De novo putative loss-of-function variants in TAF4 are associated with a neuro-developmental disorder

Hum Mutat. 2022 Dec;43(12):1844-1851. doi: 10.1002/humu.24444. Epub 2022 Aug 10.


TATA-binding protein associated factor 4 (TAF4) is a subunit of the Transcription Factor IID (TFIID) complex, a central player in transcription initiation. Other members of this multimeric complex have been implicated previously as monogenic disease genes in human developmental disorders. TAF4 has not been described to date as a monogenic disease gene. We here present a cohort of eight individuals, each carrying de novo putative loss-of-function (pLoF) variants in TAF4 and expressing phenotypes consistent with a neuro-developmental disorder (NDD). Common features include intellectual disability, abnormal behavior, and facial dysmorphisms. We propose TAF4 as a novel dominant disease gene for NDD, and coin this novel disorder "TAF4-related NDD" (T4NDD). We place T4NDD in the context of other disorders related to TFIID subunits, revealing shared features of T4NDD with other TAF-opathies.

Keywords: TAF4; TFIID; human genetics; mendelian disorders; neurodevelopmental disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Developmental Disabilities / genetics
  • Humans
  • Neurodevelopmental Disorders* / diagnosis
  • Neurodevelopmental Disorders* / genetics
  • Phenotype
  • TATA-Binding Protein Associated Factors* / genetics
  • TATA-Binding Protein Associated Factors* / metabolism
  • Transcription Factor TFIID* / genetics
  • Transcription Factor TFIID* / metabolism


  • TATA-Binding Protein Associated Factors
  • Transcription Factor TFIID
  • TAF4 protein, human