Seroatlas · Human Serome Atlas

MTHFR

Methylenetetrahydrofolate reductase (NADPH)

Also known as: MTHR_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P42898
Gene
MTHFR
Ensembl
ENSG00000177000
Chromosome
1
Canonical length
656 aa
Protein class
Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins
Subcellular location
Cell Junctions,Centrosome,Basal body
Quaternary structure
Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

656 residues, UniProt reviewed canonical sequence.

>P42898|MTHFR
     1  MVNEARGNSS LNPCLEGSAS SGSESSKDSS RCSTPGLDPE RHERLREKMR RRLESGDKWF
    61  SLEFFPPRTA EGAVNLISRF DRMAAGGPLY IDVTWHPAGD PGSDKETSSM MIASTAVNYC
   121  GLETILHMTC CRQRLEEITG HLHKAKQLGL KNIMALRGDP IGDQWEEEEG GFNYAVDLVK
   181  HIRSEFGDYF DICVAGYPKG HPEAGSFEAD LKHLKEKVSA GADFIITQLF FEADTFFRFV
   241  KACTDMGITC PIVPGIFPIQ GYHSLRQLVK LSKLEVPQEI KDVIEPIKDN DAAIRNYGIE
   301  LAVSLCQELL ASGLVPGLHF YTLNREMATT EVLKRLGMWT EDPRRPLPWA LSAHPKRREE
   361  DVRPIFWASR PKSYIYRTQE WDEFPNGRWG NSSSPAFGEL KDYYLFYLKS KSPKEELLKM
   421  WGEELTSEES VFEVFVLYLS GEPNRNGHKV TCLPWNDEPL AAETSLLKEE LLRVNRQGIL
   481  TINSQPNING KPSSDPIVGW GPSGGYVFQK AYLEFFTSRE TAEALLQVLK KYELRVNYHL
   541  VNVKGENITN APELQPNAVT WGIFPGREII QPTVVDPVSF MFWKDEAFAL WIERWGKLYE
   601  EESPSRTIIQ YIHDNYFLVN LVDNDFPLDN CLWQVVEDTL ELLNRPTQNA RETEAP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MTHFR can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Intracellular
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.27
Highest tissue expression
51 nTPM

Expression across tissuesHPA

Tissue

  • epididymis: 51 nTPM
  • bone marrow: 27 nTPM
  • heart muscle: 24 nTPM
  • ovary: 19 nTPM
  • skeletal muscle: 17 nTPM
  • spleen: 16 nTPM

Single-cell type

  • epididymal principal cells: 152 nCPM
  • pancreatic acinar cells: 110 nCPM
  • proximal tubule cells: 96 nCPM
  • cardiomyocytes: 91 nCPM
  • endometrial glandular cells: 88 nCPM
  • endometrial luminal cells: 71 nCPM

Immune cell

  • non-classical monocyte: 6.2 nTPM
  • intermediate monocyte: 4.3 nTPM
  • gdT-cell: 2.7 nTPM
  • neutrophil: 2.5 nTPM
  • classical monocyte: 2.3 nTPM
  • naive B-cell: 2.3 nTPM

Brain region

  • cerebellum: 49 nTPM
  • hippocampal formation: 44 nTPM
  • cerebral cortex: 44 nTPM
  • medulla oblongata: 44 nTPM
  • pons: 42 nTPM
  • white matter: 40 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MTHFR.

Disease | AllUniProt

Conditions MTHFR is implicated in, by any mechanism.

  • Homocystinuria due to deficiency of N(5,10)-methylenetetrahydrofolate reductase activity (MTHFRD) MIM:236250
  • Ischemic stroke (ISCHSTR) MIM:601367
  • Neural tube defects, folate-sensitive (NTDFS) MIM:601634
  • Schizophrenia (SCZD) MIM:181500

Disease | GeneticClinVar

202 pathogenic / likely-pathogenic of 982 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.92
gnomAD pLI
0
gnomAD missense Z
0.9
DepMap mean gene effect
0.02
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

  • FAD-linked oxidoreductase-like
  • Methylenetetrahydrofolate reductase-like, catalytic domain
  • Methylenetetrahydrofolate reductase, catalytic domain, eukaryotes
  • MTHFR, SAM-binding regulatory domain
  • Methylenetetrahydrofolate reductase
  • MTHFR, SAM-binding regulatory domain

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads MTHFR as an antibody target. Whether an autoantibody or antibody against MTHFR could matter depends on whether native MTHFR is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

MTHFR is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label MTHFR as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/MTHFR. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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