RNF126

ring finger protein 126, the group of Ring finger proteins

Basic information

Region (hg38): 19:647526-663233

Links

ENSG00000070423 ∙ NCBI:55658 ∙ OMIM:615177 ∙ HGNC:21151 ∙ Uniprot:Q9BV68 ∙ 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 RNF126 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNF126 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				4		4
missense			44		1	45
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	44	4	1

Variants in RNF126

This is a list of pathogenic ClinVar variants found in the RNF126 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-648132-G-A		not specified	Uncertain significance (Jul 30, 2024)
19-648145-C-T		not specified	Uncertain significance (May 28, 2024)
19-648150-T-C		not specified	Uncertain significance (Jan 13, 2023)
19-648171-G-A		not specified	Uncertain significance (May 10, 2024)
19-648174-G-A		not specified	Uncertain significance (Jun 30, 2023)
19-648201-A-T		not specified	Uncertain significance (Jul 12, 2022)
19-648217-G-C		not specified	Uncertain significance (May 15, 2024)
19-648262-C-T		not specified	Uncertain significance (Aug 28, 2023)
19-648401-C-T			Benign (Jul 18, 2018)
19-648410-G-T		not specified	Uncertain significance (Feb 15, 2023)
19-648436-C-T		not specified	Uncertain significance (Nov 07, 2022)
19-648437-G-A		not specified	Uncertain significance (Jul 09, 2024)
19-648900-C-T		not specified	Uncertain significance (Aug 04, 2024)
19-648945-G-A		not specified	Uncertain significance (May 18, 2023)
19-648969-T-C		not specified	Uncertain significance (Nov 11, 2024)
19-649738-G-A		not specified	Uncertain significance (Apr 19, 2024)
19-650259-C-T		not specified	Uncertain significance (Dec 18, 2023)
19-650280-C-T		not specified	Uncertain significance (Jan 19, 2024)
19-651615-C-G		not specified	Uncertain significance (Jul 14, 2021)
19-651627-C-T		not specified	Uncertain significance (Jul 02, 2024)
19-651634-G-T		not specified	Uncertain significance (Dec 31, 2024)
19-651650-C-T		not specified	Uncertain significance (Jun 30, 2024)
19-651653-C-T		not specified	Uncertain significance (Jan 29, 2024)
19-651665-C-T		not specified	Uncertain significance (Apr 15, 2024)
19-651669-C-T		not specified	Uncertain significance (May 28, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RNF126	protein_coding	protein_coding	ENST00000292363	9	15752

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.954	0.0462	124133	0	2	124135	0.00000806

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.729	152	179	0.847	0.0000126	1955
Missense in Polyphen		47	71.705	0.65546		749
Synonymous	-1.60	101	82.5	1.22	0.00000707	610
Loss of Function	3.23	1	14.1	0.0711	6.83e-7	169

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000182	0.0000180
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination oF target proteins (PubMed:23277564, PubMed:24275455, PubMed:24981174). Depending on the associated E2 ligase, mediates 'Lys-48'- and 'Lys-63'-linked polyubiquitination of substrates (By similarity). Part of a BAG6-dependent quality control process ensuring that proteins of the secretory pathway that are mislocalized to the cytosol are degraded by the proteasome. Probably acts by providing the ubiquitin ligase activity associated with the BAG6 complex and be responsible for ubiquitination of the hydrophobic mislocalized proteins and their targeting to the proteasome (PubMed:24981174, PubMed:29042515). May also play a role in the endosomal recycling of IGF2R, the cation-independent mannose-6-phosphate receptor (PubMed:24275455). May play a role in the endosomal sorting and degradation of several membrane receptors including EGFR, FLT3, MET and CXCR4, by mediating their ubiquitination (PubMed:23418353). By ubiquitinating CDKN1A/p21 and targeting it for degradation, may also promote cell proliferation (PubMed:23026136). May monoubiquitinate AICDA (PubMed:23277564). {ECO:0000250|UniProtKB:Q91YL2, ECO:0000269|PubMed:23277564, ECO:0000269|PubMed:23418353, ECO:0000269|PubMed:24275455, ECO:0000269|PubMed:24981174, ECO:0000269|PubMed:29042515, ECO:0000305|PubMed:23026136}.
• Pathway: Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation (Consensus)

Recessive Scores

• pRec: 0.112

Intolerance Scores

• loftool: 0.379
• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.43

Haploinsufficiency Scores

• pHI: 0.145
• hipred: Y
• hipred_score: 0.595
• ghis: 0.537

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.768

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rnf126

Gene ontology

• Biological process: ubiquitin-dependent protein catabolic process;protein monoubiquitination;protein ubiquitination;negative regulation of epidermal growth factor receptor signaling pathway;regulation of cell population proliferation;retrograde transport, endosome to Golgi;proteasome-mediated ubiquitin-dependent protein catabolic process;ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway;protein K63-linked ubiquitination;protein K48-linked ubiquitination;cytoplasm protein quality control by the ubiquitin-proteasome system
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol
• Molecular function: epidermal growth factor receptor binding;protein binding;metal ion binding;ubiquitin protein ligase activity