MTHFD1L (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 like)

Gene

• Entrez ID: 25902
• Gene name: Methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 like
• Gene symbol: MTHFD1L
• Synonyms (NCBI Gene): FTHFSDC1, MTC1THFS, dJ292B18.2
• Chromosome: 6
• Chromosome location: 6q25.1
• Summary: The protein encoded by this gene is involved in the synthesis of tetrahydrofolate (THF) in the mitochondrion. THF is important in the de novo synthesis of purines and thymidylate and in the regeneration of methionine from homocysteine. Several transcript

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT031875	hsa-miR-16-5p	Proteomics	18668040
MIRT041690	hsa-miR-484	CLASH	23622248
MIRT040048	hsa-miR-615-3p	CLASH	23622248
MIRT036804	hsa-miR-887-3p	CLASH	23622248
MIRT717592	hsa-miR-4760-3p	HITS-CLIP	19536157
MIRT717591	hsa-miR-3145-5p	HITS-CLIP	19536157
MIRT717590	hsa-miR-508-5p	HITS-CLIP	19536157
MIRT717589	hsa-miR-181a-2-3p	HITS-CLIP	19536157
MIRT717588	hsa-miR-1273g-3p	HITS-CLIP	19536157
MIRT717587	hsa-miR-6509-3p	HITS-CLIP	19536157
MIRT717592	hsa-miR-4760-3p	HITS-CLIP	19536157
MIRT717591	hsa-miR-3145-5p	HITS-CLIP	19536157
MIRT717590	hsa-miR-508-5p	HITS-CLIP	19536157
MIRT717589	hsa-miR-181a-2-3p	HITS-CLIP	19536157
MIRT717588	hsa-miR-1273g-3p	HITS-CLIP	19536157
MIRT717587	hsa-miR-6509-3p	HITS-CLIP	19536157
MIRT710150	hsa-miR-133a-5p	HITS-CLIP	19536157
MIRT710149	hsa-miR-6131	HITS-CLIP	19536157
MIRT710148	hsa-miR-138-5p	HITS-CLIP	19536157
MIRT710147	hsa-miR-92a-1-5p	HITS-CLIP	19536157
MIRT710146	hsa-miR-518d-5p	HITS-CLIP	19536157
MIRT710145	hsa-miR-518e-5p	HITS-CLIP	19536157
MIRT710144	hsa-miR-518f-5p	HITS-CLIP	19536157
MIRT710143	hsa-miR-519a-5p	HITS-CLIP	19536157
MIRT710142	hsa-miR-519b-5p	HITS-CLIP	19536157
MIRT710141	hsa-miR-519c-5p	HITS-CLIP	19536157
MIRT710140	hsa-miR-520c-5p	HITS-CLIP	19536157
MIRT710139	hsa-miR-522-5p	HITS-CLIP	19536157
MIRT710138	hsa-miR-523-5p	HITS-CLIP	19536157
MIRT710137	hsa-miR-526a	HITS-CLIP	19536157
MIRT710136	hsa-miR-4777-5p	HITS-CLIP	19536157
MIRT710135	hsa-miR-29b-2-5p	HITS-CLIP	19536157
MIRT667336	hsa-miR-3622a-5p	HITS-CLIP	23824327
MIRT667335	hsa-miR-564	HITS-CLIP	23824327
MIRT667334	hsa-miR-4284	HITS-CLIP	23824327
MIRT667333	hsa-miR-24-3p	HITS-CLIP	23824327
MIRT440206	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT440206	hsa-miR-218-5p	HITS-CLIP	23212916
MIRT717592	hsa-miR-4760-3p	HITS-CLIP	19536157
MIRT717591	hsa-miR-3145-5p	HITS-CLIP	19536157
MIRT717590	hsa-miR-508-5p	HITS-CLIP	19536157
MIRT717589	hsa-miR-181a-2-3p	HITS-CLIP	19536157
MIRT717588	hsa-miR-1273g-3p	HITS-CLIP	19536157
MIRT717587	hsa-miR-6509-3p	HITS-CLIP	19536157
MIRT717592	hsa-miR-4760-3p	HITS-CLIP	19536157
MIRT717591	hsa-miR-3145-5p	HITS-CLIP	19536157
MIRT717590	hsa-miR-508-5p	HITS-CLIP	19536157
MIRT717589	hsa-miR-181a-2-3p	HITS-CLIP	19536157
MIRT717588	hsa-miR-1273g-3p	HITS-CLIP	19536157
MIRT717587	hsa-miR-6509-3p	HITS-CLIP	19536157
MIRT710150	hsa-miR-133a-5p	HITS-CLIP	19536157
MIRT710149	hsa-miR-6131	HITS-CLIP	19536157
MIRT710148	hsa-miR-138-5p	HITS-CLIP	19536157
MIRT710147	hsa-miR-92a-1-5p	HITS-CLIP	19536157
MIRT710146	hsa-miR-518d-5p	HITS-CLIP	19536157
MIRT710145	hsa-miR-518e-5p	HITS-CLIP	19536157
MIRT710144	hsa-miR-518f-5p	HITS-CLIP	19536157
MIRT710143	hsa-miR-519a-5p	HITS-CLIP	19536157
MIRT710142	hsa-miR-519b-5p	HITS-CLIP	19536157
MIRT710141	hsa-miR-519c-5p	HITS-CLIP	19536157
MIRT710140	hsa-miR-520c-5p	HITS-CLIP	19536157
MIRT710139	hsa-miR-522-5p	HITS-CLIP	19536157
MIRT710138	hsa-miR-523-5p	HITS-CLIP	19536157
MIRT710137	hsa-miR-526a	HITS-CLIP	19536157
MIRT710136	hsa-miR-4777-5p	HITS-CLIP	19536157
MIRT710135	hsa-miR-29b-2-5p	HITS-CLIP	19536157
MIRT667336	hsa-miR-3622a-5p	HITS-CLIP	23824327
MIRT667335	hsa-miR-564	HITS-CLIP	23824327
MIRT667334	hsa-miR-4284	HITS-CLIP	23824327
MIRT667333	hsa-miR-24-3p	HITS-CLIP	23824327
MIRT755618	hsa-miR-9-5p	Luciferase reporter assay, Western blotting	37799388
MIRT1163165	hsa-miR-106a	CLIP-seq
MIRT1163166	hsa-miR-106b	CLIP-seq
MIRT1163167	hsa-miR-17	CLIP-seq
MIRT1163168	hsa-miR-188-5p	CLIP-seq
MIRT1163169	hsa-miR-20a	CLIP-seq
MIRT1163170	hsa-miR-20b	CLIP-seq
MIRT1163171	hsa-miR-2114	CLIP-seq
MIRT1163172	hsa-miR-3163	CLIP-seq
MIRT1163173	hsa-miR-3609	CLIP-seq
MIRT1163174	hsa-miR-377	CLIP-seq
MIRT1163175	hsa-miR-4509	CLIP-seq
MIRT1163176	hsa-miR-4540	CLIP-seq
MIRT1163177	hsa-miR-4744	CLIP-seq
MIRT1163178	hsa-miR-4796-3p	CLIP-seq
MIRT1163179	hsa-miR-4799-5p	CLIP-seq
MIRT1163180	hsa-miR-483-3p	CLIP-seq
MIRT1163181	hsa-miR-519d	CLIP-seq
MIRT1163182	hsa-miR-543	CLIP-seq
MIRT1163183	hsa-miR-548ah	CLIP-seq
MIRT1163184	hsa-miR-93	CLIP-seq
MIRT1163185	hsa-miR-936	CLIP-seq
MIRT2275943	hsa-miR-103a	CLIP-seq
MIRT2275944	hsa-miR-107	CLIP-seq
MIRT2275945	hsa-miR-1184	CLIP-seq
MIRT2275946	hsa-miR-153	CLIP-seq
MIRT2275947	hsa-miR-4418	CLIP-seq
MIRT2275948	hsa-miR-448	CLIP-seq
MIRT2275949	hsa-miR-4659a-3p	CLIP-seq
MIRT2275950	hsa-miR-4659b-3p	CLIP-seq
MIRT2275951	hsa-miR-509-3-5p	CLIP-seq
MIRT2275952	hsa-miR-509-5p	CLIP-seq
MIRT2275953	hsa-miR-515-5p	CLIP-seq
MIRT2275954	hsa-miR-545	CLIP-seq
MIRT2275955	hsa-miR-548p	CLIP-seq
MIRT2275956	hsa-miR-942	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0001843	Process	Neural tube closure	IEA
GO:0001843	Process	Neural tube closure	ISS
GO:0004329	Function	Formate-tetrahydrofolate ligase activity	IBA
GO:0004329	Function	Formate-tetrahydrofolate ligase activity	IDA	12937168
GO:0004329	Function	Formate-tetrahydrofolate ligase activity	IEA
GO:0004488	Function	Methylenetetrahydrofolate dehydrogenase (NADP+) activity	IEA
GO:0005524	Function	ATP binding	IDA	16171773
GO:0005524	Function	ATP binding	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA	12937168
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0005829	Component	Cytosol	IBA
GO:0006730	Process	One-carbon metabolic process	IEA
GO:0006760	Process	Folic acid-containing compound metabolic process	IDA	12937168
GO:0009257	Process	10-formyltetrahydrofolate biosynthetic process	IBA
GO:0009257	Process	10-formyltetrahydrofolate biosynthetic process	IDA	12937168
GO:0015942	Process	Formate metabolic process	IDA	16171773
GO:0015942	Process	Formate metabolic process	IEA
GO:0015943	Process	Formate biosynthetic process	IEA
GO:0016020	Component	Membrane	HDA	19946888
GO:0016874	Function	Ligase activity	IEA
GO:0035999	Process	Tetrahydrofolate interconversion	IEA
GO:0042803	Function	Protein homodimerization activity	IDA	16171773
GO:0046394	Process	Carboxylic acid biosynthetic process	IEA
GO:0046653	Process	Tetrahydrofolate metabolic process	IEA
GO:0048702	Process	Embryonic neurocranium morphogenesis	IEA
GO:0048702	Process	Embryonic neurocranium morphogenesis	ISS
GO:0048703	Process	Embryonic viscerocranium morphogenesis	IEA
GO:0048703	Process	Embryonic viscerocranium morphogenesis	ISS

Other IDs

• MIM: 611427
• HGNC: 21055
• e!Ensembl: ENSG00000120254

Protein

• UniProt ID: Q6UB35
• Protein name: Monofunctional C1-tetrahydrofolate synthase, mitochondrial (EC 6.3.4.3) (Formyltetrahydrofolate synthetase)
• Protein function: May provide the missing metabolic reaction required to link the mitochondria and the cytoplasm in the mammalian model of one-carbon folate metabolism complementing thus the enzymatic activities of MTHFD2. {ECO:0000250, ECO:0000269|PubMed:1617177
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00763	THF_DHG_CYH	70 → 180	Tetrahydrofolate dehydrogenase/cyclohydrolase, catalytic domain	Domain
  PF02882	THF_DHG_CYH_C	183 → 309	Tetrahydrofolate dehydrogenase/cyclohydrolase, NAD(P)-binding domain	Domain
  PF01268	FTHFS	360 → 978	Formate--tetrahydrofolate ligase	Family

• Tissue specificity: TISSUE SPECIFICITY: Detected in most tissues, highest expression found in placenta, thymus and brain. Low expression is found in liver and skeletal muscle. Up-regulated in colon adenocarcinoma. {ECO:0000269|PubMed:12937168, ECO:0000269|PubMed:15013446}.
• Sequence:

  MGTRLPLVLRQLRRPPQPPGPPRRLRVPCRASSGGGGGGGGGREGLLGQRRPQDGQARSS
  CSPGGRTPAARDSIVREVIQNSKEVLSLLQEKNPAFKPVLAIIQAGDDNLMQEINQNLAE
  EAGLNITHICLPPDSSEAEIIDEILKINEDTRVHGLALQISENLFSNKVLNALKPEKDVD
  GVTDINLGKLVRGDAHECFVSPVAKAVIELLEKSGVNLDGKKILVVGAHGSLEAALQCLF
  QRKGSMTMSIQWKTRQLQSKLHEADIVVLGSPKPEEIPLTWIQPGTTVLNCSHDFLSGKV
  GCGSPRIHFGGLIEEDDVILLAAALRIQNMVSSGRRWLREQQHRRWRLHCLKLQPLSPVP
  SDIEISRGQTPKAVDVLAKEIGLLADEIEIYGKSKAKVRLSVLERLKDQADGKYVLVAGI
  TPTPLGEGKSTVTIGLVQALTAHLNVNSFACLRQPSQGPTFGVKGGAAGGGYAQVIPMEE
  FNLHLTGDIHAITAANNLLAAAIDTRILHENTQTDKALYNRLVPLVNGVREFSEIQLARL
  KKLGINKTDPSTLTEEEVSKFARLDIDPSTITWQRVLDTNDRFLRKITIGQGNTEKGHYR
  QAQFDIAVASEIMAVLALTDSLADMKARLGRMVVASDKSGQPVTADDLGVTGALTVLMKD
  AIKPNLMQTLEGTPVFVHAGPFANIAHGNSSVLADKIALKLVGEEGFVVTEAGFGADIGM
  EKFFNIKCRASGLVPNVVVLVATVRALKMHGGGPSVTAGVPLKKEYTEENIQLVADGCCN
  LQKQIQITQLFGVPVVVALNVFKTDTRAEIDLVCELAKRAGAFDAVPCYHWSVGGKGSVD
  LARAVREAASKRSRFQFLYDVQVPIVDKIRTIAQAVYGAKDIELSPEAQAKIDRYTQQGF
  GNLPICMAKTHLSLSHQPDKKGVPRDFILPISDVRASIGAGFIYPLVGTMSTMPGLPTRP
  CFYDIDLDTETEQVKGLF

• Sequence length: 978

Pathways

KEGG:

One carbon pool by folate
Metabolic pathways
Biosynthesis of cofactors

Reactome:

Metabolism of folate and pterines

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ARTERY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KIDNEY CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LATE-ONSET ALZHEIMER'S DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURAL TUBE DEFECT, FOLATE-SENSITIVE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURAL TUBE DEFECTS X-LINKED	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERIPHERAL ARTERIAL DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute Coronary Syndrome	Coronary Syndrome	BEFREE	24618918, 25809277		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	20885792	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Alzheimer Disease, Late Onset	Alzheimer disease	BEFREE	20885792, 22330827		★☆☆☆☆ Found in Text Mining only
Alzheimer`s Disease	Alzheimer disease	GWASDB_DG	20885792		★☆☆☆☆ Found in Text Mining only
Alzheimer`s Disease	Alzheimer disease	GWASCAT_DG	20885792		★☆☆☆☆ Found in Text Mining only
Anemia, Megaloblastic	Anemia	BEFREE	22108709		★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar disorder	Pubtator	29257106	Associate	★☆☆☆☆ Found in Text Mining only
Bladder Neoplasm	Bladder Neoplasm	BEFREE	31401334		★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	30482855, 33605411	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of bladder	Bladder carcinoma	BEFREE	31401334		★☆☆☆☆ Found in Text Mining only
Carcinoma Pancreatic Ductal	Pancreatic ductal carcinoma	Pubtator	35459186	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	34908119	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	15013446, 31421459		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	33605411	Associate	★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	GWASDB_DG	17634449		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary Artery Disease	Coronary artery disease	Pubtator	17634449, 18675980, 19164808, 19777576, 24618918, 25528061, 40004565	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary Artery Disease	Coronary artery disease	BEFREE	24618918		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary Artery Disease Autosomal Dominant 1	Coronary artery disease	Pubtator	22216278	Associate	★☆☆☆☆ Found in Text Mining only
Coronary Disease	Coronary artery disease	Pubtator	21804106, 22042884, 24618918	Associate	★☆☆☆☆ Found in Text Mining only
Coronary heart disease	Coronary Heart Disease	GWASCAT_DG	17634449		★☆☆☆☆ Found in Text Mining only
Coronary heart disease	Coronary Heart Disease	GWASDB_DG	17634449, 21347282		★☆☆☆☆ Found in Text Mining only
Coronary heart disease	Coronary Heart Disease	BEFREE	21804106, 22042884		★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	26926881		★☆☆☆☆ Found in Text Mining only
Depressive Disorder	Major depressive disorder	Pubtator	26926881	Associate	★☆☆☆☆ Found in Text Mining only
Down Syndrome	Down Syndrome	LHGDN	15068241		★☆☆☆☆ Found in Text Mining only
Endometrial Neoplasms	Endometrial neoplasm	Pubtator	34908119	Associate	★☆☆☆☆ Found in Text Mining only
Esophageal carcinoma	Esophageal Carcinoma	BEFREE	29171320		★☆☆☆☆ Found in Text Mining only
Esophageal Neoplasms	Esophagus Neoplasm	BEFREE	29171320		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	32897363	Associate	★☆☆☆☆ Found in Text Mining only
Head and Neck Neoplasms	Head and neck neoplasm	Pubtator	34908119	Associate	★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	28394261		★☆☆☆☆ Found in Text Mining only
Liver Neoplasms	Liver neoplasm	Pubtator	33605411	Stimulate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of esophagus	Esophagus Neoplasm	BEFREE	29171320		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of urinary bladder	Urinary bladder cancer	BEFREE	31401334		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	15013446		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	26926881		★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial Infarction	BEFREE	21463265, 22216278		★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial infarction	Pubtator	24618918	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	29171320		★☆☆☆☆ Found in Text Mining only
Neural Tube Defects	Neural Tube Defect	BEFREE	12384833, 16552426, 19777576, 22520921, 24123340, 31518072, 31688093, 9611072		★☆☆☆☆ Found in Text Mining only
Neural Tube Defects	Neural tube defect	Pubtator	19777576, 22520921	Associate	★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	Pubtator	33146000	Associate	★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	35459186	Associate	★☆☆☆☆ Found in Text Mining only
Peripheral Arterial Diseases	Vascular Diseases	GWASCAT_DG	27082954		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	GWASCAT_DG	26198764		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Severe Combined Immunodeficiency	Severe combined immunodeficiency disease	BEFREE	22108709		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of esophagus	Esophagus Neoplasm	BEFREE	29171320		★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	34908119, 37919060	Associate	★☆☆☆☆ Found in Text Mining only
Vascular Calcification	Vascular calcification	Pubtator	40057183	Associate	★☆☆☆☆ Found in Text Mining only