GTF2A2

Chr 15

general transcription factor IIA subunit 2

Also known as: HsT18745, T18745, TF2A2, TFIIA, TFIIA-12, TFIIA-gamma, TFIIAS

NCBI Gene: 2958 ENSG00000140307 UniProt: P52657 OMIM: 600519

Accurate transcription initiation on TATA-containing class II genes involves the ordered assembly of RNA polymerase II (POLR2A; MIM 180660) and the general initiation factors TFIIA, TFIIB (MIM 189963), TFIID (MIM 313650), TFIIE (MIM 189962), TFIIF (MIM 189968), TFIIG/TFIIJ, and TFIIH (MIM 189972). The first step involves recognition of the TATA element by the TATA-binding subunit (TBP; MIM 600075) and may be regulated by TFIIA, a factor that interacts with both TBP and a TBP-associated factor (TAF; MIM 600475) in TFIID. TFIIA has 2 subunits (43 and 12 kD) in yeast and 3 subunits in higher eukaryotes. In HeLa extracts, it consists of a 35-kD alpha subunit and a 19-kD beta subunit encoded by the N- and C-terminal regions of GTF2A1 (MIM 600520), respectively, and a 12-kD gamma subunit encoded by GTF2A2 (DeJong et al., 1995 [PubMed 7724559]).[supplied by OMIM, Mar 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.36

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.36LOEUF

pLI 0.026

Z-score 1.02

OE 0.53 (0.24–1.36)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.98Z-score

OE missense 0.63 (0.47–0.83)

34 obs / 54.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.53 (0.24–1.36)

0≤0.351.4

Missense OE?0.63 (0.47–0.83)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 3 / 5.6Missense obs/exp: 34 / 54.4Syn Z: 0.07

Background carrier burden — how many people carry a rare variant somewhere in GTF2A2?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 1,400

102 rare PASS variants

Rare truncating (LoF)

1 in 920

36 rare PASS variants

Rare synonymous (reference)

1 in 2,300

54 rare PASS variants

Rare missense and truncating variants are carried at similar rates in GTF2A2; this gene does not show strong loss-of-function constraint by this measure. 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)	~555k	1 in 1,700	1 in 7,300
South Asian	~43k	1 in 850	1 in 3,200
Remaining (unassigned)	~30k	1 in 2,200	1 in 550
European (Finnish)	~27k	1 in 2,700	≈ 1 in 27,000
Admixed American	~22k	1 in 2,000	1 in 600
African / African American	~21k	1 in 1,600	1 in 1,200
East Asian	~20k	1 in 870	≈ 1 in 6,300
Ashkenazi Jewish	~13k	≈ 1 in 3,200	none seen
Middle Eastern	~2,880	≈ 1 in 660	≈ 1 in 850

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): 1 of 4 coding exons well covered in gnomAD exomes; exons 2, 3, 5 marginal. Genomes: all 4.? see exons ↓