GTF2E2

Chr 8AR

general transcription factor IIE subunit 2

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

NCBI Gene: 2961 ENSG00000197265 UniProt: P29084 OMIM: 189964

The GTF2E2 protein is the beta subunit of general transcription factor IIE (TFIIE), which recruits TFIIH to the RNA polymerase II initiation complex and stimulates TFIIH kinase and ATPase activities required for promoter clearance during transcription. Mutations cause autosomal recessive developmental and epileptic encephalopathy with severe intellectual disability and early-onset seizures. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.61), consistent with its essential role in basic transcription machinery.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Trichothiodystrophy 6, nonphotosensitiveMIM #616943

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Trichothiodystrophy 6, nonphotosensitive; no ClinGen or GenCC tier

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.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.61

LOEUF

Mechanism· predicted

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 OE?0.31 (0.17–0.61)

0≤0.351.4

Missense OE?0.79 (0.69–0.92)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 6 / 19.5Missense obs/exp: 121 / 152.3Syn Z: -0.15

Background carrier burden — how many people carry a rare variant somewhere in GTF2E2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

332 rare PASS variants

Rare truncating (LoF)

1 in 4,300

60 rare PASS variants

Rare synonymous (reference)

1 in 250

127 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GTF2E2. 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 190	1 in 4,300
South Asian	~43k	1 in 210	1 in 8,600
Remaining (unassigned)	~30k	1 in 220	1 in 920
European (Finnish)	~27k	1 in 150	≈ 1 in 26,000
Admixed American	~22k	1 in 150	1 in 4,500
African / African American	~21k	1 in 170	≈ 1 in 10,000
East Asian	~20k	1 in 330	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 450	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 120	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): 2 of 7 coding exons well covered in gnomAD exomes; exon 6 poorly covered; exons 3, 4, 7, 8 marginal. Genomes: all 7.? see exons ↓