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This gene encodes for protein HIG2A, found in mitochondria and the nucleus, promoting cell survival in hypoxic conditions. The genomic location of HIGD2A is in chromosome 5q35.2, where several chromosomal abnormalities are related to numerous cancers. The analysis of high definition expression profiles of HIGD2A suggests a role for HIG2A in cancer biology. Accordingly, the research objective was to perform a molecular biosystem analysis of HIGD2A aiming to discover HIG2A implications in cancer biology. For this purpose, public databases such as SWISS-MODEL protein structure homology-modelling server, Catalogue of Somatic Mutations in Cancer (COSMIC), Gene Expression Omnibus (GEO), MethHC: a database of DNA methylation and gene expression in human cancer, and microRNA-target interactions database (miRTarBase) were accessed. We also evaluated, by using Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR), the expression of Higd2a gene in healthy bone marrow-liver-spleen tissues of mice after quercetin (50 mg\/kg) treatment. Thus, among the structural features of HIG2A protein that may participate in HIG2A translocation to the nucleus are an importin \u03b1-dependent nuclear localization signal (NLS), a motif of DNA binding residues and a probable SUMOylating residue. HIGD2A gene is not implicated in cancer via mutation. In addition, DNA methylation and mRNA expression of HIGD2A gene present significant alterations in several cancers; HIGD2A gene showed significant higher expression in Diffuse Large B-cell Lymphoma (DLBCL). Hypoxic tissues characterize the \u201cbone marrow-liver-spleen\u201d DLBCL type. The relative quantification, by using qRT-PCR, showed that Higd2a expression is higher in bone marrow than in the liver or spleen. In addition, it was observed that quercetin modulated the expression of Higd2a gene in mice. As an assembly factor of mitochondrial respirasomes, HIG2A might be unexpectedly involved in the change of cellular energetics happening in cancer. As a result, it is worth continuing to explore the role of HIGD2A in cancer biology.<\/jats:p>","DOI":"10.3390\/genes11020206","type":"journal-article","created":{"date-parts":[[2020,2,25]],"date-time":"2020-02-25T08:12:22Z","timestamp":1582618342000},"page":"206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Biosystem Analysis of the Hypoxia Inducible Domain Family Member 2A: Implications in Cancer Biology"],"prefix":"10.3390","volume":"11","author":[{"given":"Celia","family":"Salazar","sequence":"first","affiliation":[{"name":"Instituto de Ciencias Biom\u00e9dicas, Facultad Ciencias de la Salud, Universidad Aut\u00f3noma de Chile, Santiago 8910060, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8993-9353","authenticated-orcid":false,"given":"Osvaldo","family":"Ya\u00f1ez","sequence":"additional","affiliation":[{"name":"Computational and Theoretical Chemistry Group, Departamento de Ciencias Qu\u00edmicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Santiago 8370251, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro A.","family":"Elorza","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Faculty of Medicine and Faculty of Life Sciences, Universidad Andres Bello, Santiago 8370146, Chile"},{"name":"Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8895-6282","authenticated-orcid":false,"given":"Natalie","family":"Cortes","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Naturales y Matem\u00e1ticas, Universidad de Ibagu\u00e9, Carrera 22 calle 67, Ibagu\u00e9 730002, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3312-1776","authenticated-orcid":false,"given":"Olimpo","family":"Garc\u00eda-Beltr\u00e1n","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Naturales y Matem\u00e1ticas, Universidad de Ibagu\u00e9, Carrera 22 calle 67, Ibagu\u00e9 730002, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Tiznado","sequence":"additional","affiliation":[{"name":"Computational and Theoretical Chemistry Group, Departamento de Ciencias Qu\u00edmicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Santiago 8370251, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9363-2730","authenticated-orcid":false,"given":"Lina Mar\u00eda","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Instituto de Ciencias Biom\u00e9dicas, Facultad Ciencias de la Salud, Universidad Aut\u00f3noma de Chile, Santiago 8910060, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/cr.2017.155","article-title":"Mitochondrial metabolism and cancer","volume":"28","author":"Porporato","year":"2018","journal-title":"Cell Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/nrc3803","article-title":"Mitochondrial ROS in cancer: Initiators, amplifiers or an Achilles\u2019 heel?","volume":"14","author":"Sabharwal","year":"2014","journal-title":"Nat. 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