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Entry version 190 (18 Sep 2019)
Sequence version 3 (07 Dec 2004)
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Protein

Methylenetetrahydrofolate reductase

Gene

MTHFR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine.1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

FAD1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Allosterically regulated by S-adenosylmethionine.

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: tetrahydrofolate interconversion

This protein is involved in the pathway tetrahydrofolate interconversion, which is part of One-carbon metabolism.
View all proteins of this organism that are known to be involved in the pathway tetrahydrofolate interconversion and in One-carbon metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei63Proton donor/acceptorBy similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei127FADBy similarity1
Binding sitei159SubstrateBy similarity1
Binding sitei197FADBy similarity1
Binding sitei210FADBy similarity1
Binding sitei217FADBy similarity1
Binding sitei228SubstrateBy similarity1
Binding sitei321SubstrateBy similarity1
Binding sitei325SubstrateBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi63 – 68NADBy similarity6
Nucleotide bindingi94 – 95NAD and FADBy similarity2
Nucleotide bindingi157 – 159FADBy similarity3
Nucleotide bindingi174 – 175FADBy similarity2
Nucleotide bindingi201 – 204FADBy similarity4

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionAllosteric enzyme, Oxidoreductase
LigandFAD, Flavoprotein, NADP

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

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BRENDAi
1.5.1.20 2681

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-196757 Metabolism of folate and pterines

SABIO-RK: Biochemical Reaction Kinetics Database

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SABIO-RKi
P42898

SIGNOR Signaling Network Open Resource

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SIGNORi
P42898

UniPathway: a resource for the exploration and annotation of metabolic pathways

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UniPathwayi
UPA00193

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Methylenetetrahydrofolate reductaseCurated (EC:1.5.1.201 Publication)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:MTHFR
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 1

Organism-specific databases

Human Gene Nomenclature Database

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HGNCi
HGNC:7436 MTHFR

Online Mendelian Inheritance in Man (OMIM)

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MIMi
607093 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_P42898

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Methylenetetrahydrofolate reductase deficiency (MTHFRD)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAutosomal recessive disorder with a wide range of features including homocysteinuria, homocysteinemia [MIM:603174], developmental delay, severe mental retardation, perinatal death, psychiatric disturbances, and later-onset neurodegenerative disorders.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_07411146R → Q in MTHFRD; reduces methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs776483190EnsemblClinVar.1
Natural variantiVAR_07411246R → W in MTHFRD; reduced methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs138189536EnsemblClinVar.1
Natural variantiVAR_00953051R → P in MTHFRD. 1 PublicationCorresponds to variant dbSNP:rs201618781Ensembl.1
Natural variantiVAR_00431952R → Q in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 2 PublicationsCorresponds to variant dbSNP:rs754980119Ensembl.1
Natural variantiVAR_07411359W → S in MTHFRD; loss of methylenetetrahydrofolate reductase activity. 1 PublicationCorresponds to variant dbSNP:rs786204007EnsemblClinVar.1
Natural variantiVAR_07411468R → G in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs763539350EnsemblClinVar.1
Natural variantiVAR_07411582R → W in MTHFRD; reduced methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204009EnsemblClinVar.1
Natural variantiVAR_074116113A → T in MTHFRD; reduced methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs147257424EnsemblClinVar.1
Natural variantiVAR_074117127H → Y in MTHFRD; loss of methylenetetrahydrofolate reductase activity. 1 PublicationCorresponds to variant dbSNP:rs769381688EnsemblClinVar.1
Natural variantiVAR_074118129T → N in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 Publication1
Natural variantiVAR_074119130C → R in MTHFRD; reduced methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204012EnsemblClinVar.1
Natural variantiVAR_074120147Q → P in MTHFRD; loss of methylenetetrahydrofolate reductase activity. 1 PublicationCorresponds to variant dbSNP:rs786204013EnsemblClinVar.1
Natural variantiVAR_074121149G → V in MTHFRD; loss of methylenetetrahydrofolate reductase activity. 1 Publication1
Natural variantiVAR_074122153I → M in MTHFRD; reduced methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs767890671Ensembl.1
Natural variantiVAR_004320157R → Q in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 2 PublicationsCorresponds to variant dbSNP:rs121434295EnsemblClinVar.1
Natural variantiVAR_074123175A → T in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs1182635980Ensembl.1
Natural variantiVAR_074124183R → Q in MTHFRD; reduced methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs574132670EnsemblClinVar.1
Natural variantiVAR_074125195A → V in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs760161369Ensembl.1
Natural variantiVAR_074126196G → D in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204014EnsemblClinVar.1
Natural variantiVAR_074127215Missing in MTHFRD; loss of methylenetetrahydrofolate reductase activity. 1 Publication1
Natural variantiVAR_074128218V → L in MTHFRD; decreased affinity for FAD cofactor. 1 Publication1
Natural variantiVAR_074129225I → L in MTHFRD; reduced methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs200100285EnsemblClinVar.1
Natural variantiVAR_074130226Missing in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 Publication1
Natural variantiVAR_004321227T → M in MTHFRD. 1 PublicationCorresponds to variant dbSNP:rs748571395Ensembl.1
Natural variantiVAR_004322251P → L in MTHFRD. 1 Publication1
Natural variantiVAR_074131253V → F in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 Publication1
Natural variantiVAR_074132254P → S in MTHFRD; reduced methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204017EnsemblClinVar.1
Natural variantiVAR_074133255G → V in MTHFRD; loss of methylenetetrahydrofolate reductase activity. 1 PublicationCorresponds to variant dbSNP:rs786204018EnsemblClinVar.1
Natural variantiVAR_074134256I → N in MTHFRD; loss of methylenetetrahydrofolate reductase activity. 1 PublicationCorresponds to variant dbSNP:rs373398993EnsemblClinVar.1
Natural variantiVAR_074135257F → V in MTHFRD; loss of methylenetetrahydrofolate reductase activity. 1 PublicationCorresponds to variant dbSNP:rs786204019EnsemblClinVar.1
Natural variantiVAR_009531323L → P in MTHFRD. 1 PublicationCorresponds to variant dbSNP:rs121434297EnsemblClinVar.1
Natural variantiVAR_009532324N → S in MTHFRD. 1 PublicationCorresponds to variant dbSNP:rs267606887EnsemblClinVar.1
Natural variantiVAR_004323325R → C in MTHFRD. 1 PublicationCorresponds to variant dbSNP:rs371085894Ensembl.1
Natural variantiVAR_004324335R → C in MTHFRD. 1 PublicationCorresponds to variant dbSNP:rs748289202Ensembl.1
Natural variantiVAR_074136335R → H in MTHFRD; reduced methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs543016186EnsemblClinVar.1
Natural variantiVAR_074137338M → T in MTHFRD; loss of methylenetetrahydrofolate reductase activity. 1 PublicationCorresponds to variant dbSNP:rs368321176Ensembl.1
Natural variantiVAR_009533339W → G in MTHFRD; loss of methylenetetrahydrofolate reductase activity. 2 PublicationsCorresponds to variant dbSNP:rs267606886EnsemblClinVar.1
Natural variantiVAR_074138348P → S in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204021EnsemblClinVar.1
Natural variantiVAR_074139354H → Y in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204022EnsemblClinVar.1
Natural variantiVAR_004325357R → C in MTHFRD. 1 PublicationCorresponds to variant dbSNP:rs779993607Ensembl.1
Natural variantiVAR_074140363R → H in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204023EnsemblClinVar.1
Natural variantiVAR_074141372K → E in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204024EnsemblClinVar.1
Natural variantiVAR_009534377R → C in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 2 PublicationsCorresponds to variant dbSNP:rs121434296EnsemblClinVar.1
Natural variantiVAR_074142377R → H in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs750323424Ensembl.1
Natural variantiVAR_009535387G → D in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 2 PublicationsCorresponds to variant dbSNP:rs1430872491Ensembl.1
Natural variantiVAR_074143421W → S in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs200137991EnsemblClinVar.1
Natural variantiVAR_074144435F → S in MTHFRD. 2 PublicationsCorresponds to variant dbSNP:rs754015864Ensembl.1
Natural variantiVAR_074145506Y → D in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204026EnsemblClinVar.1
Natural variantiVAR_074146536V → F in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204028EnsemblClinVar.1
Natural variantiVAR_009536572P → L in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 2 PublicationsCorresponds to variant dbSNP:rs144508139Ensembl.1
Natural variantiVAR_074147574V → G in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 2 Publications1
Natural variantiVAR_074148575V → G in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204031EnsemblClinVar.1
Natural variantiVAR_009537586E → K in MTHFRD. 1 PublicationCorresponds to variant dbSNP:rs983672500Ensembl.1
Natural variantiVAR_074149598L → P in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204034EnsemblClinVar.1
Natural variantiVAR_074150628L → P in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204037EnsemblClinVar.1
Ischemic stroke (ISCHSTR)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.
Related information in OMIM
Neural tube defects, folate-sensitive (NTDFS)3 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionThe most common NTDs are open spina bifida (myelomeningocele) and anencephaly.
Related information in OMIM
Schizophrenia (SCZD)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder.
Related information in OMIM

Keywords - Diseasei

Disease mutation, Schizophrenia

Organism-specific databases

DisGeNET

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DisGeNETi
4524

MalaCards human disease database

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MalaCardsi
MTHFR
MIMi181500 phenotype
236250 phenotype
601367 phenotype
601634 phenotype
603174 phenotype

Open Targets

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OpenTargetsi
ENSG00000177000

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
268392 Cervical spina bifida aperta
268762 Cervical spina bifida cystica
268397 Cervicothoracic spina bifida aperta
268766 Cervicothoracic spina bifida cystica
395 Homocystinuria due to methylene tetrahydrofolate reductase deficiency
1048 Isolated anencephaly/exencephaly
268388 Lumbosacral spina bifida aperta
268758 Lumbosacral spina bifida cystica
413690 Methotrexate toxicity or dose selection
64738 NON RARE IN EUROPE: Non rare thrombophilia
268384 Thoracolumbosacral spina bifida aperta
268752 Thoracolumbosacral spina bifida cystica
268377 Total spina bifida aperta
268748 Total spina bifida cystica
268740 Upper thoracic spina bifida aperta
268770 Upper thoracic spina bifida cystica

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA245

Chemistry databases

Drug and drug target database

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DrugBanki
DB00542 Benazepril
DB00115 Cyanocobalamin
DB00544 Fluorouracil
DB00158 Folic acid
DB00170 Menadione
DB00134 Methionine
DB00563 Methotrexate
DB00140 Riboflavin
DB00116 Tetrahydrofolic acid

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
MTHFR

Domain mapping of disease mutations (DMDM)

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DMDMi
56405339

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001902451 – 656Methylenetetrahydrofolate reductaseAdd BLAST656

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
P42898

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
P42898

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
P42898

MaxQB - The MaxQuant DataBase

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MaxQBi
P42898

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
P42898

PeptideAtlas

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PeptideAtlasi
P42898

PRoteomics IDEntifications database

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PRIDEi
P42898

ProteomicsDB human proteome resource

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ProteomicsDBi
55566 [P42898-1]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
P42898

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
P42898

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000177000 Expressed in 206 organ(s), highest expression level in corpus epididymis

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P42898 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P42898 HS

Organism-specific databases

Human Protein Atlas

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HPAi
HPA063389

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer.

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
110624, 28 interactors

Protein interaction database and analysis system

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IntActi
P42898, 21 interactors

Molecular INTeraction database

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MINTi
P42898

STRING: functional protein association networks

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STRINGi
9606.ENSP00000365777

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1656
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P42898

Database of comparative protein structure models

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ModBasei
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG0564 Eukaryota
COG0685 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00390000012490

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000246234

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P42898

KEGG Orthology (KO)

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KOi
K00297

Identification of Orthologs from Complete Genome Data

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OMAi
HPVHGWG

Database of Orthologous Groups

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OrthoDBi
338303at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
P42898

TreeFam database of animal gene trees

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TreeFami
TF105665

Family and domain databases

Conserved Domains Database

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CDDi
cd00537 MTHFR, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR029041 FAD-linked_oxidoreductase-like
IPR004621 Fadh2_euk
IPR003171 Mehydrof_redctse

Pfam protein domain database

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Pfami
View protein in Pfam
PF02219 MTHFR, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF51730 SSF51730, 1 hit

TIGRFAMs; a protein family database

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TIGRFAMsi
TIGR00677 fadh2_euk, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P42898-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MVNEARGNSS LNPCLEGSAS SGSESSKDSS RCSTPGLDPE RHERLREKMR
60 70 80 90 100
RRLESGDKWF SLEFFPPRTA EGAVNLISRF DRMAAGGPLY IDVTWHPAGD
110 120 130 140 150
PGSDKETSSM MIASTAVNYC GLETILHMTC CRQRLEEITG HLHKAKQLGL
160 170 180 190 200
KNIMALRGDP IGDQWEEEEG GFNYAVDLVK HIRSEFGDYF DICVAGYPKG
210 220 230 240 250
HPEAGSFEAD LKHLKEKVSA GADFIITQLF FEADTFFRFV KACTDMGITC
260 270 280 290 300
PIVPGIFPIQ GYHSLRQLVK LSKLEVPQEI KDVIEPIKDN DAAIRNYGIE
310 320 330 340 350
LAVSLCQELL ASGLVPGLHF YTLNREMATT EVLKRLGMWT EDPRRPLPWA
360 370 380 390 400
LSAHPKRREE DVRPIFWASR PKSYIYRTQE WDEFPNGRWG NSSSPAFGEL
410 420 430 440 450
KDYYLFYLKS KSPKEELLKM WGEELTSEES VFEVFVLYLS GEPNRNGHKV
460 470 480 490 500
TCLPWNDEPL AAETSLLKEE LLRVNRQGIL TINSQPNING KPSSDPIVGW
510 520 530 540 550
GPSGGYVFQK AYLEFFTSRE TAEALLQVLK KYELRVNYHL VNVKGENITN
560 570 580 590 600
APELQPNAVT WGIFPGREII QPTVVDPVSF MFWKDEAFAL WIERWGKLYE
610 620 630 640 650
EESPSRTIIQ YIHDNYFLVN LVDNDFPLDN CLWQVVEDTL ELLNRPTQNA

RETEAP
Length:656
Mass (Da):74,597
Last modified:December 7, 2004 - v3
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iF16E774833D054B8
GO
Isoform 2 (identifier: P42898-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MDHRKARVLPAGHYCPSLGIWASQVGSVRSSVPPSISRNPAM

Show »
Length:697
Mass (Da):78,965
Checksum:i53BD7151AA16F795
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5SNW7Q5SNW7_HUMAN
Methylenetetrahydrofolate reductase
MTHFR
696Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A286YF17A0A286YF17_HUMAN
Methylenetetrahydrofolate reductase
MTHFR
549Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A286YFD0A0A286YFD0_HUMAN
Methylenetetrahydrofolate reductase
MTHFR
642Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
L7P8G6L7P8G6_HUMAN
Methylenetetrahydrofolate reductase
MTHFR
411Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
Q5SNW5Q5SNW5_HUMAN
Methylenetetrahydrofolate reductase
MTHFR
143Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F8W9T8F8W9T8_HUMAN
Methylenetetrahydrofolate reductase
MTHFR
229Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A286YF47A0A286YF47_HUMAN
Methylenetetrahydrofolate reductase
MTHFR
82Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A1B0GXD9A0A1B0GXD9_HUMAN
Methylenetetrahydrofolate reductase
MTHFR
29Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the ‘Sequence’ section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement_in_disease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>Polymorphismi

Genetic variation in MTHFR influences susceptibility to occlusive vascular disease, neural tube defects (NTD), colon cancer and acute leukemia.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07411146R → Q in MTHFRD; reduces methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs776483190EnsemblClinVar.1
Natural variantiVAR_07411246R → W in MTHFRD; reduced methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs138189536EnsemblClinVar.1
Natural variantiVAR_00953051R → P in MTHFRD. 1 PublicationCorresponds to variant dbSNP:rs201618781Ensembl.1
Natural variantiVAR_00431952R → Q in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 2 PublicationsCorresponds to variant dbSNP:rs754980119Ensembl.1
Natural variantiVAR_07411359W → S in MTHFRD; loss of methylenetetrahydrofolate reductase activity. 1 PublicationCorresponds to variant dbSNP:rs786204007EnsemblClinVar.1
Natural variantiVAR_07411468R → G in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs763539350EnsemblClinVar.1
Natural variantiVAR_01488168R → Q1 PublicationCorresponds to variant dbSNP:rs2066472Ensembl.1
Natural variantiVAR_07411582R → W in MTHFRD; reduced methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204009EnsemblClinVar.1
Natural variantiVAR_074116113A → T in MTHFRD; reduced methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs147257424EnsemblClinVar.1
Natural variantiVAR_074117127H → Y in MTHFRD; loss of methylenetetrahydrofolate reductase activity. 1 PublicationCorresponds to variant dbSNP:rs769381688EnsemblClinVar.1
Natural variantiVAR_074118129T → N in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 Publication1
Natural variantiVAR_074119130C → R in MTHFRD; reduced methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204012EnsemblClinVar.1
Natural variantiVAR_074120147Q → P in MTHFRD; loss of methylenetetrahydrofolate reductase activity. 1 PublicationCorresponds to variant dbSNP:rs786204013EnsemblClinVar.1
Natural variantiVAR_074121149G → V in MTHFRD; loss of methylenetetrahydrofolate reductase activity. 1 Publication1
Natural variantiVAR_074122153I → M in MTHFRD; reduced methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs767890671Ensembl.1
Natural variantiVAR_004320157R → Q in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 2 PublicationsCorresponds to variant dbSNP:rs121434295EnsemblClinVar.1
Natural variantiVAR_074123175A → T in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs1182635980Ensembl.1
Natural variantiVAR_074124183R → Q in MTHFRD; reduced methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs574132670EnsemblClinVar.1
Natural variantiVAR_074125195A → V in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs760161369Ensembl.1
Natural variantiVAR_074126196G → D in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204014EnsemblClinVar.1
Natural variantiVAR_074127215Missing in MTHFRD; loss of methylenetetrahydrofolate reductase activity. 1 Publication1
Natural variantiVAR_074128218V → L in MTHFRD; decreased affinity for FAD cofactor. 1 Publication1
Natural variantiVAR_009528222A → V Common polymorphism; at homozygosity reduces the risk for colorectal cancer in individuals with adequate folate status; decreased risk for adult acute leukemia; increased risk for NTDFS; increased risk for schizophrenia; thermolabile; decreased affinity for FAD cofactor; 50% reduced activity. 8 PublicationsCorresponds to variant dbSNP:rs1801133EnsemblClinVar.1
Natural variantiVAR_074129225I → L in MTHFRD; reduced methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs200100285EnsemblClinVar.1
Natural variantiVAR_074130226Missing in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 Publication1
Natural variantiVAR_004321227T → M in MTHFRD. 1 PublicationCorresponds to variant dbSNP:rs748571395Ensembl.1
Natural variantiVAR_004322251P → L in MTHFRD. 1 Publication1
Natural variantiVAR_074131253V → F in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 Publication1
Natural variantiVAR_074132254P → S in MTHFRD; reduced methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204017EnsemblClinVar.1
Natural variantiVAR_074133255G → V in MTHFRD; loss of methylenetetrahydrofolate reductase activity. 1 PublicationCorresponds to variant dbSNP:rs786204018EnsemblClinVar.1
Natural variantiVAR_074134256I → N in MTHFRD; loss of methylenetetrahydrofolate reductase activity. 1 PublicationCorresponds to variant dbSNP:rs373398993EnsemblClinVar.1
Natural variantiVAR_074135257F → V in MTHFRD; loss of methylenetetrahydrofolate reductase activity. 1 PublicationCorresponds to variant dbSNP:rs786204019EnsemblClinVar.1
Natural variantiVAR_009531323L → P in MTHFRD. 1 PublicationCorresponds to variant dbSNP:rs121434297EnsemblClinVar.1
Natural variantiVAR_009532324N → S in MTHFRD. 1 PublicationCorresponds to variant dbSNP:rs267606887EnsemblClinVar.1
Natural variantiVAR_004323325R → C in MTHFRD. 1 PublicationCorresponds to variant dbSNP:rs371085894Ensembl.1
Natural variantiVAR_004324335R → C in MTHFRD. 1 PublicationCorresponds to variant dbSNP:rs748289202Ensembl.1
Natural variantiVAR_074136335R → H in MTHFRD; reduced methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs543016186EnsemblClinVar.1
Natural variantiVAR_074137338M → T in MTHFRD; loss of methylenetetrahydrofolate reductase activity. 1 PublicationCorresponds to variant dbSNP:rs368321176Ensembl.1
Natural variantiVAR_009533339W → G in MTHFRD; loss of methylenetetrahydrofolate reductase activity. 2 PublicationsCorresponds to variant dbSNP:rs267606886EnsemblClinVar.1
Natural variantiVAR_074138348P → S in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204021EnsemblClinVar.1
Natural variantiVAR_074139354H → Y in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204022EnsemblClinVar.1
Natural variantiVAR_004325357R → C in MTHFRD. 1 PublicationCorresponds to variant dbSNP:rs779993607Ensembl.1
Natural variantiVAR_074140363R → H in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204023EnsemblClinVar.1
Natural variantiVAR_074141372K → E in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204024EnsemblClinVar.1
Natural variantiVAR_009534377R → C in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 2 PublicationsCorresponds to variant dbSNP:rs121434296EnsemblClinVar.1
Natural variantiVAR_074142377R → H in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs750323424Ensembl.1
Natural variantiVAR_009535387G → D in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 2 PublicationsCorresponds to variant dbSNP:rs1430872491Ensembl.1
Natural variantiVAR_074143421W → S in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs200137991EnsemblClinVar.1
Natural variantiVAR_018857422G → R1 PublicationCorresponds to variant dbSNP:rs45571736Ensembl.1
Natural variantiVAR_014882429E → A Common polymorphism; decreased risk for adult acute leukemia; thermolabile; decreased activity. 4 PublicationsCorresponds to variant dbSNP:rs1801131EnsemblClinVar.1
Natural variantiVAR_074144435F → S in MTHFRD. 2 PublicationsCorresponds to variant dbSNP:rs754015864Ensembl.1
Natural variantiVAR_054158470E → A1 Publication1
Natural variantiVAR_074145506Y → D in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204026EnsemblClinVar.1
Natural variantiVAR_018858519R → C1 PublicationCorresponds to variant dbSNP:rs45496998Ensembl.1
Natural variantiVAR_050293519R → H. Corresponds to variant dbSNP:rs45449298Ensembl.1
Natural variantiVAR_074146536V → F in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204028EnsemblClinVar.1
Natural variantiVAR_050294566G → E. Corresponds to variant dbSNP:rs2274974Ensembl.1
Natural variantiVAR_009536572P → L in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 2 PublicationsCorresponds to variant dbSNP:rs144508139Ensembl.1
Natural variantiVAR_074147574V → G in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 2 Publications1
Natural variantiVAR_074148575V → G in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204031EnsemblClinVar.1
Natural variantiVAR_009537586E → K in MTHFRD. 1 PublicationCorresponds to variant dbSNP:rs983672500Ensembl.1
Natural variantiVAR_018859594R → Q2 PublicationsCorresponds to variant dbSNP:rs2274976EnsemblClinVar.1
Natural variantiVAR_074149598L → P in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204034EnsemblClinVar.1
Natural variantiVAR_074150628L → P in MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH. 1 PublicationCorresponds to variant dbSNP:rs786204037EnsemblClinVar.1
Natural variantiVAR_018860653T → M1 PublicationCorresponds to variant dbSNP:rs35737219EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0537441M → MDHRKARVLPAGHYCPSLGI WASQVGSVRSSVPPSISRNP AM in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
U09806 mRNA Translation: AAA74440.2
AF105987
, AF105977, AF105978, AF105979, AF105980, AF105981, AF105982, AF105983, AF105984, AF105985, AF105986 Genomic DNA Translation: AAD17965.1
AJ237672 mRNA Translation: CAB41971.1
AK312907 mRNA Translation: BAG35753.1
AY338232 Genomic DNA Translation: AAP88033.1
AL953897 Genomic DNA No translation available.
CH471130 Genomic DNA Translation: EAW71709.1
BC053509 mRNA Translation: AAH53509.1
AY046562 mRNA Translation: AAL17648.1
AF398930 Genomic DNA Translation: AAN40865.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS137.1 [P42898-1]
CCDS81262.1 [P42898-2]

Protein sequence database of the Protein Information Resource

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PIRi
S46454

NCBI Reference Sequences

More...
RefSeqi
NP_001317287.1, NM_001330358.1 [P42898-2]
NP_005948.3, NM_005957.4 [P42898-1]
XP_005263517.1, XM_005263460.4 [P42898-1]
XP_005263519.1, XM_005263462.4 [P42898-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000376583; ENSP00000365767; ENSG00000177000 [P42898-2]
ENST00000376585; ENSP00000365770; ENSG00000177000 [P42898-2]
ENST00000376590; ENSP00000365775; ENSG00000177000 [P42898-1]
ENST00000376592; ENSP00000365777; ENSG00000177000 [P42898-1]

Database of genes from NCBI RefSeq genomes

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GeneIDi
4524

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:4524

UCSC genome browser

More...
UCSCi
uc001atc.3 human [P42898-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs
SHMPD

The Singapore human mutation and polymorphism database

Wikipedia

Methylenetetrahydrofolate reductase entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U09806 mRNA Translation: AAA74440.2
AF105987
, AF105977, AF105978, AF105979, AF105980, AF105981, AF105982, AF105983, AF105984, AF105985, AF105986 Genomic DNA Translation: AAD17965.1
AJ237672 mRNA Translation: CAB41971.1
AK312907 mRNA Translation: BAG35753.1
AY338232 Genomic DNA Translation: AAP88033.1
AL953897 Genomic DNA No translation available.
CH471130 Genomic DNA Translation: EAW71709.1
BC053509 mRNA Translation: AAH53509.1
AY046562 mRNA Translation: AAL17648.1
AF398930 Genomic DNA Translation: AAN40865.1
CCDSiCCDS137.1 [P42898-1]
CCDS81262.1 [P42898-2]
PIRiS46454
RefSeqiNP_001317287.1, NM_001330358.1 [P42898-2]
NP_005948.3, NM_005957.4 [P42898-1]
XP_005263517.1, XM_005263460.4 [P42898-1]
XP_005263519.1, XM_005263462.4 [P42898-1]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6FCXX-ray2.50A/B37-644[»]
SMRiP42898
ModBaseiSearch...

Protein-protein interaction databases

BioGridi110624, 28 interactors
IntActiP42898, 21 interactors
MINTiP42898
STRINGi9606.ENSP00000365777

Chemistry databases

DrugBankiDB00542 Benazepril
DB00115 Cyanocobalamin
DB00544 Fluorouracil
DB00158 Folic acid
DB00170 Menadione
DB00134 Methionine
DB00563 Methotrexate
DB00140 Riboflavin
DB00116 Tetrahydrofolic acid

PTM databases

iPTMnetiP42898
PhosphoSitePlusiP42898

Polymorphism and mutation databases

BioMutaiMTHFR
DMDMi56405339

Proteomic databases

EPDiP42898
jPOSTiP42898
MassIVEiP42898
MaxQBiP42898
PaxDbiP42898
PeptideAtlasiP42898
PRIDEiP42898
ProteomicsDBi55566 [P42898-1]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000376583; ENSP00000365767; ENSG00000177000 [P42898-2]
ENST00000376585; ENSP00000365770; ENSG00000177000 [P42898-2]
ENST00000376590; ENSP00000365775; ENSG00000177000 [P42898-1]
ENST00000376592; ENSP00000365777; ENSG00000177000 [P42898-1]
GeneIDi4524
KEGGihsa:4524
UCSCiuc001atc.3 human [P42898-1]

Organism-specific databases

Comparative Toxicogenomics Database

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CTDi
4524
DisGeNETi4524

GeneCards: human genes, protein and diseases

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GeneCardsi
MTHFR
HGNCiHGNC:7436 MTHFR
HPAiHPA063389
MalaCardsiMTHFR
MIMi181500 phenotype
236250 phenotype
601367 phenotype
601634 phenotype
603174 phenotype
607093 gene
neXtProtiNX_P42898
OpenTargetsiENSG00000177000
Orphaneti268392 Cervical spina bifida aperta
268762 Cervical spina bifida cystica
268397 Cervicothoracic spina bifida aperta
268766 Cervicothoracic spina bifida cystica
395 Homocystinuria due to methylene tetrahydrofolate reductase deficiency
1048 Isolated anencephaly/exencephaly
268388 Lumbosacral spina bifida aperta
268758 Lumbosacral spina bifida cystica
413690 Methotrexate toxicity or dose selection
64738 NON RARE IN EUROPE: Non rare thrombophilia
268384 Thoracolumbosacral spina bifida aperta
268752 Thoracolumbosacral spina bifida cystica
268377 Total spina bifida aperta
268748 Total spina bifida cystica
268740 Upper thoracic spina bifida aperta
268770 Upper thoracic spina bifida cystica
PharmGKBiPA245

GenAtlas: human gene database

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GenAtlasi
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Phylogenomic databases

eggNOGiKOG0564 Eukaryota
COG0685 LUCA
GeneTreeiENSGT00390000012490
HOGENOMiHOG000246234
InParanoidiP42898
KOiK00297
OMAiHPVHGWG
OrthoDBi338303at2759
PhylomeDBiP42898
TreeFamiTF105665

Enzyme and pathway databases

UniPathwayiUPA00193
BRENDAi1.5.1.20 2681
ReactomeiR-HSA-196757 Metabolism of folate and pterines
SABIO-RKiP42898
SIGNORiP42898

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

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ChiTaRSi
MTHFR human

The Gene Wiki collection of pages on human genes and proteins

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GeneWikii
Methylenetetrahydrofolate_reductase

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

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GenomeRNAii
4524

Pharos

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Pharosi
P42898

Protein Ontology

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PROi
PR:P42898

The Stanford Online Universal Resource for Clones and ESTs

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SOURCEi
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Gene expression databases

BgeeiENSG00000177000 Expressed in 206 organ(s), highest expression level in corpus epididymis
ExpressionAtlasiP42898 baseline and differential
GenevisibleiP42898 HS

Family and domain databases

CDDicd00537 MTHFR, 1 hit
InterProiView protein in InterPro
IPR029041 FAD-linked_oxidoreductase-like
IPR004621 Fadh2_euk
IPR003171 Mehydrof_redctse
PfamiView protein in Pfam
PF02219 MTHFR, 1 hit
SUPFAMiSSF51730 SSF51730, 1 hit
TIGRFAMsiTIGR00677 fadh2_euk, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

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ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiMTHR_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P42898
Secondary accession number(s): B2R7A6
, Q5SNW6, Q5SNW9, Q7Z6M6, Q8IU73, Q9UQR2
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: December 7, 2004
Last modified: September 18, 2019
This is version 190 of the entry and version 3 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  7. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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