MTHFS

Protein identityUniProt · HPA

UniProt accession

P49914

Gene

MTHFS

Ensembl

ENSG00000136371

Chromosome

15

Canonical length

203 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Cytosol

OverviewNCBI Gene

The protein encoded by this gene is an enzyme that catalyzes the conversion of 5-formyltetrahydrofolate to 5,10-methenyltetrahydrofolate, a precursor of reduced folates involved in 1-carbon metabolism. An increased activity of the encoded protein can result in an increased folate turnover rate and folate depletion. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

Canonical amino-acid sequenceUniProt

203 residues, UniProt reviewed canonical sequence.

>P49914|MTHFS
     1  MAAAAVSSAK RSLRGELKQR LRAMSAEERL RQSRVLSQKV IAHSEYQKSK RISIFLSMQD
    61  EIETEEIIKD IFQRGKICFI PRYRFQSNHM DMVRIESPEE ISLLPKTSWN IPQPGEGDVR
   121  EEALSTGGLD LIFMPGLGFD KHGNRLGRGK GYYDAYLKRC LQHQEVKPYT LALAFKEQIC
   181  LQVPVNENDM KVDEVLYEDS STA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MTHFS 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

169 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MTHFS.

Disease | AllUniProt

Conditions MTHFS is implicated in, by any mechanism.

• Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination (NEDMEHM) MIM:618367

Disease | GeneticClinVar

5 pathogenic / likely-pathogenic of 53 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination

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)

1.55

gnomAD pLI

0

gnomAD missense Z

0.55

DepMap mean gene effect

0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• folic acid metabolic process
• formate metabolic process
• glutamate metabolic process
• tetrahydrofolate interconversion
• tetrahydrofolate metabolic process
• folic acid catabolic process
• folic acid-containing compound biosynthetic process

Molecular functions

• ATP binding
• folic acid binding
• metal ion binding
• 5-formyltetrahydrofolate cyclo-ligase activity

Cellular components

• cytoplasm
• cytosol
• mitochondrial matrix
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• 5-formyltetrahydrofolate cyclo-ligase
• 5-formyltetrahydrofolate cyclo-ligase-like domain superfamily
• NagB/RpiA transferase-like
• 5-formyltetrahydrofolate cyclo-ligase family

KeywordsUniProt

• Acetylation
• ATP-binding
• Cytoplasm
• Epilepsy
• Folate-binding
• Ligase
• Magnesium
• Metal-binding
• Nucleotide-binding