RNF6

ring finger protein 6, the group of Ring finger proteins

Basic information

Region (hg38): 13:26132114-26222314

Links

ENSG00000127870

∙ NCBI:6049 ∙ OMIM:604242 ∙ HGNC:10069 ∙ Uniprot:Q9Y252 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed

Phenotypes

GenCC

Source: genCC

esophageal cancer (No Known Disease Relationship), mode of inheritance: Unknown

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RNF6 gene.

Inborn genetic diseases (13 variants)
not provided (6 variants)
Esophageal squamous cell carcinoma, somatic (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNF6 gene is commonly pathogenic or not.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					2	2
missense	3		12	3	1	19
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice variant				1		1
non coding						0
Total	3	0	12	4	3

Variants in RNF6

This is a list of pathogenic ClinVar variants found in the RNF6 region.

Position	Phenotype	Significance	ClinVar
13-26214123-G-A	Inborn genetic diseases	Uncertain significance (Jun 12, 2023)	link
13-26214167-C-T		Benign (Aug 15, 2018)	link
13-26214183-C-T	Inborn genetic diseases	Uncertain significance (Jul 07, 2022)	link
13-26214218-G-T	Inborn genetic diseases	Uncertain significance (Nov 30, 2021)	link
13-26214257-G-T		Likely benign (Apr 11, 2018)	link
13-26214380-T-C	Inborn genetic diseases	Uncertain significance (Jun 22, 2023)	link
13-26214507-T-C	Inborn genetic diseases	Uncertain significance (Oct 05, 2022)	link
13-26214521-C-T	Inborn genetic diseases	Uncertain significance (Nov 08, 2022)	link
13-26214554-C-T	Inborn genetic diseases	Uncertain significance (Dec 21, 2022)	link
13-26214743-T-C	Inborn genetic diseases	Uncertain significance (Jul 13, 2022)	link
13-26214793-T-C		Benign (Apr 18, 2018)	link
13-26214861-C-G	Inborn genetic diseases	Uncertain significance (Oct 12, 2021)	link
13-26214920-G-C	Inborn genetic diseases	Uncertain significance (Jun 06, 2023)	link
13-26214925-A-C	Inborn genetic diseases	Uncertain significance (Mar 14, 2023)	link
13-26215017-C-T	Inborn genetic diseases	Uncertain significance (May 30, 2023)	link
13-26215062-G-A	Inborn genetic diseases	Uncertain significance (Jul 13, 2022)	link
13-26215127-C-T	Inborn genetic diseases	Likely benign (Aug 30, 2021)	link
13-26215151-C-T	Esophageal squamous cell carcinoma, somatic	Pathogenic (Aug 01, 2002)	link
13-26215158-C-T	Esophageal squamous cell carcinoma, somatic	Pathogenic (Aug 01, 2002)	link
13-26215274-A-G	Inborn genetic diseases	Uncertain significance (May 11, 2022)	link
13-26215290-T-C	Inborn genetic diseases	Uncertain significance (Dec 21, 2022)	link
13-26215314-T-C		Likely benign (Aug 15, 2018)	link
13-26215440-G-A	Inborn genetic diseases	Uncertain significance (Dec 15, 2021)	link
13-26215530-G-A	Inborn genetic diseases	Uncertain significance (Mar 06, 2023)	link
13-26215577-C-T	Esophageal squamous cell carcinoma, somatic	Pathogenic (Aug 01, 2002)	link

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RNF6	protein_coding	protein_coding	ENST00000381588	3	90539

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0139	0.986	125727	0	20	125747	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.25	310	378	0.819	0.0000219	4469
Missense in Polyphen		73	110.82	0.65875		1357
Synonymous	0.365	125	130	0.959	0.00000649	1377
Loss of Function	3.54	9	29.8	0.302	0.00000244	294

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000148	0.000148
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000796	0.0000791
Middle Eastern	0.000109	0.000109
South Asian	0.000131	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase mediating 'Lys-48'-linked polyubiquitination of LIMK1 and its subsequent targeting to the proteasome for degradation. Negatively regulates axonal outgrowth through regulation of the LIMK1 turnover. Mediates 'Lys-6' and 'Lys-27'-linked polyubiquitination of AR/androgen receptor thereby modulating its transcriptional activity. May also bind DNA and function as a transcriptional regulator. {ECO:0000269|PubMed:19345326}.;
Disease: DISEASE: Esophageal cancer (ESCR) [MIM:133239]: A malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage. {ECO:0000269|PubMed:12154016}. Note=The disease may be caused by mutations affecting the gene represented in this entry.;
Pathway: Androgen receptor signaling pathway;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;AndrogenReceptor (Consensus)

Recessive Scores

pRec: 0.0930

Intolerance Scores

loftool: 0.766
rvis_EVS: 0.16
rvis_percentile_EVS: 64.85

Haploinsufficiency Scores

pHI: 0.118
hipred: N
hipred_score: 0.344
ghis: 0.573

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.992

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Rnf6
Phenotype

Gene ontology

Biological process: regulation of transcription, DNA-templated;ubiquitin-dependent protein catabolic process;negative regulation of axon extension;protein K27-linked ubiquitination;positive regulation of transcription, DNA-templated;regulation of androgen receptor signaling pathway;protein K48-linked ubiquitination;protein K6-linked ubiquitination
Cellular component: nucleus;nucleoplasm;cytoplasm;PML body;axon;nuclear membrane;intracellular membrane-bounded organelle
Molecular function: DNA binding;ubiquitin-protein transferase activity;protein binding;metal ion binding;androgen receptor binding;ubiquitin protein ligase activity