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

ENSG00000092871

∙ NCBI:117584 ∙ OMIM:609735 ∙ HGNC:24821 ∙ Uniprot:Q8WZ73 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RFFL gene.

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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			18 clinvar		2 clinvar	20
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	18	0	2

Variants in RFFL

This is a list of pathogenic ClinVar variants found in the RFFL region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Phenotype	Significance	ClinVar
17-35012043-C-G	not specified	Uncertain significance (Sep 06, 2022)	3153374
17-35012121-C-A	not specified	Uncertain significance (Dec 02, 2022)	2332079
17-35012138-G-A	not specified	Uncertain significance (May 24, 2024)	3313863
17-35016418-C-G	not specified	Uncertain significance (Apr 23, 2024)	3313862
17-35016490-G-A	not specified	Uncertain significance (Feb 03, 2022)	2275677
17-35016525-A-C	not specified	Uncertain significance (Feb 08, 2023)	2482353
17-35016546-C-T	not specified	Uncertain significance (Nov 22, 2023)	3153379
17-35017557-C-T	not specified	Uncertain significance (Oct 30, 2023)	3153378
17-35017596-T-C	not specified	Uncertain significance (Aug 30, 2022)	2391398
17-35017602-T-C	not specified	Uncertain significance (Jul 13, 2021)	2342156
17-35021393-G-A	not specified	Uncertain significance (Jun 22, 2021)	2234212
17-35021396-G-T		Benign (Jul 21, 2018)	736128
17-35021496-G-T	not specified	Uncertain significance (Mar 05, 2024)	3153377
17-35021522-C-T		Benign (Dec 20, 2018)	713381
17-35021526-T-C	not specified	Uncertain significance (Jun 19, 2024)	3313864
17-35021591-C-T	not specified	Uncertain significance (Jun 11, 2024)	2389324
17-35021679-C-A	not specified	Uncertain significance (Apr 27, 2023)	2515031
17-35021687-C-T	not specified	Uncertain significance (Oct 12, 2021)	2376097
17-35021730-C-T	not specified	Uncertain significance (Dec 26, 2023)	3153376
17-35021755-A-T	not specified	Uncertain significance (Jan 23, 2023)	2465645
17-35026379-T-C	not specified	Uncertain significance (Dec 28, 2022)	2340288
17-35026420-G-T	not specified	Uncertain significance (Jun 29, 2023)	2607794
17-35026429-C-T	not specified	Uncertain significance (Jan 06, 2023)	3153375

GnomAD

Source: gnomAD

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: dbNSFP

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