Human Gene MTHFR (ENST00000423400.7) Description and Page Index
Description: methylenetetrahydrofolate reductase (from HGNC MTHFR)
RefSeq Summary (NM_001330358): The protein encoded by this gene catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Genetic variation in this gene influences susceptibility to occlusive vascular disease, neural tube defects, colon cancer and acute leukemia, and mutations in this gene are associated with methylenetetrahydrofolate reductase deficiency.[provided by RefSeq, Oct 2009].
Gencode Transcript: ENST00000423400.7
Gencode Gene: ENSG00000177000.12
Transcript (Including UTRs)
Position: hg38 chr1:11,790,068-11,803,526 Size: 13,459 Total Exon Count: 12 Strand: -
Position: hg38 chr1:11,790,680-11,803,514 Size: 12,835 Coding Exon Count: 12
Data last updated: 2019-09-04
Sequence and Links to Tools and Databases
MalaCards Disease Associations
MalaCards Gene Search:
MTHFR Diseases sorted by gene-association score: homocystinuria due to mthfr deficiency* (1671), thrombophilia due to thrombin defect* (578), neural tube defects, folate-sensitive* (343), schizophrenia* (284), mthfr thermolabile variant* (143), mthfr-related altered drug metabolism* (100), vascular disease (66), anencephaly* (44), homocysteinemia (39), myelomeningocele (38), acute leukemia (33), placental abruption (32), neural tube defects (30), placenta disease (24), spina bifida occulta (23), retinal vein occlusion (23), branch retinal artery occlusion (23), lemierre's syndrome (22), cerebral atherosclerosis (21), central retinal vein occlusion (21), hyperhomocysteinemia (20), amino acid metabolic disorder (19), vitamin b12 deficiency (19), nonarteritic anterior ischemic optic neuropathy (19), mthfr gene mutation (19), spinal cord infarction (18), post-traumatic epilepsy (18), methotrexate toxicity or dose selection* (18), colorectal adenoma (17), retinal artery occlusion (17), vein disease (16), arteritic anterior ischemic optic neuropathy (16), lateral sinus thrombosis (16), cerebrovascular disease (15), thrombophilia due to antithrombin iii deficiency (14), homocystinuria (14), sudden sensorineural hearing loss (13), protein s deficiency (13), inferior vena cava interruption (13), ischemic optic neuropathy (13), eclampsia (13), budd-chiari syndrome (13), hemifacial spasm (13), pediatric osteosarcoma (13), stomach cancer (13), riboflavin deficiency (13), upper thoracic spina bifida cystica* (12), cervicothoracic spina bifida cystica* (12), cervical spina bifida cystica* (12), lumbosacral spina bifida cystica* (12), thoracolumbosacral spina bifida cystica* (12), total spina bifida cystica* (12), upper thoracic spina bifida aperta* (12), thoracolumbosacral spina bifida aperta* (12), lumbosacral spina bifida aperta* (12), cervical spina bifida aperta* (12), cervicothoracic spina bifida aperta* (12), total spina bifida aperta* (12), encephalomalacia (12), porencephaly (12), protein c deficiency (12), thrombophilia (12), gastric cardia adenocarcinoma (11), portal vein thrombosis (11), lens subluxation (11), thrombophlebitis (11), antiphospholipid syndrome (11), cleft lip +/- cleft palate (10), hellp syndrome (10), migraine with aura (10), pulmonary embolism (10), neonatal stroke (10), retinal vascular disease (10), gastric cancer, somatic (9), childhood leukemia (9), livedoid vasculopathy (9), amaurosis fugax (9), catastrophic antiphospholipid syndrome (9), acute lymphoblastic leukemia, childhood (9), pyruvate kinase deficiency (9), nutritional deficiency disease (9), intracranial thrombosis (9), osteonecrosis (8), stroke, ischemic (8), osteoporotic fracture (8), cervical intraepithelial neoplasia (8), intracranial hypertension (8), vascular dementia (8), migraine with or without aura 1 (8), pregnancy loss, recurrent 1 (8), thrombophilia due to activated protein c resistance (8), exfoliation syndrome (8), blood protein disease (8), cleft lip (8), buerger disease (7), cleft palate, isolated (7), mucositis (7), glycine n-methyltransferase deficiency (7), patent foramen ovale (7), acute lymphocytic leukemia (7), carotid stenosis (7), retinal vascular occlusion (7), gastroschisis (7), thrombosis (7), schizencephaly (7), pre-eclampsia (7), cerebral palsy (7), primary angle-closure glaucoma (6), vitamin metabolic disorder (6), mesenteric vascular occlusion (6), hematopoietic stem cell transplantation (6), nephrosclerosis (6), methylmalonic acidemia (6), mastoiditis (6), gastrointestinal stromal tumor (6), intestinal benign neoplasm (6), sickle cell anemia (6), hemoglobin c disease (5), coronary artery disease (5), carotid artery dissection (5), gastric cardia carcinoma (5), moyamoya disease (5), thrombasthenia (5), gastrointestinal system benign neoplasm (5), omphalocele (5), inherited metabolic disorder (5), megaloblastic anemia (5), ischemic heart disease (5), testicular infarct (5), preeclampsia/eclampsia 1 (5), hereditary colorectal cancer (4), blood coagulation disease (4), holocarboxylase synthetase deficiency (4), ariboflavinosis (4), marantic endocarditis (4), hepatic vascular disease (4), hepatic infarction (4), uterine disease (4), bipolar disorder (4), heart disease (4), transcobalamin ii deficiency (4), down syndrome (3), myocardial infarction (3), colorectal cancer (3), differentiated thyroid carcinoma (3), artery disease (3), tetralogy of fallot (2), cleft lip/palate (2), autism spectrum disorder (1), physical disorder (1) * = Manually curated disease association
Comparative Toxicogenomics Database (CTD)
RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
Microarray Expression Data
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mRNA Secondary Structure of 3' and 5' UTRs
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Protein Domain and Structure Information
ModBase Predicted Comparative 3D Structure on Q5SNW7
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0004489 methylenetetrahydrofolate reductase (NAD(P)H) activity
Biological Process: GO:0006555 methionine metabolic process
GO:0035999 tetrahydrofolate interconversion
GO:0055114 oxidation-reduction process
Descriptions from all associated GenBank mRNAs
LF206719 - JP 2014500723-A/14222: Polycomb-Associated Non-Coding RNAs. MA442296 - JP 2018138019-A/14222: Polycomb-Associated Non-Coding RNAs. LF213889 - JP 2014500723-A/21392: Polycomb-Associated Non-Coding RNAs. MA449466 - JP 2018138019-A/21392: Polycomb-Associated Non-Coding RNAs. AB209113 - Homo sapiens mRNA for 5,10-methylenetetrahydrofolate reductase (NADPH) variant protein. BC053509 - Homo sapiens 5,10-methylenetetrahydrofolate reductase (NADPH), mRNA (cDNA clone MGC:59799 IMAGE:6374885), complete cds. AJ237672 - Homo sapiens mRNA for methylenetetrahydrofolate reductase. JQ429447 - Homo sapiens 5,10-methylenetetrahydrofolate reductase isoform 2 (MTHFR) mRNA, complete cds, alternatively spliced. AK312907 - Homo sapiens cDNA, FLJ93354, highly similar to Homo sapiens 5,10-methylenetetrahydrofolate reductase (NADPH)(MTHFR), mRNA. JD507239 - Sequence 488263 from Patent EP1572962. JD531226 - Sequence 512250 from Patent EP1572962. JD150319 - Sequence 131343 from Patent EP1572962. LF357350 - JP 2014500723-A/164853: Polycomb-Associated Non-Coding RNAs. MA592927 - JP 2018138019-A/164853: Polycomb-Associated Non-Coding RNAs. LF357348 - JP 2014500723-A/164851: Polycomb-Associated Non-Coding RNAs. MA592925 - JP 2018138019-A/164851: Polycomb-Associated Non-Coding RNAs. LF357347 - JP 2014500723-A/164850: Polycomb-Associated Non-Coding RNAs. MA592924 - JP 2018138019-A/164850: Polycomb-Associated Non-Coding RNAs. LF357342 - JP 2014500723-A/164845: Polycomb-Associated Non-Coding RNAs. MA592919 - JP 2018138019-A/164845: Polycomb-Associated Non-Coding RNAs. AY046565 - Homo sapiens methylenetetrahydrofolate reductase short isoform mRNA, partial cds; alternatively spliced. AY046561 - Homo sapiens methylenetetrahydrofolate reductase short isoform mRNA, partial cds; alternatively spliced. AY046562 - Homo sapiens methylenetetrahydrofolate reductase long isoform mRNA, partial cds; alternatively spliced. AY046563 - Homo sapiens methylenetetrahydrofolate reductase short isoform mRNA, partial cds; alternatively spliced. AY046564 - Homo sapiens methylenetetrahydrofolate reductase short isoform mRNA, partial cds; alternatively spliced. AY046560 - Homo sapiens methylenetetrahydrofolate reductase short isoform mRNA, partial cds; alternatively spliced. JD442762 - Sequence 423786 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa00670 - One carbon pool by folate hsa00680 - Methane metabolism hsa01100 - Metabolic pathways
Other Names for This Gene
Alternate Gene Symbols: BC053509, Q5SNW7, Q5SNW7_HUMAN, RP11-56N19.4-005, uc285gat.1 UCSC ID: uc285gat.1 RefSeq Accession: NM_001330358
Q5SNW7 CCDS: CCDS81262.1
Methods, Credits, and Use Restrictions
for details on how this gene model was made and data restrictions if any.