TAF8

Chr 6AR

TATA-box binding protein associated factor 8

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

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.571 OMIM phenotype
Clinical SummaryTAF8
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 53 VUS of 107 total submissions
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GeneReview available — TAF8
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.57LOEUF
pLI 0.000
Z-score -0.25
OE 1.07 (0.741.57)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.24Z-score
OE missense 0.95 (0.841.08)
186 obs / 195.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.07 (0.741.57)
00.351.4
Missense OE0.95 (0.841.08)
00.61.4
Synonymous OE1.25
01.21.6
LoF obs/exp: 18 / 16.9Missense obs/exp: 186 / 195.3Syn Z: -1.77
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateTAF8-related neurodevelopmental disorderOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.4289th %ile
GOF
0.3094th %ile
LOF
0.64top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

107 submitted variants in ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic3
VUS53
Likely Benign7
13
Pathogenic
3
Likely Pathogenic
53
VUS
7
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
8
1
13
Likely Pathogenic
2
0
1
0
3
VUS
1
48
4
0
53
Likely Benign
0
2
2
3
7
Benign
0
0
0
0
0
Total75015476

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TAF8 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC