RFFL
ring finger and FYVE like domain containing E3 ubiquitin protein ligase, the group of Ring finger proteins
Basic information
Region (hg38): 17:35005990-35089319
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (39 variants)
- not_provided (2 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RFFL gene is commonly pathogenic or not. These statistics are base on transcript: NM_001017368.2. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 38 | 41 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 38 | 1 | 2 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| RFFL | protein_coding | protein_coding | ENST00000315249 | 6 | 83330 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.407 | 0.592 | 125732 | 0 | 15 | 125747 | 0.0000596 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.40 | 149 | 205 | 0.726 | 0.0000113 | 2373 |
| Missense in Polyphen | 63 | 84.19 | 0.74831 | 1003 | ||
| Synonymous | 1.02 | 65 | 76.4 | 0.851 | 0.00000381 | 709 |
| Loss of Function | 3.08 | 4 | 18.2 | 0.220 | 0.00000101 | 197 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000629 | 0.0000615 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000795 | 0.0000791 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000991 | 0.0000980 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase that regulates several biological processes through the ubiquitin-mediated proteasomal degradation of various target proteins. Mediates 'Lys-48'-linked polyubiquitination of PRR5L and its subsequent proteasomal degradation thereby indirectly regulating cell migration through the mTORC2 complex. Ubiquitinates the caspases CASP8 and CASP10, promoting their proteasomal degradation, to negatively regulate cell death downstream of death domain receptors in the extrinsic pathway of apoptosis. Negatively regulates the tumor necrosis factor-mediated signaling pathway through targeting of RIPK1 to ubiquitin-mediated proteasomal degradation. Negatively regulates p53/TP53 through its direct ubiquitination and targeting to proteasomal degradation. Indirectly, may also negatively regulate p53/TP53 through ubiquitination and degradation of SFN. May also play a role in endocytic recycling. {ECO:0000269|PubMed:15069192, ECO:0000269|PubMed:17121812, ECO:0000269|PubMed:18382127, ECO:0000269|PubMed:18450452, ECO:0000269|PubMed:22609986}.;
- Pathway
- TNF alpha Signaling Pathway;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Regulation of TP53 Degradation;Regulation of TP53 Expression and Degradation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;TNFalpha;TNF receptor signaling pathway
(Consensus)
Recessive Scores
- pRec
- 0.0967
Intolerance Scores
- loftool
- 0.567
- rvis_EVS
- -0.16
- rvis_percentile_EVS
- 41.64
Haploinsufficiency Scores
- pHI
- 0.279
- hipred
- Y
- hipred_score
- 0.786
- ghis
- 0.565
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.883
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Rffl
- Phenotype
- normal phenotype;
Gene ontology
- Biological process
- ubiquitin-dependent protein catabolic process;apoptotic process;regulation of fibroblast migration;negative regulation of tumor necrosis factor-mediated signaling pathway;regulation of TOR signaling;proteasome-mediated ubiquitin-dependent protein catabolic process;protein K48-linked ubiquitination;negative regulation of signal transduction by p53 class mediator;negative regulation of extrinsic apoptotic signaling pathway via death domain receptors;negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis
- Cellular component
- Golgi membrane;tumor necrosis factor receptor superfamily complex;nucleoplasm;cytoplasm;lysosome;cytosol;plasma membrane;endosome membrane;membrane;recycling endosome membrane
- Molecular function
- protease binding;p53 binding;protein binding;protein kinase binding;ubiquitin protein ligase binding;metal ion binding;ubiquitin protein ligase activity