RNF217
protein-codingring finger protein 217, the group of Ring finger proteins|RBR E3 ubiquitin ligases
Gene summary
This protein encoded by this gene is a member of the RING1-IBR-RING24 (RBR) ubiquitin protein ligase family, and it belongs to a subfamily of these proteins that contain a transmembrane domain. This protein can interact with the HAX1 anti-apoptotic protein via its C-terminal RING finger motif, which suggests a role in apoptosis signaling. It is thought that deregulation of this gene can be a mechanism in leukemogenesis. Mutations in the region encoding the protein GXXXG motif, which appears to be necessary for protein self-association, have been found in human cancers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2016]
- C6orf172
- IBRDC1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~130.2 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 RNF217 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001286398.3. 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 | 1 | 1 | ||||
| missense | 23 | 23 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 25 | 0 | 0 | 25 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001273327.1 | 6 | MANE Select | |
| Ensembl | ENSP00000428698.2 | 6 | MANE Select | |
| RefSeq | NP_689766.1 | 7 | Standard | |
| Ensembl | ENSP00000352734.2 | 7 | 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
- protein polyubiquitination
- ubiquitin-dependent protein catabolic process
- positive regulation of proteasomal ubiquitin-dependent protein catabolic process
Molecular Function
- ubiquitin-protein transferase activity
- ubiquitin conjugating enzyme binding
- metal ion binding
- ubiquitin protein ligase activity
Cellular Component
- ubiquitin ligase complex
- cytoplasm
- cytosol
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000359704
- Coding exons
- 7
- Length
- 130089
- Individuals with no LoFs
- 125661
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 18
- Defined
- 125679
- p
- 0.0000716
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.31 | 101 | 146 | 0.694 | 0.00000733 | 1801 |
| Missense (PolyPhen) | 38 | 66.25 | 0.57358 | 811 | ||
| Synonymous | -0.565 | 56 | 50.9 | 1.10 | 0.00000252 | 480 |
| Loss of Function | 1.57 | 10 | 17.0 | 0.588 | 9.86e-7 | 205 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00019 | 0.00018 | rare |
| European (Non-Finnish) | 0.000054 | 0.000053 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. {ECO:0000250}.;
Intolerance Scores
- LoFtool
- 0.743
- RVIS EVS
- 0.33
- RVIS percentile EVS
- 73.41
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.267
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |