Mthfr methylenetetrahydrofolate reductase [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Mthfrprovided by MGI
Official Full Name: methylenetetrahydrofolate reductaseprovided by MGI
Primary source: MGI:MGI:106639
See related: Ensembl:ENSMUSG00000029009 AllianceGenome:MGI:106639
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Summary: Enables methylenetetrahydrofolate reductase (NAD(P)H) activity. Acts upstream of or within methionine biosynthetic process. Predicted to be located in synapse. Predicted to be active in cytosol. Is expressed in several structures, including central nervous system; cranium; heart; sensory organ; and testis. Used to study neural tube defect. Human ortholog(s) of this gene implicated in several diseases, including autoimmune disease (multiple); carcinoma (multiple); cardiovascular system disease (multiple); hematologic cancer (multiple); and kidney failure (multiple). Orthologous to human MTHFR (methylenetetrahydrofolate reductase). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in ovary adult (RPKM 9.7), testis adult (RPKM 8.0) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 4 E1; 4 78.67 cM

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	4	NC_000070.7 (148123534..148144019)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	4	NC_000070.6 (148039077..148059562)

Chromosome 4 - NC_000070.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Mild methylenetetrahydrofolate reductase deficiency accelerates liver triacylglycerol and uric acid accumulation in fructose-fed mice.
Title: Mild methylenetetrahydrofolate reductase deficiency accelerates liver triacylglycerol and uric acid accumulation in fructose-fed mice.
MTHFR epigenetic derepression protects against diabetes cardiac fibrosis.
Title: MTHFR epigenetic derepression protects against diabetes cardiac fibrosis.
The 677C > T variant in methylenetetrahydrofolate reductase causes morphological and functional cerebrovascular deficits in mice.
Title: The 677C > T variant in methylenetetrahydrofolate reductase causes morphological and functional cerebrovascular deficits in mice.
SIRT1 pharmacological activation rescues vascular dysfunction and prevents thrombosis in MTHFR deficiency.
Title: SIRT1 pharmacological activation rescues vascular dysfunction and prevents thrombosis in MTHFR deficiency.
Paternal MTHFR deficiency leads to hypomethylation of young retrotransposons and reproductive decline across two successive generations.
Title: Paternal MTHFR deficiency leads to hypomethylation of young retrotransposons and reproductive decline across two successive generations.
Maternal and offspring Mthfr genotypes interact in a mouse model to induce autism spectrum disorder-like behavior.
Title: Maternal and offspring methylenetetrahydrofolate-reductase genotypes interact in a mouse model to induce autism spectrum disorder-like behavior.
The data suggest that MTHFR deficiency decreases recovery after stroke by reducing neuronal and astrocyte viability.
Title: A genetic deficiency in folic acid metabolism impairs recovery after ischemic stroke.
data provide evidence for a similar cross-species response to high dose folic acid supplementation, of sperm DNA hypomethylation, and implicate MTHFR downregulation as a possible mechanism.
Title: Testicular MTHFR deficiency may explain sperm DNA hypomethylation associated with high dose folic acid supplementation.
findings indicate that the loss of folate as a methyl donor is a modifier of allergic airway disease, and that epigenetic and expression changes correlate with this modification.
Title: Methylene-tetrahydrofolate reductase contributes to allergic airway disease.
Ganglion cell loss and vasculopathy observed in Mthfr+/- and Cbs+/- mouse retinas may be milder than expected, not because of compensatory increases of enzymes in remethylation/transsulfuration pathways, but because downstream transsulfuration pathway products GSH, taurine, and H2S are maintained at robust levels.
Title: Analysis of MTHFR, CBS, Glutathione, Taurine, and Hydrogen Sulfide Levels in Retinas of Hyperhomocysteinemic Mice.

Submit: New GeneRIF Correction See all GeneRIFs (38)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (4) 1 citation
Endonuclease-mediated (3) 1 citation

General gene information

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Markers

AI323986 (e-PCR)
- UniSTS:159320

Mthfr (e-PCR), detects polymorphism
- UniSTS:526048

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables FAD binding	IBA Inferred from Biological aspect of Ancestor more info
enables NADP binding	ISO Inferred from Sequence Orthology more info
enables catalytic activity	IEA Inferred from Electronic Annotation more info
enables flavin adenine dinucleotide binding	ISO Inferred from Sequence Orthology more info
enables methylenetetrahydrofolate reductase (NAD(P)H) activity	IBA Inferred from Biological aspect of Ancestor more info
enables methylenetetrahydrofolate reductase (NAD(P)H) activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables methylenetetrahydrofolate reductase (NAD(P)H) activity	ISO Inferred from Sequence Orthology more info
enables modified amino acid binding	ISO Inferred from Sequence Orthology more info
enables oxidoreductase activity	IEA Inferred from Electronic Annotation more info
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of heterochromatin organization	ISO Inferred from Sequence Orthology more info
involved_in homocysteine metabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within metabolic process	IEA Inferred from Electronic Annotation more info
involved_in methionine biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within methionine biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in methionine metabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of neural tube closure	ISO Inferred from Sequence Orthology more info
involved_in tetrahydrofolate interconversion	IBA Inferred from Biological aspect of Ancestor more info
involved_in tetrahydrofolate interconversion	ISO Inferred from Sequence Orthology more info
involved_in tetrahydrofolate metabolic process	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: methylenetetrahydrofolate reductase (NADPH)

Names: 5,10-methylenetetrahydrofolate reductase

NP_001155270.1

EC 1.5.1.53

NP_034970.2

EC 1.5.1.53

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001161798.1 → NP_001155270.1 methylenetetrahydrofolate reductase (NADPH) isoform a

See identical proteins and their annotated locations for NP_001155270.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (a).

Source sequence(s)

AK150159, BB726553, BC100550

Consensus CDS

CCDS51376.1

UniProtKB/TrEMBL

A2A7F7, Q3UDB2

Related

ENSMUSP00000069774.9, ENSMUST00000069604.15

Conserved Domains (1) summary

cl00246
Location:100 → 666

MTHFR; Methylenetetrahydrofolate reductase (MTHFR). 5,10-Methylenetetrahydrofolate is reduced to 5-methyltetrahydrofolate by methylenetetrahydrofolate reductase, a cytoplasmic, NAD(P)-dependent enzyme. 5-methyltetrahydrofolate is utilized by methionine synthase ...
NM_010840.3 → NP_034970.2 methylenetetrahydrofolate reductase (NADPH) isoform b

See identical proteins and their annotated locations for NP_034970.2

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and uses a downstream translational start codon, compared to variant 1. The encoded isoform (b) is shorter at the N-terminus, compared to isoform a.

Source sequence(s)

AK030192, AL606929, BB726553, BC100550

Consensus CDS

CCDS18929.1

UniProtKB/Swiss-Prot

Q8CDE4, Q9WU20

UniProtKB/TrEMBL

F6Z4F8

Related

ENSMUSP00000095395.5, ENSMUST00000097788.11

Conserved Domains (1) summary

cl00246
Location:59 → 625

MTHFR; Methylenetetrahydrofolate reductase (MTHFR). 5,10-Methylenetetrahydrofolate is reduced to 5-methyltetrahydrofolate by methylenetetrahydrofolate reductase, a cytoplasmic, NAD(P)-dependent enzyme. 5-methyltetrahydrofolate is utilized by methionine synthase ...

RNA

NR_027809.1 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (3) lacks a segment of the 3' region, compared to variant 1. This variant has an intact ORF compared to variant 1, but it is represented as non-coding because it is a nonsense-mediated mRNA decay (NMD) candidate due to the presence of an intron at the 3' end.

Source sequence(s)

AK149795, AK150159, BB726553, BC100550