GTF3C4
protein-codinggeneral transcription factor IIIC subunit 4, the group of Lysine acetyltransferases|General transcription factor IIIC complex subunits
Gene summary
Enables RNA polymerase III general transcription initiation factor activity and histone H3K14 acetyltransferase activity. Involved in transcription initiation at RNA polymerase III promoter. Located in nucleoplasm. Part of transcription factor TFIIIC complex. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~24.9 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 GTF3C4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012204.4. 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 | 73 | 3 | 76 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 76 | 4 | 0 | 80 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036336.2 | 5 | MANE Select | |
| Ensembl | ENSP00000361219.4 | 5 | MANE Select | |
| Ensembl | ENSP00000431378.1 | 3 | Standard | |
| Ensembl | ENSP00000431378.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gene expression (Transcription)
- rna polymerase iii transcription
- RNA Polymerase III Abortive And Retractive Initiation
- RNA Polymerase III Transcription Initiation From Type 1 Promoter
- RNA Polymerase III Transcription Initiation From Type 2 Promoter
Biological Process
- transcription by RNA polymerase III
- transcription initiation from RNA polymerase III promoter
- histone acetylation
- 5S class rRNA transcription by RNA polymerase III
- tRNA transcription by RNA polymerase III
Molecular Function
- DNA binding
- histone acetyltransferase activity
- protein binding
- enzyme activator activity
Cellular Component
- transcription factor TFIIIC complex
- nucleus
- nucleoplasm
- mitochondrion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000372146
- Coding exons
- 5
- Length
- 24921
- Individuals with no LoFs
- 125741
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125747
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.42 | 302 | 445 | 0.678 | 0.0000232 | 5384 |
| Missense (PolyPhen) | 98 | 177.65 | 0.55166 | 2186 | ||
| Synonymous | 0.148 | 173 | 175 | 0.986 | 0.00000985 | 1602 |
| Loss of Function | 3.85 | 7 | 29.6 | 0.236 | 0.00000142 | 370 |
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 | 0.0 | absent |
| Finnish | 0.000094 | 0.000046 | rare |
| European (Non-Finnish) | 0.000026 | 0.000026 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Essential for RNA polymerase III to make a number of small nuclear and cytoplasmic RNAs, including 5S RNA, tRNA, and adenovirus-associated (VA) RNA of both cellular and viral origin. Has histone acetyltransferase activity (HAT) with unique specificity for free and nucleosomal H3. May cooperate with GTF3C5 in facilitating the recruitment of TFIIIB and RNA polymerase through direct interactions with BRF1, POLR3C and POLR3F. May be localized close to the A box.;
Recessive Scores
- pRec
- 0.245
Intolerance Scores
- LoFtool
- 0.494
- RVIS EVS
- -0.2
- RVIS percentile EVS
- 38.98
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.638
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |