The protein encoded by this gene contains a RING-H2 finger motif. Deletions and mutations in this gene were detected in esophageal squamous cell carcinoma (ESCC), suggesting that this protein may be a potential tumor suppressor. Studies of the mouse counterpart suggested a role of this protein in the transcription regulation that controls germinal differentiation. Multiple alte... See more...

Aliases for RNF6 Gene

Aliases for RNF6 Gene

  • Ring Finger Protein 6 2 3 5
  • RING-Type E3 Ubiquitin Transferase RNF6 3 4
  • Ring Finger Protein (C3H2C3 Type) 6 2 3
  • E3 Ubiquitin-Protein Ligase RNF6 3 4
  • RING-H2 Protein RNF-6 2 3
  • DKFZp686P0776 2
  • EC 2.3.2.27 4
  • RNF6 5
  • SPG2 4

External Ids for RNF6 Gene

Previous GeneCards Identifiers for RNF6 Gene

  • GC13M024766
  • GC13M020766
  • GC13M025636
  • GC13M024584
  • GC13M024504
  • GC13M025604
  • GC13M026706
  • GC13M007604

Summaries for RNF6 Gene

Entrez Gene Summary for RNF6 Gene

  • The protein encoded by this gene contains a RING-H2 finger motif. Deletions and mutations in this gene were detected in esophageal squamous cell carcinoma (ESCC), suggesting that this protein may be a potential tumor suppressor. Studies of the mouse counterpart suggested a role of this protein in the transcription regulation that controls germinal differentiation. Multiple alternatively spliced transcript variants encoding the same protein are observed. [provided by RefSeq, Jul 2008]

GeneCards Summary for RNF6 Gene

RNF6 (Ring Finger Protein 6) is a Protein Coding gene. Diseases associated with RNF6 include Esophageal Cancer and Squamous Cell Carcinoma. Among its related pathways are Androgen receptor signaling pathway and Class I MHC mediated antigen processing and presentation. Gene Ontology (GO) annotations related to this gene include ligase activity and androgen receptor binding. An important paralog of this gene is RLIM.

UniProtKB/Swiss-Prot Summary for RNF6 Gene

  • 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.

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for RNF6 Gene

Genomics for RNF6 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for RNF6 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH13J026219 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 257.5 +1.3 1267 3.6 BCLAF1 SP1 ZNF207 MYC ZNF600 IKZF1 ZNF580 POLR2A NFIC ZBTB10 RNF6 ENSG00000277368 lnc-RNF6-4 piR-48965-034 SHISA2
GH13J026253 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 11.7 -32.3 -32316 4.4 BCLAF1 SP1 ZNF207 MYC IKZF1 ZNF600 SIX5 ZNF592 POLR2A NFIC CDK8 RNF6 lnc-ATP8A2-4 WASF3
GH13J026185 Promoter/Enhancer 1.5 FANTOM5 ENCODE CraniofacialAtlas 11.7 +36.3 36344 2.6 BCLAF1 ZNF207 MYC ZNF592 YY1 MXD4 NONO REST TRIM22 BHLHE40 HSALNG0095863 RNF6 WASF3 piR-48965-034 lnc-RNF6-4 SHISA2
GH13J026496 Enhancer 1 Ensembl ENCODE dbSUPER 10.1 -275.0 -275004 3.1 JUND REST CTCF ZNF217 RAD21 SMC3 YY1 EGR1 ZNF362 POLR2A HSALNG0095880 RNF6 WASF3 HSALNG0095882 CDK8
GH13J026412 Enhancer 0.7 Ensembl ENCODE 10.1 -189.4 -189416 3.8 TEAD3 FOSL2 SCRT1 ZMYM3 GATA2 ARID3A CHD2 TEAD1 SCRT2 HSALNG0095876 RNF6 CDK8 RF00994-266 WASF3
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around RNF6 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for RNF6

Top Transcription factor binding sites by QIAGEN in the RNF6 gene promoter:
  • Nkx3-1
  • Nkx3-1 v1
  • Nkx3-1 v2
  • TBP

Genomic Locations for RNF6 Gene

Latest Assembly
chr13:26,132,115-26,223,085
(GRCh38/hg38)
Size:
90,971 bases
Orientation:
Minus strand

Previous Assembly
chr13:26,706,253-26,796,508
(GRCh37/hg19 by Entrez Gene)
Size:
90,256 bases
Orientation:
Minus strand

chr13:26,706,253-26,796,791
(GRCh37/hg19 by Ensembl)
Size:
90,539 bases
Orientation:
Minus strand

Genomic View for RNF6 Gene

Genes around RNF6 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RNF6 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RNF6 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RNF6 Gene

Proteins for RNF6 Gene

  • Protein details for RNF6 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y252-RNF6_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase RNF6
    Protein Accession:
    Q9Y252
    Secondary Accessions:
    • B4DDP0
    • Q5W0H0
    • Q9BZP5
    • Q9UF41

    Protein attributes for RNF6 Gene

    Size:
    685 amino acids
    Molecular mass:
    78091 Da
    Quaternary structure:
    • Interacts with LIMK1 (By similarity). Interacts with AR.
    Miscellaneous:
    • Required for prostate tumor cell growth.

    Alternative splice isoforms for RNF6 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RNF6 Gene

Post-translational modifications for RNF6 Gene

  • Ubiquitination at Lys608
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for RNF6 Gene

Domains & Families for RNF6 Gene

Gene Families for RNF6 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Plasma proteins
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for RNF6 Gene

InterPro:
Blocks:
  • Zn-finger, RING

Suggested Antigen Peptide Sequences for RNF6 Gene

GenScript: Design optimal peptide antigens:
  • cDNA, FLJ92781, Homo sapiens ring finger protein (C3H2C3 type) 6 (RNF6), mRNA (Q5W0H0_HUMAN)
  • RNF6 protein (Q9BZP5_HUMAN)
  • E3 ubiquitin-protein ligase RNF6 (RNF6_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9Y252

UniProtKB/Swiss-Prot:

RNF6_HUMAN :
  • Belongs to the RNF12 family.
Family:
  • Belongs to the RNF12 family.
genes like me logo Genes that share domains with RNF6: view

Function for RNF6 Gene

Molecular function for RNF6 Gene

UniProtKB/Swiss-Prot 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.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;.
GENATLAS Biochemistry:
RING finger protein 6,not disrupted in the translocation t(4;13) associated with myeloproliferative disorders

Enzyme Numbers (IUBMB) for RNF6 Gene

Phenotypes From GWAS Catalog for RNF6 Gene

Gene Ontology (GO) - Molecular Function for RNF6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 ubiquitin-protein transferase activity IMP 19345326
GO:0005515 protein binding IPI 19345326
GO:0016740 transferase activity IEA --
GO:0046872 metal ion binding IEA --
GO:0050681 androgen receptor binding IPI 19345326
genes like me logo Genes that share ontologies with RNF6: view
genes like me logo Genes that share phenotypes with RNF6: view

Human Phenotype Ontology for RNF6 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RNF6

Clone products for research

  • Addgene plasmids for RNF6

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for RNF6 Gene

Localization for RNF6 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RNF6 Gene

Nucleus. Cytoplasm. Cell projection, axon. Nucleus, PML body. Note=Localizes to the PML nuclear bodies in Sertoli cells. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for RNF6 gene
Compartment Confidence
nucleus 5
cytosol 2
plasma membrane 1
extracellular 1
cytoskeleton 1
mitochondrion 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear membrane (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for RNF6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA,IDA 19345326
GO:0005654 nucleoplasm IBA 21873635
GO:0005737 cytoplasm IBA,IDA 19345326
GO:0016605 PML body IEA --
GO:0030424 axon ISS --
genes like me logo Genes that share ontologies with RNF6: view

Pathways & Interactions for RNF6 Gene

genes like me logo Genes that share pathways with RNF6: view

UniProtKB/Swiss-Prot Q9Y252-RNF6_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

Gene Ontology (GO) - Biological Process for RNF6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006355 regulation of transcription, DNA-templated IMP 19345326
GO:0006511 ubiquitin-dependent protein catabolic process IBA,ISS --
GO:0016567 protein ubiquitination IBA 21873635
GO:0030517 negative regulation of axon extension ISS --
GO:0044314 protein K27-linked ubiquitination IDA 19345326
genes like me logo Genes that share ontologies with RNF6: view

No data available for SIGNOR curated interactions for RNF6 Gene

Drugs & Compounds for RNF6 Gene

No Compound Related Data Available

Transcripts for RNF6 Gene

mRNA/cDNA for RNF6 Gene

4 REFSEQ mRNAs :
16 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RNF6

Clone products for research

  • Addgene plasmids for RNF6

Alternative Splicing Database (ASD) splice patterns (SP) for RNF6 Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b · 2c · 2d ^ 3a · 3b · 3c ^ 4a · 4b ^ 5a · 5b · 5c · 5d ^ 6a · 6b ^ 7a · 7b · 7c · 7d · 7e · 7f ^ 8
SP1: - - - - - - - - - - - - - -
SP2: - - - - - - - - -
SP3: - - - - -
SP4: - - - - -
SP5: - -
SP6: - - -
SP7: - -
SP8: - - - - - -
SP9: - - - - - - - -
SP10: - - -
SP11: -

Relevant External Links for RNF6 Gene

GeneLoc Exon Structure for
RNF6

Expression for RNF6 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for RNF6 Gene

Protein differential expression in normal tissues from HIPED for RNF6 Gene

This gene is overexpressed in Platelet (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for RNF6 Gene



Protein tissue co-expression partners for RNF6 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for RNF6

SOURCE GeneReport for Unigene cluster for RNF6 Gene:

Hs.136885

mRNA Expression by UniProt/SwissProt for RNF6 Gene:

Q9Y252-RNF6_HUMAN
Tissue specificity: Weakly expressed in peripheral blood, spleen, prostate, testis and ovary. According to PubMed:18368307, it is preferentially expressed in testis and ovary and hardly detected in other tissues.

Evidence on tissue expression from TISSUES for RNF6 Gene

  • Nervous system(4.9)
  • Blood(4.2)
  • Kidney(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for RNF6 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • digestive
  • integumentary
  • nervous
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • head
  • larynx
  • neck
  • vocal cord
Thorax:
  • esophagus
Abdomen:
  • stomach
General:
  • skin
genes like me logo Genes that share expression patterns with RNF6: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for RNF6 Gene

Orthologs for RNF6 Gene

This gene was present in the common ancestor of animals.

Orthologs for RNF6 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia RNF6 29 30
  • 99.66 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia RNF6 29 30
  • 91.64 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Rnf6 29 16 30
  • 78.9 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Rnf6 29
  • 76.93 (n)
Cow
(Bos Taurus)
Mammalia RNF6 29 30
  • 74.5 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia RNF6 30
  • 68 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia RNF6 30
  • 44 (a)
OneToOne
Chicken
(Gallus gallus)
Aves RNF6 29 30
  • 66.17 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia RNF6 30
  • 52 (a)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii rnf6 30
  • 45 (a)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta mura 30
  • 10 (a)
OneToMany
Species where no ortholog for RNF6 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for RNF6 Gene

ENSEMBL:
Gene Tree for RNF6 (if available)
TreeFam:
Gene Tree for RNF6 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for RNF6: view image
Alliance of Genome Resources:
Additional Orthologs for RNF6

Paralogs for RNF6 Gene

Paralogs for RNF6 Gene

(2) SIMAP similar genes for RNF6 Gene using alignment to 3 proteins:

  • RNF6_HUMAN
  • B4DDP0_HUMAN
  • Q9BZP5_HUMAN

Pseudogenes.org Pseudogenes for RNF6 Gene

genes like me logo Genes that share paralogs with RNF6: view

Variants for RNF6 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for RNF6 Gene

SNP ID Clinical significance and condition Chr 13 pos Variation AA Info Type
rs121434522 Pathogenic: Esophageal squamous cell carcinoma, somatic 26,215,577(-) C/Tp.Arg102Lys
NM_005977.4(RNF6):c.305G>A (p.Arg102Lys)
MISSENSE
rs121434523 Pathogenic: Esophageal squamous cell carcinoma, somatic 26,215,158(-) C/Tp.Ala242Thr
NM_005977.4(RNF6):c.724G>A (p.Ala242Thr)
MISSENSE_VARIANT,INTRON
rs121434524 Pathogenic: Esophageal squamous cell carcinoma, somatic 26,215,151(-) C/Tp.Gly244Asp
NM_005977.4(RNF6):c.731G>A (p.Gly244Asp)
MISSENSE_VARIANT,INTRON
rs138379662 Benign: not provided 26,214,167(-) C/Tp.Arg572Gln
NM_005977.4(RNF6):c.1715G>A (p.Arg572Gln)
MISSENSE_VARIANT,INTRON
rs139551586 Benign: not provided 26,218,551(-) T/C
NM_005977.4(RNF6):c.249A>G (p.Leu83=)
SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for RNF6 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for RNF6 Gene

Variant ID Type Subtype PubMed ID
esv2469087 CNV deletion 19546169

Variation tolerance for RNF6 Gene

Residual Variation Intolerance Score: 67.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.91; 35.61% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RNF6 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
RNF6
Leiden Open Variation Database (LOVD)
RNF6

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RNF6 Gene

Disorders for RNF6 Gene

MalaCards: The human disease database

(2) MalaCards diseases for RNF6 Gene - From: OMI, CVR, ORP, COP, and GCD

Disorder Aliases PubMed IDs
esophageal cancer
  • esophageal cancer, somatic
squamous cell carcinoma
  • epidermoid carcinoma
- elite association - COSMIC cancer census association via MalaCards
Search RNF6 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

RNF6_HUMAN
  • 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 variants affecting the gene represented in this entry.

Additional Disease Information for RNF6

genes like me logo Genes that share disorders with RNF6: view

No data available for Genatlas for RNF6 Gene

Publications for RNF6 Gene

  1. Identification of somatic mutations of the RNF6 gene in human esophageal squamous cell carcinoma. (PMID: 12154016) Lo HS … Lee MP (Cancer research 2002) 3 4 72
  2. Cloning and characterization of RNF6, a novel RING finger gene mapping to 13q12. (PMID: 10331950) Macdonald DH … Cross NC (Genomics 1999) 2 3 4
  3. Regulation of androgen receptor transcriptional activity and specificity by RNF6-induced ubiquitination. (PMID: 19345326) Xu K … Qiu Y (Cancer cell 2009) 3 4
  4. Cloning and identification of a novel RNF6 transcriptional splice variant Spg2 in human development. (PMID: 18368307) Zhu L … Ma J (Science in China. Series C, Life sciences 2008) 3 4
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4

Products for RNF6 Gene

Sources for RNF6 Gene