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General transcription factor IIH subunit 2 (GTF2H2)
- Target
- GTF2H2
- Molecular classification
- Transcription factor (subunit of general transcription factor complex), Other (component of multiprotein complex TFIIH)
01
Overview
General transcription factor IIH subunit 2 (GTF2H2) is a 44 kDa protein component of the TFIIH complex, which is essential for both basal transcription initiation by RNA polymerase II and nucleotide excision repair of DNA[1][2][3][4][7]. GTF2H2 participates in the core TFIIH complex, enabling promoter opening, promoter escape, and repair of damaged DNA by facilitating unwinding around lesions for excision-repair processes[2][3][4]. Although widely expressed in human tissues, alterations in GTF2H2 have not been firmly established as causal in human disease, but its parent complex TFIIH is associated with several DNA repair disorders and may contribute to cancer risk[5][7]. GTF2H2 interacts with other TFIIH subunits such as GTF2H5, XPB (ERCC3), and XPD (ERCC2), but there are no drugs known to directly target it as of now[1][2][7].
- Other names
- BTF2P44Basic transcription factor 2 44 kDa subunitBTF2 p44TFIIH basal transcription factor complex p44 subunitGeneral transcription factor IIH polypeptide 2General transcription factor IIH, polypeptide 2, 44kDa subunitp44
02
Biological functions
Transcription initiation (RNA polymerase II-dependent)Nucleotide excision repair (DNA repair)Promoter opening and promoter escape
03
Disease associations
Cancer (via link to TFIIH dysfunction)Neurodegenerative disease (involvement in spinal muscular atrophy, though unclear direct pathogenic role)DNA repair syndromes (as part of TFIIH complex in diseases such as xeroderma pigmentosum, trichothiodystrophy, Cockayne syndrome)
04
Safety considerations
Dysfunction or deletion may accompany genetic deletions found in spinal muscular atrophy, but there is no clear evidence that GTF2H2 loss drives the disease phenotype independently[1][7].Mutations in TFIIH complex subunits (in general) can cause defects in transcription and DNA repair, possibly leading to cancer predisposition and multisystem disorders[5].
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