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BNIP3L (BCL2/adenovirus E1B 19kDa interacting protein 3-like)

Written2012-11Paul Ney, Ji Zhang
Cell & Molecular Biology, New York Blood Center, 310 E 67th St, New York, NY 10065, USA (PN); Cancer Biology & Genetics, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA (JZ)

(Note : for Links provided by Atlas : click)


Alias (NCBI)BNIP3a
HGNC Alias symbNix
HGNC Alias nameNIP-3-like protein X
HGNC Previous nameBCL2/adenovirus E1B 19kDa interacting protein 3 like
LocusID (NCBI) 665
Atlas_Id 823
Location 8p21.2  [Link to chromosome band 8p21]
Location_base_pair Starts at 26383054 and ends at 26413127 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping BNIP3L.png]
Local_order Cdca2 -Ebf2 - Ppp2r2a - Bnip3l - Pnma2 - Dpysl2 - Adra1a
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
BNIP3L (8p21.2)::ABHD14B (3p21.2)BNIP3L (8p21.2)::MKI67 (10q26.2)BNIP3L (8p21.2)::PMP22 (17p12)
EPHX2 (8p21.2)::BNIP3L (8p21.2)


  Organization of the human BNIP3L gene. The boxes represent exons, the line introns (not drawn to scale). Black areas represent coding sequence.
Description The gene spans 30122 bp and has 6 exons. The cytogenetic location of the gene is 8p21.2. The genomic coordinates are 8: 26240522 - 26270643.
Transcription The mRNA is 3505 bp, and has a 657 bp open reading frame.


  Functional domains of BNIP3L protein. LIR: LC3-interaction region (WVEL) (Schwarten et al., 2009; Novak et al., 2010); MER: minimal essential region (DMEKILLDAQHE) (Zhang et al., 2012); BH3-like: BCL2 homology 3-like domain (LKKSADWVSDW) (Yasuda et al., 1999); TM: transmembrane domain.
Description The protein is 219 amino acids, with a predicted MW of 23,8 kDa. The carboxy-terminal transmembrane domain of BNIP3L has been characterized by nuclear magnetic resonance and shown to form a kinked α-helix (Bocharov et al., 2007). Structural bioinformatics analysis indicates that the rest of the protein is mostly disordered. The LIR and the MER are predicted to form secondary structure (β-strand and α-helix, respectively) (Zhang et al., 2012).
Expression BNIP3L is ubiquitously expressed. Northern blot hybridization reveals two transcripts of 1,6 kb and 3,9 kb. These are expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney, and pancreas (Yasuda et al., 1999). In another study, transcripts were identified in heart, brain, placenta, lung (low), liver, skeletal muscle (low), kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon, and peripheral blood leukocyte (Farooq et al., 2001). In the same study, there was also expression in cancer cell lines, including promyelocytic HL-60 (low), Hela S3 (low), K562, lymphoblastic leukemia Molt-5, Burkitt's lymphoma-Raji, colorectal adenocarcinoma SW480, and lung carcinoma A549 cells. In another study, 1,4 and 4,0 kb BNIP3L transcripts were found in primary hematopoietic cells and in cell lines, including K562, Hela, and Jurkat cells (Aerbajinai et al., 2003). BNIP3L is upregulated during erythroid maturation.
BNIP3L protein can form an SDS-resistant dimer, which migrates at twice its predicted MW in SDS-PAGE gels. BNIP3L dimerization is mediated through its transmembrane domain (Imazu et al., 1999).
Localisation BNIP3L primarily localizes to the mitochondrial outer membrane (Chen et al., 1999; Imazu et al., 1999; Yasuda et al., 1999; Vande Velde et al., 2000). BNIP3L is oriented so that its amino terminus is in the cytoplasm, and its carboxy-terminal tail is in the mitochondrial intermembrane space. It also localizes to nuclear envelope, sarcoplasmic reticulum, and endoplasmic reticulum (Ohi et al., 1999; Diwan et al., 2009).
Function BNIP3L and BNIP3 can cause cell death by several mechanisms, which are mediated by their BH3-like and transmembrane domains. In cardiomyocytes, mitochondria-targeted BNIP3L causes BAX/BAK-dependent mitochondrial outer membrane permeabilization, whereas ER/SR-targeted BNIP3L causes cyclophilin D-dependent opening of the MPT pore and mitochondrial depolarization (Chen et al., 2010). In tumor cells, BNIP3 expression is associated with opening of the MPT pore and autophagy (Vande Velde et al., 2000). Another property of BNIP3L and BNIP3 is their ability to mediate mitochondrial clearance during erythroid development (Schweers et al., 2007; Sandoval et al., 2008) and in response to hypoxia (Zhang et al., 2008; Liu et al., 2012), respectively. BNIP3L mediates mitochondrial clearance in erythroid cells through its LIR (Schwarten et al., 2009; Novak et al., 2010) and MER (Zhang et al., 2012) domains.
Homology BNIP3L is conserved from zebrafish to man.


Note Not yet described.

Implicated in

Entity Various cancers
Oncogenesis BNIP3L and the related protein BNIP3 (56% identical overall) are implicated in cancer progression. BNIP3 deregulation is more often implicated in cancer than BNIP3L, but the two proteins have a similar mechanism of action, so both are potentially relevant. BNIP3 and BNIP3L are reported to function as both tumor suppressors and oncogenes. This dual nature presumably reflects the roles of BNIP3 and BNIP3L in cell death pathways and autophagy; autophagy can promote cell survival. The frequent finding of BNIP3 deregulation in cancer is likely related to its induction by hypoxia, and HIF1α signaling (Bruick, 2000). BNIP3L is also induced during hypoxia, by p53 (Fei et al., 2004). There are several mechanisms of BNIP3 and BNIP3L-induced cell death, which have recently been reviewed (Zhang and Ney, 2011). The role of BNIP3 and BNIP3L in cell death may explain their frequent deletion and silencing in tumors by promoter methylation (see below). By contrast, some advanced cancers express abnormally high levels of BNIP3 and BNIP3L. In these cases, the prosurvival role of these proteins in the induction of autophagy appears to dominate.
Entity Prostate cancer
Note BNIP3 is expressed in 95% of prostate cancer samples and is either nuclear, cytoplasmic, or both. Cytoplasmic BNIP3 expression correlates with Gleason score, but not other clinicopathological parameters. By contrast, nuclear BNIP3 correlates with HIF1α and HIF2α expression (Shaida et al., 2008). BNIP3 promoter hypermethylation is present in 16% of prostate cancers, and BNIP3 expression is decreased in 21% of prostate cancers, but the two do not correlate (Murphy et al., 2011). BNIP3L exhibits homozygous deletion in a prostate cancer cell line and primary prostate tumor (Liu et al., 2008). Another study showed LOH of BNIP3L in 5% of prostate cancers, and a correlation with increasing disease stage (Cheng et al., 2012).
Entity Breast cancer
Note BNIP3 expression in ductal carcinoma in situ is associated with higher grade, necrosis and invasive disease, whereas BNIP3L expression does not correlate with these parameters (Sowter et al., 2003). BNIP3L is not deregulated and infrequently mutated in ovarian and breast cancer (Lai et al., 2003). Loss of BNIP3 expression correlates with lymph node metastases and mitotic index, but not with the hypoxic response (Koop et al., 2009). Proteasome inhibition with Bortezomib blocks autophagy-mediated catabolism of long-lived proteins, and is associated with increased BNIP3 and cell death in breast cancer cell lines (Periyasamy-Thandavan et al., 2010). On the other hand, resistance to the cytotoxic effects of TNFα in a subclone of breast cancer MCF-7 cells is associated with increased BNIP3 and upregulation of the autophagy program (Moussay et al., 2011). Notably, hypoxic induction of BNIP3 and BNIP3L can cause breast cancer cell death and at the same time promote the survival of cancer-associated fibroblasts (Chiavarina et al., 2010). Thus, BNIP3 and BNIP3L may have compartment-specific effects on cell death and survival.
Entity Colorectal and gastric cancers
Note BNIP3 promoter hypermethylation is found in 66% of primary colorectal and 49% of gastric cancers, but not in adjacent normal tissue (Murai et al., 2005b). Promoter hypermethylation but not gene mutation correlates with decreased BNIP3 expression.
Entity Pancreatic cancer
Note BNIP3 is silenced by promoter hypermethylation in 80% of pancreatic adenocarcinoma samples (Okami et al., 2004). BNIP3 expression is diminished in chronic pancreatitis and pancreatic ductal adenocarcinoma, and loss of BNIP3 expression correlates with decreased survival and chemotherapy resistance (Erkan et al., 2005). Similarly, BNIP3L is reduced in liver metastases and the tumor invasion front compared with the primary pancreatic tumor, in an orthotopic SCID mouse model (Niedergethmann et al., 2007).
Entity Liver cancer
Note Epigenetic silencing of BNIP3 and BNIP3L is associated with poor prognosis in hepatocellular carcinoma (Calvisi et al., 2007). In addition, a cSNP that causes premature termination of BNIP3L was reported in 40% of hepatocellular carcinoma cases (Wang et al., 2005). BNIP3 is a HIF1α target in HepG2 tumor spheroids, and its expression is associated with increased autophagy and attenuation of apoptosis (Menrad et al., 2010).
Entity Lung cancer
Note There is strong cytoplasmic expression of BNIP3 in 38% of non-small cell lung cancer, which was associated with an aggressive phenotype and decreased survival (Giatromanolaki et al., 2004).
Entity Malignant glioblastoma
Note BNIP3 is expressed in hypoxic regions of glioblastoma multiforme (GBM), but is sequestered in the nucleus in ~80% of tumors (Burton et al., 2006). In another study, BNIP3L appeared to act as a tumor suppressor in low-grade astrocytomas, and as an oncogene in high grade GBM. In the latter case, BNIP3L expression correlated with NFκB activation through an unknown mechanism (Lu et al., 2012).
Entity Hematopoietic malignancy
Note BNIP3 promoter hypermethylation is found in 15% of acute lymphocytic leukemia, 17% of acute myelogenous leukemia, and 21% of multiple myeloma. Promoter hypermethylation correlates with decreased BNIP3 expression (Murai et al., 2005a). BNIP3 promoter hypermethylation correlates with decreased survival in multiple myeloma (Heller et al., 2008). Another study found BNIP3 promoter hypermethylation in 13% of newly diagnosed multiple myeloma but no association with prognosis (Braggio et al., 2010).
Entity Ischemic and hypertrophic heart disease
Note Most of the evidence that BNIP3 and BNIP3L have a role in heart disease comes from animal models. BNIP3 is regulated by hypoxia in cardiomyocytes through HIF1α binding sites in its promoter (Bruick, 2000). By contrast, BNIP3L is regulated by Gαq signaling in the setting of cardiac hypertrophy (Gálvez et al., 2006). Enforced expression of BNIP3L causes lethal cardiomyopathy in mice, whereas BNIP3L deficiency protects mice from Gαq-mediated and pressure overload cardiomyopathy (Yussman et al., 2002; Diwan et al., 2008). Further, BNIP3 deficiency protects against post-infarction ventricular remodeling (Diwan et al., 2007). Mice with combined deficiency of BNIP3 and BNIP3L in the heart develop normally, but by 30 weeks exhibit cardiac enlargement and decreased left ventricular ejection fraction (Dorn, 2010). Mitochondria in the hearts of these mice are increased in number and show variation in size and internal structure. Furthermore, young BNIP3/BNIP3L-deficient mice subjected to aortic banding rapidly develop heart failure.
Entity Cerebral ischemia
Note Animal models and in vitro studies also provide evidence that BNIP3 and to a lesser extent BNIP3L are a cause of neuronal cell death after hypoxia or denervation. BNIP3 is expressed in striatal and cortical neurons following transient focal ischemia in rats; prolonged BNIP3 expression in this setting is associated with delayed neuronal cell death (Althaus et al., 2006). BNIP3 knockdown inhibits nuclear translocation of EndoG and protects against hypoxia-induced, caspase-independent, delayed neuronal cell death (Zhang et al., 2007). Hypoxic mimetics cause BAX/BAK- and caspase-dependent neuronal precursor cell death in vitro, but also cause HIF1α and BNIP3 upregulation. BNIP3 knockdown failed to prevent caspase activation, but inhibits nuclear translocation of apoptosis-inducing factor and cell death (Walls et al., 2009). Thus, BNIP3 mediates hypoxia-induced, caspase-independent neuronal cell death. Also, following neonatal nerve axotomy, BNIP3 and to a lesser extent BNIP3L, are induced in facial motoneurons and associated with cell death (Cho et al., 2012).


Note Not yet described.


The proapoptotic factor Nix is coexpressed with Bcl-xL during terminal erythroid differentiation.
Aerbajinai W, Giattina M, Lee YT, Raffeld M, Miller JL.
Blood. 2003 Jul 15;102(2):712-7. Epub 2003 Mar 27.
PMID 12663450
Expression of the gene encoding the pro-apoptotic BNIP3 protein and stimulation of hypoxia-inducible factor-1alpha (HIF-1alpha) protein following focal cerebral ischemia in rats.
Althaus J, Bernaudin M, Petit E, Toutain J, Touzani O, Rami A.
Neurochem Int. 2006 Jun;48(8):687-95. Epub 2006 Feb 7.
PMID 16464515
Unique dimeric structure of BNip3 transmembrane domain suggests membrane permeabilization as a cell death trigger.
Bocharov EV, Pustovalova YE, Pavlov KV, Volynsky PE, Goncharuk MV, Ermolyuk YS, Karpunin DV, Schulga AA, Kirpichnikov MP, Efremov RG, Maslennikov IV, Arseniev AS.
J Biol Chem. 2007 Jun 1;282(22):16256-66. Epub 2007 Apr 4.
PMID 17412696
Adenovirus E1B 19 kDa and Bcl-2 proteins interact with a common set of cellular proteins.
Boyd JM, Malstrom S, Subramanian T, Venkatesh LK, Schaeper U, Elangovan B, D'Sa-Eipper C, Chinnadurai G.
Cell. 1994 Oct 21;79(2):341-51.
PMID 7954800
Methylation status of nine tumor suppressor genes in multiple myeloma.
Braggio E, Maiolino A, Gouveia ME, Magalhaes R, Souto Filho JT, Garnica M, Nucci M, Renault IZ.
Int J Hematol. 2010 Jan;91(1):87-96. doi: 10.1007/s12185-009-0459-2.
PMID 20037750
Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia.
Bruick RK.
Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9082-7.
PMID 10922063
The pro-cell death Bcl-2 family member, BNIP3, is localized to the nucleus of human glial cells: Implications for glioblastoma multiforme tumor cell survival under hypoxia.
Burton TR, Henson ES, Baijal P, Eisenstat DD, Gibson SB.
Int J Cancer. 2006 Apr 1;118(7):1660-9.
PMID 16217754
Mechanistic and prognostic significance of aberrant methylation in the molecular pathogenesis of human hepatocellular carcinoma.
Calvisi DF, Ladu S, Gorden A, Farina M, Lee JS, Conner EA, Schroeder I, Factor VM, Thorgeirsson SS.
J Clin Invest. 2007 Sep;117(9):2713-22.
PMID 17717605
Nix and Nip3 form a subfamily of pro-apoptotic mitochondrial proteins.
Chen G, Cizeau J, Vande Velde C, Park JH, Bozek G, Bolton J, Shi L, Dubik D, Greenberg A.
J Biol Chem. 1999 Jan 1;274(1):7-10.
PMID 9867803
Dual autonomous mitochondrial cell death pathways are activated by Nix/BNip3L and induce cardiomyopathy.
Chen Y, Lewis W, Diwan A, Cheng EH, Matkovich SJ, Dorn GW 2nd.
Proc Natl Acad Sci U S A. 2010 May 18;107(20):9035-42. doi: 10.1073/pnas.0914013107. Epub 2010 Apr 23.
PMID 20418503
Copy number alterations in prostate tumors and disease aggressiveness.
Cheng I, Levin AM, Tai YC, Plummer S, Chen GK, Neslund-Dudas C, Casey G, Rybicki BA, Witte JS.
Genes Chromosomes Cancer. 2012 Jan;51(1):66-76. doi: 10.1002/gcc.20932. Epub 2011 Oct 2.
PMID 21965145
HIF1-alpha functions as a tumor promoter in cancer associated fibroblasts, and as a tumor suppressor in breast cancer cells: Autophagy drives compartment-specific oncogenesis.
Chiavarina B, Whitaker-Menezes D, Migneco G, Martinez-Outschoorn UE, Pavlides S, Howell A, Tanowitz HB, Casimiro MC, Wang C, Pestell RG, Grieshaber P, Caro J, Sotgia F, Lisanti MP.
Cell Cycle. 2010 Sep 1;9(17):3534-51. Epub 2010 Sep 4.
PMID 20864819
Differential expression of BNIP family members of BH3-only proteins during the development and after axotomy in the rat.
Cho B, Choi SY, Park OH, Sun W, Geum D.
Mol Cells. 2012 Jun;33(6):605-10. doi: 10.1007/s10059-012-0051-0. Epub 2012 May 23.
PMID 22639046
Inhibition of ischemic cardiomyocyte apoptosis through targeted ablation of Bnip3 restrains postinfarction remodeling in mice.
Diwan A, Krenz M, Syed FM, Wansapura J, Ren X, Koesters AG, Li H, Kirshenbaum LA, Hahn HS, Robbins J, Jones WK, Dorn GW.
J Clin Invest. 2007 Oct;117(10):2825-33.
PMID 17909626
Endoplasmic reticulum-mitochondria crosstalk in NIX-mediated murine cell death.
Diwan A, Matkovich SJ, Yuan Q, Zhao W, Yatani A, Brown JH, Molkentin JD, Kranias EG, Dorn GW 2nd.
J Clin Invest. 2009 Jan;119(1):203-12. doi: 10.1172/JCI36445. Epub 2008 Dec 8.
PMID 19065046
Nix-mediated apoptosis links myocardial fibrosis, cardiac remodeling, and hypertrophy decompensation.
Diwan A, Wansapura J, Syed FM, Matkovich SJ, Lorenz JN, Dorn GW 2nd.
Circulation. 2008 Jan 22;117(3):396-404. doi: 10.1161/CIRCULATIONAHA.107.727073. Epub 2008 Jan 4.
PMID 18178777
Mitochondrial pruning by Nix and BNip3: an essential function for cardiac-expressed death factors.
Dorn GW 2nd.
J Cardiovasc Transl Res. 2010 Aug;3(4):374-83. doi: 10.1007/s12265-010-9174-x. Epub 2010 Mar 16. (REVIEW)
PMID 20559783
Loss of BNIP3 expression is a late event in pancreatic cancer contributing to chemoresistance and worsened prognosis.
Erkan M, Kleeff J, Esposito I, Giese T, Ketterer K, Buchler MW, Giese NA, Friess H.
Oncogene. 2005 Jun 23;24(27):4421-32.
PMID 15856026
Cloning of BNIP3h, a member of proapoptotic BNIP3 family genes.
Farooq M, Kim Y, Im S, Chung E, Hwang S, Sohn M, Kim M, Kim J.
Exp Mol Med. 2001 Sep 30;33(3):169-73.
PMID 11642554
Bnip3L is induced by p53 under hypoxia, and its knockdown promotes tumor growth.
Fei P, Wang W, Kim SH, Wang S, Burns TF, Sax JK, Buzzai M, Dicker DT, McKenna WG, Bernhard EJ, El-Deiry WS.
Cancer Cell. 2004 Dec;6(6):597-609.
PMID 15607964
Distinct pathways regulate proapoptotic Nix and BNip3 in cardiac stress.
Galvez AS, Brunskill EW, Marreez Y, Benner BJ, Regula KM, Kirschenbaum LA, Dorn GW 2nd.
J Biol Chem. 2006 Jan 20;281(3):1442-8. Epub 2005 Nov 16.
PMID 16291751
BNIP3 expression is linked with hypoxia-regulated protein expression and with poor prognosis in non-small cell lung cancer.
Giatromanolaki A, Koukourakis MI, Sowter HM, Sivridis E, Gibson S, Gatter KC, Harris AL.
Clin Cancer Res. 2004 Aug 15;10(16):5566-71.
PMID 15328198
Genome-wide transcriptional response to 5-aza-2'-deoxycytidine and trichostatin a in multiple myeloma cells.
Heller G, Schmidt WM, Ziegler B, Holzer S, Mullauer L, Bilban M, Zielinski CC, Drach J, Zochbauer-Muller S.
Cancer Res. 2008 Jan 1;68(1):44-54. doi: 10.1158/0008-5472.CAN-07-2531.
PMID 18172295
Bcl-2/E1B 19 kDa-interacting protein 3-like protein (Bnip3L) interacts with bcl-2/Bcl-xL and induces apoptosis by altering mitochondrial membrane permeability.
Imazu T, Shimizu S, Tagami S, Matsushima M, Nakamura Y, Miki T, Okuyama A, Tsujimoto Y.
Oncogene. 1999 Aug 12;18(32):4523-9.
PMID 10467396
Expression of BNIP3 in invasive breast cancer: correlations with the hypoxic response and clinicopathological features.
Koop EA, van Laar T, van Wichen DF, de Weger RA, Wall Ev, van Diest PJ.
BMC Cancer. 2009 Jun 9;9:175. doi: 10.1186/1471-2407-9-175.
PMID 19505343
Analysis of the candidate 8p21 tumour suppressor, BNIP3L, in breast and ovarian cancer.
Lai J, Flanagan J, Phillips WA, Chenevix-Trench G, Arnold J.
Br J Cancer. 2003 Jan 27;88(2):270-6.
PMID 12610513
Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells.
Liu L, Feng D, Chen G, Chen M, Zheng Q, Song P, Ma Q, Zhu C, Wang R, Qi W, Huang L, Xue P, Li B, Wang X, Jin H, Wang J, Yang F, Liu P, Zhu Y, Sui S, Chen Q.
Nat Cell Biol. 2012 Jan 22;14(2):177-85. doi: 10.1038/ncb2422.
PMID 22267086
Homozygous deletions and recurrent amplifications implicate new genes involved in prostate cancer.
Liu W, Xie CC, Zhu Y, Li T, Sun J, Cheng Y, Ewing CM, Dalrymple S, Turner AR, Sun J, Isaacs JT, Chang BL, Zheng SL, Isaacs WB, Xu J.
Neoplasia. 2008 Aug;10(8):897-907.
PMID 18670647
Nix protein positively regulates NF-?B activation in gliomas.
Lu Y, Wang L, He M, Huang W, Li H, Wang Y, Kong J, Qi S, Ouyang J, Qiu X.
PLoS One. 2012;7(9):e44559. doi: 10.1371/journal.pone.0044559. Epub 2012 Sep 12.
PMID 22984526
Isolation, mapping, and functional analysis of a novel human cDNA (BNIP3L) encoding a protein homologous to human NIP3.
Matsushima M, Fujiwara T, Takahashi E, Minaguchi T, Eguchi Y, Tsujimoto Y, Suzumori K, Nakamura Y.
Genes Chromosomes Cancer. 1998 Mar;21(3):230-5.
PMID 9523198
Roles of hypoxia-inducible factor-1alpha (HIF-1alpha) versus HIF-2alpha in the survival of hepatocellular tumor spheroids.
Menrad H, Werno C, Schmid T, Copanaki E, Deller T, Dehne N, Brune B.
Hepatology. 2010 Jun;51(6):2183-92. doi: 10.1002/hep.23597.
PMID 20513003
The acquisition of resistance to TNFa in breast cancer cells is associated with constitutive activation of autophagy as revealed by a transcriptome analysis using a custom microarray.
Moussay E, Kaoma T, Baginska J, Muller A, Van Moer K, Nicot N, Nazarov PV, Vallar L, Chouaib S, Berchem G, Janji B.
Autophagy. 2011 Jul;7(7):760-70. Epub 2011 Jul 1.
PMID 21490427
Aberrant methylation and silencing of the BNIP3 gene in colorectal and gastric cancer.
Murai M, Toyota M, Suzuki H, Satoh A, Sasaki Y, Akino K, Ueno M, Takahashi F, Kusano M, Mita H, Yanagihara K, Endo T, Hinoda Y, Tokino T, Imai K.
Clin Cancer Res. 2005b Feb 1;11(3):1021-7.
PMID 15709167
In silico analysis and DHPLC screening strategy identifies novel apoptotic gene targets of aberrant promoter hypermethylation in prostate cancer.
Murphy TM, Sullivan L, Lane C, O'Connor L, Barrett C, Hollywood D, Lynch T, Lawler M, Perry AS.
Prostate. 2011 Jan 1;71(1):1-17. doi: 10.1002/pros.21212.
PMID 20564325
Gene expression profiling of liver metastases and tumour invasion in pancreatic cancer using an orthotopic SCID mouse model.
Niedergethmann M, Alves F, Neff JK, Heidrich B, Aramin N, Li L, Pilarsky C, Grutzmann R, Allgayer H, Post S, Gretz N.
Br J Cancer. 2007 Nov 19;97(10):1432-40. Epub 2007 Oct 16.
PMID 17940512
Nix is a selective autophagy receptor for mitochondrial clearance.
Novak I, Kirkin V, McEwan DG, Zhang J, Wild P, Rozenknop A, Rogov V, Lohr F, Popovic D, Occhipinti A, Reichert AS, Terzic J, Dotsch V, Ney PA, Dikic I.
EMBO Rep. 2010 Jan;11(1):45-51. doi: 10.1038/embor.2009.256. Epub 2009 Dec 11.
PMID 20010802
A novel adenovirus E1B19K-binding protein B5 inhibits apoptosis induced by Nip3 by forming a heterodimer through the C-terminal hydrophobic region.
Ohi N, Tokunaga A, Tsunoda H, Nakano K, Haraguchi K, Oda K, Motoyama N, Nakajima T.
Cell Death Differ. 1999 Apr;6(4):314-25.
PMID 10381623
Silencing of the hypoxia-inducible cell death protein BNIP3 in pancreatic cancer.
Okami J, Simeone DM, Logsdon CD.
Cancer Res. 2004 Aug 1;64(15):5338-46.
PMID 15289340
Bortezomib blocks the catabolic process of autophagy via a cathepsin-dependent mechanism, affects endoplasmic reticulum stress and induces caspase-dependent cell death in antiestrogen-sensitive and resistant ER+ breast cancer cells.
Periyasamy-Thandavan S, Jackson WH, Samaddar JS, Erickson B, Barrett JR, Raney L, Gopal E, Ganapathy V, Hill WD, Bhalla KN, Schoenlein PV.
Autophagy. 2010 Jan;6(1):19-35.
PMID 20110775
Essential role for Nix in autophagic maturation of erythroid cells.
Sandoval H, Thiagarajan P, Dasgupta SK, Schumacher A, Prchal JT, Chen M, Wang J.
Nature. 2008 Jul 10;454(7201):232-5. doi: 10.1038/nature07006. Epub 2008 May 4.
PMID 18454133
Nix directly binds to GABARAP: a possible crosstalk between apoptosis and autophagy.
Schwarten M, Mohrluder J, Ma P, Stoldt M, Thielmann Y, Stangler T, Hersch N, Hoffmann B, Merkel R, Willbold D.
Autophagy. 2009 Jul;5(5):690-8. Epub 2009 Jul 20.
PMID 19363302
NIX is required for programmed mitochondrial clearance during reticulocyte maturation.
Schweers RL, Zhang J, Randall MS, Loyd MR, Li W, Dorsey FC, Kundu M, Opferman JT, Cleveland JL, Miller JL, Ney PA.
Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19500-5. Epub 2007 Nov 29.
PMID 18048346
Expression of BNIP3 correlates with hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha and the androgen receptor in prostate cancer and is regulated directly by hypoxia but not androgens in cell lines.
Shaida N, Launchbury R, Boddy JL, Jones C, Campo L, Turley H, Kanga S, Banham AH, Malone PR, Harris AL, Fox SB.
Prostate. 2008 Feb 15;68(3):336-43. doi: 10.1002/pros.20707.
PMID 18163427
Expression of the cell death genes BNip3 and NIX in ductal carcinoma in situ of the breast; correlation of BNip3 levels with necrosis and grade.
Sowter HM, Ferguson M, Pym C, Watson P, Fox SB, Han C, Harris AL.
J Pathol. 2003 Dec;201(4):573-80.
PMID 14648660
BNIP3 and genetic control of necrosis-like cell death through the mitochondrial permeability transition pore.
Vande Velde C, Cizeau J, Dubik D, Alimonti J, Brown T, Israels S, Hakem R, Greenberg AH.
Mol Cell Biol. 2000 Aug;20(15):5454-68.
PMID 10891486
bcl-2/Adenovirus E1B 19-kd interacting protein 3 (BNIP3) regulates hypoxia-induced neural precursor cell death.
Walls KC, Ghosh AP, Ballestas ME, Klocke BJ, Roth KA.
J Neuropathol Exp Neurol. 2009 Dec;68(12):1326-38. doi: 10.1097/NEN.0b013e3181c3b9be.
PMID 19915483
Preparation and analysis of cSNP chip on hepatocellular carcinoma-related genes.
Wang J, Ni H, Chen L, Liu YX, Chen CB, Song WQ.
Hepatobiliary Pancreat Dis Int. 2005 Aug;4(3):398-402.
PMID 16109524
BNIP3alpha: a human homolog of mitochondrial proapoptotic protein BNIP3.
Yasuda M, Han JW, Dionne CA, Boyd JM, Chinnadurai G.
Cancer Res. 1999 Feb 1;59(3):533-7.
PMID 9973195
Mitochondrial death protein Nix is induced in cardiac hypertrophy and triggers apoptotic cardiomyopathy.
Yussman MG, Toyokawa T, Odley A, Lynch RA, Wu G, Colbert MC, Aronow BJ, Lorenz JN, Dorn GW 2nd.
Nat Med. 2002 Jul;8(7):725-30. Epub 2002 Jun 10.
PMID 12053174
Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia.
Zhang H, Bosch-Marce M, Shimoda LA, Tan YS, Baek JH, Wesley JB, Gonzalez FJ, Semenza GL.
J Biol Chem. 2008 Apr 18;283(16):10892-903. doi: 10.1074/jbc.M800102200. Epub 2008 Feb 15.
PMID 18281291
A short linear motif in BNIP3L (NIX) mediates mitochondrial clearance in reticulocytes.
Zhang J, Loyd MR, Randall MS, Waddell MB, Kriwacki RW, Ney PA.
Autophagy. 2012 Sep;8(9):1325-32. doi: 10.4161/auto.20764. Epub 2012 Aug 21.
PMID 22906961
Mechanisms and biology of B-cell leukemia/lymphoma 2/adenovirus E1B interacting protein 3 and Nip-like protein X.
Zhang J, Ney PA.
Antioxid Redox Signal. 2011 May 15;14(10):1959-69. doi: 10.1089/ars.2010.3772. Epub 2011 Mar 4.
PMID 21126215
BNIP3 upregulation and EndoG translocation in delayed neuronal death in stroke and in hypoxia.
Zhang Z, Yang X, Zhang S, Ma X, Kong J.
Stroke. 2007 May;38(5):1606-13. Epub 2007 Mar 22.
PMID 17379825


This paper should be referenced as such :
Ney, P ; Zhang, J
BNIP3L (BCL2/adenovirus E1B 19kDa interacting protein 3-like)
Atlas Genet Cytogenet Oncol Haematol. 2013;17(4):253-258.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)BNIP3L   1085
Atlas Explorer : (Salamanque)BNIP3L
Entrez_Gene (NCBI)BNIP3L    BCL2 interacting protein 3 like
AliasesBNIP3a; NIX
GeneCards (Weizmann)BNIP3L
Ensembl hg19 (Hinxton)ENSG00000104765 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000104765 [Gene_View]  ENSG00000104765 [Sequence]  chr8:26383054-26413127 [Contig_View]  BNIP3L [Vega]
ICGC DataPortalENSG00000104765
Genatlas (Paris)BNIP3L
SOURCE (Princeton)BNIP3L
Genetics Home Reference (NIH)BNIP3L
Genomic and cartography
GoldenPath hg38 (UCSC)BNIP3L  -     chr8:26383054-26413127 +  8p21.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)BNIP3L  -     8p21.2   [Description]    (hg19-Feb_2009)
GoldenPathBNIP3L - 8p21.2 [CytoView hg19]  BNIP3L - 8p21.2 [CytoView hg38]
Genome Data Viewer NCBIBNIP3L [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AA946755 AB004788 AF060922 AF067396 AF079221
RefSeq transcript (Entrez)NM_001330491 NM_004331
Consensus coding sequences : CCDS (NCBI)BNIP3L
Gene ExpressionBNIP3L [ NCBI-GEO ]   BNIP3L [ EBI - ARRAY_EXPRESS ]   BNIP3L [ SEEK ]   BNIP3L [ MEM ]
Gene Expression Viewer (FireBrowse)BNIP3L [ Firebrowse - Broad ]
GenevisibleExpression of BNIP3L in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)665
GTEX Portal (Tissue expression)BNIP3L
Human Protein AtlasENSG00000104765-BNIP3L [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO60238   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO60238  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO60238
Domains : Interpro (EBI)BNIP3   
Domain families : Pfam (Sanger)BNIP3 (PF06553)   
Domain families : Pfam (NCBI)pfam06553   
Conserved Domain (NCBI)BNIP3L
AlphaFold pdb e-kbO60238   
Human Protein Atlas [tissue]ENSG00000104765-BNIP3L [tissue]
Protein Interaction databases
IntAct (EBI)O60238
Ontologies - Pathways
Ontology : AmiGOprotein binding  lamin binding  lamin binding  nucleus  nuclear envelope  nuclear envelope  mitochondrion  mitochondrial outer membrane  mitochondrial outer membrane  mitochondrial outer membrane  endoplasmic reticulum  endoplasmic reticulum  integral component of membrane  positive regulation of macroautophagy  nuclear speck  intrinsic component of membrane  mitochondrial protein catabolic process  identical protein binding  protein homodimerization activity  positive regulation of apoptotic process  negative regulation of apoptotic process  regulation of programmed cell death  defense response to virus  defense response to virus  negative regulation of cell death  cellular response to hypoxia  mitochondrial outer membrane permeabilization  regulation of autophagy of mitochondrion  regulation of protein targeting to mitochondrion  
Ontology : EGO-EBIprotein binding  lamin binding  lamin binding  nucleus  nuclear envelope  nuclear envelope  mitochondrion  mitochondrial outer membrane  mitochondrial outer membrane  mitochondrial outer membrane  endoplasmic reticulum  endoplasmic reticulum  integral component of membrane  positive regulation of macroautophagy  nuclear speck  intrinsic component of membrane  mitochondrial protein catabolic process  identical protein binding  protein homodimerization activity  positive regulation of apoptotic process  negative regulation of apoptotic process  regulation of programmed cell death  defense response to virus  defense response to virus  negative regulation of cell death  cellular response to hypoxia  mitochondrial outer membrane permeabilization  regulation of autophagy of mitochondrion  regulation of protein targeting to mitochondrion  
REACTOMEO60238 [protein]
REACTOME PathwaysR-HSA-6803204 [pathway]   
NDEx NetworkBNIP3L
Atlas of Cancer Signalling NetworkBNIP3L
Wikipedia pathwaysBNIP3L
Orthology - Evolution
GeneTree (enSembl)ENSG00000104765
Phylogenetic Trees/Animal Genes : TreeFamBNIP3L
Homologs : HomoloGeneBNIP3L
Homology/Alignments : Family Browser (UCSC)BNIP3L
Gene fusions - Rearrangements
Fusion : MitelmanEPHX2::BNIP3L [8p21.2/8p21.2]  
Fusion : QuiverBNIP3L
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerBNIP3L [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)BNIP3L
Exome Variant ServerBNIP3L
GNOMAD BrowserENSG00000104765
Varsome BrowserBNIP3L
ACMGBNIP3L variants
Genomic Variants (DGV)BNIP3L [DGVbeta]
DECIPHERBNIP3L [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisBNIP3L 
ICGC Data PortalBNIP3L 
TCGA Data PortalBNIP3L 
Broad Tumor PortalBNIP3L
OASIS PortalBNIP3L [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICBNIP3L  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DBNIP3L
Mutations and Diseases : HGMDBNIP3L
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)BNIP3L
DoCM (Curated mutations)BNIP3L
CIViC (Clinical Interpretations of Variants in Cancer)BNIP3L
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry BNIP3L
NextProtO60238 [Medical]
Target ValidationBNIP3L
Huge Navigator BNIP3L [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDBNIP3L
Pharm GKB GenePA25395
Clinical trialBNIP3L
DataMed IndexBNIP3L
Other databaseMGI
PubMed79 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Jan 19 18:42:58 CET 2022

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