Genomic structure and transcript variants of the human methylenetetrahydrofolate reductase gene

ABSTRACT The human 5,10-methylenetetrahydrofolate reductase (MTHFR) represents a major enzyme in the folate-dependent regulation of methionine and homocysteine concentrations. Different

MTHFR mutations lead either to severe homocystinuria as a multisystem disorder or to moderate hyperhomocysteinaemia, which is a common risk factor for disorders ranging from

cardiovasculopathy to spina bifida. The N-terminal part of the human _MTHFR_ gene is incompletely characterised. We report the completed genomic structure of this gene including three novel

exonic sequences on the basis of a 5′-RACE and a 4.2 kb cloned fragment of human genomic DNA. We demonstrate the existence of four MTHFR transcripts differing in their first exons. The

diversity of transcripts is due to alternative transcription initiation and alternative splicing. Three putative polypeptides of 657, 698, and 680 amino acids are encoded. The novel genomic

sequence described here includes putative promoter regions as suggested by the presence of regions homologue to binding sites for SP1, AP1, AP2, CAAT or GC boxes. Furthermore, we provide

evidence that there are no TATA-box elements to regulate the human _MTHFR_ gene. The results of our study render the full-length characterisation of affected alleles in severe homocystinuria

and moderate hyperhomocysteinaemia due to MTHFR deficiency and provide a basis for investigating the regulation of the human _MTHFR_ gene. SIMILAR CONTENT BEING VIEWED BY OTHERS SEVEN NOVEL

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29 May 2025 ARTICLE PDF AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Universität Münster, Klinik und Poliklinik für Kinderheilkunde, Albert-Schweitzer-Strasse 33, Münster, 48129 , Germany

Anja Homberger, Michael Linnebank, Carsten Winter, Holger Willenbring, Thorsten Marquardt, Erik Harms & Hans Georg Koch Authors * Anja Homberger View author publications You can also

search for this author inPubMed Google Scholar * Michael Linnebank View author publications You can also search for this author inPubMed Google Scholar * Carsten Winter View author

publications You can also search for this author inPubMed Google Scholar * Holger Willenbring View author publications You can also search for this author inPubMed Google Scholar * Thorsten

Marquardt View author publications You can also search for this author inPubMed Google Scholar * Erik Harms View author publications You can also search for this author inPubMed Google

Scholar * Hans Georg Koch View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Hans Georg Koch. RIGHTS AND PERMISSIONS

Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Homberger, A., Linnebank, M., Winter, C. _et al._ Genomic structure and transcript variants of the human

methylenetetrahydrofolate reductase gene. _Eur J Hum Genet_ 8, 725–729 (2000). https://doi.org/10.1038/sj.ejhg.5200522 Download citation * Received: 23 January 2000 * Revised: 08 May 2000 *

Accepted: 18 May 2000 * Published: 31 August 2000 * Issue Date: 01 September 2000 * DOI: https://doi.org/10.1038/sj.ejhg.5200522 SHARE THIS ARTICLE Anyone you share the following link with

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content-sharing initiative KEYWORDS * methylenetetrahydrofolate reductase * MTHFR * promoter * transcripts * genomic structure