GTF2H4

GTF2H4 Full Name

general transcription factor IIH, polypeptide 4, 52kDa

GTF2H4 Introduction

GTF2H4 encodes the p52 subunit of the general transcription factor IIH (TFIIH) complex, a ten-subunit assembly that plays dual roles in transcription initiation by RNA polymerase II and in nucleotide excision repair (NER). The p52 subunit lies within the core TFIIH module and helps stabilize the complex on DNA at promoters and at sites of UV-induced damage. Although p52 itself does not have catalytic activity, mutations in GTF2H4 destabilize the entire TFIIH complex and compromise both transcription and repair, underscoring its structural importance.

Figure 1. The structure of GTF2H4.

Core Subunit of the TFIIH Transcription–Repair Complex
TFIIH associates with the pre-initiation complex at RNA polymerase II promoters and unwinds the DNA around the transcription start site through its XPB and XPD ATPase/helicase activities. The p52 subunit, encoded by GTF2H4, binds directly to XPB and helps position the helicase on promoter DNA; it also makes contact with the CAK subcomplex and contributes to the conformational rearrangements that switch TFIIH between its transcription and repair modes. In NER, TFIIH is recruited to UV- and chemical-induced lesions, where it opens the DNA around the damage to allow xeroderma pigmentosum group A and C proteins to verify the lesion before dual-incision by XPF–ERCC1 and XPG.

Xeroderma Pigmentosum and Trichothiodystrophy
Biallelic mutations in GTF2H4 have been reported in a small number of patients with xeroderma pigmentosum, in whom defective NER leads to extreme UV sensitivity, freckling, and a markedly elevated risk of cutaneous malignancies. Other GTF2H4 variants produce a trichothiodystrophy phenotype—characterized by sulfur-deficient brittle hair, intellectual disability, and ichthyosis—because partial TFIIH dysfunction impairs transcription of heavily expressed skin and hair genes. Because TFIIH dysfunction sensitizes cells to platinum-based chemotherapies, GTF2H4 status is sometimes evaluated as a biomarker of therapeutic response.

Alternate Names for GTF2H4

GTF2H4; general transcription factor IIH, polypeptide 4, 52kDa; general transcription factor IIH, polypeptide 4 (52kD subunit); general transcription factor IIH subunit 4; TFB2; TFIIH; Basic transcription factor 2 52 kDa subunit; Basic transcription facto