Gene Summary

Gene:NBR1; NBR1 autophagy cargo receptor
Aliases: IAI3B, M17S2, MIG19, 1A1-3B
Summary:The protein encoded by this gene was originally identified as an ovarian tumor antigen monitored in ovarian cancer. The encoded protein contains a B-box/coiled-coil motif, which is present in many genes with transformation potential. It functions as a specific autophagy receptor for the selective autophagic degradation of peroxisomes by forming intracellular inclusions with ubiquitylated autophagic substrates. This gene is located on a region of chromosome 17q21.1 that is in close proximity to the BRCA1 tumor suppressor gene. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2014]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:next to BRCA1 gene 1 protein
Source:NCBIAccessed: 30 August, 2019


What does this gene/protein do?
Show (16)

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.

  • Polymerase Chain Reaction
  • Chromosome Mapping
  • Hereditary Breast and Ovarian Cancer Syndrome
  • Genetic Predisposition
  • Pedigree
  • BRCA2
  • DNA Mutational Analysis
  • Cancer Gene Expression Regulation
  • Protein Isoforms
  • RNA Splicing Factors
  • Amino Acid Sequence
  • High-Throughput Nucleotide Sequencing
  • NBR1
  • Base Sequence
  • Ovarian Cancer
  • Exons
  • Survival Rate
  • BRCA1
  • Introns
  • Zinc Fingers
  • Oligodendroglioma
  • Neoplasm Proteins
  • Chromosome 17
  • Loss of Heterozygosity
  • Molecular Sequence Data
  • Breast Cancer
  • Protein Structure, Tertiary
  • Autophagy
  • Mutation
  • Acute Myeloid Leukaemia
  • Gene Deletion
  • VHL
  • Transfection
  • Cancer Stem Cells
  • BRCA1 Protein
  • DNA, Complementary
  • Proteins
  • Cell Cycle Proteins
  • Cell Line
  • Transcription Factors
Tag cloud generated 30 August, 2019 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: NBR1 (cancer-related)

Rizza R, Hackmann K, Paris I, et al.
Novel BRCA1 Large Genomic Rearrangements in Italian Breast/Ovarian Cancer Patients.
Mol Diagn Ther. 2019; 23(1):121-126 [PubMed] Related Publications
BACKGROUND: In recent years, the number of patients being offered BRCA1/2 testing has changed dramatically. Advances in high-throughput sequencing technology have led many diagnostic laboratories to test next-generation sequencing (NGS)-based platforms as the main technology for clinical testing. As a consequence, the proportion of novel BRCA1/2 variants detected has greatly increased. Here, we describe two novel BRCA1 large deletions detected in Italian patients affected by hereditary breast and ovarian cancer syndrome (HBOC).
METHODS: We applied an NGS pipeline with a reliable copy number variation (CNV) prediction algorithm. Successively, samples were investigated using the Multiplex Amplicon Quantification (MAQ) assay and array comparative genomic hybridization (CGH). In a single case, long-range polymerase chain reaction (PCR) was employed for careful detection of the breakpoint region, while the RepeatMasker program was used to identify Alu sequences at the junction point.
RESULTS: A 137.8 kb deletion, involving the first six exons of BRCA1 and the full NBR2, BRCA1P1, NBR1, and TMEM106a genes, was detected in an Italian woman diagnosed with high-grade serous ovarian carcinoma. A second rearrangement, involving the deletion of BRCA1 11-14 exons, was detected in a breast cancer patient and was fully characterized and reported according to recommended Human Genome Variation Society (HGVS) nomenclature: NG_005905.2: g.125038_143266del; NM_007294.3: c.2817_4716del; NP_009225: p.Lys862Metfs?
CONCLUSION: Although it was not possible to perform a familial segregation analysis and more direct evidence of the relationship between genotype and phenotype is necessary, both of the novel reported rearrangements cause the loss of crucial functional domains of the BRCA1 protein and this event supports their pathogenicity.

Du C, Mark D, Wappenschmidt B, et al.
A tandem duplication of BRCA1 exons 1-19 through DHX8 exon 2 in four families with hereditary breast and ovarian cancer syndrome.
Breast Cancer Res Treat. 2018; 172(3):561-569 [PubMed] Related Publications
PURPOSE: The purpose of this study is to characterize a novel structural variant, a large duplication involving exons 1-19 of the BRCA1 gene in four independent families, and to provide diagnostically valuable information including the position of the breakpoints as well as clues to its clinical significance.
METHODS: The duplication of exons 1-19 of the BRCA1 gene was initially detected by routine laboratory testing including MLPA analysis and next generation sequencing. For detailed characterization we performed array-comparative genome hybridization analysis, fluorescent in situ hybridization, next generation mapping, and long-distance PCR for break-point sequencing.
RESULTS: Our data revealed a tandem duplication on chromosome 17 that encompassed 357 kb and included exons 1-19 of the BRCA1 gene and the genes NBR2, NBR1, TMEM106A, LOC100130581, ARL4D, MIR2117 up to parts of the DHX8 gene. This structural variant appeared as a tandem duplication with breakpoints in intron 19 of the BRCA1 gene and in intron 3 of the DHX8 gene (HGVS:chr17(hg19):g.41210776_41568516dup). Segregation analysis indicated that this structural rearrangement is phased in trans with a known pathogenic exon deletion of the BRCA1 gene in one family.
CONCLUSIONS: The copy number variation initially recognized as duplication of exon 1-19 of the BRCA1 gene by MLPA analysis is a structural variation with breakpoints in the BRCA1 and DHX8 genes. Although currently to be classified as a variant of unknown significance, our family data indicates that this duplication may be a benign variation or at least of markedly reduced penetrance since it occurs in trans with another known fully pathogenic variant in the BRCA1 gene.

Liang PQ, Miao M, Liu ZG, et al.
Expression of autophagy genes in acute myeloid leukemia: associations with clinical characteristics and prognosis.
Neoplasma. 2018; 65(5):807-814 [PubMed] Related Publications
The relationships between autophagy-associated gene expression and clinical characteristics and prognosis in acute myeloid leukemia (AML) have not been well revealed. We examined mRNA expression of Bcl-2, p62, Beclin 1, VPS34, Rubicon, ALFY, UVRAG, ULK1, LC3 and NBR1 in 20 AML cases and 10 benign hematological cases by real-time PCR. Clinical information, treatment responses and outcomes of the AML patients were collected. Beclin 1, LC3, UVRAG, Rubicon and NBR1 were downregulated in AML patients compared with control group (P<0.05). Low ULK1 expression was associated with high white blood cell counts (P<0.05). Autophagy-associated gene expression was not correlated with chemotherapy response. Finally, we analyzed overall survival and found no obvious association with gene expression. However, in unfavorable outcome patients, low Beclin 1 and p62 expression showed worse overall survival than high-expression. Autophagy genes are associated with outcome in AML patients and may be biomarkers or targets in the future.

Ferguson SD, Zhou S, Huse JT, et al.
Targetable Gene Fusions Associate With the IDH Wild-Type Astrocytic Lineage in Adult Gliomas.
J Neuropathol Exp Neurol. 2018; 77(6):437-442 [PubMed] Free Access to Full Article Related Publications
Gene fusions involving oncogenes have been reported in gliomas and may serve as novel therapeutic targets. Using RNA-sequencing, we interrogated a large cohort of gliomas to assess for the incidence of targetable genetic fusions. Gliomas (n = 390) were profiled using the ArcherDx FusionPlex Assay. Fifty-two gene targets were analyzed and fusions with preserved kinase domains were investigated. Overall, 36 gliomas (9%) harbored a total of 37 potentially targetable fusions, the majority of which were found in astrocytomas (n = 34). Within this lineage 11% (25/235) of glioblastomas, 12% (5/42) of anaplastic astrocytomas, 8% (2/25) of grade II astrocytomas, and 33% (2/6) of pilocytic astrocytoma harbored targetable fusions. Fusions were significantly more frequent in IDH wild-type tumors (12%, n = 31/261) relative to IDH mutants (4%; n = 4/109) (p = 0.011). No fusions were seen in oligodendrogliomas. The most frequently observed therapeutically targetable fusions were in FGFR (n = 12), MET (n = 11), and NTRK (n = 8). Several additional novel fusions that have not been previously described in gliomas were identified including EGFR:VWC2 and FGFR3:NBR1. In summary, targetable gene fusions are enriched in IDH wild-type high-grade astrocytic tumors, which will influence enrollment in and interpretation of clinical trials of glioma patients.

Walter KM, Schönenberger MJ, Trötzmüller M, et al.
Hif-2α promotes degradation of mammalian peroxisomes by selective autophagy.
Cell Metab. 2014; 20(5):882-897 [PubMed] Related Publications
Peroxisomes play a central role in lipid metabolism, and their function depends on molecular oxygen. Low oxygen tension or von Hippel-Lindau (Vhl) tumor suppressor loss is known to stabilize hypoxia-inducible factors alpha (Hif-1α and Hif-2α) to mediate adaptive responses, but it remains unknown if peroxisome homeostasis and metabolism are interconnected with Hif-α signaling. By studying liver-specific Vhl, Vhl/Hif1α, and Vhl/Hif2α knockout mice, we demonstrate a regulatory function of Hif-2α signaling on peroxisomes. Hif-2α activation augments peroxisome turnover by selective autophagy (pexophagy) and thereby changes lipid composition reminiscent of peroxisomal disorders. The autophagy receptor Nbr1 localizes to peroxisomes and is likewise degraded by Hif-2α-mediated pexophagy. Furthermore, we demonstrate that peroxisome abundance is reduced in VHL-deficient human clear cell renal cell carcinomas with high HIF-2α levels. These results establish Hif-2α as a negative regulator of peroxisome abundance and metabolism and suggest a mechanism by which cells attune peroxisomal function with oxygen availability.

Garcia-Casado Z, Romero I, Fernandez-Serra A, et al.
A de novo complete BRCA1 gene deletion identified in a Spanish woman with early bilateral breast cancer.
BMC Med Genet. 2011; 12:134 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Germline mutations in either of the two tumor-suppressor genes, BRCA1 and BRCA2, account for a significant proportion of hereditary breast and ovarian cancer cases. Most of these mutations consist of deletions, insertions, nonsense mutations, and splice variants, however an increasing number of large genomic rearrangements have been identified in these genes.
METHODS: We analysed BRCA1 and BRCA2 genes by direct sequencing and MLPA. We confirmed the results by an alternative MLPA kit and characterized the BRCA1 deletion by Array CGH.
RESULTS: We describe the first case of a patient with no strong family history of the disease who developed early-onset bilateral breast cancer with a de novo complete BRCA1 gene deletion in the germinal line. The detected deletion started from the region surrounding the VAT1 locus to the beginning of NBR1 gene, including the RND2, ΨBRCA1, BRCA1 and NBR2 complete genes.
CONCLUSION: This finding supports the large genomic rearrangement screening of BRCA genes in young breast cancer patients without family history, as well as in hereditary breast and ovarian cancer families previously tested negative for other variations.

Alhopuro P, Björklund M, Sammalkorpi H, et al.
Mutations in the circadian gene CLOCK in colorectal cancer.
Mol Cancer Res. 2010; 8(7):952-60 [PubMed] Related Publications
The circadian clock regulates daily variations in physiologic processes. CLOCK acts as a regulator in the circadian apparatus controlling the expression of other clock genes, including PER1. Clock genes have been implicated in cancer-related functions; in this work, we investigated CLOCK as a possible target of somatic mutations in microsatellite unstable colorectal cancers. Combining microarray gene expression data and public gene sequence information, we identified CLOCK as 1 of 790 putative novel microsatellite instability (MSI) target genes. A total of 101 MSI colorectal carcinomas (CRC) were sequenced for a coding microsatellite in CLOCK. The effect of restoring CLOCK expression was studied in LS180 cells lacking wild-type CLOCK by stably expressing GST-CLOCK or glutathione S-transferase empty vector and testing the effects of UV-induced apoptosis and radiation by DNA content analysis using flow cytometry. Putative novel CLOCK target genes were searched by using ChIP-seq. CLOCK mutations occurred in 53% of MSI CRCs. Restoring CLOCK expression in cells with biallelic CLOCK inactivation resulted in protection against UV-induced apoptosis and decreased G(2)-M arrest in response to ionizing radiation. Using ChIP-Seq, novel CLOCK-binding elements were identified near DNA damage genes p21, NBR1, BRCA1, and RAD50. CLOCK is shown to be mutated in cancer, and altered response to DNA damage provides one plausible mechanism of tumorigenesis.

Li J, Sherman-Baust CA, Tsai-Turton M, et al.
Claudin-containing exosomes in the peripheral circulation of women with ovarian cancer.
BMC Cancer. 2009; 9:244 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The absence of highly sensitive and specific serum biomarkers makes mass screening for ovarian cancer impossible. The claudin proteins are frequently overexpressed in ovarian cancers, but their potential as prognostic, diagnostic, or detection markers remains unclear. Here, we have explored the possible use of these proteins as screening biomarkers for ovarian cancer detection.
METHODS: Claudin protein shedding from cells was examined by immunoblotting of conditioned culture media. The presence of claudins in exosomes released from ovarian cancer cells was demonstrated by sucrose gradient separation and immunogold electron microscopy experiments. Claudin-4-containing exosomes in the plasma of ovarian cancer patients were evaluated in a pilot panel of 63 ovarian cancer patients and 50 healthy volunteers. The CA125 marker was also assessed in these samples and compared with claudin-4 positivity.
RESULTS: We show that full-length claudins can be shed from ovarian cancer cells in culture and found in the media as part of small lipid vesicles known as exosomes. Moreover, 32 of 63 plasma samples from ovarian cancer patients exhibited the presence of claudin-4-containing exosomes. In contrast, only one of 50 samples from individuals without cancer exhibited claudin-4-positive exosomes. In our small panel, at a specificity of 98%, the claudin-4 and CA125 tests had sensitivities of 51% and 71%, respectively. The two tests did not appear to be independent and were strongly correlated.
CONCLUSION: Our work shows for the first time that claudin-4 can be released from ovarian cancer cells and can be detected in the peripheral circulation of ovarian cancer patients. The development of sensitive assays for the detection of claudin-4 in blood will be crucial in determining whether this approach can be useful, alone or in combination with other screening methods, for the detection of ovarian cancer.

Verbruggen MB, Zweemer RP, Piek JM, et al.
A case of loss of heterozygosity in the BRCA2 gene of a borderline ovarian tumor: case report and review of literature.
Int J Gynecol Cancer. 2007 Sep-Oct; 17(5):1143-7 [PubMed] Related Publications
Germline BRCA1 and BRCA2 mutations highly increase the risk of breast and female adnexal cancer. The role of these genes in the tumorigenesis of other malignancies is still under debate. Borderline ovarian tumors (BOT) are occasionally found in families with a strong history of breast and/or female adnexal cancer with or without proven germline mutations. We investigated whether a BOT arising in a germline BRCA2 mutation carrier could be attributed to this mutation, in which case BOT should be added to the BRCA2 related tumor spectrum. Tumor DNA of a serous borderline ovarian tumor (sBOT) of a 55-year-old female carrier of a pathogenic BRCA2 mutation (6085G>T) was analyzed for loss of heterozygosity (LOH) of BRCA2. The sBOT cells, unexpectedly, revealed loss of the mutant allele of BRCA2, while ovarian stroma cells and peripheral blood lymphocytes contained both wild-type and mutant allele of BRCA2. The finding that no loss of the wild-type BRCA2 allele was found in the tumor tissue but loss of the mutant allele was seen suggests that sBOT are not part of the BRCA2 related tumor spectrum. In the literature BOT's in germline BRCA1 and BRCA2 mutation carriers are described incidentally, while in patients with a BOT a germline BRCA1 or BRCA2 mutation is rarely found. Therefore, we conclude that borderline ovarian tumors are neither part of the BRCA1- nor the BRCA2- related tumor spectrum.

Ou SW, Kameyama A, Hao LY, et al.
Tetrodotoxin-resistant Na+ channels in human neuroblastoma cells are encoded by new variants of Nav1.5/SCN5A.
Eur J Neurosci. 2005; 22(4):793-801 [PubMed] Related Publications
Both tetrodotoxin-sensitive (TTX-S) and TTX-resistant (TTX-R) voltage-dependent Na+ channels are expressed in the human neuroblastoma cell line NB-1, but a gene encoding the TTX-R Na+ channel has not been identified. In this study, we have cloned cDNA encoding the alpha subunit of the TTX-R Na+ channel in NB-1 cells and designated it hNbR1. The longest open reading frame of hNbR1 (accession no. AB158469) encodes 2016 amino acid residues. Sequence analysis has indicated that hNbR1 is highly homologous with human cardiac Nav1.5/SCN5A with > 99% amino acid identity. The presence of a cysteine residue (Cys373) in the pore-loop region of domain I is consistent with the supposition that hNbR1 is resistant to TTX. Analysis of the genomic sequence of SCN5A revealed a new exon encoding S3 and S4 of domain I (exon 6A). In addition, an alternative splicing variant, lacking exon 18, that encodes 54 amino acids in the intracellular loop between domains II and III was found (hNbR1-2; accession no. AB158470). Na+ currents in human embryonic kidney cells (HEK293) transfected with hNbR1 or hNbR1-2 showed electrophysiological properties similar to those for TTX-R I(Na) in NB-1 cells. The IC50 for the TTX block was approximately 8 microM in both variants. These results suggest that SCN5A has a newly identified exon for alternative splicing and is more widely expressed than previously thought.

Sun P, Sehouli J, Denkert C, et al.
Expression of estrogen receptor-related receptors, a subfamily of orphan nuclear receptors, as new tumor biomarkers in ovarian cancer cells.
J Mol Med (Berl). 2005; 83(6):457-67 [PubMed] Related Publications
A subfamily of orphan receptors, estrogen receptor-related receptors (ERRs), has been demonstrated to modulate the transcription of some estrogen responsive genes via variant estrogen response elements (EREs). This study was conducted to determine whether human ERRalpha, ERRbeta, and ERRgamma might be involved in the tumorigenesis of ovarian cancer. RT-PCR was performed to analyze the expression of hERRalpha, hERRbeta, hERRbeta-2, and hERRgamma mRNA in five ovarian cancer cell lines as well as 33 samples of ovarian cancer and 12 samples of normal ovary. Serum CA-125 levels were also analyzed in all samples by ELISA. Progression-free survival and overall survival of patients with different expression of ERRs were analyzed by the Kaplan-Meier method. To analyze the subcellular localization of ERRalpha, a green fluorescent protein (GFP)-reporter plasmid of hERRalpha was constructed and transfected into the ovarian cancer cell line OVCAR-3. Expression of hERRalpha-GFP fusion protein was observed in the nucleus of OVCAR-3 ovarian cancer cell lines. We observed increased expression of hERRalpha mRNA (P = 0.020) and hERRgamma mRNA (P = 0.045) in ovarian cancers compared to normal ovaries. In contrast, hERRbeta was only observed in 9.1% of ovarian cancers. We found a positive correlation between the serum CA-125 levels and hERRalpha expression (P = 0.012), but not hERRbeta and hERRgamma expression. Survival analysis showed that the hERRalpha-positive group has a reduced overall survival (P = 0.015), and the ERRgamma-positive group has a longer progression-free survival (P = 0.020). In multivariate analysis, expression of hERRalpha was an independent prognostic factor for poor survival (relative risk, 3.032; 95% CI, 1.27-6.06). Based on our results, ERRs may play an important role in ovarian cancer. hERRalpha may represent a biomarker of poor prognosis, and hERRgamma may be a new therapeutic target in ovarian cancer.

Gad S, Bièche I, Barrois M, et al.
Characterisation of a 161 kb deletion extending from the NBR1 to the BRCA1 genes in a French breast-ovarian cancer family.
Hum Mutat. 2003; 21(6):654 [PubMed] Related Publications
A large germline deletion removing exons 1 to 22 of the BRCA1 gene has been previously detected using quantitative PCR based methods (QMPSF and real time PCR gene dosage assay) in a woman affected with breast and ovarian cancer. Here, we report its characterisation by using colour bar code on combed DNA of the BRCA1 region. The 5' boundary is located in a Alu Y sequence in NBR1 intron 18 whereas the 3' boundary is located in a Alu Sc sequence in BRCA1 intron 22. This 161 kb deletion encompassing the NBR1, PsiBRCA1, NBR2 and BRCA1 genes is the largest BRCA1 deletion reported so far. No specific phenotype was associated with the hemizygosity of these four genes.

Brown MA, Lo LJ, Catteau A, et al.
Germline BRCA1 promoter deletions in UK and Australian familial breast cancer patients: Identification of a novel deletion consistent with BRCA1:psiBRCA1 recombination.
Hum Mutat. 2002; 19(4):435-42 [PubMed] Related Publications
Inherited susceptibility to breast cancer results from germline mutations in one of a number of genes including BRCA1. A significant number of BRCA1-linked familial breast cancer patients, however, have no detectable BRCA1 mutation. This could be due in part to the inability of commonly used mutation-detection techniques to identify mutations outside the BRCA1 coding region. This paper addresses the hypothesis that non-coding region mutations, specifically in the BRCA1 promoter, account for some of these cases. We describe a new and detailed restriction map of the 5' region of the BRCA1 gene including the nearby NBR2, psiBRCA1, and NBR1 genes and the isolation of a number of new informative hybridization probes suitable for Southern analysis. Using this information we screened DNA from lymphoblastoid cell-lines made from 114 UK familial breast cancer patients and detected one large deletion in the 5' region of BRCA1. We show that the breakpoints for this deletion are in BRCA1 intron 2 and between NBR2 and exon 2 of psiBRCA1, raising the possibility that this deletion arose via a novel mechanism involving BRCA1:psiBRCA1 recombination. We have also screened 60 familial breast cancer patients from the Australian population, using an amplification refractory mutation system (ARMS) technique described previously by our group, and found one patient with a genotype consistent with a BRCA1 promoter deletion. These findings indicate that germline BRCA1 promoter deletions are a rare and yet significant mutation event and that they could arise via a novel genetic mechanism.

Dimitrov SD, Matousková E, Forejt J
Expression of BRCA1, NBR1 and NBR2 genes in human breast cancer cells.
Folia Biol (Praha). 2001; 47(4):120-7 [PubMed] Related Publications
BRCA1 is a tumour suppressor gene with a caretaker function in the DNA-damage repair and the maintenance of genome integrity. The human BRCA1 and NBR2 genes and the homologous Brcal and Nbr1 mouse genes are situated head-to-head on human chromosome 17q21 and on mouse chromosome 11, respectively. Their transcription start sites, located on opposite DNA strands, are separated by 218 bp in humans, and by 289 bp in mice. Because of this intimate contact and because of our previous observation of a quasi-reciprocal expression pattern of Brca1 and Nbr1 in mouse spermatogenesis, we estimated here the relative mRNA expression of BRCA1, NBR1 (next-to-BRCA1) and NBR2 genes in a panel of permanent cell lines and primary cell cultures derived from human breast cancer or normal mammary tissue. The analysis revealed highly significant downregulation of BRCA1 in 11 out of 12 examined tumour cell lines and primary cell cultures as compared to non-malignant mammary cells. Two isoforms of NBR1(1A) and the classical NBR1(1B) transcripts were found in cells from malignant mammary tissues, all of them downregulated in respect to normal cells. The expression of NBR2 differed, being increased in three permanent tumour cell lines and slightly decreased in all primary breast cancer cell cultures. The in silico analysis revealed two new putative domains of the predicted NBR1 protein, suggesting its role in the ubiquitin pathway. The recent identification of the ubiquitin protein ligase activity of BRCA1 implies a possible functional connection between both genes.

Xu CF, Brown MA, Nicolai H, et al.
Isolation and characterisation of the NBR2 gene which lies head to head with the human BRCA1 gene.
Hum Mol Genet. 1997; 6(7):1057-62 [PubMed] Related Publications
To study the regulation of BRCA1 gene expression and the potential importance of dysregulation of this gene in breast and ovarian cancer, we have examined the 5' region of the human BRCA1 gene in detail. We have identified a new gene, NBR2, which is partially related to the NBR1 gene (formerly known as 1A1-3B and mapping directly adjacent to the pseudo-BRCA1 gene) and which lies head to head with the BRCA1 gene. The physical distance between the transcription start sites of the NBR2 and BRCA1 genes is 218 bp, suggesting that regulation of the expression of both genes may be co-ordinated through a bi-directional promoter. The NBR2 gene contains five exons spanning a genomic region of approximately 30 kb between the BRCA1 and pseudo-BRCA1 genes. Northern analysis showed that the NBR2 gene is expressed in all the tissues examined. The NBR2 cDNA contains an open reading frame of 112 amino acids and is predicted to encode a protein of approximately 12 kDa. Single-strand conformation polymorphism (SSCP) analysis of the NBR2 gene failed to identify any mutations in either breast or ovarian cancer, suggesting that if the NBR2 gene is involved in the development of these cancers, other mechanisms for tumorigenesis may exist. Hybridisation of NBR2 probes to zoo blots showed that the NBR2 gene is present in human and other primates. No hybridisation to DNA from other species was observed, suggesting that genomic elements controlling BRCA1 expression may differ between species.

Smith TM, Lee MK, Szabo CI, et al.
Complete genomic sequence and analysis of 117 kb of human DNA containing the gene BRCA1.
Genome Res. 1996; 6(11):1029-49 [PubMed] Related Publications
Over 100 distinct disease-associated mutations have been identified in the breast-ovarian cancer susceptibility gene BRCA1. Loss of the wild-type allele in > 90% of tumors from patients with inherited BRCA1 mutations indicates tumor suppressive function. The low incidence of somatic mutations suggests that BRCA1 inactivation in sporadic tumors occurs by alternative mechanisms, such as interstitial chromosomal deletion or reduced transcription. To identify possible features of the BRCA1 genomic region that may contribute to chromosomal instability as well as potential transcriptional regulatory elements, a 117,143-bp DNA sequence encompassing BRCA1 was obtained by random sequencing of four cosmids identified from a human chromosome 17 specific library. The 24 exons of BRCA1 span an 81-kb region that has an unusually high density of Alu repetitive DNA (41.5%), but relatively low density (4.8%) of other repetitive sequences. BRCA1 intron lengths range in size from 403 bp to 9.2 kb and contain the intragenic microsatellite markers D17S1323, D17S1322, and D17S855, which localize to introns 12, 19, and 20, respectively. In addition to BRCA1, the contig contains two complete genes: Rho7, a member of the rho family of GTP binding proteins, and VAT1, an abundant membrane protein of cholinergic synaptic vesicles. Partial sequences of the 1A1-3B B-box protein pseudogene and IFP 35, an interferon induced leucine zipper protein, reside within the contig. An L21 ribosomal protein pseudogene is embedded in BRCA1 intron 13. The order of genes on the chromosome is: centromere-1FP 35-VAT1-Rho7-BRCA1-1A1-3B-telomere.

Campbell IG, Nicolai HM, Foulkes WD, et al.
A novel gene encoding a B-box protein within the BRCA1 region at 17q21.1.
Hum Mol Genet. 1994; 3(4):589-94 [PubMed] Related Publications
A novel cDNA clone was isolated using a polyclonal serum directed against partially purified ovarian carcinoma antigen CA125. The deduced peptide sequence lacked membrane protein characteristics expected for CA125 but encompassed a B-box/coiled coil motif present in many genes with transformation potential. The gene was mapped by fluorescence in situ hybridization within the minimum region known to contain the familial breast/ovarian carcinoma gene, BRCA1. YAC and cosmid clones were isolated and used to refine the location of this gene adjacent and proximal to the RNU2 locus. The exon structure of the gene was determined. Extensive SSCP and sequence analysis of over 100 tumour and normal DNAs from familial and sporadic breast cancers and sporadic ovarian cancers failed to detect mutations in the coding region of this gene.

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Cite this page: Cotterill SJ. NBR1, Cancer Genetics Web: http://www.cancer-genetics.org/NBR1.htm Accessed:

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