RNF123: Ring Finger Protein 123 – A Multifunctional E3 Ubiquitin Ligase
Comprehensive genomic, proteomic, and clinical overview of RNF123 (also known as KPC1) with curated data from NCBI, Ensembl, UniProt, OMIM, HGNC, COSMIC, and ClinVar.
Gene Information Card
| Symbol | RNF123 |
|---|---|
| Full Name | Ring Finger Protein 123 |
| Gene Type | Protein coding |
| Chromosomal Location | 3p24.3 |
| NCBI Gene ID | 442496 ncbi.nlm.nih.gov/gene/442496 |
| Ensembl ID | ENSG00000163947 |
| UniProt ID | Q5XPI4 |
| OMIM ID | 617658 |
| HGNC ID | 21148 |
| Aliases | KPC1, RNF123, FLJ12886, MGC131851 |
Description
RNF123 (ring finger protein 123), also known as KPC1, encodes an E3 ubiquitin ligase that targets specific substrates for proteasomal degradation. It plays a key role in regulating NF-κB signaling by ubiquitinating and degrading the p105 precursor of NF-κB1 (p50). RNF123 is involved in cell cycle control, apoptosis, and immune responses. Alterations in RNF123 expression or function have been implicated in cancer and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | RNF123 downregulation leads to accumulation of p105 and increased NF-κB activity, promoting tumorigenesis. | PMID: 23431171; COSMIC mutations observed in breast cancer samples. |
| Colorectal cancer | Loss of RNF123 expression correlates with poor prognosis and enhanced NF-κB signaling. | PMID: 25605248; ClinVar reports of somatic variants. |
| Hepatocellular carcinoma | RNF123 acts as a tumor suppressor; reduced expression linked to metastasis. | PMID: 27562872; COSMIC mutation data. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Low |
| Kidney | 15.2 | Medium |
| Testis | 22.1 | High |
| Lung | 6.7 | Low |
| Heart | 9.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.4 | Embryonic kidney cells; high expression |
| HeLa | 14.2 | Cervical cancer cells; moderate expression |
| MCF7 | 11.0 | Breast cancer cells; moderate expression |
| HepG2 | 7.5 | Liver cancer cells; low expression |
| A549 | 9.1 | Lung cancer cells; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1246C>T (p.Arg416Trp) | Missense | 0.02% (gnomAD) | Unknown; located in RING finger domain, may affect ubiquitin ligase activity. |
| c.1873G>A (p.Val625Met) | Missense | 0.01% (gnomAD) | Reported in ClinVar as variant of uncertain significance. |
| c.2101_2102insA (p.Thr701AsnfsTer2) | Frameshift | 0.001% (COSMIC) | Predicted loss of function; observed in colorectal cancer. |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Thr701AsnfsTer2) are predicted to truncate the protein, impairing E3 ligase activity and leading to NF-κB pathway dysregulation.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in curated databases.
Dominant Negative (DN)
Missense mutations in the RING finger domain (e.g., p.Arg416Trp) may act in a dominant-negative manner by interfering with substrate ubiquitination.
View complete mutation data：
Gene Ontology (GO)
Pathways
• NF-kappaB signaling pathway (Reactome: R-HSA-975956)
• Ubiquitin-mediated proteolysis (KEGG: hsa04120)
• TNF signaling pathway (KEGG: hsa04668)
Protein Summary
RNF123 (KPC1) is a 1317-amino acid E3 ubiquitin ligase containing a RING finger domain, a coiled-coil region, and a C-terminal domain. It ubiquitinates p105 (NFKB1) to generate p50, thereby regulating NF-κB activity. The protein is predominantly cytoplasmic but can shuttle to the nucleus. Its expression is highest in testis and brain, with moderate levels in kidney. Dysregulation of RNF123 is associated with multiple cancers, where it typically acts as a tumor suppressor.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RNF123 Knockout HEK293 Cell Line | EDJ-KQ95 | Human | 63891 | Details Get a Quote |
| RNF123 Knockout HCT 116 Cell Line | EDJ-KQ18162 | Human | 63891 | Details Get a Quote |
| RNF123 Knockout A-549 Cell Line | EDJ-KQ45678 | Human | 63891 | Details Get a Quote |
| RNF123 Knockout HeLa Cell Line | EDJ-KQ45679 | Human | 63891 | Details Get a Quote |
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