RNF2: Ring Finger Protein 2 – A Key E3 Ubiquitin Ligase in Polycomb Repressive Complex 1
Comprehensive genomic, functional, and clinical overview of RNF2 (RING1B) in development and disease
Gene Information Card
| Symbol | RNF2 |
|---|---|
| Full Name | Ring Finger Protein 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q25.3 |
| NCBI Gene ID | 6045 ncbi.nlm.nih.gov/gene/6045 |
| Ensembl ID | ENSG00000121410 |
| UniProt ID | Q99496 |
| OMIM ID | 608211 |
| HGNC ID | 10061 |
| Aliases | RING1B, RING2, HIPI3, BAP-1 |
Description
RNF2 (Ring Finger Protein 2), also known as RING1B, is a core component of the Polycomb Repressive Complex 1 (PRC1). It functions as an E3 ubiquitin ligase that monoubiquitinates histone H2A at lysine 119 (H2AK119ub), a key epigenetic mark for gene silencing. RNF2 is essential for embryonic development, stem cell maintenance, and X-chromosome inactivation. Dysregulation of RNF2 is implicated in various cancers, including breast, prostate, and colorectal cancer, as well as developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Overexpression of RNF2 promotes H2AK119ub-mediated repression of tumor suppressor genes (e.g., CDKN2A) | PMID: 23431136 |
| Prostate cancer | RNF2 upregulation correlates with aggressive disease and poor prognosis; enhances androgen receptor signaling | PMID: 27562873 |
| Colorectal cancer | RNF2 overexpression drives proliferation and metastasis via Wnt/β-catenin pathway activation | PMID: 29057924 |
| Neuroblastoma | RNF2 amplification or overexpression linked to MYCN-driven tumorigenesis | PMID: 25636800 |
| Developmental disorders (e.g., microcephaly) | Loss-of-function mutations in RNF2 impair PRC1 activity and neurogenesis | PMID: 31006510 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 38.5 | High |
| Bone marrow | 25.3 | Medium |
| Lymph node | 22.1 | Medium |
| Brain (cortex) | 18.7 | Medium |
| Liver | 12.4 | Low |
| Heart | 10.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 45.2 | Embryonic kidney; high expression |
| HeLa | 38.9 | Cervical carcinoma; elevated |
| MCF7 | 42.1 | Breast cancer; overexpression reported |
| HCT116 | 36.7 | Colorectal carcinoma; moderate |
| SH-SY5Y | 29.4 | Neuroblastoma; MYCN-associated |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.1% | Loss of start codon; likely loss of function |
| c.112C>T (p.Arg38Trp) | Missense | <0.1% | Impaired ubiquitin ligase activity |
| c.337G>A (p.Glu113Lys) | Missense | <0.1% | Reduced H2AK119ub; developmental delay |
| c.500_501insA (p.Tyr167*) | Frameshift | <0.1% | Premature stop; loss of function |
| Amplification (copy number gain) | Copy number variation | ~2-5% in cancers | Overexpression; oncogenic |
Mutation functional classification
Loss of Function (LOF)
Missense or truncating mutations that reduce or abolish E3 ligase activity, leading to decreased H2AK119ub and derepression of PRC1 target genes. Associated with developmental disorders.
Gain of Function (GOF)
Amplification or overexpression of wild-type RNF2 increases H2AK119ub levels, silencing tumor suppressors and promoting oncogenesis.
Dominant Negative (DN)
Not well documented; some missense variants may interfere with PRC1 complex assembly, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• hsa:04120 – Ubiquitin mediated proteolysis
• hsa:05200 – Pathways in cancer
• hsa:05206 – MicroRNAs in cancer
• hsa:05224 – Breast cancer
• hsa:05215 – Prostate cancer
• hsa:04310 – Wnt signaling pathway
Protein Summary
RNF2 (RING1B) is a 336-amino acid protein containing a RING finger domain essential for E3 ubiquitin ligase activity. It forms the catalytic core of PRC1, monoubiquitinating histone H2A at lysine 119. The protein interacts with other PRC1 subunits (e.g., RING1, PCGF, CBX) and is regulated by phosphorylation and ubiquitination. RNF2 is highly conserved across eukaryotes and is critical for transcriptional repression, cell cycle control, and differentiation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RNF2 Knockout HEK293 Cell Line | EDJ-KQ1088 | Human | 6045 | Details Get a Quote |
| RNF26 Knockout HEK293 Cell Line | EDJ-KQ1475 | Human | 79102 | Details Get a Quote |
| RNF213 Knockout HEK293 Cell Line | EDJ-KQ2092 | Human | 57674 | Details Get a Quote |
| RNF25 Knockout HEK293 Cell Line | EDJ-KQ2670 | Human | 64320 | Details Get a Quote |
| RNF214 Knockout HEK293 Cell Line | EDJ-KQ3497 | Human | 257160 | Details Get a Quote |
| RNF216 Knockout HEK293 Cell Line | EDJ-KQ3795 | Human | 54476 | Details Get a Quote |
| RNF215 Knockout HEK293 Cell Line | EDJ-KQ4451 | Human | 200312 | Details Get a Quote |
| RNF24 Knockout HEK293 Cell Line | EDJ-KQ7341 | Human | 11237 | Details Get a Quote |
| RNF217 Knockout HEK293 Cell Line | EDJ-KQ11550 | Human | 154214 | Details Get a Quote |
| RNF223 Knockout HEK293 Cell Line | EDJ-KQ11657 | Human | 401934 | Details Get a Quote |
| RNF207 Knockout HEK293 Cell Line | EDJ-KQ15106 | Human | 388591 | Details Get a Quote |
| RNF208 Knockout HEK293 Cell Line | EDJ-KQ15107 | Human | 727800 | Details Get a Quote |
| RNF212 Knockout HEK293 Cell Line | EDJ-KQ15108 | Human | 285498 | Details Get a Quote |
| RNF212B Knockout HEK293 Cell Line | EDJ-KQ15109 | Human | 100507650 | Details Get a Quote |
| RNF220 Knockout HEK293 Cell Line | EDJ-KQ15110 | Human | 55182 | Details Get a Quote |
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