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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RNGTT
RNA guanylyltransferase and 5'-phosphatase
Chromosome 6 · 6q15
NCBI Gene: 8732Ensembl: ENSG00000111880.17HGNC: HGNC:10073UniProt: B4DSJ8
80PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
7-methylguanosine mRNA cappingRNA guanylyltransferase activityinorganic triphosphate phosphatase activityRNA processingneurodegenerative diseaseHIV infectionneuroinflammatory disorderliver disease
✦AI Summary

RNGTT (RNA guanylyltransferase and 5'-phosphatase) is a bifunctional mRNA-capping enzyme catalyzing the first two steps of 5' cap formation on nascent pre-mRNA 1. The enzyme removes the gamma-phosphate from the 5'-triphosphate end of mRNA to generate a diphosphate intermediate, then transfers the GMP moiety of GTP to create the 7-methylguanosine cap structure 2. This co-transcriptional capping occurs during RNA polymerase II (RNAPII) transcription, with RNGTT docking to the RNAPII stalk and repositioning as RNA synthesis proceeds 23. The mRNA cap protects transcripts from degradation and recruits factors promoting splicing, export, and translation initiation 4. RNGTT expression is regulated by m6A methylation of its 3'UTR via METTL3, and reduced RNGTT expression impairs capping of ribosomal protein mRNAs, disrupting mTOR signaling 1. Beyond canonical capping, RNGTT regulates Hedgehog pathway signaling by antagonizing protein kinase A activity through cytoplasmic capping-enzyme functions 5. In liver regeneration, RNGTT controls biliary epithelial cell-to-hepatocyte transdifferentiation by transcriptionally regulating mTORC1 components and DNMT1 6. RNGTT functions within quality-control checkpoints at promoter-proximal pausing sites that remove defective RNAPII complexes 7, highlighting its essential role in transcriptional integrity and cellular proliferation.

Sources cited
1
RNGTT (RNA guanylyltransferase and 5'-phosphatase) is a bifunctional mRNA-capping enzyme catalyzing the first two steps of 5' cap formation on nascent pre-mRNA .
PMID: 39532922
2
The enzyme removes the gamma-phosphate from the 5'-triphosphate end of mRNA to generate a diphosphate intermediate, then transfers the GMP moiety of GTP to create the 7-methylguanosine cap structure .
PMID: 37369200
3
The mRNA cap protects transcripts from degradation and recruits factors promoting splicing, export, and translation initiation .
PMID: 24681440
4
Beyond canonical capping, RNGTT regulates Hedgehog pathway signaling by antagonizing protein kinase A activity through cytoplasmic capping-enzyme functions .
PMID: 28588207
5
In liver regeneration, RNGTT controls biliary epithelial cell-to-hepatocyte transdifferentiation by transcriptionally regulating mTORC1 components and DNMT1 .
PMID: 36724876
6
RNGTT functions within quality-control checkpoints at promoter-proximal pausing sites that remove defective RNAPII complexes , highlighting its essential role in transcriptional integrity and cellular proliferation.
PMID: 39504960
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.51Moderate
HIV infectionOpen Targets
0.50Moderate
neuroinflammatory disorderOpen Targets
0.44Moderate
liver diseaseOpen Targets
0.37Weak
corneal neovascularizationOpen Targets
0.28Weak
ocular hypotensionOpen Targets
0.26Weak
Abruptio PlacentaeOpen Targets
0.25Weak
systemic inflammatory response syndromeOpen Targets
0.23Weak
lacrimal apparatus diseaseOpen Targets
0.23Weak
major salivary gland cancerOpen Targets
0.23Weak
trauma complicationOpen Targets
0.23Weak
endocrine neoplasmOpen Targets
0.15Weak
placental retentionOpen Targets
0.12Weak
HypercholesterolemiaOpen Targets
0.12Weak
cholelithiasisOpen Targets
0.07Suggestive
enteritisOpen Targets
0.05Suggestive
BlindnessOpen Targets
0.04Suggestive
acute myeloid leukemiaOpen Targets
0.04Suggestive
aortic diseaseOpen Targets
0.04Suggestive
diabetic ketoacidosisOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
POLR2BProtein interaction100%POLR2LProtein interaction100%POLR2DProtein interaction100%POLR2AProtein interaction100%POLR2GProtein interaction100%POLR2IProtein interaction100%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
80%
Heart
56%
Liver
41%
Lung
35%
Ovary
32%
Gene Interaction Network
Click a node to explore
RNGTTPOLR2BPOLR2LPOLR2DPOLR2APOLR2GPOLR2I
PROTEIN STRUCTURE
Preparing viewer…
PDB2C46 · 1.60 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.56Moderately Constrained
pLIⓘ
0.80Intermediate
Observed/Expected LoF0.36 [0.24–0.56]
RankingsWhere RNGTT stands among ~20K protein-coding genes
  • #5,961of 20,598
    Most Researched80
  • #3,660of 17,882
    Most Constrained (LOEUF)0.56 · top quartile
Genes detectedRNGTT
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Redundant pathways for removal of defective RNA polymerase II complexes at a promoter-proximal pause checkpoint.
PMID: 39504960
Mol Cell · 2024
1.00
2
METTL3 alters capping enzyme expression and its activity on ribosomal proteins.
PMID: 39532922
Sci Rep · 2024
0.90
3
Myc and mRNA capping.
PMID: 24681440
Biochim Biophys Acta · 2015
0.80
4
Structural insights into human co-transcriptional capping.
PMID: 37369200
Mol Cell · 2023
0.70
5
Structures of co-transcriptional RNA capping enzymes on paused transcription complex.
PMID: 38816438
Nat Commun · 2024
0.60