RNF126
protein-codingring finger protein 126, the group of Ring finger proteins
Gene summary
The protein encoded by this gene contains a RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to RNF126 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_194460.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 4 | 8 | |||
| missense | 76 | 1 | 77 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 82 | 4 | 1 | 87 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_919442.1 | 9 | MANE Select | |
| Ensembl | ENSP00000292363.3 | 9 | MANE Select | |
| RefSeq | NP_001352947.1 | 9 | Standard | |
| Ensembl | ENSP00000464945.2 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Immune System
- Adaptive Immune System
- Antigen processing: Ubiquitination & Proteasome degradation
- Class I MHC mediated antigen processing & presentation
Biological Process
- ubiquitin-dependent protein catabolic process
- protein monoubiquitination
- protein ubiquitination
- negative regulation of epidermal growth factor receptor signaling pathway
- regulation of cell population proliferation
Molecular Function
- epidermal growth factor receptor binding
- protein binding
- metal ion binding
- ubiquitin protein ligase activity
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000292363
- Coding exons
- 9
- Length
- 15752
- Individuals with no LoFs
- 124133
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 124135
- p
- 0.00000806
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.729 | 152 | 179 | 0.847 | 0.0000126 | 1955 |
| Missense (PolyPhen) | 47 | 71.705 | 0.65546 | 749 | ||
| Synonymous | -1.60 | 101 | 82.5 | 1.22 | 0.00000707 | 610 |
| Loss of Function | 3.23 | 1 | 14.1 | 0.0711 | 6.83e-7 | 169 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination oF target proteins (PubMed:23277564, PubMed:24275455, PubMed:24981174). Depending on the associated E2 ligase, mediates 'Lys-48'- and 'Lys-63'-linked polyubiquitination of substrates (By similarity). Part of a BAG6-dependent quality control process ensuring that proteins of the secretory pathway that are mislocalized to the cytosol are degraded by the proteasome. Probably acts by providing the ubiquitin ligase activity associated with the BAG6 complex and be responsible for ubiquitination of the hydrophobic mislocalized proteins and their targeting to the proteasome (PubMed:24981174, PubMed:29042515). May also play a role in the endosomal recycling of IGF2R, the cation-independent mannose-6-phosphate receptor (PubMed:24275455). May play a role in the endosomal sorting and degradation of several membrane receptors including EGFR, FLT3, MET and CXCR4, by mediating their ubiquitination (PubMed:23418353). By ubiquitinating CDKN1A/p21 and targeting it for degradation, may also promote cell proliferation (PubMed:23026136). May monoubiquitinate AICDA (PubMed:23277564). {ECO:0000250|UniProtKB:Q91YL2, ECO:0000269|PubMed:23277564, ECO:0000269|PubMed:23418353, ECO:0000269|PubMed:24275455, ECO:0000269|PubMed:24981174, ECO:0000269|PubMed:29042515, ECO:0000305|PubMed:23026136}.;
Recessive Scores
- pRec
- 0.112
Intolerance Scores
- LoFtool
- 0.379
- RVIS EVS
- -0.47
- RVIS percentile EVS
- 23.43
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.768
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |