GTF2E2

Chr 8AR

general transcription factor IIE subunit 2

Also known as: FE, TF2E2, TFIIE-B, TTD6

NCBI Gene: 2961ENSG00000197265UniProt: P29084

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. [provided by RefSeq, Jan 2017]

Primary Disease Associations & Inheritance

Trichothiodystrophy 6, nonphotosensitiveMIM #616943
AR
0
Active trials
68
Pathogenic / LP
267
ClinVar variants
1
Pubs (1 yr)
0.9
Missense Z
0.61
LOEUF
Clinical Summary— GTF2E2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
68 Pathogenic / Likely Pathogenic· 93 VUS of 267 total submissions
Some data sources returned errors (1)

pubtator: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.61LOEUF
pLI 0.039
Z-score 2.83
OE 0.31 (0.17–0.61)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.90Z-score
OE missense 0.79 (0.69–0.92)
121 obs / 152.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.31 (0.17–0.61)
0≤0.351.4
Missense OE0.79 (0.69–0.92)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 6 / 19.5Missense obs/exp: 121 / 152.3Syn Z: -0.15
DN
DN
0.6453th %ile
GOF
0.3788th %ile
LOF
0.4726th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

267 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic66
Likely Pathogenic2
VUS93
Likely Benign88
Benign17
Conflicting1
66
Pathogenic
2
Likely Pathogenic
93
VUS
88
Likely Benign
17
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
64
0
66
Likely Pathogenic
0
0
2
0
2
VUS
1
74
18
0
93
Likely Benign
0
2
37
49
88
Benign
0
1
15
1
17
Conflicting
—1
Total17913650267

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

GTF2E2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

GTF2E2-related DNA repair-proficient trichothiodystrophy

strong
ARUndeterminedAltered Gene Product Structure
Dev. DisordersSkin
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Pan-cancer analysis and validation show GTF2E2's diagnostic, prognostic, and immunological roles in regulating ferroptosis in endometrial cancer.
Zhang N et al.·PLoS One
2025Open Access
GTF2E2 downregulated by miR-340-5p inhibits the malignant progression of glioblastoma.
Qiao X et al.·Cancer Gene Ther
2023
GTF2E2 is a novel biomarker for recurrence after surgery and promotes progression of esophageal squamous cell carcinoma via miR-139-5p/GTF2E2/FUS axis.
Zhang Y et al.·Oncogene
2022Open Access
Knockdown of GTF2E2 inhibits the growth and progression of lung adenocarcinoma via RPS4X in vitro and in vivo.
Bi G et al.·Cancer Cell Int
2021Open Access
Bioinformatical Analysis of Gene Expression Omnibus Database Associates TAF7/CCNB1, TAF7/CCNA2, and GTF2E2/CDC20 Pathways with Glioblastoma Development and Prognosis.
Yang L et al.·World Neurosurg
2020
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients