TAF3

Chr 10

TATA-box binding protein associated factor 3

Also known as: TAF140, TAFII-140, TAFII140

NCBI Gene: 83860 ENSG00000165632 UniProt: Q5VWG9 OMIM: 606576

TAF3 encodes a subunit of the TFIID transcription factor complex that recognizes promoters and initiates RNA polymerase II-dependent transcription, and also functions in muscle cell differentiation by forming complexes that replace TFIID at specific promoters. Mutations cause autosomal recessive intellectual disability with dysmorphic facies and behavioral abnormalities. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

The highly conserved RNA polymerase II transcription factor TFIID (see TAF1; MIM 313650) comprises the TATA box-binding protein (TBP; MIM 600075) and a set of TBP-associated factors (TAFs), including TAF3. TAFs contribute to promoter recognition and selectivity and act as antiapoptotic factors (Gangloff et al., 2001 [PubMed 11438666]).[supplied by OMIM, May 2009]

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

0.14

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.14LOEUF

pLI 1.000

Z-score 5.27

OE 0.03 (0.01–0.14)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

2.21Z-score

OE missense 0.72 (0.66–0.79)

360 obs / 498.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.03 (0.01–0.14)

0≤0.351.4

Missense OE?0.72 (0.66–0.79)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 1 / 34.3Missense obs/exp: 360 / 498.6Syn Z: -0.15

Background carrier burden — how many people carry a rare variant somewhere in TAF3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 80

990 rare PASS variants

Rare truncating (LoF)

1 in 1,400

25 rare PASS variants

Rare synonymous (reference)

1 in 130

492 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TAF3. 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 100	1 in 2,100
South Asian	~43k	1 in 71	1 in 5,100
Remaining (unassigned)	~30k	1 in 61	1 in 1,400
European (Finnish)	~27k	1 in 350	1 in 1,000
Admixed American	~22k	1 in 100	≈ 1 in 6,900
African / African American	~21k	1 in 97	1 in 840
East Asian	~20k	1 in 92	1 in 1,300
Ashkenazi Jewish	~13k	1 in 410	1 in 930
Middle Eastern	~2,884	1 in 59	≈ 1 in 1,400

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): 6 of 7 coding exons well covered in gnomAD exomes; exon 5 marginal. Genomes: all 7.? see exons ↓