MTHFD2L methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2 like [Homo sapiens (human)] - Gene

Summary

Official Symbol: MTHFD2Lprovided by HGNC
Official Full Name: methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2 likeprovided by HGNC
Primary source: HGNC:HGNC:31865
See related: Ensembl:ENSG00000163738 MIM:614047; AllianceGenome:HGNC:31865
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary: Predicted to enable methenyltetrahydrofolate cyclohydrolase activity; methylenetetrahydrofolate dehydrogenase (NAD+) activity; and methylenetetrahydrofolate dehydrogenase (NADP+) activity. Predicted to be involved in tetrahydrofolate interconversion. Located in mitochondrion. [provided by Alliance of Genome Resources, Nov 2024]
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: 4q13.3

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (74114560..74303099)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (77457787..77646724)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (74988990..75168816)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The First Structure of Human MTHFD2L and Its Implications for the Development of Isoform-Selective Inhibitors.
Title: The First Structure of Human MTHFD2L and Its Implications for the Development of Isoform-Selective Inhibitors.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.

Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH101940 (e-PCR)
- UniSTS:96275

SHGC-8172 (e-PCR)
- UniSTS:52246

RH104258 (e-PCR)
- UniSTS:98583

SHGC-106408 (e-PCR)
- UniSTS:169828

G35510 (e-PCR)
- UniSTS:44150

SHGC4-1555 (e-PCR)
- UniSTS:67749

G33909 (e-PCR)
- UniSTS:68522

SHGC-145327 (e-PCR)
- UniSTS:174514

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables methenyltetrahydrofolate cyclohydrolase activity	IBA Inferred from Biological aspect of Ancestor more info
enables methenyltetrahydrofolate cyclohydrolase activity	ISS Inferred from Sequence or Structural Similarity more info
enables methenyltetrahydrofolate cyclohydrolase activity	TAS Traceable Author Statement more info
enables methylenetetrahydrofolate dehydrogenase (NAD+) activity	ISS Inferred from Sequence or Structural Similarity more info
enables methylenetetrahydrofolate dehydrogenase (NAD+) activity	TAS Traceable Author Statement more info
enables methylenetetrahydrofolate dehydrogenase (NADP+) activity	IBA Inferred from Biological aspect of Ancestor more info
enables methylenetetrahydrofolate dehydrogenase (NADP+) activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in 10-formyltetrahydrofolate metabolic process	IEA Inferred from Electronic Annotation more info
involved_in L-histidine biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in folic acid metabolic process	TAS Traceable Author Statement more info
involved_in methionine biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in purine nucleotide biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in tetrahydrofolate interconversion	IBA Inferred from Biological aspect of Ancestor more info
involved_in tetrahydrofolate interconversion	IEA Inferred from Electronic Annotation more info
involved_in tetrahydrofolate interconversion	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in mitochondrial inner membrane	IEA Inferred from Electronic Annotation more info
located_in mitochondrial matrix	TAS Traceable Author Statement more info
located_in mitochondrion	HTP more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial

Names: MTHFD2-like; NADP-dependent methylenetetrahydrofolate dehydrogenase 2-like protein; probable bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2; tetrahydrofolate dehydrogenase/cyclohydrolase

NP_001004346.2

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

NP_001138450.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

NP_001338239.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

NP_001338240.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

NP_001338243.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

NP_001338258.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

NP_001338260.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_016863707.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_016863708.2

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_016863709.2

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_016863711.2

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_016863713.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_047271666.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_047271667.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_047271668.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_047271669.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_047271670.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_047271671.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_047271672.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_047271673.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_054206043.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_054206044.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_054206045.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_054206046.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_054206047.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_054206048.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_054206049.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_054206050.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_054206051.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_054206052.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_054206053.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

XP_054206054.1

EC 1.5.1.15

EC 1.5.1.5

EC 3.5.4.9

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.

mRNA and Protein(s)

NM_001004346.4 → NP_001004346.2 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform 1

Status: VALIDATED

Source sequence(s)

AC093677, AC097470

Conserved Domains (3) summary

cd01080
Location:106 → 285

NAD_bind_m-THF_DH_Cyclohyd; NADP binding domain of methylene-tetrahydrofolate dehydrogenase/cyclohydrolase

COG0190
Location:2 → 286

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

pfam00763
Location:2 → 111

THF_DHG_CYH; Tetrahydrofolate dehydrogenase/cyclohydrolase, catalytic domain
NM_001144978.3 → NP_001138450.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform 2

See identical proteins and their annotated locations for NP_001138450.1

Status: VALIDATED

Source sequence(s)

AC093677, AI219460, AK122799, AV720429, BC032771, BC065771, CA438481

Consensus CDS

CCDS47075.1

UniProtKB/Swiss-Prot

Q6P079, Q8N560, Q9H903

Related

ENSP00000321984.7, ENST00000325278.7

Conserved Domains (3) summary

cd01080
Location:164 → 343

NAD_bind_m-THF_DH_Cyclohyd; NADP binding domain of methylene-tetrahydrofolate dehydrogenase/cyclohydrolase

COG0190
Location:52 → 344

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

pfam00763
Location:53 → 169

THF_DHG_CYH; Tetrahydrofolate dehydrogenase/cyclohydrolase, catalytic domain
NM_001351310.2 → NP_001338239.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform 3

Status: VALIDATED

Source sequence(s)

AC093677, AC097470

Related

ENST00000433372.5

Conserved Domains (1) summary

COG0190
Location:2 → 211

FolD; 5,10-methylene-tetrahydrofolate dehydrogenase/Methenyl tetrahydrofolate cyclohydrolase [Coenzyme transport and metabolism]
NM_001351311.2 → NP_001338240.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform 3

Status: VALIDATED

Source sequence(s)

AC093677, AC097470

Conserved Domains (1) summary

COG0190
Location:2 → 211

FolD; 5,10-methylene-tetrahydrofolate dehydrogenase/Methenyl tetrahydrofolate cyclohydrolase [Coenzyme transport and metabolism]
NM_001351314.2 → NP_001338243.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform 4

Status: VALIDATED

Source sequence(s)

AC093677, AC097470, BQ015209

Conserved Domains (2) summary

cd01080
Location:37 → 216

NAD_bind_m-THF_DH_Cyclohyd; NADP binding domain of methylene-tetrahydrofolate dehydrogenase/cyclohydrolase

cl27642
Location:24 → 42

THF_DHG_CYH; Tetrahydrofolate dehydrogenase/cyclohydrolase, catalytic domain
NM_001351329.2 → NP_001338258.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform 5

Status: VALIDATED

Source sequence(s)

AC093677

Related

ENST00000461101.1
NM_001351331.2 → NP_001338260.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform 6

Status: VALIDATED

Source sequence(s)

AC093677, BX090674

RNA

NR_147097.2 RNA Sequence

Status: VALIDATED

Source sequence(s)

AC093677, AC097470, BQ015209

Related

ENST00000359107.10

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

74114560..74303099

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047415712.1 → XP_047271668.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X8
XM_047415715.1 → XP_047271671.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X9
XM_047415716.1 → XP_047271672.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X10
XM_047415713.1 → XP_047271669.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X8
XM_047415714.1 → XP_047271670.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X8
XM_047415717.1 → XP_047271673.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X11
XM_017008218.3 → XP_016863707.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X1
XM_017008219.3 → XP_016863708.2 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X2
XM_047415710.1 → XP_047271666.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X3
XM_047415711.1 → XP_047271667.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X5
XM_017008220.3 → XP_016863709.2 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X4
XM_017008222.3 → XP_016863711.2 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X6
XM_017008224.2 → XP_016863713.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X7

RNA

XR_001741223.3 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060928.1 Alternate T2T-CHM13v2.0

Range

77457787..77646724

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054350079.1 → XP_054206054.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X18
XM_054350068.1 → XP_054206043.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X1
XM_054350069.1 → XP_054206044.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X12
XM_054350070.1 → XP_054206045.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X13
XM_054350071.1 → XP_054206046.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X14
XM_054350073.1 → XP_054206048.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X16
XM_054350072.1 → XP_054206047.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X15
XM_054350075.1 → XP_054206050.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X9
XM_054350076.1 → XP_054206051.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X10
XM_054350077.1 → XP_054206052.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X11
XM_054350074.1 → XP_054206049.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X7
XM_054350078.1 → XP_054206053.1 bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial isoform X17