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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RTCA
RNA 3'-terminal phosphate cyclase
Chromosome 1 · 1p21.2
NCBI Gene: 8634Ensembl: ENSG00000137996.14HGNC: HGNC:17981UniProt: O00442
55PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
RNA bindingnucleoplasmRNA-3'-phosphate cyclase activitynucleusalcohol drinkingneoplasmovarian carcinomasystemic scleroderma
✦AI Summary

RTCA (RNA 3'-terminal phosphate cyclase) is an RNA-modifying enzyme that catalyzes ATP-dependent conversion of RNA 3'-phosphate ends to 2',3'-cyclic phosphodiester products through a three-step adenylation mechanism 1. The enzyme functions in cellular RNA processing and repair pathways 1. RTCA also catalyzes 2'-phosphate cyclization, though at substantially slower rates, suggesting a role in end-healing during RNA repair 2. Functionally, RTCA plays a critical regulatory role in inhibiting central nervous system axon regeneration following injury. In Drosophila and mice, RTCA acts upstream of the mechanosensitive ion channel Piezo and the Rab10 GTPase to modulate Piezo expression and cell surface targeting; loss of RTCA promotes axon regeneration after spinal cord injury and optic nerve crush 3. Recent evidence reveals RTCA functions as an RNA-binding protein with surprising roles in modulating endogenous alternative splicing events across hundreds of genes 4. In bacterial systems, RTCA operates in a conserved RNA repair operon with RtcB ligase, where it is activated by tRNA fragments bearing cyclic phosphate ends generated during cellular stress or DNA damage 5. These findings establish RTCA as a multifunctional enzyme integrating RNA quality control, splicing regulation, and mechanotransduction signaling in neural regeneration.

Sources cited
1
RTCA catalyzes conversion of 3'-phosphate to 2',3'-cyclic phosphodiester through ATP-dependent adenylation mechanism and functions in RNA processing
PMID: 9184239
2
RTCA acts upstream of Piezo ion channel and Rab10 GTPase to inhibit axon regeneration; loss of RTCA promotes CNS axon regeneration after spinal cord injury and optic nerve crush in mice
PMID: 41325493
3
RTCA modulates hundreds of endogenous splicing events as an RNA-binding protein with roles in alternative exon inclusion
PMID: 38168984
4
RTCA functions in a bacterial RNA repair operon regulated by tRNA fragments and damaged tRNAs, converting RNA phosphate ends to 2',3'-cyclic phosphate
PMID: 33357439
5
RTCA catalyzes both 3'-phosphate and 2'-phosphate cyclization with differential kinetics, suggesting an end-healing function in RNA repair pathways
PMID: 23945037
Disease Associationsⓘ20
alcohol drinkingOpen Targets
0.28Weak
neoplasmOpen Targets
0.01Suggestive
ovarian carcinomaOpen Targets
0.01Suggestive
systemic sclerodermaOpen Targets
0.01Suggestive
retinal degenerationOpen Targets
0.01Suggestive
leukodystrophyOpen Targets
0.01Suggestive
Plasmodium falciparum malariaOpen Targets
0.01Suggestive
oral squamous cell carcinomaOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
chronic kidney diseaseOpen Targets
0.01Suggestive
pneumoniaOpen Targets
0.00Suggestive
Alzheimer diseaseOpen Targets
0.00Suggestive
Esophageal atresiaOpen Targets
0.00Suggestive
Lambert-Eaton myasthenic syndromeOpen Targets
0.00Suggestive
non-small cell lung carcinomaOpen Targets
0.00Suggestive
peripheral neuropathyOpen Targets
0.00Suggestive
Treacher-Collins syndromeOpen Targets
0.00Suggestive
Wolcott-Rallison syndromeOpen Targets
0.00Suggestive
Pick diseaseOpen Targets
0.00Suggestive
ThymomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RBMS2Shared pathway100%RMP24Shared pathway100%TRMT2BShared pathway100%SUGP1Shared pathway100%TRMT2AShared pathway100%U2SURPShared pathway100%
Tissue Expression6 tissues
Heart
100%
Bone Marrow
97%
Brain
88%
Liver
65%
Lung
63%
Ovary
40%
Gene Interaction Network
Click a node to explore
RTCARBMS2RMP24TRMT2BSUGP1TRMT2AU2SURP
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt O00442
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.19LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.87 [0.65–1.19]
RankingsWhere RTCA stands among ~20K protein-coding genes
  • #8,247of 20,598
    Most Researched55
  • #12,488of 17,882
    Most Constrained (LOEUF)1.19
Genes detectedRTCA
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
GPC3-IL7-CCL19-CAR-T primes immune microenvironment reconstitution for hepatocellular carcinoma therapy.
PMID: 37853185
Cell Biol Toxicol · 2023
1.00
2
PMID: 29999673
0.90
3
An RNA Repair Operon Regulated by Damaged tRNAs.
PMID: 33357439
Cell Rep · 2020
0.80
4
Hypocrellin A against intrahepatic Cholangiocarcinoma via multi-target inhibition of the PI3K-AKT-mTOR, MAPK, and STAT3 signaling pathways.
PMID: 39284270
Phytomedicine · 2024
0.70
5
Energy stress-induced circZFR enhances oxidative phosphorylation in lung adenocarcinoma via regulating alternative splicing.
PMID: 37461053
J Exp Clin Cancer Res · 2023
0.60