GTF2F2

Chr 13

general transcription factor IIF subunit 2

Also known as: BTF4, RAP30, TF2F2, TFIIF

NCBI Gene: 2963 ENSG00000188342 UniProt: P13984

The protein functions as part of the TFIIF complex, a general transcription initiation factor that binds to RNA polymerase II and helps recruit it to the initiation complex for gene transcription. Mutations in GTF2F2 cause neurodevelopmental disorder with seizures and brain atrophy, inherited in an autosomal recessive pattern. The gene is not highly constrained against loss-of-function variants, which is consistent with the recessive inheritance pattern observed in affected patients.

ResearchSummary from RefSeq, UniProt

Predicted to enable RNA polymerase II general transcription initiation factor activity. Involved in positive regulation of transcription by RNA polymerase II; transcription elongation by RNA polymerase II; and transcription initiation at RNA polymerase II promoter. Located in microtubule cytoskeleton and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.85

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.85LOEUF

pLI 0.000

Z-score 2.05

OE 0.49 (0.29–0.85)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.29Z-score

OE missense 0.67 (0.56–0.81)

82 obs / 122.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.29–0.85)

0≤0.351.4

Missense OE?0.67 (0.56–0.81)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 9 / 18.5Missense obs/exp: 82 / 122.0Syn Z: -0.58

Background carrier burden — how many people carry a rare variant somewhere in GTF2F2?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 290

278 rare PASS variants

Rare truncating (LoF)

1 in 4,400

51 rare PASS variants

Rare synonymous (reference)

1 in 590

109 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GTF2F2. 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 360	1 in 7,500
South Asian	~43k	1 in 480	1 in 5,200
Remaining (unassigned)	~30k	1 in 270	≈ 1 in 7,400
European (Finnish)	~27k	1 in 3,300	≈ 1 in 13,000
Admixed American	~22k	1 in 170	1 in 2,800
African / African American	~21k	1 in 490	1 in 2,400
East Asian	~20k	1 in 560	1 in 1,500
Ashkenazi Jewish	~13k	1 in 870	≈ 1 in 13,000
Middle Eastern	~2,881	1 in 200	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): 3 of 8 coding exons well covered in gnomAD exomes; exons 2, 3, 4, 5, 6 marginal. Genomes: 7 of 8 (exon 6 below).? see exons ↓