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 RNA polymerase II preinitiation complex assembly. Located in nucleoplasm. Part of transcription factor TFIID complex. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.39

LOEUF

—

Mechanism

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

Background carrier burden — how many people carry a rare variant somewhere in GTF2E1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

499 rare PASS variants

Rare truncating (LoF)

1 in 6,000

42 rare PASS variants

Rare synonymous (reference)

1 in 310

204 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GTF2E1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 200	1 in 5,800
South Asian	~43k	1 in 83	none seen
Remaining (unassigned)	~30k	1 in 130	1 in 5,000
European (Finnish)	~27k	1 in 920	≈ 1 in 13,000
Admixed American	~22k	1 in 79	≈ 1 in 11,000
African / African American	~21k	1 in 100	≈ 1 in 9,300
East Asian	~20k	1 in 180	1 in 3,900
Ashkenazi Jewish	~13k	1 in 340	none seen
Middle Eastern	~2,884	1 in 91	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓