MTHFD1 - methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 Gene

Homo sapiens

Also known as CIMAH; MTHFC; MTHFD

Gene ID: 4522 | Gene type: protein coding

About MTHFD1

Cytogenetic location: 14q23.3 Genomic coordinates (GRCh38): 14:64,388,353-64,460,025 (from NCBI)

This gene has 34 transcripts (splice variants), 270 orthologues, 3 paralogues and is associated with 14 phenotypes. Broad expression in liver (RPKM 96.4), fat (RPKM 36.5) and 22 other tissues.

Summary

This gene encodes a protein that possesses three distinct enzymatic activities, 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase. Each of these activities catalyzes one of three sequential reactions in the interconversion of 1-carbon derivatives of tetrahydrofolate, which are substrates for methionine, thymidylate, and de novo purine syntheses. The trifunctional enzymatic activities are conferred by two major domains, an aminoterminal portion containing the dehydrogenase and cyclohydrolase activities and a larger synthetase domain. [provided by RefSeq, Jul 2008]

MTHFD1 Products(2)

mRNA	Protein	Name
NM_001364837.1	NP_001351766.1	C-1-tetrahydrofolate synthase, cytoplasmic isoform 2
NM_005956.4	NP_005947.3	C-1-tetrahydrofolate synthase, cytoplasmic isoform 1

Gene Ontology

Molecular Function
Biological Process

Molecular Function GO Annotation	Evidence	Reference	Source
enables formate-tetrahydrofolate ligase activity	IDA IDA: Inferred from direct assay	1881876	GOA
enables methenyltetrahydrofolate cyclohydrolase activity	IDA IDA: Inferred from direct assay	1881876	GOA
enables methylenetetrahydrofolate dehydrogenase (NADP+) activity	IDA IDA: Inferred from direct assay	10828945	GOA
enables methylenetetrahydrofolate dehydrogenase [NAD(P)+] activity	IDA IDA: Inferred from direct assay	1881876	GOA
enables protein binding	IPI IPI: Inferred from physical interaction	24169621	GOA

Biological Process GO Annotation	Evidence	Reference	Source
involved in 10-formyltetrahydrofolate biosynthetic process	IDA IDA: Inferred from direct assay	1881876	GOA
involved in methionine biosynthetic process	IMP IMP: Inferred from mutant phenotype	25633902	GOA
involved in one-carbon metabolic process	IMP IMP: Inferred from mutant phenotype	25633902	GOA
acts upstream of purine nucleotide biosynthetic process	IMP IMP: Inferred from mutant phenotype	18767138	GOA
involved in serine family amino acid biosynthetic process	IMP IMP: Inferred from mutant phenotype	25633902	GOA
involved in tetrahydrofolate interconversion	IDA IDA: Inferred from direct assay	1881876	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

MTHFD1 Protein Structure

THF_DHG_CYH

THF_DHG_CYH_C

FTHFS

0
200
400
600
800
935 a.a.

Protein Preferred Names

Protein Names

C-1-tetrahydrofolate synthase, cytoplasmic

5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methylenetetrahydrofolate cyclohydrolase, 10-formyltetrahydrofolate synthetase

Related Diseases

Diseases

Alias

Combined Immunodeficiency And Megaloblastic Anemia With Or Without Hyperhomocysteinemia

CIMAH

Methylenetetrahydrofolate Dehydrogenase 1 Deficiency

Neural Tube Defects, Folate-Sensitive

Neural Tube Defects, Folate-Sensitive, Susceptibility To	Neural Tube Defect, Folate-Sensitive
NTDFS	Ntd, Folate-Sensitive
Neural Tube Defects, Susceptibility To	Neural Tube Defects

Severe Combined Immunodeficiency

Scid	Severe Combined Immunodeficiency Disease
Combined T And B Cell Inborn Immunodeficiency	Immunodeficiency, Severe Combined
Scid - [Severe Combined Immunodeficiencies]

Upper Thoracic Spina Bifida Cystica

Cervicothoracic Spina Bifida Cystica

Cervical Spina Bifida Cystica

Lumbosacral Spina Bifida Cystica

Thoracolumbosacral Spina Bifida Cystica

Total Spina Bifida Cystica

Upper Thoracic Spina Bifida Aperta

Thoracolumbosacral Spina Bifida Aperta

Lumbosacral Spina Bifida Aperta

Cervical Spina Bifida Aperta

Spina Bifida Aperta Of Cervical Spine

Cervicothoracic Spina Bifida Aperta

Total Spina Bifida Aperta

Neural Tube Defects

Spina Bifida	Neural Tube Defect
NTD	Neural Tube Defects, Susceptibility To
Spinal Dysraphism	Spina Bifida, Susceptibility To
Rachischisis	Cleft Spine
Open Spine	Hydrocele Spinalis
Neural Tube Defect Nos	Sb - [Spina Bifida]
Spinal Hernia Nos	Spinal Fissure Nos

Megaloblastic Anemia

Imerslund-Grasbeck Syndrome	Igs
Defect Of Enterocyte Intrinsic Factor Receptor	Enterocyte Cobalamin Malabsorption
Familial Megaloblastic Anemia	Megaloblastic Anemia 1
Selective Cobalamin Malabsorption With Proteinuria	Imerslund-Gräsbeck Syndrome
Anemia, Megaloblastic	Grasbeck-Imerslund Syndrome
Megaloblastic Anaemia	Mga1 Norwegian Type
Recessive Hereditary Megaloblastic Anaemia 1	Recessive Hereditary Megaloblastic Anemia 1
Rh-Mga1	Gräsbeck-Imerslund Disease
Pernicious Anemia, Juvenile, Due To Selective Intestinal Malabsorption Of Vitamin B12, With Proteinuria	Juvenile Pernicious Anemia With Proteinuria Due To Selective Intestinal Malabsorption Of Vitamin B12
Anemia Megaloblastic	Megaloblastic Anemia Due To Inborn Errors Of Metabolism
3-@Methylglutaconic Aciduria, Type I

Hyperhomocysteinemia

Combined Immunodeficiency

Combined T Cell And B Cell Immunodeficiency	Congenital Combined Immunodeficiency
Syndrome With Combined Immunodeficiency	Combined T And B Cell Immunodeficiency
Combined Immunity Deficiency	Combined Immunodeficiency Syndrome
Combined T-Cell And B-Cell Immunodeficiency	Lymphopenic Agammaglobulinaemia

Myelomeningocele

Meningomyelocele

Anencephaly

Aprosencephaly	Anencephalus
Congenital Absence Of Brain	Absence Of A Large Part Of The Brain And The Skull
Anencephalia	Anencephalic Monster
Brain Absence	Brain Agenesis
Brain Aplasia	Absent Brain
Anencephalic	Congenital Absence Of Cerebrum
Congenital Hemicrania	Incomplete Anencephaly

Choline Deficiency Disease

Choline Deficiency

Childhood Acute Lymphocytic Leukemia

Childhood Acute Lymphoblastic Leukemia	Childhood All
Pediatric Acute Lymphoblastic Leukemia	Lymphoblastic Leukemia Acute Childhood

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

Spina Bifida Occulta

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

Tethered Spinal Cord Syndrome

Spinal Dysraphism	Tethered Cord Syndrome
Occult Spinal Dysraphism	Occult Spinal Dysraphism Sequence
Segmental Vertebral Anomalies	Tethered Spinal Cord Disease
Tethered Cord	Spina Bifida Occulta
Cryptomerorachischisis	Spina Bifida Occulta With Tethered Spinal Cord
Sbo - [Spina Bifida Occulta]

Colorectal Cancer

Colon Cancer	Colorectal Carcinoma
Colon Carcinoma	Colorectal Cancer, Susceptibility To
Carcinoma Of Colon	CRC
Colorectal Cancer With Chromosomal Instability, Somatic	Colon Cancer, Somatic
Colon Cancer, Susceptibility To	Colonic Neoplasms
Colorectal Neoplasms	Colorectal Cancer, Somatic
Colon Cancer, Advanced, Somatic	Colonic Carcinoma
Colorectal Carcinomas	Colon Cancers
Colorectal Cancers	Cancer, Colorectal, Somatic
Cancer, Colon	Cancer, Colorectal, Susceptibility To
Colorectal Neoplasm	Colonic Neoplasm
Malignant Tumor Of Colon

Folate Malabsorption, Hereditary

Hereditary Folate Malabsorption	Congenital Defect Of Folate Absorption
Congenital Folate Malabsorption	Folic Acid Transport Defect
HFM

Heart Disease

Heart Failure	Congenital Heart Disease
Heart Diseases	Congenital Heart Defects
Congenital Heart Defect	Heart Malformation
Congenital Anomaly Of Heart	Heart Defect
Heart-Congenital Defect	Congenital Heart Disorder
Heart Defects Congenital	Heart Defects, Congenital
Heart Defects	Heart Disease, Congenital
Disease, Heart, Congenital	Congestive Heart Failure

Cleft Palate, Isolated

Cleft Palate	Isolated Cleft Palate
CPI	Cp
Palatoschisis	Cleft Palate Isolated
Uranostaphyloschisis	Congenital Fissure Of Palate
Cleft Of Secondary Palate

Type 2 Diabetes Mellitus

Insulin Resistance	NIDDM
Type 2 Diabetes	Diabetes Mellitus, Non-Insulin-Dependent
T2D	Noninsulin-Dependent Diabetes Mellitus
Diabetes Mellitus, Type Ii	Maturity-Onset Diabetes
Insulin Resistance, Severe, Digenic	Diabetes Mellitus, Type 2
Diabetes Mellitus, Noninsulin-Dependent	Diabetes Mellitus, Noninsulin-Dependent, Association With
Diabetes Mellitus, Noninsulin-Dependent, Late Onset	Hypertension, Insulin Resistance-Related, Susceptibility To
Insulin Resistance, Susceptibility To	Non-Insulin-Dependent Diabetes Mellitus
Type Ii Diabetes Mellitus	Adult-Onset Diabetes Mellitus
Maturity-Onset Diabetes Mellitus	Diabetes Mellitus Type 2
Type Ii Diabetes	Type 2 Diabetes Mellitus, Susceptibility To
Diabetes, Type 2	Diabetes Mellitus, Noninsulin-Dependent, Susceptibility To
Diabetes Mellitus, Non-Insulin-Dependent, Susceptibility To	Diabetes Mellitus, Type 2, Susceptibility To
Diabetes Mellitus, Noninsulin-Dependent, 2	Diabetes Mellitus, Type Ii, Susceptibility To
Hypertension, Insulin Resistance-Related	Adult-Onset Diabetes
Aodm	Diabetes Mellitus, Adult-Onset
Diabetes Mellitus Type Ii	Diabetes Mellitus Type 2, Susceptibility To
Diabetes, Type Ii, Susceptibility To	Diabetes Type 2
Diabetes Mellitus	Adult Onset Diabetes
Maturity Onset Diabetes	Nonketotic Diabetes
Non-Insulin Dependent Diabetes Mellitus	T2dm - [Type 2 Diabetes Mellitus]
Niddm - [Non Insulin Dependent Diabetes Mellitus]	Dm2
Dm Type Ii	Diabetic Type 2
Insulin Requiring Type 2 Diabetes	Noninsulin Dependent Diabetes
Non-Insulin-Dependent Diabetes Mellitus Without Complications	Diabetes Due To Insulin Secretory Defect
Diabetes Mellitus Due To Insulin Secretory Defect	Non-Insulin-Dependent Diabetes Of The Young
Senile Diabetes	Nonketotic Hyperglycaemia
Stable Diabetes

Orofacial Cleft

Cleft, Orofacial

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

Pre-clinical Phase

Bioactive Molecules (7)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-130251	DS18561882		99.87%	Unkown
HY-101943	LY 345899		≥98.0%	Unkown
HY-131943	DS44960156		99.36%	Unkown
HY-155950	TH9619		99.33%	Unkown
HY-155219	TH9028	Inhibitor	/	Unkown
HY-RS08774	MTHFD1 Human Pre-designed siRNA Set A	Pre-designed Sets	/	Unkown
HY-RS08775	MTHFD1L Human Pre-designed siRNA Set A	Pre-designed Sets	/	Unkown

Orthologs Information

Species	Symbol	Source	ID
Mus musculus	MTHFD1	MGD	MGI:1342005
Canis familiaris	MTHFD1	VGNC	VGNC:43472
Macaca mulatta	MTHFD1	VGNC	VGNC:84399
Rattus norvegicus	MTHFD1	RGD	RGD:708531
Bos taurus	MTHFD1	VGNC	VGNC:31730
Felis catus	MTHFD1	VGNC	VGNC:80909