RNF139

ring finger protein 139, the group of Ring finger proteins

Basic information

Region (hg38): 8:124474879-124488618

Links

ENSG00000170881 ∙ NCBI:11236 ∙ OMIM:603046 ∙ HGNC:17023 ∙ Uniprot:Q8WU17 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nonpapillary renal cell carcinoma (No Known Disease Relationship), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Renal cell carcinoma, clear cell	AD	Oncologic	Surveillance and early detection of and treatment for malignancy (a number of cancer types have been described, including renal cell cancer and dysgerminoma) may decrease morbidity and mortality	Oncologic	17539022; 19642973
Genomic disruptions have been reported

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RNF139 gene.

• Inborn genetic diseases (18 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNF139 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			16			16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			2			2
Total	0	0	18	0	0

Variants in RNF139

This is a list of pathogenic ClinVar variants found in the RNF139 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-124475128-C-T		not specified	Uncertain significance (Nov 06, 2023)
8-124475173-C-T		not specified	Uncertain significance (Feb 12, 2024)
8-124475225-A-C		not specified	Uncertain significance (Dec 11, 2023)
8-124475225-A-G		not specified	Uncertain significance (Jan 30, 2024)
8-124485971-G-A		not specified	Uncertain significance (Nov 17, 2023)
8-124486038-T-G		not specified	Uncertain significance (Sep 20, 2023)
8-124486139-A-G		not specified	Uncertain significance (Nov 15, 2021)
8-124486358-A-G		not specified	Uncertain significance (May 26, 2023)
8-124486422-G-T		not specified	Uncertain significance (Sep 12, 2023)
8-124486424-A-G		not specified	Uncertain significance (Dec 21, 2022)
8-124486557-A-G		not specified	Uncertain significance (Aug 23, 2021)
8-124486614-G-A		not specified	Uncertain significance (Feb 13, 2024)
8-124486796-G-C		not specified	Uncertain significance (Jun 28, 2022)
8-124486871-T-G		not specified	Uncertain significance (Sep 22, 2022)
8-124486974-C-T		not specified	Uncertain significance (Dec 06, 2022)
8-124486986-T-C		not specified	Uncertain significance (Feb 23, 2023)
8-124487039-G-A		not specified	Uncertain significance (Jan 10, 2022)
8-124487255-A-G		not specified	Uncertain significance (Mar 16, 2022)
8-124487280-A-G		not specified	Uncertain significance (Feb 21, 2024)
8-124487357-C-T		not specified	Uncertain significance (May 26, 2023)
8-124487381-A-G		not specified	Uncertain significance (Nov 01, 2022)
8-124487399-A-G		not specified	Uncertain significance (Oct 29, 2021)
8-124487437-G-C		not specified	Uncertain significance (Oct 04, 2022)
8-124487523-C-G		not specified	Uncertain significance (Jul 06, 2021)
8-124487552-A-T		not specified	Uncertain significance (Dec 13, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RNF139	protein_coding	protein_coding	ENST00000303545	2	13177

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.538	0.462	125708	0	40	125748	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.84	261	359	0.727	0.0000189	4338
Missense in Polyphen		57	108.17	0.52697		1354
Synonymous	-0.887	150	137	1.10	0.00000713	1333
Loss of Function	3.59	5	24.0	0.208	0.00000147	285

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000438	0.000438
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000278	0.000277
European (Non-Finnish)	0.000116	0.000114
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
Other	0.000491	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E3-ubiquitin ligase; acts as a negative regulator of the cell proliferation through mechanisms involving G2/M arrest and cell death. Required for MHC class I ubiquitination in cells expressing the cytomegalovirus protein US2 before dislocation from the endoplasmic reticulum (ER). Affects SREBP processing by hindering the SREBP/SCAP complex translocation from the ER to the Golgi, thereby reducing SREBF2 target gene expression. Required for INSIG1 ubiquitination. May be required for EIF3 complex ubiquitination. May function as a signaling receptor. {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:12032852, ECO:0000269|PubMed:17016439, ECO:0000269|PubMed:19706601, ECO:0000269|PubMed:19720873, ECO:0000269|PubMed:20068067}.
• Disease: DISEASE: Renal cell carcinoma (RCC) [MIM:144700]: Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma. Clear cell renal cell carcinoma is the most common subtype. Note=The disease may be caused by mutations affecting the gene represented in this entry. A chromosomal aberration involving RNF139 has been found in a lymphoblastoid cell line established from a family with renal cell carcinoma and thyroid carcinoma. Translocation (3;8)(q14.2;q24.1) with FHIT. RNF139 is found to be fused to FHIT and disrupted within the sterol-sensing domain. In contrast, the FHIT coding region is maintained and expressed. Sporadic cases of renal carcinoma, where an acquired mutation in RNF139 results in the duplication of 12 nucleotides in the 5'-UTR, has also been identified.
• Pathway: Sterol Regulatory Element-Binding Proteins (SREBP) signalling;ER Quality Control Compartment (ERQC);Calnexin/calreticulin cycle;Post-translational protein modification;Metabolism of proteins;Asparagine N-linked glycosylation;N-glycan trimming in the ER and Calnexin/Calreticulin cycle (Consensus)

Recessive Scores

• pRec: 0.115

Intolerance Scores

• loftool: 0.463
• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.5

Haploinsufficiency Scores

• pHI: 0.307
• hipred: Y
• hipred_score: 0.704
• ghis: 0.580

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.844

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Rnf139
• Phenotype: cellular phenotype; immune system phenotype; liver/biliary system phenotype

Gene ontology

• Biological process: negative regulation of cell population proliferation;protein ubiquitination;negative regulation of translation;protein destabilization;ERAD pathway;regulation of ER to Golgi vesicle-mediated transport;regulation of protein processing;endoplasmic reticulum mannose trimming;positive regulation of ubiquitin-dependent protein catabolic process
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;endomembrane system;integral component of membrane;Derlin-1 retrotranslocation complex;endoplasmic reticulum quality control compartment
• Molecular function: protease binding;ubiquitin-protein transferase activity;protein binding;zinc ion binding;ubiquitin-like protein transferase activity;signaling receptor activity;ubiquitin protein ligase activity