TAF6

Chr 7AR

TATA-box binding protein associated factor 6

Also known as: ALYUS, MGC:8964, TAF(II)70, TAF(II)80, TAF2E, TAFII-70, TAFII-80, TAFII70

NCBI Gene: 6878 ENSG00000106290 UniProt: P49848 OMIM: 602955

TAF6 encodes a subunit of transcription factor IID (TFIID) that binds to TAF1 and participates in RNA polymerase II transcription initiation at gene promoters. Biallelic mutations cause Alazami-Yuan syndrome, an autosomal recessive disorder. The pathogenic mechanism involves disruption of basal transcription machinery essential for proper gene expression regulation.

OMIM ResearchSummary from RefSeq, OMIM, 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 one of the smaller subunits of TFIID that binds weakly to TBP but strongly to TAF1, the largest subunit of TFIID. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2010]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Alazami-Yuan syndromeMIM #617126

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Alazami-Yuan syndrome; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.78

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.78LOEUF

pLI 0.000

Z-score 2.58

OE 0.53 (0.37–0.78)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.97Z-score

OE missense 0.74 (0.68–0.81)

333 obs / 450.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.53 (0.37–0.78)

0≤0.351.4

Missense OE?0.74 (0.68–0.81)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 19 / 35.6Missense obs/exp: 333 / 450.4Syn Z: -1.64

Background carrier burden — how many people carry a rare variant somewhere in TAF6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 68

865 rare PASS variants

Rare truncating (LoF)

1 in 790

137 rare PASS variants

Rare synonymous (reference)

1 in 83

455 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TAF6. 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 86	1 in 1,800
South Asian	~43k	1 in 64	1 in 330
Remaining (unassigned)	~30k	1 in 76	1 in 720
European (Finnish)	~27k	1 in 180	1 in 4,400
Admixed American	~22k	1 in 67	1 in 320
African / African American	~21k	1 in 97	1 in 800
East Asian	~20k	1 in 110	1 in 700
Ashkenazi Jewish	~13k	1 in 230	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 93	≈ 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 14 coding exons well covered in gnomAD exomes and genomes.? see exons ↓