MTHFD1L methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like [Homo sapiens (human)] - Gene

Summary

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Official Symbol: MTHFD1Lprovided by HGNC
Official Full Name: methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-likeprovided by HGNC
Primary source: HGNC:21055
Locus tag: RP1-292B18.2
See related: Ensembl:ENSG00000120254; HPRD:09967; MIM:611427; Vega:OTTHUMG00000015828
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FTHFSDC1; MTC1THFS; dJ292B18.2; RP1-292B18.2
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 variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jun 2011]

Genomic context

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Location :: 6q25.1

Sequence :: Chromosome: 6; NC_000006.11 (151186815..151423023)

See MTHFD1L in Epigenomics, MapViewer

Chromosome 6 - NC_000006.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

The rs3832406 polymorphism was associated with isolated cleft lip with or without cleft palate.(MTHFD1L)
Title: Genotyping of a tri-allelic polymorphism by a novel melting curve assay in MTHFD1L: an association study of nonsyndromic Cleft in Ireland.
This study support a role of MTHFD1L gene in late-onset Alzheimer's disease in a Northern Han Chinese population.
Title: Replication of the MTHFD1L gene association with late-onset Alzheimer's disease in a Northern Han Chinese population.
No evidence of association between the MTHFD1L marker and susceptibility to Alzheimer's disease is found in a sample from a Spanish population.
Title: The MTHFD1L gene rs11754661 marker is not associated with Alzheimer's disease in a sample of the Spanish population.
Prevalence of minor allele A (adenosine) in rs11754661 single nucleotide polymorphism of MTHFD1L contributes to the risk of Alzheimer's disease in a Han population of mainland China.
Title: The MTHFD1L gene rs11754661 marker is associated with susceptibility to Alzheimer's disease in the Chinese Han population.
Strong candidate gene for mitochondrial disease, based on recessive mutations detected in infantile patients
Title: Molecular diagnosis of infantile mitochondrial disease with targeted next-generation sequencing.
Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
Title: Dementia revealed: novel chromosome 6 locus for late-onset Alzheimer disease provides genetic evidence for folate-pathway abnormalities.
Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
Title: Additive effect of multiple genetic variants on the risk of coronary artery disease.
mitochondrial C1-tetrahydrofolate synthase gene structure and tissue distribution
Title: Human mitochondrial C1-tetrahydrofolate synthase: gene structure, tissue distribution of the mRNA, and immunolocalization in Chinese hamster ovary calls.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
association of rs6922269 with coronary heart disease not replicated in Tunisian sample
Title: Association of three polymorphisms selected from a genome-wide association study with coronary heart disease in the Tunisian population.

Submit: New GeneRIF Correction See all (14)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

A genome-wide association study identifies novel loci associated with susceptibility to chronic myeloid leukemia.

Dementia revealed: novel chromosome 6 locus for late-onset Alzheimer disease provides genetic evidence for folate-pathway abnormalities.

Genomewide association analysis of coronary artery disease.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
BioGRID:117409	BioGRID:107287	CASP4	BioGRID	PubMed	Affinity Capture-MS
BioGRID:117409	BioGRID:116183	COPS5	BioGRID	PubMed	Affinity Capture-MS
BioGRID:117409	BioGRID:114030	CUL3	BioGRID	PubMed	Affinity Capture-MS
BioGRID:117409	BioGRID:114593	HGS	BioGRID	PubMed	Reconstituted Complex
BioGRID:117409	BioGRID:114879	MAGED1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:117409	BioGRID:119602	SIRT7	BioGRID	PubMed	Affinity Capture-MS
BioGRID:117409	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:117409	BioGRID:131884	USP50	BioGRID	PubMed	Affinity Capture-MS
BioGRID:117409	BioGRID:119068	WRAP73	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

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C1-unit interconversion, eukaryotes, organism-specific biosystem (from KEGG)
C1-unit interconversion, eukaryotes, organism-specific biosystemPathway module; Nucleotide and amino acid metabolism; Cofactor and vitamin biosynthesis
C1-unit interconversion, eukaryotes, conserved biosystem (from KEGG)
C1-unit interconversion, eukaryotes, conserved biosystemPathway module; Nucleotide and amino acid metabolism; Cofactor and vitamin biosynthesis
One Carbon Metabolism, organism-specific biosystem (from WikiPathways)
One Carbon Metabolism, organism-specific biosystemThis one-carbon metabolism pathway is centered around folate. Folate has two key carbon-carbon double bonds. Saturating one of them yields dihydrofolate (DHF) and adding an additional molecule of hyd...
One carbon pool by folate, organism-specific biosystem (from KEGG)
One carbon pool by folate, organism-specific biosystem
One carbon pool by folate
One carbon pool by folate, conserved biosystem (from KEGG)
One carbon pool by folate, conserved biosystem
One carbon pool by folate

General gene information

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Markers

STS-N30148 (e-PCR)
- UniSTS:45583

RH102196 (e-PCR)
- UniSTS:96530

RH93531 (e-PCR)
- UniSTS:85541

WI-13575 (e-PCR)
- UniSTS:46641

D6S956 (e-PCR)
- UniSTS:25915

RH15823 (e-PCR)
- UniSTS:20799

RH123123 (e-PCR)
- UniSTS:135504

D2S337 (e-PCR), detects polymorphism
- UniSTS:57473

RH48516 (e-PCR)
- UniSTS:20692

Genotypes

See MTHFD1L SNP Geneview Report
See MTHFD1L SNP Genotype Report
See MTHFD1L SNP Variation Viewer Report

Homology

Homologs of the MTHFD1L gene: The MTHFD1L gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, chicken, and zebrafish.
Map Viewer (Mouse)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IDA Inferred from Direct Assay more info	PubMed
formate-tetrahydrofolate ligase activity	IDA Inferred from Direct Assay more info	PubMed
NOT methenyltetrahydrofolate cyclohydrolase activity	IBA Inferred from Biological aspect of Ancestor more info
NOT methylenetetrahydrofolate dehydrogenase (NADP+) activity	IBA Inferred from Biological aspect of Ancestor more info
protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
folic acid-containing compound biosynthetic process	IEA Inferred from Electronic Annotation more info
folic acid-containing compound metabolic process	IDA Inferred from Direct Assay more info	PubMed
formate metabolic process	IDA Inferred from Direct Assay more info	PubMed
one-carbon metabolic process	IBA Inferred from Biological aspect of Ancestor more info
tetrahydrofolate interconversion	IEA Inferred from Electronic Annotation more info
tetrahydrofolate metabolic process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
NOT cytosol	IBA Inferred from Biological aspect of Ancestor more info
mitochondrion	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: monofunctional C1-tetrahydrofolate synthase, mitochondrial

Names: monofunctional C1-tetrahydrofolate synthase, mitochondrial; 10-formyl-THF synthetase; formyltetrahydrofolate synthetase domain containing 1

NP_001229696.1

EC 6.3.4.3

NP_001229697.1

EC 6.3.4.3

NP_001229698.1

EC 6.3.4.3

NP_056255.2

EC 6.3.4.3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029185.1 RefSeqGene

Range

5001..241209

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001242767.1 → NP_001229696.1 monofunctional C1-tetrahydrofolate synthase, mitochondrial isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

BC110319, BC144368, DB727926

UniProtKB/TrEMBL

B7ZM99

UniProtKB/Swiss-Prot

Q6UB35

Conserved Domains (5) summary

COG0190
Location:72 – 289
Blast Score: 315

FolD; 5,10-methylene-tetrahydrofolate dehydrogenase/Methenyl tetrahydrofolate cyclohydrolase [Coenzyme metabolism]

cd00477
Location:378 – 962
Blast Score: 2002

FTHFS; Formyltetrahydrofolate synthetase (FTHFS) catalyzes the ATP-dependent activation of formate ion via its addition to the N10 position of tetrahydrofolate. FTHFS is a highly expressed key enzyme in both the Wood-Ljungdahl pathway of autotrophic CO2 ...

cd05212
Location:193 – 336
Blast Score: 536

NAD_bind_m-THF_DH_Cyclohyd_like; NAD(P) binding domain of methylene-tetrahydrofolate dehydrogenase and methylene-tetrahydrofolate dehydrogenase/cyclohydrolase

PLN02759
Location:353 – 979
Blast Score: 2492

PLN02759; Formate--tetrahydrofolate ligase

pfam00763
Location:74 – 180
Blast Score: 202

THF_DHG_CYH; Tetrahydrofolate dehydrogenase/cyclohydrolase, catalytic domain
NM_001242768.1 → NP_001229697.1 monofunctional C1-tetrahydrofolate synthase, mitochondrial isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (3) has a shorter and distinct N-terminus compared to isoform 1.

Source sequence(s)

AK315378, BC110319, DA195967

UniProtKB/TrEMBL

B2RD24

UniProtKB/Swiss-Prot

Q6UB35

Conserved Domains (5) summary

COG0190
Location:9 – 223
Blast Score: 312

FolD; 5,10-methylene-tetrahydrofolate dehydrogenase/Methenyl tetrahydrofolate cyclohydrolase [Coenzyme metabolism]

cd00477
Location:312 – 896
Blast Score: 2002

FTHFS; Formyltetrahydrofolate synthetase (FTHFS) catalyzes the ATP-dependent activation of formate ion via its addition to the N10 position of tetrahydrofolate. FTHFS is a highly expressed key enzyme in both the Wood-Ljungdahl pathway of autotrophic CO2 ...

cd05212
Location:127 – 270
Blast Score: 537

NAD_bind_m-THF_DH_Cyclohyd_like; NAD(P) binding domain of methylene-tetrahydrofolate dehydrogenase and methylene-tetrahydrofolate dehydrogenase/cyclohydrolase

PLN02759
Location:287 – 913
Blast Score: 2497

PLN02759; Formate--tetrahydrofolate ligase

pfam00763
Location:10 – 114
Blast Score: 198

THF_DHG_CYH; Tetrahydrofolate dehydrogenase/cyclohydrolase, catalytic domain
NM_001242769.1 → NP_001229698.1 monofunctional C1-tetrahydrofolate synthase, mitochondrial isoform 4 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 3' UTR and coding sequence and uses an alternate in-frame splice junction at the 5' end of an exon compared to variant 1. The resulting isoform (4) has a shorter and distinct C-terminus and lacks a single internal aa compared to isoform 1. Isoform 4 is thought to lack THF synthase activity.

Source sequence(s)

AW593866, AY374131, DB727926

Consensus CDS

CCDS56457.1

UniProtKB/Swiss-Prot

Q6UB35

Related

ENSP00000356276, ENST00000367307

Conserved Domains (3) summary

COG0190
Location:72 – 228
Blast Score: 271

FolD; 5,10-methylene-tetrahydrofolate dehydrogenase/Methenyl tetrahydrofolate cyclohydrolase [Coenzyme metabolism]

pfam00763
Location:74 – 180
Blast Score: 196

THF_DHG_CYH; Tetrahydrofolate dehydrogenase/cyclohydrolase, catalytic domain

cl09931
Location:193 – 260
Blast Score: 275

NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins
NM_015440.4 → NP_056255.2 monofunctional C1-tetrahydrofolate synthase, mitochondrial isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice junction at the 5' end of an exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is 1 aa shorter compared to isoform 1.

Source sequence(s)

AY374130, BC110319, DB727926

Consensus CDS

CCDS5228.1

UniProtKB/Swiss-Prot

Q6UB35

Related

ENSP00000356290, OTTHUMP00000017418, ENST00000367321, OTTHUMT00000042699

Conserved Domains (5) summary

COG0190
Location:72 – 288
Blast Score: 325

FolD; 5,10-methylene-tetrahydrofolate dehydrogenase/Methenyl tetrahydrofolate cyclohydrolase [Coenzyme metabolism]

cd00477
Location:377 – 961
Blast Score: 2002

FTHFS; Formyltetrahydrofolate synthetase (FTHFS) catalyzes the ATP-dependent activation of formate ion via its addition to the N10 position of tetrahydrofolate. FTHFS is a highly expressed key enzyme in both the Wood-Ljungdahl pathway of autotrophic CO2 ...

cd05212
Location:193 – 335
Blast Score: 548

NAD_bind_m-THF_DH_Cyclohyd_like; NAD(P) binding domain of methylene-tetrahydrofolate dehydrogenase and methylene-tetrahydrofolate dehydrogenase/cyclohydrolase

PLN02759
Location:352 – 978
Blast Score: 2492

PLN02759; Formate--tetrahydrofolate ligase

pfam00763
Location:74 – 180
Blast Score: 202

THF_DHG_CYH; Tetrahydrofolate dehydrogenase/cyclohydrolase, catalytic domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000006.11 Reference GRCh37.p10 Primary Assembly

Range

151186815..151423023

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000138.1 Alternate HuRef

Range

148750394..148986848

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018917.1 Alternate CHM1_1.0

Range

151186022..151422279

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01025652.1 (48462..70440)	None
genomic	ABBA01025653.1	None
genomic	ABBA01025654.1	None
genomic	AL035086.12	None
genomic	AL049694.9	None
genomic	AL133260.12 (31817..109206)	None
genomic	AMYH01016745.1 (61432..297689)	None
genomic	CH471051.2	EAW47760.1
		EAW47761.1
		EAW47762.1
		EAW47763.1
genomic	CS482713.1	CAM36319.1
genomic	CS482716.1	CAM36320.1
genomic	HB883499.1	CBF65969.1
genomic	HB895224.1	CBF74049.1
genomic	HC940908.1	CBU90841.1
genomic	HC952633.1	CBU96477.1
mRNA	AA478842.1	None
mRNA	AB127387.1	BAD93193.1
mRNA	AK024798.1	BAB15009.1
mRNA	AK127089.1	None
mRNA	AK310342.1	None
mRNA	AK315378.1	BAG37771.1
mRNA	AL117452.1	CAB55934.1
mRNA	AV704883.1	None
mRNA	AW593866.1	None
mRNA	AY374130.1	AAQ82696.1
mRNA	AY374131.1	AAQ82697.1
mRNA	BC008629.1	AAH08629.1
mRNA	BC017477.1	AAH17477.2
mRNA	BC110319.1	AAI10320.1
mRNA	BC136685.1	AAI36686.1
mRNA	BC144368.1	AAI44369.1
mRNA	BC144369.1	None
mRNA	BE735249.1	None
mRNA	BQ062382.1	None
mRNA	DA195967.1	None
mRNA	DB727926.1	None