TAF6L

Chr 11

TATA-box binding protein associated factor 6 like

Also known as: PAF65A

NCBI Gene: 10629 ENSG00000162227 UniProt: Q9Y6J9

TAF6L encodes a component of the PCAF histone acetylase complex that acetylates histones and regulates gene expression through chromatin modification, particularly functioning as an epigenetic regulator essential for somatic reprogramming and embryonic stem cell state control. This gene is highly constrained against loss-of-function variants (LOEUF 0.516), suggesting that mutations would likely cause severe developmental disorders, though specific disease associations have not yet been established. The inheritance pattern for TAF6L-related disorders has not been determined.

ResearchSummary from RefSeq, UniProt

Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes a protein that is a component of the PCAF histone acetylase complex and structurally similar to one of the histone-like TAFs, TAF6. The PCAF histone acetylase complex, which is composed of more than 20 polypeptides some of which are TAFs, is required for myogenic transcription and differentiation. [provided by RefSeq, Jul 2008]

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

0.52

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

Moderate LoF intolerance

LoF Constraint?

0.52LOEUF

pLI 0.070

Z-score 3.40

OE 0.27 (0.15–0.52)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.85Z-score

OE missense 0.87 (0.80–0.96)

308 obs / 352.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.27 (0.15–0.52)

0≤0.351.4

Missense OE?0.87 (0.80–0.96)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 7 / 25.5Missense obs/exp: 308 / 352.7Syn Z: -0.97

Background carrier burden — how many people carry a rare variant somewhere in TAF6L?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 89

839 rare PASS variants

Rare truncating (LoF)

1 in 3,600

97 rare PASS variants

Rare synonymous (reference)

1 in 77

439 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TAF6L. 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 99	1 in 4,400
South Asian	~43k	1 in 68	1 in 2,300
Remaining (unassigned)	~30k	1 in 86	1 in 4,900
European (Finnish)	~27k	1 in 260	1 in 4,600
Admixed American	~22k	1 in 64	1 in 1,000
African / African American	~21k	1 in 84	1 in 2,900
East Asian	~20k	1 in 110	1 in 1,700
Ashkenazi Jewish	~13k	1 in 330	≈ 1 in 5,600
Middle Eastern	~2,884	1 in 100	≈ 1 in 710

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 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓