GTF3A
protein-codinggeneral transcription factor IIIA, the group of General transcription factors|Zinc fingers C2H2-type
Gene summary
The product of this gene is a zinc finger protein with nine Cis[2]-His[2] zinc finger domains. It functions as an RNA polymerase III transcription factor to induce transcription of the 5S rRNA genes. The protein binds to a 50 bp internal promoter in the 5S genes called the internal control region (ICR), and nucleates formation of a stable preinitiation complex. This complex recruits the TFIIIC and TFIIIB transcription factors and RNA polymerase III to form the complete transcription complex. The protein is thought to be translated using a non-AUG translation initiation site in mammals based on sequence analysis, protein homology, and the size of the purified protein. [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 ~11.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0012521
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GTF3A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002097.3. 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 | 0 | |||||
| missense | 47 | 3 | 50 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 1 | 48 | 3 | 0 | 52 |
Highest pathogenic variant AF is 0.000035163954
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002088.2 | 9 | MANE Select | |
| Ensembl | ENSP00000370532.5 | 9 | MANE Select | |
| Ensembl | ENSP00000389655.1 | 5 | Standard | |
| Ensembl | ENSP00000409175.1 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| gtf3aa | Danio rerio | Structure: head Quality: decreased size abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Adipogenesis
- Gene expression (Transcription)
- the information processing pathway at the ifn beta enhancer
- carm1 and regulation of the estrogen receptor
- phosphoinositides and their downstream targets
Biological Process
- regulation of transcription by RNA polymerase II
- transcription by RNA polymerase III
- rRNA transcription
- ribosomal large subunit biogenesis
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA binding
- 5S rRNA binding
- metal ion binding
Cellular Component
- nucleus
- nucleoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000381140
- Coding exons
- 9
- Length
- 11278
- Individuals with no LoFs
- 124360
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 95
- Defined
- 124455
- p
- 0.000382
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.135 | 195 | 190 | 1.03 | 0.00000978 | 2399 |
| Missense (PolyPhen) | 66 | 73.995 | 0.89196 | 932 | ||
| Synonymous | 0.541 | 62 | 67.7 | 0.916 | 0.00000344 | 642 |
| Loss of Function | -0.218 | 16 | 15.1 | 1.06 | 7.30e-7 | 217 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000065 | rare |
| Latino/Admixed American | 0.00021 | 0.00020 | rare |
| Ashkenazi Jewish | 0.0036 | 0.0036 | notable |
| East Asian | 0.00040 | 0.00039 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00029 | 0.00028 | rare |
| South Asian | 0.00017 | 0.00016 | rare |
| Other | 0.00067 | 0.00066 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in ribosomal large subunit biogenesis. Binds the approximately 50 base pairs internal control region (ICR) of 5S ribosomal RNA genes. It is required for their RNA polymerase III-dependent transcription and may also maintain the transcription of other genes (PubMed:24120868). Also binds the transcribed 5S RNA's (By similarity). {ECO:0000250|UniProtKB:P17842, ECO:0000269|PubMed:24120868}.;
Recessive Scores
- pRec
- 0.118
Intolerance Scores
- RVIS EVS
- 0.44
- RVIS percentile EVS
- 77.57
Essentials
- Essential (CRISPR)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.992
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |