RNGTT
protein-codingRNA guanylyltransferase and 5'-phosphatase, the group of Atypical dual specificity phosphatases
Gene summary
Enables inorganic triphosphate phosphatase activity and mRNA guanylyltransferase activity. Involved in 7-methylguanosine mRNA capping. Predicted to be located in nucleoplasm. [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 ~353.7 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 RNGTT variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003800.5. 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 | 3 | 1 | 4 | |||
| missense | 48 | 1 | 49 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 56 | 2 | 0 | 58 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003791.3 | 16 | MANE Select | |
| Ensembl | ENSP00000358497.4 | 16 | MANE Select | |
| RefSeq | NP_001273355.1 | 15 | Standard | |
| RefSeq | NP_001273357.1 | 13 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| rngtt | Danio rerio | Structure: anatomical system Quality: quality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- mRNA surveillance pathway - Homo sapiens (human)
- mRNA Processing
- Disease
- RNA Pol II CTD phosphorylation and interaction with CE during HIV infection
- Gene expression (Transcription)
Biological Process
- transcription by RNA polymerase II
- 7-methylguanosine mRNA capping
- RNA processing
- viral process
- peptidyl-tyrosine dephosphorylation
Molecular Function
- mRNA guanylyltransferase activity
- polynucleotide 5'-phosphatase activity
- protein tyrosine phosphatase activity
- protein binding
- GTP binding
Cellular Component
- nucleus
- nucleoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000369485
- Coding exons
- 16
- Length
- 353364
- Individuals with no LoFs
- 125731
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 17
- Defined
- 125748
- p
- 0.0000676
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.00 | 174 | 326 | 0.533 | 0.0000170 | 3943 |
| Missense (PolyPhen) | 37 | 110.82 | 0.33388 | 1386 | ||
| Synonymous | 0.555 | 99 | 106 | 0.932 | 0.00000536 | 1061 |
| Loss of Function | 4.27 | 8 | 35.4 | 0.226 | 0.00000200 | 430 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00012 | 0.00011 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000064 | 0.000062 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Bifunctional mRNA-capping enzyme exhibiting RNA 5'- triphosphatase activity in the N-terminal part and mRNA guanylyltransferase activity in the C-terminal part. Catalyzes the first two steps of cap formation: by removing the gamma-phosphate from the 5'-triphosphate end of nascent mRNA to yield a diphosphate end, and by transferring the gmp moiety of GTP to the 5'-diphosphate terminus. {ECO:0000269|PubMed:21636784, ECO:0000269|PubMed:9473487, ECO:0000269|PubMed:9512541}.;
Recessive Scores
- pRec
- 0.197
Intolerance Scores
- LoFtool
- 0.263
- RVIS EVS
- -0.56
- RVIS percentile EVS
- 19.54
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.988
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |