RNF135: Ring Finger Protein 135
A ubiquitin ligase implicated in neurodevelopmental disorders and tumorigenesis
Gene Information Card
| Symbol | RNF135 |
|---|---|
| Full Name | Ring Finger Protein 135 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q11.2 |
| NCBI Gene ID | 84282 ncbi.nlm.nih.gov/gene/84282 |
| Ensembl ID | ENSG00000141425 |
| UniProt ID | Q8IUD6 |
| OMIM ID | 611358 |
| HGNC ID | 21158 |
| Aliases | FLJ12443, MGC131831, RNF135_HUMAN |
Description
RNF135 (Ring Finger Protein 135) encodes a protein containing a RING finger domain characteristic of E3 ubiquitin ligases. It is involved in ubiquitination and proteasomal degradation, playing roles in cell growth regulation, neurodevelopment, and tumor suppression. Mutations in RNF135 are associated with macrocephaly, autism spectrum disorder, and susceptibility to certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Macrocephaly / Autism Spectrum Disorder | Loss-of-function mutations impair ubiquitin ligase activity, disrupting neuronal development pathways | PMID: 23542741, ClinVar |
| Neurofibromatosis type 1-like phenotype | RNF135 deletions or mutations may mimic NF1 due to genomic location at 17q11.2 | PMID: 17694336, OMIM #611358 |
| Breast cancer | Somatic mutations and altered expression may contribute to tumorigenesis via defective protein degradation | COSMIC, PMID: 21798893 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.3 | Low |
| Lung | 6.1 | Low |
| Liver | 4.2 | Not detected |
| Kidney | 3.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | Moderate expression |
| HeLa | 10.5 | Low expression |
| MCF7 | 7.8 | Low expression |
| SH-SY5Y | 18.1 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon, likely loss of function |
| c.497C>T (p.Pro166Leu) | Missense | Rare | Impaired ubiquitin ligase activity |
| c.1042C>T (p.Arg348*) | Nonsense | Rare | Premature truncation, loss of function |
| Whole gene deletion | Structural variant | Rare | Haploinsufficiency, associated with macrocephaly |
Mutation functional classification
Loss of Function (LOF)
Most reported pathogenic mutations (nonsense, frameshift, deletions) lead to loss of E3 ubiquitin ligase activity, contributing to neurodevelopmental phenotypes.
Gain of Function (GOF)
Not established; no clear gain-of-function mutations reported.
Dominant Negative (DN)
Possible for missense mutations that retain interaction but impair catalytic activity, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin-protein transferase activity (GO:0004842) | • zinc ion binding (GO:0008270) |
| • protein ubiquitination (GO:0016567) | • nucleus (GO:0005634) |
| • cytoplasm (GO:0005737) |
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• Protein processing in endoplasmic reticulum (KEGG: hsa04141)
Protein Summary
RNF135 is a 428-amino acid protein with a RING-type zinc finger domain at the N-terminus (residues 33-73) that mediates E3 ubiquitin ligase activity. It interacts with UBE2D2 and UBE2D3 E2 enzymes, targeting substrates for proteasomal degradation. The protein is localized to the nucleus and cytoplasm, and its expression is highest in brain and testis. Structural studies suggest a role in regulating cell proliferation and neuronal development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RNF135 Knockout HEK293 Cell Line | EDJ-KQ10051 | Human | 84282 | Details Get a Quote |
| RNF135 Knockout A-549 Cell Line | EDJ-KQ37080 | Human | 84282 | Details Get a Quote |
| RNF135 Knockout HCT 116 Cell Line | EDJ-KQ37081 | Human | 84282 | Details Get a Quote |
| RNF135 Knockout HeLa Cell Line | EDJ-KQ37082 | Human | 84282 | Details Get a Quote |
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