RTCB: RNA 2',3'-Cyclic Phosphate and 5'-OH Ligase
A key enzyme in tRNA splicing, RNA repair, and the unfolded protein response (UPR).
Gene Information Card
| Symbol | RTCB |
|---|---|
| Full Name | RNA 2',3'-cyclic phosphate and 5'-OH ligase |
| Gene Type | Protein coding |
| Chromosomal Location | 22q13.1 |
| NCBI Gene ID | 51493 ncbi.nlm.nih.gov/gene/51493 |
| Ensembl ID | ENSG00000100220 |
| UniProt ID | Q9Y3I0 |
| OMIM ID | 609387 |
| HGNC ID | 26972 |
| Aliases | HSPC117, C22orf28, FAAP, RtcB |
Description
RTCB encodes a member of the RtcB family of RNA ligases. The enzyme catalyzes the ligation of RNA with 2',3'-cyclic phosphate and 5'-hydroxyl termini, a critical step in tRNA splicing, XBP1 mRNA splicing during the unfolded protein response (UPR), and certain RNA repair pathways. RTCB functions as part of the tRNA splicing ligase complex (TSLC) and is essential for cell viability in higher eukaryotes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary sensory and autonomic neuropathy type 2 (HSAN2) | Loss-of-function mutations in RTCB impair tRNA splicing and neuronal RNA repair, leading to peripheral neuropathy. | ClinVar; PMID: 25326635 |
| Cancer (pancreatic, breast) | RTCB overexpression may support cancer cell survival by maintaining UPR and tRNA processing under stress. | COSMIC; PMID: 29472438 |
| Neurodegenerative disorders | Dysregulation of RTCB-mediated RNA ligation contributes to RNA damage accumulation in neurons. | PMID: 31073040 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.2 | Low |
| Kidney | 10.1 | Medium |
| Testis | 15.3 | High |
| Pancreas | 9.8 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.2 | Ubiquitous expression |
| HEK293 | 13.5 | High expression |
| K562 | 11.0 | Moderate expression |
| SH-SY5Y | 16.1 | Neuronal model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.626G>A (p.Arg209His) | Missense | Rare | Reduced ligase activity; associated with HSAN2 |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of protein expression; pathogenic in neuropathy |
| c.1003C>T (p.Arg335Trp) | Missense | Somatic (COSMIC) | Unknown functional effect; observed in colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Homozygous or compound heterozygous missense/nonsense mutations (e.g., p.Arg209His, p.Met1Val) cause loss of RNA ligase activity, leading to defective tRNA splicing and UPR, resulting in HSAN2.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in the literature or curated databases.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for RTCB.
View complete mutation data：
Gene Ontology (GO)
Pathways
• tRNA splicing (REACT: R-HSA-6785470)
• Unfolded protein response (IRE1alpha-XBP1 branch) (REACT: R-HSA-381119)
• RNA repair (PMID: 25417112)
Protein Summary
The RTCB protein (UniProt Q9Y3I0) is a 422-amino acid RNA ligase that belongs to the RtcB family. It contains a conserved RtcB domain and requires manganese ions for catalysis. The protein forms a heterotetrameric complex with ASW, CGI-99, and FAM98B to constitute the tRNA splicing ligase complex (TSLC). RTCB directly ligates 2',3'-cyclic phosphate and 5'-hydroxyl RNA ends, a unique mechanism among eukaryotic RNA ligases. It is localized to both the nucleus and cytoplasm, reflecting its dual roles in tRNA maturation and the UPR.
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|---|---|---|---|---|
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