TAF8

Chr 6AR

TATA-box binding protein associated factor 8

Also known as: II, NEDMLHB, TAF, TAF(II)43, TAFII-43, TAFII43, TBN

NCBI Gene: 129685 ENSG00000137413 UniProt: Q7Z7C8 OMIM: 609514

TAF8 encodes a TATA-binding protein-associated factor that is an integral subunit of the TFIID transcription complex, which recognizes gene promoters and initiates RNA polymerase II-dependent transcription. Biallelic mutations cause a neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, inherited in an autosomal recessive pattern. The gene shows extreme intolerance to loss-of-function variants (pLI nearly 1), reflecting its essential role in basic cellular transcription machinery.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes one of several TATA-binding protein (TBP)-associated factors (TAFs), which are integral subunits of the general transcription factor complex TFIID. TFIID recognizes the core promoter of many genes and nucleates the assembly of a transcription preinitiation complex containing RNA polymerase II and other initiation factors. The protein encoded by this gene contains an H4-like histone fold domain, and interacts with several subunits of TFIID including TBP and the histone-fold protein TAF10. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophyMIM #619972

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.57

LOEUF

LOF

Mechanism· predicted

📖

GeneReview available — TAF8

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.57LOEUF

pLI 0.000

Z-score -0.25

OE 1.07 (0.74–1.57)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.24Z-score

OE missense 0.95 (0.84–1.08)

186 obs / 195.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.07 (0.74–1.57)

0≤0.351.4

Missense OE?0.95 (0.84–1.08)

0≤0.61.4

Synonymous OE?1.25

0≤1.21.6

LoF obs/exp: 18 / 16.9Missense obs/exp: 186 / 195.3Syn Z: -1.77

Background carrier burden — how many people carry a rare variant somewhere in TAF8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

537 rare PASS variants

Rare truncating (LoF)

1 in 690

157 rare PASS variants

Rare synonymous (reference)

1 in 270

190 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TAF8. 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 130	1 in 880
South Asian	~43k	1 in 65	1 in 600
Remaining (unassigned)	~30k	1 in 100	1 in 760
European (Finnish)	~27k	1 in 780	1 in 1,300
Admixed American	~22k	1 in 110	1 in 560
African / African American	~21k	1 in 82	1 in 490
East Asian	~20k	1 in 110	1 in 630
Ashkenazi Jewish	~13k	1 in 200	1 in 1,700
Middle Eastern	~2,884	1 in 90	≈ 1 in 2,900

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): 8 of 9 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: all 9.? see exons ↓