TAF8

Chr 6

TATA-box binding protein associated factor 8

NCBI Gene: 129685 ENSG00000137413 UniProt: Q7Z7C8

The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (PubMed:33795473). TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC) (PubMed:33795473). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (PubMed:33795473). The TFIID complex structure can be divided into 3 modules TFIID-A, TFIID-B, and TFIID-C (PubMed:33795473). TAF8 is involved in forming the TFIID-B module, together with TAF5 (PubMed:33795473). Mediates both basal and activator-dependent transcription (PubMed:14580349). Plays a role in the differentiation of preadipocyte fibroblasts to adipocytes, however, does not seem to play a role in differentiation of myoblasts (PubMed:14580349). Required for the integration of TAF10 in the TAF complex (PubMed:14580349). May be important for survival of cells of the inner cell mass which constitute the pluripotent cell population of the early embryo (By similarity)

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy

ClinVar variants

Pathogenic / LP

0.00

pLI score

Active trials

Clinical Summary— TAF8

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

16 Pathogenic / Likely Pathogenic· 53 VUS of 76 total submissions

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

0.24Z-score

OE missense 0.95 (0.84–1.08)

186 obs / 195.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.07 (0.74–1.57)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.84–1.08)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.25

0≤1.21.6

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