GTF2E1

Chr 3

general transcription factor IIE subunit 1

Also known as: FE, TF2E1, TFIIE-A

NCBI Gene: 2960 ENSG00000153767 UniProt: P29083 OMIM: 189962

The GTF2E1 protein recruits TFIIH to the RNA polymerase II transcription initiation complex and stimulates TFIIH's kinase and ATPase activities required for promoter clearance during gene transcription. Mutations cause autosomal recessive trichothiodystrophy with severe intellectual disability and developmental delay. The gene is highly constrained against loss-of-function variants, indicating that functional copies are critical for normal development.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA polymerase II general transcription initiation factor activity. Involved in transcription by RNA polymerase II. Located in cytosol and nucleoplasm. Part of transcription factor TFIID complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.39

Clinical Summary— GTF2E1

⚡

Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.89) — some intolerance to loss-of-function variants.

📋

ClinVar Variants

49 VUS of 59 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.39LOEUF

pLI 0.892

Z-score 3.25

OE 0.12 (0.05–0.39)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.09Z-score

OE missense 0.81 (0.72–0.91)

206 obs / 254.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.12 (0.05–0.39)

0≤0.351.4

Missense OE?0.81 (0.72–0.91)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 2 / 16.0Missense obs/exp: 206 / 254.9Syn Z: -0.81

ClinVar Variant Classifications

59 submitted variants in ClinVar

ClinVar

Classification Summary

VUS49

Likely Benign1

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	49	0	49
Likely Benign	1	0	1
Benign	0	1	1
Total	50	1	51

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

View in ClinVar →

17 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap GTF2E1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →