Gene Summary

Gene:RNF213; ring finger protein 213
Aliases: ALO17, MYMY2, MYSTR, NET57, C17orf27, KIAA1618
Summary:This gene encodes a protein containing a C3HC4-type RING finger domain, which is a specialized type of Zn-finger that binds two atoms of zinc and is thought to be involved in mediating protein-protein interactions. The protein also contains an AAA domain, which is associated with ATPase activity. This gene is a susceptibility gene for Moyamoya disease, a vascular disorder of intracranial arteries. This gene is also a translocation partner in anaplastic large cell lymphoma and inflammatory myofibroblastic tumor cases, where a t(2;17)(p23;q25) translocation has been identified with the anaplastic lymphoma kinase (ALK) gene on chromosome 2, and a t(8;17)(q24;q25) translocation has been identified with the MYC gene on chromosome 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:E3 ubiquitin-protein ligase RNF213
Source:NCBIAccessed: 30 August, 2019


What does this gene/protein do?
Show (10)

Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 30 August 2019 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Receptor Protein-Tyrosine Kinases
  • Head and Neck Cancers
  • Lymphoma, Large-Cell, Anaplastic
  • DNA Mutational Analysis
  • Moyamoya Disease
  • Chromosome 17
  • Signal Transduction
  • Wnt Proteins
  • Ovarian Cancer
  • Oncogene Fusion Proteins
  • High-Throughput Nucleotide Sequencing
  • Transcription Factors
  • ALK
  • Base Sequence
  • Genome-Wide Association Study
  • alpha Catenin
  • Immunohistochemistry
  • Phosphoproteins
  • Notch Receptors
  • TPM3 protein, human
  • Adolescents
  • Mutation
  • Young Adult
  • Childhood Cancer
  • Cohort Studies
  • ALK protein, human
  • Whole Exome Sequencing
  • Synovial Sarcoma
  • Genetic Association Studies
  • Neurofibromatosis 1
  • Tongue Neoplasms
  • Tropomyosin
  • Brain Stem Glioma, Childhood
  • Translocation
  • Single Nucleotide Polymorphism
  • Pedigree
  • Adenosine Triphosphatases
  • Cancer Gene Expression Regulation
  • Ubiquitin-Protein Ligases
  • Infant
  • Sequence Analysis, RNA
  • Deoxycytidine
  • Brain Tumours
Tag cloud generated 30 August, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (6)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: RNF213 (cancer-related)

Santoro C, Giugliano T, Kraemer M, et al.
Whole exome sequencing identifies MRVI1 as a susceptibility gene for moyamoya syndrome in neurofibromatosis type 1.
PLoS One. 2018; 13(7):e0200446 [PubMed] Free Access to Full Article Related Publications
BACKGROUND AND PURPOSE: Moyamoya angiopathy is a progressive cerebral vasculopathy. The p.R4810K substitution in RNF213 has previously been linked to moyamoya disease in Asian populations. When associated with other medical conditions, such as neurofibromatosis type 1, this vasculopathy is frequently reported as moyamoya syndrome. Intriguingly, most cases of moyamoya-complicated neurofibromatosis type 1 have been described in Caucasians, inverting the population ratio observed in Asians, although prevalence of neurofibromatosis type 1 is constant worldwide. Our aim was to investigate whether, among Caucasians, additive genetic factors may contribute to the occurrence of moyamoya in neurofibromatosis type 1.
METHODS: Whole exome sequencing was carried out on an Italian family with moyamoya-complicated neurofibromatosis type 1 to identify putative genetic modifiers independent of the NF1 locus and potentially involved in moyamoya pathogenesis. Results were validated in an unrelated family of German ancestry.
RESULTS: We identified the p.P186S substitution (rs35857561) in MRVI1 that segregated with moyamoya syndrome in both the Italian and German family.
CONCLUSIONS: The rs35857561 polymorphism in MRVI1 may be a genetic susceptibility factor for moyamoya in European patients with neurofibromatosis type 1. MRVI1 is a functional partner of ITPR1, PRKG1 and GUCY1A3, which are involved in response to nitric oxide. Mutations in GUCY1A3 have been recently linked to a recessive syndromic form of moyamoya with esophageal achalasia.

Li X, Xu W, Kang W, et al.
Genomic analysis of liver cancer unveils novel driver genes and distinct prognostic features.
Theranostics. 2018; 8(6):1740-1751 [PubMed] Free Access to Full Article Related Publications

Warejko JK, Schueler M, Vivante A, et al.
Whole Exome Sequencing Reveals a Monogenic Cause of Disease in ≈43% of 35 Families With Midaortic Syndrome.
Hypertension. 2018; 71(4):691-699 [PubMed] Free Access to Full Article Related Publications
Midaortic syndrome (MAS) is a rare cause of severe childhood hypertension characterized by narrowing of the abdominal aorta in children and is associated with extensive vascular disease. It may occur as part of a genetic syndrome, such as neurofibromatosis, or as consequence of a pathological inflammatory disease. However, most cases are considered idiopathic. We hypothesized that in a high percentage of these patients, a monogenic cause of disease may be detected by evaluating whole exome sequencing data for mutations in 1 of 38 candidate genes previously described to cause vasculopathy. We studied a cohort of 36 individuals from 35 different families with MAS by exome sequencing. In 15 of 35 families (42.9%), we detected likely causal dominant mutations. In 15 of 35 (42.9%) families with MAS, whole exome sequencing revealed a mutation in one of the genes previously associated with vascular disease (

Kohutek ZA, Rosati LM, Hong J, et al.
An unusual genomic variant of pancreatic ductal adenocarcinoma with an indolent clinical course.
Cold Spring Harb Mol Case Stud. 2017; 3(4) [PubMed] Free Access to Full Article Related Publications
We describe an 85-yr-old male of Ashkenazi Jewish descent with biopsy-proven locally advanced pancreatic ductal adenocarcinoma (PDA). The patient underwent a modified course of gemcitabine and stereotactic body radiation therapy and survived for 42 mo with a stable pancreatic head mass and no evidence of metastatic disease before death due to complications from a stroke. Whole-exome sequencing of his tumor revealed a simple genome landscape with no evidence of mutations, copy-number changes, or structural alterations in genes most commonly associated with PDA (i.e.,

van der Krogt JA, Bempt MV, Ferreiro JF, et al.
Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with the variant RNF213-, ATIC- and TPM3-ALK fusions is characterized by copy number gain of the rearranged ALK gene.
Haematologica. 2017; 102(9):1605-1616 [PubMed] Free Access to Full Article Related Publications
Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma is characterized by 2p23/

Banh RS, Iorio C, Marcotte R, et al.
PTP1B controls non-mitochondrial oxygen consumption by regulating RNF213 to promote tumour survival during hypoxia.
Nat Cell Biol. 2016; 18(7):803-813 [PubMed] Free Access to Full Article Related Publications
Tumours exist in a hypoxic microenvironment and must limit excessive oxygen consumption. Hypoxia-inducible factor (HIF) controls mitochondrial oxygen consumption, but how/if tumours regulate non-mitochondrial oxygen consumption (NMOC) is unknown. Protein-tyrosine phosphatase-1B (PTP1B) is required for Her2/Neu-driven breast cancer (BC) in mice, although the underlying mechanism and human relevance remain unclear. We found that PTP1B-deficient HER2(+) xenografts have increased hypoxia, necrosis and impaired growth. In vitro, PTP1B deficiency sensitizes HER2(+) BC lines to hypoxia by increasing NMOC by α-KG-dependent dioxygenases (α-KGDDs). The moyamoya disease gene product RNF213, an E3 ligase, is negatively regulated by PTP1B in HER2(+) BC cells. RNF213 knockdown reverses the effects of PTP1B deficiency on α-KGDDs, NMOC and hypoxia-induced death of HER2(+) BC cells, and partially restores tumorigenicity. We conclude that PTP1B acts via RNF213 to suppress α-KGDD activity and NMOC. This PTP1B/RNF213/α-KGDD pathway is critical for survival of HER2(+) BC, and possibly other malignancies, in the hypoxic tumour microenvironment.

Er TK, Su YF, Wu CC, et al.
Targeted next-generation sequencing for molecular diagnosis of endometriosis-associated ovarian cancer.
J Mol Med (Berl). 2016; 94(7):835-47 [PubMed] Related Publications
UNLABELLED: Recent molecular and pathological studies suggest that endometriosis may serve as a precursor of ovarian cancer (endometriosis-associated ovarian cancer, EAOC), especially of the endometrioid and clear cell subtypes. Accordingly, this study had two cardinal aims: first, to obtain mutation profiles of EAOC from Taiwanese patients; and second, to determine whether somatic mutations present in EAOC can be detected in preneoplastic lesions. Formalin-fixed paraffin-embedded (FFPE) tissues were obtained from ten endometriosis patients with malignant transformation. Macrodissection was performed to separate four different types of cells from FFPE sections in six patients. The four types of samples included normal endometrium, ectopic endometriotic lesion, atypical endometriosis, and carcinoma. Ultra-deep (>1000×) targeted sequencing was performed on 409 cancer-related genes to identify pathogenic mutations associated with EAOC. The most frequently mutated genes were PIK3CA (6/10) and ARID1A (5/10). Other recurrently mutated genes included ETS1, MLH1, PRKDC (3/10 each), and AMER1, ARID2, BCL11A, CREBBP, ERBB2, EXT1, FANCD2, MSH6, NF1, NOTCH1, NUMA1, PDE4DIP, PPP2R1A, RNF213, and SYNE1 (2/10 each). Importantly, in five of the six patients, identical somatic mutations were detected in atypical endometriosis and tumor lesions. In two patients, genetic alterations were also detected in ectopic endometriotic lesions, indicating the presence of genetic alterations in preneoplastic lesion. Genetic analysis in preneoplastic lesions may help to identify high-risk patients at early stage of malignant transformation and also shed new light on fundamental aspects of the molecular pathogenesis of EAOC.
KEY MESSAGES: Molecular characterization of endometriosis-associated ovarian cancer genes by targeted NGS. Candidate genes predictive of malignant transformation were identified. Chromatin remodeling, PI3K-AKT-mTOR, Notch signaling, and Wnt/β-catenin pathway may promote cell malignant transformation.

Phi JH, Choi JW, Seong MW, et al.
Association between moyamoya syndrome and the RNF213 c.14576G>A variant in patients with neurofibromatosis Type 1.
J Neurosurg Pediatr. 2016; 17(6):717-22 [PubMed] Related Publications
OBJECTIVE In a minority of patients with neurofibromatosis Type 1 (NF-1), cerebral vasculopathy reminiscent of moyamoya disease develops. This phenomenon is called moyamoya syndrome (MMS), but there are no known risk factors for the prediction of MMS in NF-1 patients. Polymorphism of the RNF213 gene has exhibited strong associations with familial and sporadic moyamoya disease and other cerebral vasculopathies. The aim of this study is to find whether the RNF213 c.14576G>A variant is associated with MMS development in the NF-1 population or not. METHODS The MMS group included 16 NF-1 patients with documented MMS. The control group consisted of 97 NF-1 patients without MMS. Genomic DNA samples were obtained from the saliva or blood of both groups, and the presence of the RNF213 c.14576G>A variant was assessed by Sanger sequencing. RESULTS In the MMS group, 3 patients had the RNF213 c.14576G>A variant (18.7%), whereas no patients with this genetic variation were observed in the control group (0%). There was a meaningful association between the RNF213 c.14576G>A variant and MMS development (p = 0.0024). The crude odds ratio was calculated as 50.57 (95% CI 1.57-1624.41). All 3 patients with MMS and the c.14576G>A variant were diagnosed with MMS at an early age and had bilateral involvement. CONCLUSIONS The RNF213 c.14576G>A variant is more common in NF-1 patients who develop MMS than in NF-1 patients without MMS. This variant might be a susceptibility gene for the NF-1-moyamoya connection.

Vlenterie M, Hillebrandt-Roeffen MH, Flucke UE, et al.
Next generation sequencing in synovial sarcoma reveals novel gene mutations.
Oncotarget. 2015; 6(33):34680-90 [PubMed] Free Access to Full Article Related Publications
Over 95% of all synovial sarcomas (SS) share a unique translocation, t(X;18), however, they show heterogeneous clinical behavior. We analyzed multiple SS to reveal additional genetic alterations besides the translocation. Twenty-six SS from 22 patients were sequenced for 409 cancer-related genes using the Comprehensive Cancer Panel (Life Technologies, USA) on an Ion Torrent platform. The detected variants were verified by Sanger sequencing and compared to matched normal DNAs. Copy number variation was assessed in six tumors using the Oncoscan array (Affymetrix, USA). In total, eight somatic mutations were detected in eight samples. These mutations have not been reported previously in SS. Two of these, in KRAS and CCND1, represent known oncogenic mutations in other malignancies. Additional mutations were detected in RNF213, SEPT9, KDR, CSMD3, MLH1 and ERBB4. DNA alterations occurred more often in adult tumors. A distinctive loss of 6q was found in a metastatic lesion progressing under pazopanib, but not in the responding lesion. Our results emphasize t(X;18) as a single initiating event in SS and as the main oncogenic driver. Our results also show the occurrence of additional genetic events, mutations or chromosomal aberrations, occurring more frequently in SS with an onset in adults.

Vettore AL, Ramnarayanan K, Poore G, et al.
Mutational landscapes of tongue carcinoma reveal recurrent mutations in genes of therapeutic and prognostic relevance.
Genome Med. 2015; 7:98 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Carcinoma of the oral tongue (OTSCC) is the most common malignancy of the oral cavity, characterized by frequent recurrence and poor survival. The last three decades has witnessed a change in the OTSCC epidemiological profile, with increasing incidence in younger patients, females and never-smokers. Here, we sought to characterize the OTSCC genomic landscape and to determine factors that may delineate the genetic basis of this disease, inform prognosis and identify targets for therapeutic intervention.
METHODS: Seventy-eight cases were subjected to whole-exome (n = 18) and targeted deep sequencing (n = 60).
RESULTS: While the most common mutation was in TP53, the OTSCC genetic landscape differed from previously described cohorts of patients with head and neck tumors: OTSCCs demonstrated frequent mutations in DST and RNF213, while alterations in CDKN2A and NOTCH1 were significantly less frequent. Despite a lack of previously reported NOTCH1 mutations, integrated analysis showed enrichments of alterations affecting Notch signaling in OTSCC. Importantly, these Notch pathway alterations were prognostic on multivariate analyses. A high proportion of OTSCCs also presented with alterations in drug targetable and chromatin remodeling genes. Patients harboring mutations in actionable pathways were more likely to succumb from recurrent disease compared with those who did not, suggesting that the former should be considered for treatment with targeted compounds in future trials.
CONCLUSIONS: Our study defines the Asian OTSCC mutational landscape, highlighting the key role of Notch signaling in oral tongue tumorigenesis. We also observed somatic mutations in multiple therapeutically relevant genes, which may represent candidate drug targets in this highly lethal tumor type.

Bao ZS, Chen HM, Yang MY, et al.
RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas.
Genome Res. 2014; 24(11):1765-73 [PubMed] Free Access to Full Article Related Publications
Studies of gene rearrangements and the consequent oncogenic fusion proteins have laid the foundation for targeted cancer therapy. To identify oncogenic fusions associated with glioma progression, we catalogued fusion transcripts by RNA-seq of 272 gliomas. Fusion transcripts were more frequently found in high-grade gliomas, in the classical subtype of gliomas, and in gliomas treated with radiation/temozolomide. Sixty-seven in-frame fusion transcripts were identified, including three recurrent fusion transcripts: FGFR3-TACC3, RNF213-SLC26A11, and PTPRZ1-MET (ZM). Interestingly, the ZM fusion was found only in grade III astrocytomas (1/13; 7.7%) or secondary GBMs (sGBMs, 3/20; 15.0%). In an independent cohort of sGBMs, the ZM fusion was found in three of 20 (15%) specimens. Genomic analysis revealed that the fusion arose from translocation events involving introns 3 or 8 of PTPRZ and intron 1 of MET. ZM fusion transcripts were found in GBMs irrespective of isocitrate dehydrogenase 1 (IDH1) mutation status. sGBMs harboring ZM fusion showed higher expression of genes required for PIK3CA signaling and lowered expression of genes that suppressed RB1 or TP53 function. Expression of the ZM fusion was mutually exclusive with EGFR overexpression in sGBMs. Exogenous expression of the ZM fusion in the U87MG glioblastoma line enhanced cell migration and invasion. Clinically, patients afflicted with ZM fusion harboring glioblastomas survived poorly relative to those afflicted with non-ZM-harboring sGBMs (P < 0.001). Our study profiles the shifting RNA landscape of gliomas during progression and reveled ZM as a novel, recurrent fusion transcript in sGBMs.

Zhou JB, Zhang T, Wang BF, et al.
Identification of a novel gene fusion RNF213‑SLC26A11 in chronic myeloid leukemia by RNA-Seq.
Mol Med Rep. 2013; 7(2):591-7 [PubMed] Related Publications
Chronic myeloid leukemia (CML) was the first hematological malignancy to be associated with a specific genetic lesion. The Philadelphia translocation, producing a BCR‑ABL hybrid oncogene, is the most common mechanism of CML development. However, in the present study, b3a2, b2a2 and ela2 fusion junctions of the breakpoint cluster region (BCR)-V-abl Abelson murine leukemia viral oncogene homolog 1 (ABL) gene were not detected in patients diagnosed with CML three and four years previously. RNA-Seq technology, with an average coverage of ~30‑fold, was used to detect gene fusion events in a patient with a 6-year history of CML, identified to be in the chronic phase of the disease. Using deFuse and TopHat‑fusion programs with improved filtering methods, we identified two reliable gene fusions in a blood sample obtained from the CML patient, including extremely low expression levels of the classic BCR‑ABL1 gene fusion. In addition, a novel gene fusion involving the ring finger protein 213 (RNF213)-solute carrier family 26, member 11 (SLC26A11) was identified and validated by reverse transcription polymerase chain reaction. Further bioinformatic analysis revealed that specific domains of SLC26A11 were damaged, which may affect the function of sulfate transportation of the normal gene. The present study demonstrated that, in specific cases, alternative gene fusions, besides BCR‑ABL, may be associated with the development of CML.

Moritake H, Shimonodan H, Marutsuka K, et al.
C-MYC rearrangement may induce an aggressive phenotype in anaplastic lymphoma kinase positive anaplastic large cell lymphoma: Identification of a novel fusion gene ALO17/C-MYC.
Am J Hematol. 2011; 86(1):75-8 [PubMed] Related Publications
Anaplastic lymphoma kinase (ALK) positive anaplastic large cell lymphoma (ALCL) is usually associated with a favorable prognosis. We describe an 11-year-old girl patient with ALK positive ALCL bearing t(2;5)(p23;q35) and t(8;17)(q24;q25) translocations who had an aggressive clinical course despite various combinations of intensive chemotherapy. Southern blot analysis identified C-MYC rearrangement. Immunohistochemistry and Northern and Western blot analyses revealed cmyc overexpression. A new fusion between ALO17 (ALK lymphoma oligomerization partner on chromosome 17) and C-MYC was identified by the 50-rapid amplification of cDNA ends. This new fusion may have possibly provoked the poor prognosis in this patient with ALK positive ALCL, and C-MYC rearrangement may indicate poor prognosis in ALCL.

Lamant L, Gascoyne RD, Duplantier MM, et al.
Non-muscle myosin heavy chain (MYH9): a new partner fused to ALK in anaplastic large cell lymphoma.
Genes Chromosomes Cancer. 2003; 37(4):427-32 [PubMed] Related Publications
In anaplastic large cell lymphoma, the ALK gene at 2p23 is known to be fused to NPM, TPM3, TPM4, TFG, ATIC, CLTC, MSN, and ALO17. All of these translocations result in the expression of chimeric ALK transcripts that are translated into fusion proteins with tyrosine kinase activity and oncogenic properties. We report a case showing a restricted cytoplasmic staining pattern of ALK and a novel chromosomal abnormality, t(2;22)(p23;q11.2), demonstrated by fluorescence in situ hybridization analysis. The result of 5' RACE analysis showed that the ALK gene was fused in-frame to a portion of the non-muscle myosin heavy chain gene, MYH9. Nucleotide sequence of the MYH9-ALK chimeric cDNA revealed that the ALK breakpoint was different from all those previously reported. It is localized in the same exonic sequence as MSN-ALK, but 6 bp downstream, resulting in an in-frame fusion of the two partner proteins. In contrast to the previously reported ALK fusion proteins, MYH9-ALK may lack a functional oligomerization domain. However, biochemical analysis showed that the new fusion protein is tyrosine phosphorylated in vivo but seems to lack tyrosine kinase activity in vitro. If further investigations confirm this latter result, the in vivo tyrosine phosphorylation of MYH9-ALK protein could involve mechanisms different from those described in the other ALK hybrid proteins.

Cools J, Wlodarska I, Somers R, et al.
Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor.
Genes Chromosomes Cancer. 2002; 34(4):354-62 [PubMed] Related Publications
ALK-positive anaplastic large-cell lymphoma (ALCL) has been recognized as a distinct type of lymphoma in the heterogeneous group of T/Null-ALCL. While most of the ALK-positive ALCL (ALKomas) are characterized by the presence of the NPM-ALK fusion protein, the product of the t(2;5)(p23;q35), 10-20% of ALKomas contain variant ALK fusions, including ATIC-ALK, TFG-ALK, CLTC-ALK (previously designated CLTCL-ALK), TMP3-ALK, and MSN-ALK. TMP3-ALK and TMP4-ALK fusions also have been detected in inflammatory myofibroblastic tumors (IMTs), making clear that aberrations of the ALK gene are not associated exclusively with the pathogenesis of ALK-positive ALCL. Here we report results of molecular studies on two lymphoma cases and one IMT case with variant rearrangements of ALK. Our study led to the detection of the CLTC-ALK fusion in an ALCL case and to the identification of two novel fusion partners of ALK: ALO17 (KIAA1618), a gene with unknown function, which was fused to ALK in an ALCL case with a t(2;17)(p23;q25), and CARS, encoding the cysteinyl-tRNA synthetase, which was fused to ALK in an IMT case with a t(2;11;2)(p23;p15;q31). These results confirm the recurrent involvement of ALK in IMT and further demonstrate the diversity of ALK fusion partners, with the ability to homodimerize as a common characteristic.

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Cite this page: Cotterill SJ. ALO17, Cancer Genetics Web: http://www.cancer-genetics.org/ALO17.htm Accessed:

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