GTF2H2
protein-codinggeneral transcription factor IIH subunit 2, the group of General transcription factor IIH complex subunits|Nucleotide excision repair
Gene summary
This gene is part of a 500 kb inverted duplication on chromosome 5q13. This duplicated region contains at least four genes and repetitive elements which make it prone to rearrangements and deletions. The repetitiveness and complexity of the sequence have also caused difficulty in determining the organization of this genomic region. This gene is within the telomeric copy of the duplication. Deletion of this gene sometimes accompanies deletion of the neighboring SMN1 gene in spinal muscular atrophy (SMA) patients but it is unclear if deletion of this gene contributes to the SMA phenotype. This gene encodes the 44 kDa subunit of RNA polymerase II transcription initiation factor IIH which is involved in basal transcription and nucleotide excision repair. Transcript variants for this gene have been described, but their full length nature has not been determined. A second copy of this gene within the centromeric copy of the duplication has been described in the literature. It is reported to be different by either two or four base pairs; however, no sequence data is currently available for the centromeric copy of the gene. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~32.7 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 GTF2H2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001515.4. 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 | 2 | |||
| missense | 19 | 19 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 23 | 1 | 0 | 24 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001506.1 | 15 | MANE Select | |
| Ensembl | ENSP00000274400.5 | 15 | MANE Select | |
| RefSeq | NP_001351496.1 | 15 | Standard | |
| RefSeq | NP_001351497.1 | 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
- G protein-coupled receptor internalization
- transcription-coupled nucleotide-excision repair
- nucleotide-excision repair
- nucleotide-excision repair, preincision complex stabilization
- nucleotide-excision repair, preincision complex assembly
Molecular Function
- nucleic acid binding
- DNA-binding transcription factor activity
- protein kinase activity
- protein binding
- DNA-dependent ATPase activity
Cellular Component
- core TFIIH complex portion of holo TFIIH complex
- transcription factor TFIIH core complex
- nucleus
- nucleoplasm
- transcription factor TFIID complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000330280
- Coding exons
- 15
- Length
- 32733
- Individuals with no LoFs
- 122305
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 122307
- p
- 0.00000818
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.641 | 28 | 39.3 | 0.712 | 0.00000199 | 2566 |
| Missense (PolyPhen) | 6 | 9.7723 | 0.61398 | 803 | ||
| Synonymous | 0.928 | 9 | 13.3 | 0.676 | 6.58e-7 | 722 |
| Loss of Function | 0.674 | 3 | 4.55 | 0.659 | 1.90e-7 | 334 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000067 | 0.000067 | rare |
| 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. The N-terminus of GTF2H2 interacts with and regulates XPD whereas an intact C-terminus is required for a successful escape of RNAP II form the promoter. {ECO:0000269|PubMed:11319235, ECO:0000269|PubMed:27193682, ECO:0000269|PubMed:8194529, ECO:0000269|PubMed:9852112}.;
Recessive Scores
- pRec
- 0.176
Essentials
- Essential (CRISPR)
- E
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.914
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |