RNF6
protein-codingring finger protein 6, the group of Ring finger proteins
Gene summary
The protein encoded by this gene contains a RING-H2 finger motif. Deletions and mutations in this gene were detected in esophageal squamous cell carcinoma (ESCC), suggesting that this protein may be a potential tumor suppressor. Studies of the mouse counterpart suggested a role of this protein in the transcription regulation that controls germinal differentiation. Multiple alternatively spliced transcript variants encoding the same protein are observed. [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 ~90.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0007576
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to RNF6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005977.4. 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 | 2 | 2 | ||||
| missense | 3 | 88 | 7 | 1 | 99 | |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 3 | 0 | 90 | 7 | 3 | 103 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005968.1 | 3 | MANE Select | |
| Ensembl | ENSP00000371000.4 | 3 | MANE Select | |
| RefSeq | NP_898864.1 | 3 | Standard | |
| RefSeq | NP_898865.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Androgen receptor signaling pathway
- Immune System
- Adaptive Immune System
- Antigen processing: Ubiquitination & Proteasome degradation
- Class I MHC mediated antigen processing & presentation
Biological Process
- regulation of transcription, DNA-templated
- ubiquitin-dependent protein catabolic process
- negative regulation of axon extension
- protein K27-linked ubiquitination
- positive regulation of transcription, DNA-templated
Molecular Function
- DNA binding
- ubiquitin-protein transferase activity
- protein binding
- metal ion binding
- androgen receptor binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- PML body
- axon
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000381588
- Coding exons
- 3
- Length
- 90539
- Individuals with no LoFs
- 125727
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 20
- Defined
- 125747
- p
- 0.0000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.25 | 310 | 378 | 0.819 | 0.0000219 | 4469 |
| Missense (PolyPhen) | 73 | 110.82 | 0.65875 | 1357 | ||
| Synonymous | 0.365 | 125 | 130 | 0.959 | 0.00000649 | 1377 |
| Loss of Function | 3.54 | 9 | 29.8 | 0.302 | 0.00000244 | 294 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000080 | 0.000079 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase mediating 'Lys-48'-linked polyubiquitination of LIMK1 and its subsequent targeting to the proteasome for degradation. Negatively regulates axonal outgrowth through regulation of the LIMK1 turnover. Mediates 'Lys-6' and 'Lys-27'-linked polyubiquitination of AR/androgen receptor thereby modulating its transcriptional activity. May also bind DNA and function as a transcriptional regulator. {ECO:0000269|PubMed:19345326}.;
- Disease
- DISEASE: Esophageal cancer (ESCR) [MIM:133239]: A malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage. {ECO:0000269|PubMed:12154016}. Note=The disease may be caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.0930
Intolerance Scores
- LoFtool
- 0.766
- RVIS EVS
- 0.16
- RVIS percentile EVS
- 64.85
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.992
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |