Gene Summary

Gene:RPN1; ribophorin I
Aliases: OST1, RBPH1
Summary:This gene encodes a type I integral membrane protein found only in the rough endoplasmic reticulum. The encoded protein is part of an N-oligosaccharyl transferase complex that links high mannose oligosaccharides to asparagine residues found in the Asn-X-Ser/Thr consensus motif of nascent polypeptide chains. This protein forms part of the regulatory subunit of the 26S proteasome and may mediate binding of ubiquitin-like domains to this proteasome. [provided by RefSeq, Jul 2008]
Databases:OMIM, VEGA, HGNC, Ensembl, GeneCard, Gene
Protein:dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 1
Source:NCBIAccessed: 17 August, 2015


What does this gene/protein do?
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Pathways:What pathways are this gene/protein implicaed in?
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Cancer Overview

Research Indicators

Publications Per Year (1990-2015)
Graph generated 17 August 2015 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.

Tag cloud generated 17 August, 2015 using data from PubMed, MeSH and CancerIndex

Specific Cancers (5)

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: RPN1 (cancer-related)

Duhoux FP, Ameye G, Montano-Almendras CP, et al.
PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies.
Br J Haematol. 2012; 156(1):76-88 [PubMed] Related Publications
The PRDM16 (1p36) gene is rearranged in acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) with t(1;3)(p36;q21), sharing characteristics with AML and MDS with MECOM (3q26.2) translocations. We used fluorescence in situ hybridization to study 39 haematological malignancies with translocations involving PRDM16 to assess the precise breakpoint on 1p36 and the identity of the partner locus. Reverse-transcription polymerase chain reaction (PCR) was performed in selected cases in order to confirm the partner locus. PRDM16 expression studies were performed on bone marrow samples of patients, normal controls and CD34(+) cells using TaqMan real-time quantitative PCR. PRDM16 was rearranged with the RPN1 (3q21) locus in 30 cases and with other loci in nine cases. The diagnosis was AML or MDS in most cases, except for two cases of lymphoid proliferation. We identified novel translocation partners of PRDM16, including the transcription factors ETV6 and IKZF1. Translocations involving PRDM16 lead to its overexpression irrespective of the consequence of the rearrangement (fusion gene or promoter swap). Survival data suggest that patients with AML/MDS and PRDM16 translocations have a poor prognosis despite a simple karyotype and a median age of 65 years. There seems to be an over-representation of late-onset therapy-related myeloid malignancies.

De Braekeleer E, Douet-Guilbert N, Basinko A, et al.
Conventional cytogenetics and breakpoint distribution by fluorescent in situ hybridization in patients with malignant hemopathies associated with inv(3)(q21;q26) and t(3;3)(q21;q26).
Anticancer Res. 2011; 31(10):3441-8 [PubMed] Related Publications
Inv(3)(q21q26)/t(3;3)(q21;q26) is recognized as a distinctive entity of acute myeloid leukemia (AML) with recurrent genetic abnormalities of prognostic significance. It occurs in 1-2.5% of AML and is also observed in myelodysplastic syndromes and in the blastic phase of chronic myeloid leukemia. The molecular consequence of the inv(3)/t(3;3) rearrangements is the juxtaposition of the ribophorin I (RPN1) gene (located in band 3q21) with the ecotropic viral integration site 1 (EVI1) gene (located in band 3q26.2). Following conventional cytogenetics to determine the karyotype, fluorescent in situ hybridization (FISH) with a panel of bacterial artificial chromosome clones was used to map the breakpoints involved in 15 inv(3)/t(3;3). Inv(3) or t(3;3) was the sole karyotypic anomaly in 6 patients, while additional abnormalities were identified in the remaining 9 patients, including 4 with monosomy of chromosome7 (-7) or a deletion of its long arm (7q-). Breakpoints in band 3q21 were distributed in a 235 kb region centromeric to and including the RPN1 locus, while those in band 3q26.2 were scattered in a 900 kb region located on each side of and including the EVI1 locus. In contrast to most of the inversions and translocations associated with AML that lead to fusion genes, inv(3)/t(3;3) does not generate a chimeric gene, but rather induces gene overexpression. The wide dispersion of the breakpoints in bands 3q21 and 3q26 and the heterogeneity of the genomic consequences could explain why the mechanisms leading to leukemogenesis are still poorly understood. Therefore, it is important to further characterize these chromosomal abnormalities by FISH.

Shearer BM, Sukov WR, Flynn HC, et al.
Development of a dual-color, double fusion FISH assay to detect RPN1/EVI1 gene fusion associated with inv(3), t(3;3), and ins(3;3) in patients with myelodysplasia and acute myeloid leukemia.
Am J Hematol. 2010; 85(8):569-74 [PubMed] Related Publications
Approximately 2-3% of adult patients with acute myeloid leukemia harbor a rearrangement of RPN1 (at 3q21) and EVI1 (at 3q26.2) as inv(3)(q21q26.2), t(3;3)(q21;q26.2), or ins(3;3)(q26.2;q21q26.2). The most recent World Health Organization (WHO) classification has designated AML with inv(3) or t(3;3) and associated RPN1/EVI1 fusion, as a distinct AML subgroup associated with an unfavorable prognosis. We have created a dual color, double fusion fluorescence in situ hybridization (D-FISH) assay to detect fusion of the RPN1 and EVI1 genes. A blinded investigation was performed using 30 normal bone marrow samples and 51 bone marrow samples from 17 patients with inv(3)(q21q26.2), 11 patients with t(3;3)(q21;q26.2), and one patient with ins(3;3)(q26.2;q21q26.2) previously defined by chromosome analysis. The unblinded results indicated abnormal RPN1/EVI1 fusion results in 30 (97%) of 31 samples from the inv(3)(q21q26.2) group including seven bone marrow samples for which chromosome analysis was unsuccessful or failed to detect an inv(3)(q21q26.2). Abnormal FISH results were detected in 14 (88%) of 16 samples with t(3;3)(q21;q26.2) and in the sole sample with an ins(3;3)(q26.2;q21q26.2). All 30 negative controls were normal and were used to establish a normal cutoff of 0.6% for the typical abnormal D-FISH signal pattern. Overall, this D-FISH assay was more accurate than chromosome analysis and based on the normal cutoff of 0.6%, this assay can be used for minimal residual disease detection and disease monitoring in patients with RPN1/EVI1 fusion.

Senchenko VN, Anedchenko EA, Kondratieva TT, et al.
Simultaneous down-regulation of tumor suppressor genes RBSP3/CTDSPL, NPRL2/G21 and RASSF1A in primary non-small cell lung cancer.
BMC Cancer. 2010; 10:75 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The short arm of human chromosome 3 is involved in the development of many cancers including lung cancer. Three bona fide lung cancer tumor suppressor genes namely RBSP3 (AP20 region),NPRL2 and RASSF1A (LUCA region) were identified in the 3p21.3 region. We have shown previously that homozygous deletions in AP20 and LUCA sub-regions often occurred in the same tumor (P < 10-6).
METHODS: We estimated the quantity of RBSP3, NPRL2, RASSF1A, GAPDH, RPN1 mRNA and RBSP3 DNA copy number in 59 primary non-small cell lung cancers, including 41 squamous cell and 18 adenocarcinomas by real-time reverse transcription-polymerase chain reaction based on TaqMan technology and relative quantification.
RESULTS: We evaluated the relationship between mRNA level and clinicopathologic characteristics in non-small cell lung cancer. A significant expression decrease (> or =2) was found for all three genes early in tumor development: in 85% of cases for RBSP3; 73% for NPRL2 and 67% for RASSF1A (P < 0.001), more strongly pronounced in squamous cell than in adenocarcinomas. Strong suppression of both, NPRL2 and RBSP3 was seen in 100% of cases already at Stage I of squamous cell carcinomas. Deregulation of RASSF1A correlated with tumor progression of squamous cell (P = 0.196) and adenocarcinomas (P < 0.05). Most likely, genetic and epigenetic mechanisms might be responsible for transcriptional inactivation of RBSP3 in non-small cell lung cancers as promoter methylation of RBSP3 according to NotI microarrays data was detected in 80% of squamous cell and in 38% of adenocarcinomas. With NotI microarrays we tested how often LUCA (NPRL2, RASSF1A) and AP20 (RBSP3) regions were deleted or methylated in the same tumor sample and found that this occured in 39% of all studied samples (P < 0.05).
CONCLUSION: Our data support the hypothesis that these TSG are involved in tumorigenesis of NSCLC. Both genetic and epigenetic mechanisms contribute to down-regulation of these three genes representing two tumor suppressor clusters in 3p21.3. Most importantly expression of RBSP3, NPRL2 and RASSF1A was simultaneously decreased in the same sample of primary NSCLC: in 39% of cases all these three genes showed reduced expression (P < 0.05).

Bui C, Ouzzine M, Talhaoui I, et al.
Epigenetics: methylation-associated repression of heparan sulfate 3-O-sulfotransferase gene expression contributes to the invasive phenotype of H-EMC-SS chondrosarcoma cells.
FASEB J. 2010; 24(2):436-50 [PubMed] Related Publications
Heparan sulfate proteoglycans (HSPGs), strategically located at the cell-tissue-organ interface, regulate major biological processes, including cell proliferation, migration, and adhesion. These vital functions are compromised in tumors, due, in part, to alterations in heparan sulfate (HS) expression and structure. How these modifications occur is largely unknown. Here, we investigated whether epigenetic abnormalities involving aberrant DNA methylation affect HS biosynthetic enzymes in cancer cells. Analysis of the methylation status of glycosyltransferase and sulfotransferase genes in H-HEMC-SS chondrosarcoma cells showed a typical hypermethylation profile of 3-OST sulfotransferase genes. Exposure of chondrosarcoma cells to 5-aza-2'-deoxycytidine (5-Aza-dc), a DNA-methyltransferase inhibitor, up-regulated expression of 3-OST1, 3-OST2, and 3-OST3A mRNAs, indicating that aberrant methylation affects transcription of these genes. Furthermore, HS expression was restored on 5-Aza-dc treatment or reintroduction of 3-OST expression, as shown by indirect immunofluorescence microscopy and/or analysis of HS chains by anion-exchange and gel-filtration chromatography. Notably, 5-Aza-dc treatment of HEMC cells or expression of 3-OST3A cDNA reduced their proliferative and invading properties and augmented adhesion of chondrosarcoma cells. These results provide the first evidence for specific epigenetic regulation of 3-OST genes resulting in altered HSPG sulfation and point to a defect of HS-3-O-sulfation as a factor in cancer progression.

Martinelli G, Ottaviani E, Buonamici S, et al.
Association of 3q21q26 syndrome with different RPN1/EVI1 fusion transcripts.
Haematologica. 2003; 88(11):1221-8 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: Patients with acute myeloblastic leukemia (AML) with features of myelodysplastic syndrome and abnormalities of megakaryocytopoiesis often have cytogenetic aberrations of 3q21 and 3q26 bands involving the paracentric inversion [inv(3) (q21q26)] or a reciprocal translocation [t(3;3) (q21;q26)]. These abnormalities frequently cause inappropriate expression of the EVI1 gene located at 3q26. Other genes that have been implicated at the rearrangement breakpoint are GR6 and RPN1 (both on 3q21). The aim of this study was to investigate the expression of the EVI1 fusion genes in AML patients with 3q21q26 syndrome.
DESIGN AND METHODS: We used reverse transcription polymerase chain reaction to evaluate the expression of EVI1 and GR6, and particularly of the fusion genes RPN1-EVI1 and GR6-EVI1 in 9 AML patients with either inv(3)(q21q26) (7 cases) or t(3;3)(q21;q26) (2 cases).
RESULTS: EVI1 and GR6 were always expressed, as was RPN1-EVI1; GR6-EVI1 was absent. In 8/9 patients, the part of EVI1 retained in RPN1-DEVI1 contained blocks B and C of the PR domain commonly found in the MDS1-EVI1 gene. In the remaining patient [with inv(3) (q21q26)], only block C was retained: we named this variant fusion gene RPN1-DEVI1. This patient lacked the micromegakaryocytopoiesis frequently found in 3q21q26 syndrome.
INTERPRETATION AND CONCLUSIONS: These findings support the hypothesis that EVI1 activation plays a dominant role in the pathogenesis of the 3q21q26 syndrome. EVI1 expression might occur either as a consequence of rearrangements leading to the formation of different fusion transcripts, such as RPN1-EVI1 and RPN1-DEVI1 or following disruption of the PR activation domain of the MDS1-EVI1 gene.

Barjesteh van Waalwijk van Doorn-Khosrovani S, Erpelinck C, Löwenberg B, Delwel R
Low expression of MDS1-EVI1-like-1 (MEL1) and EVI1-like-1 (EL1) genes in favorable-risk acute myeloid leukemia.
Exp Hematol. 2003; 31(11):1066-72 [PubMed] Related Publications
OBJECTIVE: The expression of an MDS1-EVI1-like-1 (MEL1) gene is reported in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with translocation t(1;3)(p36;q21). MEL1 (at chromosome band 1p36.3) is thought to be transcriptionally activated as a result of juxtaposition to the RPN1 gene at 3q21. It is not known whether MEL1 expression is restricted to cases with this particular translocation.
MATERIALS AND METHODS: Using real-time polymerase chain reaction, we measured MEL1 expression levels, normal bone marrow, and distinct blood cell fractions in 162 de novo AML patients. We also investigated the existence of an EVI1-like gene (EL1) by applying the same method. The existence of these transcripts was confirmed by Northern blot analysis.
RESULTS: MEL1 expression was detected in 87% (141/162) of de novo AML patients. The EL1 transcript also was detected in the majority of the patients. EL1 expression levels highly correlated with MEL1 expression levels in AML cases. Variable MEL1/EL1 expression levels were observed. However, all the patients with favorable-risk karyotypes, i.e., with t(15;17), t(8;21), or inv(16), showed low MEL1/EL1 expression levels. Expression analysis of MEL1/EL1 compared with MDS1-EVI1/EVI1 in distinct normal marrow or blood cell fractions revealed that 1) all four gene products are expressed in CD34(+) progenitor cell fractions; 2) both MEL1 and EVI1 are turned down in neutrophils and monocytes/macrophages; while 3) MDS1-EVI1 and EL1 remain expressed in mature blood cell fractions.
CONCLUSION: Our data suggest that simultaneous low MEL1/EL1 expression in AML is abnormal and that favorable disease is highly associated with this abnormal phenotype.

Xinh PT, Tri NK, Nagao H, et al.
Breakpoints at 1p36.3 in three MDS/AML(M4) patients with t(1;3)(p36;q21) occur in the first intron and in the 5' region of MEL1.
Genes Chromosomes Cancer. 2003; 36(3):313-6 [PubMed] Related Publications
The recurrent translocation t(1;3)(p36;q21) is associated with myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) characterized by trilineage dysplasia, especially dysmegakaryopoiesis and a poor prognosis. Recently, the two genes involved in this translocation have been identified: the MEL1 gene at 1p36.3, and the RPN1 gene at 3q21. The breakpoint in RPN1 is centromeric to the breakpoint cluster region of the inv(3) abnormality. Because the MEL1 transcript is detected only in leukemic cells with t(1;3)(p36;q21), ectopic expression of MEL1 driven by RPN1 at 3q21 is thought to contribute to the pathogenesis of t(1;3)(p36;q21) leukemia. However, the precise breakpoint in the patients has not yet been identified. With fluorescence in situ hybridization analysis by use of BAC/PAC probes, we identified the breakpoint at 1p36.3 in three MDS/AML patients with t(1;3)(p36;q21): within the first intron of the MEL1 gene (one patient) or within a 29-kb region located in the 5' region of MEL1 (two other patients). We detected several sizes of MEL1 transcript in two patients including the first patient, although we have not yet clarified whether MEL1 transcripts were different among the patients and whether a truncated MEL1 transcript was expressed in the first patient. This patient showed an unusual clinical profile, repeating progression to overt leukemia and conversion to MDS three times during the 29-month survival period, which might be related to a different molecular mechanism in this patient.

Shimizu S, Suzukawa K, Kodera T, et al.
Identification of breakpoint cluster regions at 1p36.3 and 3q21 in hematologic malignancies with t(1;3)(p36;q21).
Genes Chromosomes Cancer. 2000; 27(3):229-38 [PubMed] Related Publications
The reciprocal translocation t(1;3)(p36;q21) is associated with myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML) characterized by trilineage dysplasia, in particular dysmegakaryocytopoiesis, and a poor prognosis. As yet no molecular genetic analyses of the t(1;3) have been reported. In four patients with t(1;3), all of whom had AML-M4, which evolved from MDS, the breakpoints at 3q21 clustered within a 60-kb region centromeric to the breakpoint of the inv(3)(q21q26), whereas the breakpoints at 1p36 clustered within a 90-kb region at 1p36.3. The presence of novel clusters in both the 3q21 and 1p36 breakpoints (BCRs) suggests a common, underlying molecular mechanism for the development of t(1;3)-positive MDS/AML. The Ribophorin I (RPN1) gene close to the BCR at 3q21 was highly expressed without gross structural changes, whereas the GR6 gene located within the BCR at 3q21 was not expressed. No other highly expressed genes were isolated in a 150-kb region at 3q21. Thus, it is likely that a gene at 1p36.3 is activated by the translocation of the 3q21 region or a gene important for transformation lies on 3q21, outside the 150-kb region. Further characterization of the BCRs at 1p36.3 and 3q21 should provide important insights into the molecular genetic mechanisms involved in the genesis of t(1;3)-positive MDS/AML. Genes Chromosomes Cancer 27:229-238, 2000.

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Cite this page: Cotterill SJ. RPN1, Cancer Genetics Web: http://www.cancer-genetics.org/RPN1.htm Accessed:

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