Gene Gene information from NCBI Gene database.
Entrez ID 4524
Gene name Methylenetetrahydrofolate reductase
Gene symbol MTHFR
Synonyms (NCBI Gene)
-
Chromosome 1
Chromosome location 1p36.22
Summary 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 vas
SNPs SNP information provided by dbSNP.
81
SNP ID Visualize variation Clinical significance Consequence
rs1801131 T>G Benign, benign-likely-benign, other, risk-factor, uncertain-significance Non coding transcript variant, coding sequence variant, missense variant
rs1801133 G>A,C Likely-benign, not-provided, conflicting-interpretations-of-pathogenicity, drug-response, other, uncertain-significance Non coding transcript variant, coding sequence variant, missense variant
rs2066464 T>C Conflicting-interpretations-of-pathogenicity Intron variant, non coding transcript variant
rs34279942 G>A,T Conflicting-interpretations-of-pathogenicity Coding sequence variant, synonymous variant, missense variant, non coding transcript variant
rs45449298 C>A,T Uncertain-significance, conflicting-interpretations-of-pathogenicity Coding sequence variant, missense variant, non coding transcript variant
miRNA miRNA information provided by mirtarbase database.
820
miRTarBase ID miRNA Experiments Reference
MIRT027114 hsa-miR-103a-3p Sequencing 20371350
MIRT031648 hsa-miR-16-5p Sequencing 20371350
MIRT042604 hsa-miR-423-3p CLASH 23622248
MIRT618790 hsa-miR-1972 HITS-CLIP 23824327
MIRT618789 hsa-miR-4480 HITS-CLIP 23824327
Transcription factors Transcription factors information provided by TRRUST V2 database.
1
Transcription factor Regulation Reference
NFE2L2 Activation 16551619
Gene ontology (GO) Gene Ontology (GO) annotations describing the biological processes, molecular functions, and cellular components associated with a gene.
39
GO ID Ontology Definition Evidence Reference
GO:0001666 Process Response to hypoxia IEA
GO:0001843 Process Neural tube closure IMP 25855017, 29222906
GO:0001843 Process Neural tube closure NAS 9349452
GO:0003824 Function Catalytic activity IEA
GO:0004489 Function Methylenetetrahydrofolate reductase [NAD(P)H] activity IBA
Other IDs Other IDs provides unique identifiers for this gene in OMIM, HGNC, and Ensembl databases.
MIM HGNC e!Ensembl
607093 7436 ENSG00000177000
Protein Protein information from UniProt database.
UniProt ID Unique identifier for the protein in the UniProt database. Click to view detailed protein information.
P42898
Protein name Methylenetetrahydrofolate reductase (NADPH) (EC 1.5.1.53)
Protein function Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine (PubMed:29891918). Represents a key regulatory connection between the folate and methionine cycles
PDB 6FCX , 8QA4 , 8QA5 , 8QA6
Family and domains

Pfam

Accession ID Position in sequence Description Type
PF02219 MTHFR 48 337 Methylenetetrahydrofolate reductase Domain
Sequence
MVNEARGNSSLNPCLEGSASSGSESSKDSSRCSTPGLDPERHERLREKMRRRLESGDKWF
SLEFFPPRTAEGAVNLISRFDRMAAGGPLYIDVTWHPAGDPGSDKETSSMMIASTAVNYC
GLETILHMTCCRQRLEEITGHLHKAKQLGLKNIMALRGDPIGDQWEEEEGGFNYAVDLVK
HIRSEFGDYFDICVAGYPKGHPEAGSFEADLKHLKEKVSAGADFIITQLFFEADTFFRFV
KACTDMGITCPIVPGIFPIQGYHSLRQLVKLSKLEVPQEIKDVIEPIKDNDAAIRNYGIE
LAVSLCQELLASGLVPGLHFYTLNREMATTEVLKRLG
MWTEDPRRPLPWALSAHPKRREE
DVRPIFWASRPKSYIYRTQEWDEFPNGRWGNSSSPAFGELKDYYLFYLKSKSPKEELLKM
WGEELTSEESVFEVFVLYLSGEPNRNGHKVTCLPWNDEPLAAETSLLKEELLRVNRQGIL
TINSQPNINGKPSSDPIVGWGPSGGYVFQKAYLEFFTSRETAEALLQVLKKYELRVNYHL
VNVKGENITNAPELQPNAVTWGIFPGREIIQPTVVDPVSFMFWKDEAFALWIERWGKLYE
EESPSRTIIQYIHDNYFLVNLVDNDFPLDNCLWQVVEDTLELLNRPTQNARETEAP
Sequence length 656
Interactions View interactions
Pathways Pathway information has different metabolic/signaling pathways associated with genes.
  KEGG  Reactome
  One carbon pool by folate
Metabolic pathways
Antifolate resistance
Folate transport and metabolism
  Metabolism of folate and pterines
Associated diseases Disease associations from ClinVar (causal & non-causal) and other databases (OMIM, Orphanet, GWAS, etc.).
166
Evidence Score: ★☆☆☆☆  Gene-disease association found in Text Mining only ★★☆☆☆  Found in Text Mining and Unknown/Other Associations ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants) ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)
Causal Diseases associated with Pathogenic or Likely Pathogenic variants in ClinVar
Phenotype Name Clinical Significance dbSNP ID RCV Accession Evidence Score
Abnormality of metabolism/homeostasis Pathogenic rs121434294 RCV001813944
★★★★☆
ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Bilateral tonic-clonic seizure Pathogenic rs763186690 RCV001261544
★★★★☆
ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Clear cell carcinoma of kidney Likely pathogenic rs1057519359 RCV005893802
★★★★☆
ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Familial cancer of breast Likely pathogenic; Pathogenic rs748397580 RCV005909223
★★★★☆
ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Unknown / Other Associations ClinVar entries with uncertain/conflicting evidence, and associations from other databases (OMIM, Orphanet, GWAS, etc.) where the gene is not established as causal.
Phenotype Name Clinical Significance Source Evidence Score
ALZHEIMERS DISEASE Disgenet
★★☆☆☆
Found in Text Mining + Unknown/Other Associations
AMYOTROPHIC LATERAL SCLEROSIS Disgenet
★★☆☆☆
Found in Text Mining + Unknown/Other Associations
ANEMIA CTD, Disgenet
CTD, Disgenet
★★☆☆☆
Found in Text Mining + Unknown/Other Associations
ANEMIA, SICKLE CELL Disgenet
★★☆☆☆
Found in Text Mining + Unknown/Other Associations
Associations from Text MiningDisease associations identified through Pubtator
Disease Name Relationship Type References Evidence Score
Abnormal Karyotype Associate 31737664
★☆☆☆☆
Found in Text Mining only
Abnormalities Drug Induced Associate 36619555
★☆☆☆☆
Found in Text Mining only
Abortion Habitual Associate 12738509, 15821810, 24235948, 24484533, 26060483, 27525841, 28703660, 28819944, 29785531, 30680517
★☆☆☆☆
Found in Text Mining only
Abortion Spontaneous Associate 11821094, 12623486, 23288205, 25153695, 27068821, 28488549, 28580572, 28703660, 29564022, 32021228, 33914208, 35232413, 36008980, 38057822
★☆☆☆☆
Found in Text Mining only
Activated Protein C Resistance Associate 16015408
★☆☆☆☆
Found in Text Mining only
Acute Coronary Syndrome Associate 27051002, 29245302, 32160861, 35721657
★☆☆☆☆
Found in Text Mining only
Acute Disease Associate 15886665
★☆☆☆☆
Found in Text Mining only
Acute Febrile Encephalopathy Associate 16906320
★☆☆☆☆
Found in Text Mining only
Acute Kidney Injury Associate 22129510
★☆☆☆☆
Found in Text Mining only
Adenocarcinoma Associate 12115343, 24490800
★☆☆☆☆
Found in Text Mining only