterodimer (and sometimes heterotetramer) of alpha and beta subunits. The protein encoded by this gene represents the beta subunit of TFIIE.

Source: NCBI Gene 2961 — RefSeq curated summary.

At a glance

• Gene–disease (curated): trichothiodystrophy 6, nonphotosensitive (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 204 total — 2 pathogenic
• Phenotypes (HPO): 105
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_002095

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4651
Approved symbol	GTF2E2
Name	general transcription factor IIE subunit 2
Location	8p12
Locus type	gene with protein product
Status	Approved
Aliases	TFIIE-B, FE, TF2E2
Ensembl gene	ENSG00000197265
Ensembl biotype	protein_coding
OMIM	189964
Entrez	2961

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 20 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000355904, ENST00000518445, ENST00000518599, ENST00000522833, ENST00000523499, ENST00000868886, ENST00000868887, ENST00000868888, ENST00000868889, ENST00000868890, ENST00000868891, ENST00000868892, ENST00000868893, ENST00000868894, ENST00000868895, ENST00000917975, ENST00000917976, ENST00000917977, ENST00000943595, ENST00000943596, ENST00000943597, ENST00000943598

RefSeq mRNA: 2 — MANE Select: NM_002095 NM_001348353, NM_002095

CCDS: CCDS6078

Canonical transcript exons

ENST00000355904 — 8 exons

Exon	Start	End
ENSE00000687873	30580281	30580396
ENSE00001092687	30653433	30653602
ENSE00001092688	30578318	30579037
ENSE00001374568	30657973	30658236
ENSE00003526605	30635032	30635123
ENSE00003611595	30607057	30607150
ENSE00003656693	30614608	30614715
ENSE00003688578	30612299	30612481

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 95.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.8624 / max 227.5841, expressed in 1824 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92622	30.4704	1824
92620	0.8145	487
92621	0.3477	153
92623	0.2299	57

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	95.67	gold quality
body of pancreas	UBERON:0001150	94.13	gold quality
pancreas	UBERON:0001264	92.33	gold quality
right testis	UBERON:0004534	92.01	gold quality
left testis	UBERON:0004533	91.84	gold quality
calcaneal tendon	UBERON:0003701	91.13	gold quality
testis	UBERON:0000473	90.81	gold quality
sperm	CL:0000019	90.78	gold quality
cortical plate	UBERON:0005343	90.75	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.68	gold quality
islet of Langerhans	UBERON:0000006	90.64	gold quality
right adrenal gland	UBERON:0001233	90.64	gold quality
lower esophagus mucosa	UBERON:0035834	90.61	gold quality
right adrenal gland cortex	UBERON:0035827	90.54	gold quality
stromal cell of endometrium	CL:0002255	90.00	gold quality
left adrenal gland	UBERON:0001234	89.99	gold quality
left ovary	UBERON:0002119	89.72	gold quality
left adrenal gland cortex	UBERON:0035825	89.67	gold quality
adrenal gland	UBERON:0002369	89.66	gold quality
right ovary	UBERON:0002118	89.47	gold quality
esophagus mucosa	UBERON:0002469	89.31	gold quality
granulocyte	CL:0000094	89.19	gold quality
omental fat pad	UBERON:0010414	89.17	gold quality
peritoneum	UBERON:0002358	89.14	gold quality
male germ cell	CL:0000015	89.11	gold quality
mucosa of transverse colon	UBERON:0004991	89.04	gold quality
adrenal cortex	UBERON:0001235	88.99	gold quality
ganglionic eminence	UBERON:0004023	88.86	gold quality
esophagus	UBERON:0001043	88.81	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.80	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-5	no	2.22
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting GTF2E2, 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-340-5P	100.00	72.50	4437
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-194-5P	99.01	69.65	1465
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-6500-3P	97.42	67.20	867
HSA-MIR-3914	94.91	65.77	643

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 11)

• introduced point mutations into two regions located near the carboxy terminus of TFIIE beta and identified the functionally essential amino acid residues that bind to RNA polymerase II (PMID:12665589)
• TFIIE is an alpha/beta heterodimer in solution; A model for the quaternary architecture of the complex is proposed that provides a structural framework to discuss the function of TFIIE in the context of RNA polymerase II transcription initiation. (PMID:16547462)
• These data suggest a model in which TFIIE binds to a position adjacent to the initiation site via the forkhead domain, enabling TFIIH to begin opening the promoter. (PMID:19210545)
• PC4 plays essential roles in the transition step from transcription initiation to elongation by binding to melted DNA in collaboration with TFIIEbeta. (PMID:25308091)
• We underline role of TFIIE in transcription and its distinction from nucleotide excision repair. Trichothiodystrophy individuals with mutations in GTF2E2 highlight the importance of the direct interaction between TFIIH and TFIIE in transcription process. (PMID:26996949)
• The N-terminal half of TFIIEalpha forms an extended winged helix (WH) domain with an additional helix, followed by a zinc-finger domain. TFIIEbeta contains the WH2 domain, followed by two coiled-coil helices intertwining with TFIIEalpha. (PMID:27639436)
• functional analysis of Trichothiodystrophy causative TFIIEbeta mutation demonstrates that mutant TFIIEbeta strongly reduces the total amount of the entire TFIIE complex, with a remarkable temperature-sensitive transcription defect. (PMID:28973399)
• Nucleolar TFIIE plays a role in ribosomal biogenesis and performance. (PMID:34581812)
• GTF2E2 is a novel biomarker for recurrence after surgery and promotes progression of esophageal squamous cell carcinoma via miR-139-5p/GTF2E2/FUS axis. (PMID:34853466)
• Mayaro Virus Non-Structural Protein 2 Circumvents the Induction of Interferon in Part by Depleting Host Transcription Initiation Factor IIE Subunit 2. (PMID:34944018)
• GTF2E2 downregulated by miR-340-5p inhibits the malignant progression of glioblastoma. (PMID:37845349)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gtf2e2	ENSDARG00000012672
mus_musculus	Gtf2e2	ENSMUSG00000031585
rattus_norvegicus	Gtf2e2	ENSRNOG00000014422
drosophila_melanogaster	TfIIEbeta	FBGN0015829
caenorhabditis_elegans		WBGENE00010054

Protein

Protein identifiers

Transcription initiation factor IIE subunit beta — P29084 (reviewed: P29084)

Alternative names: General transcription factor IIE subunit 2

All UniProt accessions (4): E5RH41, E5RIW4, E5RK24, P29084

UniProt curated annotations — full annotation on UniProt →

Function. Recruits TFIIH to the initiation complex and stimulates the RNA polymerase II C-terminal domain kinase and DNA-dependent ATPase activities of TFIIH. Both TFIIH and TFIIE are required for promoter clearance by RNA polymerase.

Subunit / interactions. Tetramer of two alpha and two beta chains. Interacts with FACT subunit SUPT16H. Interacts with ATF7IP. Interacts with SND1. 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.

Disease relevance. Trichothiodystrophy 6, non-photosensitive (TTD6) [MIM:616943] A form of trichothiodystrophy, a disease characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The spectrum of clinical features varies from mild disease with only hair involvement to severe disease with cutaneous, neurologic and profound developmental defects. Ichthyosis, intellectual and developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections are common manifestations. There are both photosensitive and non-photosensitive forms of the disorder. TTD6 patients do not manifest cutaneous photosensitivity. Inheritance pattern has been reported to be autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TFIIE beta subunit family.

RefSeq proteins (2): NP_001335282, NP_002086* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003166	TFIIE_bsu_DNA-bd	Domain
IPR016656	TFIIE-bsu	Family
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR040501	TFA2_Winged_2	Domain

Pfam: PF02186, PF18121

UniProt features (34 total): helix 11, strand 7, sequence variant 4, compositionally biased region 3, modified residue 3, region of interest 2, chain 1, DNA-binding region 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

42 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5GPY	X-RAY DIFFRACTION	2.1
7NVU	ELECTRON MICROSCOPY	2.5
7NVS	ELECTRON MICROSCOPY	2.8
7NVT	ELECTRON MICROSCOPY	2.9
8S52	ELECTRON MICROSCOPY	2.9
8S51	ELECTRON MICROSCOPY	3.1
7EGB	ELECTRON MICROSCOPY	3.3
8S55	ELECTRON MICROSCOPY	3.4
8S5N	ELECTRON MICROSCOPY	3.4
7EG9	ELECTRON MICROSCOPY	3.7
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
7NVR	ELECTRON MICROSCOPY	4.5
7LBM	ELECTRON MICROSCOPY	4.8
8GXQ	ELECTRON MICROSCOPY	5.04
5IYA	ELECTRON MICROSCOPY	5.4
8WAK	ELECTRON MICROSCOPY	5.47
8WAP	ELECTRON MICROSCOPY	5.85
8WAN	ELECTRON MICROSCOPY	6.07
8WAS	ELECTRON MICROSCOPY	6.13
8WAQ	ELECTRON MICROSCOPY	6.29
5IY9	ELECTRON MICROSCOPY	6.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29084-F1	68.97	0.04

Functional residue map

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

Post-translational modifications (3): 1, 61, 74

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: 409 (showing top): BECKER_TAMOXIFEN_RESISTANCE_UP, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, PUJANA_CHEK2_PCC_NETWORK, REACTOME_HIV_INFECTION, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, SCHLOSSER_SERUM_RESPONSE_DN, AACTTT_UNKNOWN, GOCC_RNA_POLYMERASE_COMPLEX, chr8p12, GOBP_PROTEIN_DNA_COMPLEX_ORGANIZATION, MODULE_124

GO Biological Process (2): transcription by RNA polymerase II (GO:0006366), transcription initiation at RNA polymerase II promoter (GO:0006367)

GO Molecular Function (5): DNA binding (GO:0003677), RNA binding (GO:0003723), RNA polymerase II general transcription initiation factor activity (GO:0016251), TFIIH-class transcription factor complex binding (GO:0001097), protein binding (GO:0005515)

GO Cellular Component (5): nucleoplasm (GO:0005654), transcription factor TFIID complex (GO:0005669), transcription factor TFIIE complex (GO:0005673), cytosol (GO:0005829), nucleus (GO:0005634)

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
transcription by RNA polymerase II	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
general transcription initiation factor activity	1
RNA polymerase II general transcription initiation factor binding	1
binding	1
nuclear lumen	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2066 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GTF2E2	GTF2E1	P29083	994
GTF2E2	GTF2F2	P13984	951
GTF2E2	GTF2B	Q00403	912
GTF2E2	GTF2F1	P35269	838
GTF2E2	ERCC3	P19447	788
GTF2E2	TAF7	Q15545	756
GTF2E2	TAF12	Q16514	753
GTF2E2	ERCC2	P18074	664
GTF2E2	TBP	P20226	641
GTF2E2	ATF7IP2	Q5U623	640
GTF2E2	TAF6	P49848	617
GTF2E2	TAF1	P21675	565
GTF2E2	EPRS1	P07814	553
GTF2E2	RNF113A	O15541	552
GTF2E2	SETDB1	Q15047	548
GTF2E2	MPLKIP	Q8TAP9	548

IntAct

48 interactions, top by confidence:

A	B	Type	Score
GTF2E1	GTF2E2	psi-mi:“MI:0915”(physical association)	0.870
GTF2E2	GTF2E1	psi-mi:“MI:0407”(direct interaction)	0.870
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
POLR2E	POLR2D	psi-mi:“MI:0915”(physical association)	0.790
GTF2E2	OIP5	psi-mi:“MI:0914”(association)	0.640
GTF2E2	EXOC8	psi-mi:“MI:0915”(physical association)	0.560
GTF2E2	PICK1	psi-mi:“MI:0915”(physical association)	0.560
GTF2E2	KAT5	psi-mi:“MI:0915”(physical association)	0.560
MCC	GTF2E2	psi-mi:“MI:0915”(physical association)	0.510
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
GTF2E2	H1-2	psi-mi:“MI:0915”(physical association)	0.400
HSCB	GTF2E2	psi-mi:“MI:0915”(physical association)	0.370
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
GTF2E2	UBA6	psi-mi:“MI:0914”(association)	0.350
TAGLN	LOC392647	psi-mi:“MI:0914”(association)	0.350
CASP8	CCN1	psi-mi:“MI:0914”(association)	0.350
CACNA1C	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
GTF2E2	STX7	psi-mi:“MI:0914”(association)	0.350
	SUPT5H	psi-mi:“MI:0914”(association)	0.350
ASPH	POTEF	psi-mi:“MI:0914”(association)	0.350
GTF2E2	RP2	psi-mi:“MI:0914”(association)	0.350
ERCC2	POLR2D	psi-mi:“MI:0915”(physical association)	0.320
CCNH	MED19	psi-mi:“MI:0915”(physical association)	0.320

BioGRID (263): GTF2E2 (Affinity Capture-RNA), GTF2E2 (Affinity Capture-RNA), GTF2E2 (Affinity Capture-RNA), EEF1G (Co-fractionation), GTF2E2 (Co-fractionation), GTF2E2 (Co-fractionation), GTF2E2 (Co-fractionation), GTF2E2 (Co-fractionation), GTF2E2 (Reconstituted Complex), KLF5 (Reconstituted Complex), GTF2E2 (Reconstituted Complex), GTF2E1 (Affinity Capture-MS), EIF2A (Affinity Capture-MS), SBDS (Affinity Capture-MS), OIP5 (Affinity Capture-MS)

ESM2 similar proteins: A0JPM9, A2AQ19, O43395, O75391, O75822, P04973, P09496, P29084, P29540, Q02614, Q0VCU8, Q13123, Q15650, Q2HJ41, Q2KIA6, Q2KJF9, Q3MHJ0, Q3UGC7, Q5BK07, Q5I0B5, Q5NVI3, Q5R5F1, Q5R8D1, Q5RAD5, Q5RE03, Q5ZJ85, Q5ZJ97, Q5ZK25, Q5ZKA4, Q66HG8, Q66JS6, Q6GMH0, Q6INR1, Q6P320, Q7SXU0, Q7SYJ9, Q7TNE3, Q8BM39, Q91WE2, Q922U1

Diamond homologs: P29084, P29540, Q2KJF9, Q9D902, P79011

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GTF2E2	“form complex”	TFIIE	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 40 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
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	6	84.4×	2e-09
RNA Pol II CTD phosphorylation and interaction with CE	6	84.4×	2e-09
mRNA Capping	6	78.8×	3e-09
Formation of the Early Elongation Complex	6	69.5×	6e-09
Formation of the HIV-1 Early Elongation Complex	6	69.5×	6e-09
HIV Transcription Elongation	5	57.9×	3e-07
HIV Transcription Initiation	7	56.3×	1e-09
RNA Polymerase II HIV Promoter Escape	7	56.3×	1e-09

GO biological processes:

GO term	Partners	Fold	FDR
transcription initiation at RNA polymerase II promoter	6	60.7×	2e-07
transcription by RNA polymerase II	6	11.4×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	87
Likely benign	87
Benign	17

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
225840	NM_002095.6(GTF2E2):c.448G>C (p.Ala150Pro)	Pathogenic
225841	NM_002095.6(GTF2E2):c.559G>T (p.Asp187Tyr)	Pathogenic

SpliceAI

2592 predictions. Top by Δscore:

Variant	Effect	Δscore
8:30580280:CCA:C	donor_gain	1.0000
8:30580394:ATT:A	acceptor_gain	1.0000
8:30580395:TT:T	acceptor_gain	1.0000
8:30580397:C:CC	acceptor_gain	1.0000
8:30581721:A:C	donor_gain	1.0000
8:30607051:GCTCA:G	donor_loss	1.0000
8:30607052:CTCAC:C	donor_loss	1.0000
8:30607053:TCA:T	donor_loss	1.0000
8:30607054:CA:C	donor_loss	1.0000
8:30607150:CCTTA:C	acceptor_loss	1.0000
8:30607151:C:CG	acceptor_loss	1.0000
8:30607152:T:C	acceptor_gain	1.0000
8:30612294:ATTAC:A	donor_loss	1.0000
8:30612295:TTA:T	donor_loss	1.0000
8:30612296:TA:T	donor_loss	1.0000
8:30612297:A:AC	donor_gain	1.0000
8:30612297:A:AT	donor_loss	1.0000
8:30612298:C:CC	donor_gain	1.0000
8:30612479:AGCC:A	acceptor_loss	1.0000
8:30612480:GC:G	acceptor_gain	1.0000
8:30612481:CC:C	acceptor_gain	1.0000
8:30612482:C:CA	acceptor_loss	1.0000
8:30612482:C:CC	acceptor_gain	1.0000
8:30613878:A:AC	donor_gain	1.0000
8:30613879:C:CC	donor_gain	1.0000
8:30614602:TCTTA:T	donor_loss	1.0000
8:30614603:CTTAC:C	donor_loss	1.0000
8:30614604:TTAC:T	donor_loss	1.0000
8:30614605:TA:T	donor_loss	1.0000
8:30614606:A:C	donor_loss	1.0000

AlphaMissense

1893 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:30580330:A:G	L237P	1.000
8:30580382:A:G	W220R	1.000
8:30580382:A:T	W220R	1.000
8:30614618:A:G	L119P	1.000
8:30614711:C:G	R88P	1.000
8:30607098:A:G	L201P	0.999
8:30612354:C:T	G165E	0.999
8:30612355:C:G	G165R	0.999
8:30612355:C:T	G165R	0.999
8:30612396:A:G	L151P	0.999
8:30612431:G:C	F139L	0.999
8:30612431:G:T	F139L	0.999
8:30612433:A:G	F139L	0.999
8:30612467:A:C	N127K	0.999
8:30612467:A:T	N127K	0.999
8:30612477:A:G	L124S	0.999
8:30614618:A:T	L119Q	0.999
8:30614620:C:A	W118C	0.999
8:30614620:C:G	W118C	0.999
8:30614622:A:G	W118R	0.999
8:30614622:A:T	W118R	0.999
8:30614684:A:G	L97P	0.999
8:30614709:G:C	H89D	0.999
8:30635032:C:A	K86N	0.999
8:30635032:C:G	K86N	0.999
8:30635045:A:T	V82E	0.999
8:30635054:G:T	A79D	0.999
8:30635057:A:G	L78P	0.999
8:30635057:A:T	L78H	0.999
8:30635065:A:C	F75L	0.999

dbSNP variants (sampled 300 via entrez): RS1000061362 (8:30600059 A>G,T), RS1000092014 (8:30599925 G>A), RS1000188450 (8:30602926 C>A,T), RS1000212560 (8:30621807 T>C,G), RS1000259393 (8:30643713 T>C), RS1000267453 (8:30655116 G>A,C), RS1000283730 (8:30612630 G>A), RS1000296050 (8:30648183 T>C), RS1000315878 (8:30637129 T>C), RS1000347021 (8:30637323 G>C), RS1000394498 (8:30591394 G>A), RS1000400102 (8:30597602 G>GT), RS1000434741 (8:30594079 T>C), RS1000478463 (8:30619037 G>A), RS1000543383 (8:30641657 A>C)

Disease associations

OMIM: gene MIM:189964 | disease phenotypes: MIM:616943

GenCC curated gene-disease

Disease	Classification	Inheritance
trichothiodystrophy 6, nonphotosensitive	Strong	Autosomal recessive
trichothiodystrophy	Supportive	Autosomal recessive

Mondo (2): trichothiodystrophy 6, nonphotosensitive (MONDO:0014841), trichothiodystrophy (MONDO:0018053)

Orphanet (1): Trichothiodystrophy (Orphanet:33364)

HPO phenotypes

105 total (30 of 105 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000133	Gonadal dysgenesis
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000320	Bird-like facies
HP:0000411	Protruding ear
HP:0000482	Microcornea
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000509	Conjunctivitis
HP:0000519	Developmental cataract
HP:0000545	Myopia
HP:0000546	Retinal degeneration
HP:0000565	Esotropia
HP:0000601	Hypotelorism
HP:0000608	Macular degeneration
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000656	Ectropion
HP:0000670	Carious teeth
HP:0000938	Osteopenia
HP:0000958	Dry skin
HP:0000964	Eczematoid dermatitis
HP:0000992	Cutaneous photosensitivity
HP:0001097	Keratoconjunctivitis sicca
HP:0001197	Abnormality of prenatal development or birth

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000579_35	Cognitive performance	8.000000e-06
GCST002119_16	Metabolite levels (X-11787)	3.000000e-06
GCST90002392_576	Mean corpuscular volume	1.000000e-09
GCST90011770_15	Glaucoma (primary open-angle)	7.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test
EFO:0005276	hydroxy-leucine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066458 (SINGLE PROTEIN)

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
6.21	Kd	615.3	nM	CHEMBL5653589
6.17	ED50	676.2	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148470: Binding affinity to human GTF2E2 incubated for 45 mins by Kinobead based pull down assay	kd	0.6153	uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, increases expression	3
Rotenone	decreases expression, increases expression	2
dicrotophos	decreases expression	1
bisphenol A	affects expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
deguelin	increases expression	1
ICG 001	increases expression	1
bisphenol S	decreases methylation	1
picoxystrobin	increases expression	1
Decitabine	affects expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects expression	1
Ellagic Acid	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1
Phenobarbital	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651512	Binding	Binding affinity to human GTF2E2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_GZ88	K562 eGFP-GTF2E2	Cancer cell line	Female
CVCL_HA15	MCF-7 eGFP-GTF2E2	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00001813	Not specified	COMPLETED	Examination of Clinical and Laboratory Abnormalities in Patients With Defective DNA Repair: Xeroderma Pigmentosum, Cockayne Syndrome, or Trichothiodystrophy
NCT05484570	Not specified	RECRUITING	Natural History Study for DNA Repair Disorders