MTHFD1 - methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 Gene

Also Known as CIMAH; MTHFC; MTHFD

Species: Homo sapiens

Gene Type: protein coding

Gene ID: 4522

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	References	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	References	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

Clinical Phase
Pre-clinical Phase

Clinical Phase

Bioactive Molecules (1)

Cat. No.	Product Name	Effect	Purity	Phase
HY-155950	TH9619		99.33%	Phase 2

Pre-clinical Phase

Bioactive Molecules (20)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-130251	DS18561882		99.95%	Unkown
HY-101943	LY 345899		98.0%	Unkown
HY-131943	DS44960156	Inhibitor	≥99.0%	Unkown
HY-155219	TH9028		/	Unkown
HY-149825	MTHFD2-IN-1	Inhibitor	/	Unkown
HY-149826	MTHFD2-IN-2	Inhibitor	/	Unkown
HY-149827	MTHFD2-IN-3	Inhibitor	/	Unkown
HY-149828	MTHFD2-IN-4	Inhibitor	/	Unkown
HY-149828A	MTHFD2-IN-4 sodium	Inhibitor	/	Unkown
HY-170361	MTHFD2-IN-5	Inhibitor	/	Unkown
HY-172910	MTHFD2-IN-6		/	Unkown
HY-182355	MTHFD2-IN-7	Inhibitor	/	Unkown
HY-182356	MTHFD1/2-IN-1	Inhibitor	/	Unkown
HY-RS08774	MTHFD1 Human Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-RS08775	MTHFD1L Human Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-148014	TH7299		/	Unkown
HY-RS17098	Mthfd1 Mouse Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-RS20214	Mthfd1l Mouse Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-RS23542	Mthfd1 Rat Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-RS26720	Mthfd1l Rat Pre-designed siRNA Set A	Pre-designed Set	/	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
Others	MTHFD1	NCBI