MTHFS - methenyltetrahydrofolate synthetase Gene

Also Known as NEDMEHM; HsT19268

Species: Homo sapiens

Gene Type: protein coding

Gene ID: 10588

About MTHFS

Cytogenetic location: 15q25.1 Genomic coordinates (GRCh38): 15:79,843,547-79,897,285 (from NCBI)

This gene has 4 transcripts (splice variants), 206 orthologues, 1 paralogue and is associated with 2 phenotypes. Broad expression in liver (RPKM 20.2), kidney (RPKM 14.0) and 23 other tissues.

Summary

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]

MTHFS Products (2)

mRNA	Protein	Name
NM_001199758.1	NP_001186687.1	5-formyltetrahydrofolate cyclo-ligase isoform b
NM_006441.4	NP_006432.1	5-formyltetrahydrofolate cyclo-ligase isoform a

Gene Ontology

Molecular Function
Biological Process
Cellular Component

Molecular Function GO Annotation	Evidence	References	Source
enables 5-formyltetrahydrofolate cyclo-ligase activity	IDA IDA: Inferred from direct assay	7766710	GOA
enables 5-formyltetrahydrofolate cyclo-ligase activity	IMP IMP: Inferred from mutant phenotype	12764149	GOA
enables ATP binding	IDA IDA: Inferred from direct assay	19738041	GOA
enables folic acid binding	IDA IDA: Inferred from direct assay	7766710	GOA
enables protein binding	IPI IPI: Inferred from physical interaction	28514442	GOA

Biological Process GO Annotation	Evidence	References	Source
involved in folic acid catabolic process	IMP IMP: Inferred from mutant phenotype	12764149	GOA
involved in glutamate metabolic process	IMP IMP: Inferred from mutant phenotype	12764149	GOA
involved in tetrahydrofolate interconversion	IMP IMP: Inferred from mutant phenotype	12764149	GOA
involved in tetrahydrofolate metabolic process	IDA IDA: Inferred from direct assay	7766710	GOA

Cellular Component GO Annotation	Evidence	References	Source
located in cytoplasm	IDA IDA: Inferred from direct assay	7766710	GOA
located in mitochondrial matrix	IDA IDA: Inferred from direct assay	7766710	GOA

EXP: Inferred from Experiment IDA: Inferred from direct assay IPI: Inferred from physical interaction IMP: Inferred from mutant phenotype IGI: Inferred from genetic interaction IEP: Inferred from expression pattern

MTHFS Protein Structure

5-FTHF_cyc-lig

0
100
203 a.a.

Protein Preferred Names	Protein Names
5-formyltetrahydrofolate cyclo-ligase	5,10-methenyltetrahydrofolate synthetase (5-formyltetrahydrofolate cyclo-ligase)

MTHFS Protein-protein interaction Information

Type	Protein Name	Protein ID	Interactor	Interactor Species	Interactor ID	Detection Method	References
Intra	MTHFS	P49914	PLCL2	Homo sapiens	Q9UPR0	Anti Tag CoIP	33961781
Intra	MTHFS	P49914	PLCL2	Homo sapiens	Q9UPR0	Anti Tag CoIP	28514442

Cross: Cross-species interaction Intra: Intraspecies interaction

Recombinant MTHFS Proteins

Cat. No.	Product Name	Accession	Purity
HY-P70362	MTHFS Protein, Human (His)	P49914-1 (M1-A203)	≥ 95%, as determined by reducing SDS-PAGE.

Related Diseases

Diseases	Alias
Neurodevelopmental Disorder With Microcephaly, Epilepsy, And Hypomyelination	NEDMEHM Mthfs-Related Developmental Delay-Microcephaly-Short Stature-Epilepsy Syndrome
Cutis Laxa, Autosomal Dominant 1	Cutis Laxa, Autosomal Dominant Autosomal Dominant Cutis Laxa ADCL1 Adcl Autosomal Dominant Cutis Laxa 1 Cutis Laxa, Autosomal Dominant, 1 Cutis Laxa, Autosomal Dominant, Type 1
Cutis Laxa, Autosomal Dominant 3	ADCL3 Autosomal Dominant Cutis Laxa 3 Cutis Laxa, Autosomal Dominant, 3
Cutis Laxa, Autosomal Dominant 2	ADCL2 Autosomal Dominant Cutis Laxa 2 Cutis Laxa, Autosomal Dominant, 2 Cutis Laxa, Autosomal Dominant, Type 2
Frank-Ter Haar Syndrome	Ter Haar Syndrome Borrone Dermatocardioskeletal Syndrome FTHS Autosomal Recessive Melnick-Needles Syndrome Borrone Di Rocco Crovato Syndrome Megalocornea, Multiple Skeletal Anomalies, And Developmental Delay Melnick-Needles Syndrome, Autosomal Recessive, Formerly Frank Ter Haar Syndrome
Focal Dermal Hypoplasia	Goltz Syndrome Goltz-Gorlin Syndrome FDH FODH Dhof Goltz Gorlin Syndrome Hypoplasia, Dermal, Focal
Microcephaly	Microencephaly Microcephalus Microcephalic Nanocephaly Congenital Microcephaly Brain Hypoplasia Brain Nondevelopment Cephalic Hypoplasia Undeveloped Cerebrum Undeveloped Brain Micrencephalon Micrencephaly
Epilepsy	Epilepsy Syndrome Epileptic Syndrome Epilepsies Symptomatic Epilepsies Post Traumatic Epilepsy Traumatic Epilepsy Traumatic Epileptic Epilepsy Due To Hippocampal Sclerosis Epilepsy With Ammon'S Horn Sclerosis Epilepsy Due To Cortical Dysplasia Epilepsy Due To Neuronal Migration Disorders
Otopalatodigital Syndrome Spectrum Disorder	Opd Spectrum Disorder Opsd Fronto-Otopalatodigital Osteodysplasia

Diseases	Alias
Waldenstroem'S Macroglobulinemia	Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma

Related Agents

Approval
Clinical Phase
Pre-clinical Phase

Approval

Bioactive Molecules (1)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-14781	Levomefolic acid		98.55%	Unkown

Clinical Phase

Bioactive Molecules (1)

Cat. No.	Product Name	Effect	Purity	Phase
HY-109051C	Arfolitixorin sulfate		/	Phase 3

Pre-clinical Phase

Bioactive Molecules (7)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-14781S1	Levomefolic acid-13C,d3		98.93%	Unkown
HY-109051	Arfolitixorin		/	Unkown
HY-14781S2	Levomefolic acid-13C5		/	Unkown
HY-RS08779	MTHFS Human Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-14781S3	Levomefolic acid-d3		/	Unkown
HY-RS20058	Mthfs Mouse Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-RS26562	Mthfs Rat Pre-designed siRNA Set A	Pre-designed Set	/	Unkown

Orthologs Information

Species	Symbol	Source	ID
Mus musculus	MTHFS	MGD	MGI:1340032
Macaca mulatta	MTHFS	VGNC	VGNC:84401
Rattus norvegicus	MTHFS	RGD	RGD:1306876
Others	MTHFS	NCBI