{"entity":{"id":"mthfr","kind":"target","name":"MTHFR","aka":["methylenetetrahydrofolate reductase","Methylenetetrahydrofolate reductase (NADPH)"],"tldr":"MTHFR (Methylenetetrahydrofolate reductase (NADPH)) is an enzyme. The public catalogues list it as a drug target and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Gastric & gastro-oesophageal junction cancer and Prostate cancer.","summary":"Catalyses the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine. Represents a key regulatory connection between the folate and methionine cycles.\n\nCIViC holds 3 clinical evidence items and 0 assertions across 1 variant, naming Fluorouracil.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:7436","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7436"},{"label":"UniProt P42898","url":"https://www.uniprot.org/uniprotkb/P42898/entry"},{"label":"NCBI Gene 4524","url":"https://www.ncbi.nlm.nih.gov/gene/4524"},{"label":"Ensembl ENSG00000177000","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000177000"}],"tags":["cancer-genes-wave"],"related":["civic"],"cancers":["gastric","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 1 therapies; CIViC holds 3 clinical evidence items on its variants. Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate.","Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Rectum Cancer."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"MTHFR","role":["drug-target","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:7436","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7436","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P42898","url":"https://www.uniprot.org/uniprotkb/P42898/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene MTHFR","url":"https://civicdb.org/features/3672","note":"3 evidence items, 0 assertions, 1 variants; diseases: Stomach Cancer, Prostate Adenocarcinoma, Rectum Cancer (GraphQL API, CC0)"}],"specificity":"broadly-expressed","distribution":"few-types","specificityNote":"Broadly expressed or essential: HPA finds the RNA at low tissue specificity; a medicine acting on the wild-type protein would expose normal tissue too. HPA MTHFR: RNA low tissue specificity; high antibody staining in 7 normal tissues; highest cancer staining thyroid cancer (3 of 4 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Gastric & gastro-oesophageal junction cancer, Prostate cancer); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas MTHFR tissue","url":"https://www.proteinatlas.org/ENSG00000177000-MTHFR/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000177000 associations","url":"https://platform.opentargets.org/target/ENSG00000177000/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:7436","ensembl":"ENSG00000177000","uniprot":"P42898","entrez":"4524","firstDescribed":1994,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Goyette et al, Nat. Genet, 1994, \"Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/7920641/","biology":"Catalyses the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine. Represents a key regulatory connection between the folate and methionine cycles. Locus 1p36.22 (HGNC).","whereFound":["Gastric & gastro-oesophageal junction cancer: CIViC evidence names this disease","Prostate cancer: CIViC evidence names this disease"],"targetClass":"enzyme","prevalence":[]},"route":"/targets/mthfr/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"}],"cancer":[{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}]}}