GTF2H1
protein-codinggeneral transcription factor IIH subunit 1, the group of Nucleotide excision repair|General transcription factor IIH complex subunits
Gene summary
Enables nuclear thyroid hormone receptor binding activity. Involved in positive regulation of DNA-templated transcription and transcription initiation at RNA polymerase II promoter. Located in nucleoplasm. Part of transcription factor TFIIH core complex and transcription factor TFIIH holo complex. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~44.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GTF2H1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005316.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 68 | 1 | 69 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 70 | 1 | 1 | 72 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005307.1 | 14 | MANE Select | |
| Ensembl | ENSP00000265963.4 | 14 | MANE Select | |
| RefSeq | NP_001135779.1 | 14 | Standard | |
| Ensembl | ENSP00000393638.2 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Nucleotide excision repair - Homo sapiens (human)
- Basal transcription factors - Homo sapiens (human)
- Viral carcinogenesis - Homo sapiens (human)
- Eukaryotic Transcription Initiation
- DNA Repair
Biological Process
- regulation of cyclin-dependent protein serine/threonine kinase activity
- DNA repair
- transcription-coupled nucleotide-excision repair
- nucleotide-excision repair, preincision complex stabilization
- nucleotide-excision repair, preincision complex assembly
Molecular Function
- chromatin binding
- protein kinase activity
- protein binding
- DNA-dependent ATPase activity
- RNA polymerase II CTD heptapeptide repeat kinase activity
Cellular Component
- transcription factor TFIIH core complex
- nucleoplasm
- transcription factor TFIIH holo complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000265963
- Coding exons
- 14
- Length
- 44750
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125745
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.80 | 202 | 288 | 0.702 | 0.0000145 | 3629 |
| Missense (PolyPhen) | 24 | 68.642 | 0.34964 | 940 | ||
| Synonymous | 0.202 | 97 | 99.6 | 0.974 | 0.00000481 | 997 |
| Loss of Function | 4.53 | 4 | 31.4 | 0.127 | 0.00000170 | 376 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000054 | 0.000053 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre- initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription. {ECO:0000269|PubMed:9852112}.;
Recessive Scores
- pRec
- 0.159
Intolerance Scores
- LoFtool
- 0.571
- RVIS EVS
- -0.38
- RVIS percentile EVS
- 27.69
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.996
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |