MTHFD2L

Summary

MTHFD2L (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2 like, HGNC:31865) is a protein-coding gene on chromosome 4q13.3, encoding Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial (Q9H903). Bifunctional mitochondrial folate-interconverting enzyme that has both NAD/NADP-dependent methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase activities.

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.

Source: NCBI Gene 441024 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 55 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001144978

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31865
Approved symbol	MTHFD2L
Name	methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2 like
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC72244
Ensembl gene	ENSG00000163738
Ensembl biotype	protein_coding
OMIM	614047
Entrez	441024

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 7 protein_coding_CDS_not_defined, 4 protein_coding, 3 nonsense_mediated_decay, 3 retained_intron

ENST00000325278, ENST00000359107, ENST00000395759, ENST00000423607, ENST00000429335, ENST00000429519, ENST00000433372, ENST00000461101, ENST00000461856, ENST00000465255, ENST00000475291, ENST00000484725, ENST00000490128, ENST00000490698, ENST00000492183, ENST00000887811, ENST00000963607

RefSeq mRNA: 7 — MANE Select: NM_001144978 NM_001004346, NM_001144978, NM_001351310, NM_001351311, NM_001351314, NM_001351329, NM_001351331

CCDS: CCDS47075

Canonical transcript exons

ENST00000325278 — 8 exons

Exon	Start	End
ENSE00001764903	74158118	74158281
ENSE00001767097	74301697	74303099
ENSE00003489509	74174506	74174690
ENSE00003784026	74281425	74281550
ENSE00003971820	74175281	74175403
ENSE00003971822	74225302	74225394
ENSE00003971823	74201263	74201370
ENSE00003971824	74199794	74199946

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 91.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.2367 / max 242.9265, expressed in 1810 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48257	13.5027	1804
48252	0.5834	140
48262	0.4157	55
48258	0.2842	109
48255	0.1295	16
48263	0.1080	31
48253	0.0830	34
48256	0.0737	31
48254	0.0449	16
48251	0.0116	3

Top tissues by expression

277 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	91.60	gold quality
right lobe of liver	UBERON:0001114	89.75	gold quality
adrenal tissue	UBERON:0018303	88.18	gold quality
calcaneal tendon	UBERON:0003701	88.01	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.68	gold quality
monocyte	CL:0000576	85.52	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.46	gold quality
mononuclear cell	CL:0000842	85.20	gold quality
ganglionic eminence	UBERON:0004023	85.05	gold quality
leukocyte	CL:0000738	84.51	gold quality
colonic epithelium	UBERON:0000397	83.88	gold quality
ventricular zone	UBERON:0003053	83.79	gold quality
left adrenal gland cortex	UBERON:0035825	82.98	gold quality
left adrenal gland	UBERON:0001234	82.90	gold quality
gastrocnemius	UBERON:0001388	82.63	gold quality
muscle of leg	UBERON:0001383	82.55	gold quality
left lobe of thyroid gland	UBERON:0001120	82.40	gold quality
adrenal gland	UBERON:0002369	82.31	gold quality
right adrenal gland	UBERON:0001233	82.19	gold quality
right uterine tube	UBERON:0001302	82.18	gold quality
tibial artery	UBERON:0007610	82.08	gold quality
popliteal artery	UBERON:0002250	82.07	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.07	gold quality
right adrenal gland cortex	UBERON:0035827	82.05	gold quality
thyroid gland	UBERON:0002046	81.97	gold quality
adenohypophysis	UBERON:0002196	81.93	gold quality
body of pancreas	UBERON:0001150	81.88	gold quality
mucosa of stomach	UBERON:0001199	81.84	gold quality
liver	UBERON:0002107	81.71	gold quality
right lobe of thyroid gland	UBERON:0001119	81.63	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.64

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• The First Structure of Human MTHFD2L and Its Implications for the Development of Isoform-Selective Inhibitors. (PMID:35712863)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mthfd2l	ENSDARG00000054199
mus_musculus	Mthfd2l	ENSMUSG00000029376
rattus_norvegicus	Mthfd2l	ENSRNOG00000021347
drosophila_melanogaster	Nmdmc	FBGN0010222

Paralogs (3): MTHFD2 (ENSG00000065911), MTHFD1 (ENSG00000100714), MTHFD1L (ENSG00000120254)

Protein

Protein identifiers

Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial — Q9H903 (reviewed: Q9H903)

Alternative names: NADP-dependent methylenetetrahydrofolate dehydrogenase 2-like protein

All UniProt accessions (3): Q9H903, F8W7P9, Q8IY64

UniProt curated annotations — full annotation on UniProt →

Function. Bifunctional mitochondrial folate-interconverting enzyme that has both NAD/NADP-dependent methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase activities.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Isoform 1, isoform 4 and isoform 5 are expressed in brain and placenta.

Pathway. One-carbon metabolism; tetrahydrofolate interconversion.

Similarity. Belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9H903-4	4	yes
Q9H903-1	1
Q9H903-2	2
Q9H903-3	3
Q9H903-5	5

RefSeq proteins (5): NP_001004346, NP_001138450, NP_001338239, NP_001338240, NP_001338243 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000672	THF_DH/CycHdrlase	Family
IPR020630	THF_DH/CycHdrlase_cat_dom	Domain
IPR020631	THF_DH/CycHdrlase_NAD-bd_dom	Domain
IPR020867	THF_DH/CycHdrlase_CS	Conserved_site
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR046346	Aminoacid_DH-like_N_sf	Homologous_superfamily

Pfam: PF00763, PF02882

Enzyme classification (BRENDA):

• EC 1.5.1.15 — methylenetetrahydrofolate dehydrogenase (NAD+) (BRENDA: 20 organisms, 33 substrates, 7 inhibitors, 59 Km, 21 kcat entries)
• EC 1.5.1.5 — methylenetetrahydrofolate dehydrogenase (NADP+) (BRENDA: 24 organisms, 41 substrates, 41 inhibitors, 70 Km, 28 kcat entries)
• EC 3.5.4.9 — methenyltetrahydrofolate cyclohydrolase (BRENDA: 53 organisms, 34 substrates, 29 inhibitors, 57 Km, 13 kcat entries)

Substrate kinetics (BRENDA)

35 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
5,10-METHENYLTETRAHYDROFOLATE	0.0045–2.36	30
NADP+	0.0004–0.69	23
5,10-METHYLENETETRAHYDROFOLATE	0.0011–4.76	20
10-FORMYLTETRAHYDROFOLATE	0.009–0.47	14
NAD+	0.013–4	13
NADH	0.0035–2	10
METHENYLTETRAHYDROFOLATE	0.019–0.23	7
L-5,10-METHYLENETETRAHYDROFOLATE	0.0046–0.26	6
NADP+	0.255–2.12	6
5,10-METHENYLTETRAHYDROFOLATE	0.0632–1	5
5,10-METHYLENETETRAHYDROFOLATE	0.0004–0.29	5
5,10-METHENYLTETRAHYDROFOLATE	0.068–0.302	5
5,10-METHYLENETETRAHYDROPTEROYLPOLY-L-GLUTAMATE	0.04–0.153	4
MG2+	0.171–0.25	3
5,10-METHYLENETETRAHYDROPTEROYLGLUTAMATE	0.123–0.133	2

Catalyzed reactions (Rhea), 3 shown:

• (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NADP(+) = (6R)-5,10-methenyltetrahydrofolate + NADPH (RHEA:22812)
• (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NAD(+) = (6R)-5,10-methenyltetrahydrofolate + NADH (RHEA:22892)
• (6R)-5,10-methenyltetrahydrofolate + H2O = (6R)-10-formyltetrahydrofolate + H(+) (RHEA:23700)

UniProt features (35 total): helix 12, strand 10, binding site 5, splice variant 5, turn 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7QEI	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H903-F1	89.24	0.83

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 98–102; 145–147; 214–216; 247; 323–327

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-196757	Metabolism of folate and pterines
R-HSA-1430728	Metabolism
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors
R-HSA-196854	Metabolism of vitamins and cofactors

MSigDB gene sets: 171 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, WANG_CLIM2_TARGETS_UP, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_AMINO_ACID_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ASPARTATE_FAMILY_AMINO_ACID_BIOSYNTHETIC_PROCESS, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_DICARBOXYLIC_ACID_METABOLIC_PROCESS, chr4q13, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS

GO Biological Process (10): purine nucleotide biosynthetic process (GO:0006164), obsolete methionine biosynthetic process (GO:0009086), 10-formyltetrahydrofolate metabolic process (GO:0009256), tetrahydrofolate interconversion (GO:0035999), folic acid metabolic process (GO:0046655), L-histidine biosynthetic process (GO:0000105), one-carbon metabolic process (GO:0006730), folic acid-containing compound metabolic process (GO:0006760), amino acid biosynthetic process (GO:0008652), small molecule metabolic process (GO:0044281)

GO Molecular Function (7): methenyltetrahydrofolate cyclohydrolase activity (GO:0004477), methylenetetrahydrofolate dehydrogenase (NAD+) activity (GO:0004487), methylenetetrahydrofolate dehydrogenase (NADP+) activity (GO:0004488), catalytic activity (GO:0003824), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), hydrolase activity (GO:0016787)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	1
Metabolism of vitamins and cofactors	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
dicarboxylic acid metabolic process	2
tetrahydrofolate metabolic process	2
oxidoreductase activity, acting on the CH-NH group of donors, NAD or NADP as acceptor	2
catalytic activity	2
purine nucleotide metabolic process	1
nucleotide biosynthetic process	1
purine-containing compound biosynthetic process	1
one-carbon metabolic process	1
folic acid-containing compound metabolic process	1
aromatic amino acid biosynthetic process	1
imidazole-containing compound metabolic process	1
L-amino acid biosynthetic process	1
proteinogenic amino acid biosynthetic process	1
small molecule metabolic process	1
modified amino acid metabolic process	1
pteridine-containing compound metabolic process	1
amino acid metabolic process	1
biosynthetic process	1
metabolic process	1
cyclohydrolase activity	1
molecular_function	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrion	1
intracellular organelle lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1746 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTHFD2L	SHMT1	P34896	815
MTHFD2L	GLDC	P23378	763
MTHFD2L	GART	P22102	744
MTHFD2L	ATIC	P31939	743
MTHFD2L	SHMT2	P34897	743
MTHFD2L	MTHFD1L	Q6UB35	677
MTHFD2L	ALDH1L2	Q3SY69	635
MTHFD2L	GMPS	P49915	631
MTHFD2L	MTHFD1	P11586	616
MTHFD2L	TYMS	P04818	598
MTHFD2L	DMGDH	Q9UI17	587
MTHFD2L	FPGS	Q05932	587
MTHFD2L	DHFR	P00374	576
MTHFD2L	ACLY	P53396	576
MTHFD2L	MTHFR	P42898	574

IntAct

20 interactions, top by confidence:

A	B	Type	Score
SRP9	SRP72	psi-mi:“MI:0914”(association)	0.730
MTHFD2	HRAS	psi-mi:“MI:0914”(association)	0.730
HDHD3	MTHFD2L	psi-mi:“MI:0915”(physical association)	0.590
HENMT1	SNX2	psi-mi:“MI:0914”(association)	0.530
MTHFD2L	MTHFD2	psi-mi:“MI:0914”(association)	0.530
MTHFD2L	CST4	psi-mi:“MI:0915”(physical association)	0.400
PROSER2	VWA8	psi-mi:“MI:0914”(association)	0.350
HENMT1	RAD51C	psi-mi:“MI:0914”(association)	0.350
RAB2B	BTAF1	psi-mi:“MI:0914”(association)	0.350
ISCA2	ARHGEF11	psi-mi:“MI:0914”(association)	0.350
LAMTOR5	ERI3	psi-mi:“MI:0914”(association)	0.350
TESMIN	TRAPPC3	psi-mi:“MI:0914”(association)	0.350
BTLA	TUBB8	psi-mi:“MI:0914”(association)	0.350
MAPKAPK2	ZFC3H1	psi-mi:“MI:0914”(association)	0.350
MTHFD2	MACROD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (25): MTHFD2L (Affinity Capture-MS), MTHFD2L (Affinity Capture-MS), MTHFD2L (Affinity Capture-MS), MTHFD2L (Affinity Capture-MS), MTHFD2L (Affinity Capture-MS), CST4 (Affinity Capture-MS), MTHFD2L (Two-hybrid), RNASE7 (Affinity Capture-MS), ZHX2 (Affinity Capture-MS), MTHFD2L (Affinity Capture-MS), MTHFD2L (Affinity Capture-MS), MTHFD2L (Affinity Capture-MS), MTHFD2L (Affinity Capture-MS), MTHFD2L (Affinity Capture-MS), MTHFD2L (Affinity Capture-MS)

ESM2 similar proteins: A2ADU8, A2ADU9, A6QP72, F6ZFR0, O74850, O94361, P51658, Q08650, Q16635, Q22267, Q32LS6, Q3UN02, Q41745, Q4V8A1, Q4V9F0, Q502J0, Q54GC1, Q58HT5, Q58NB6, Q5F3X0, Q62730, Q6CF02, Q6E1M8, Q6E213, Q6IV76, Q6IV77, Q6IV78, Q6IV82, Q6IV83, Q6IV84, Q6IWY1, Q6P342, Q6PAZ3, Q6ZPD8, Q7TQA3, Q8LG50, Q8N3Y7, Q8TC12, Q8VD48, Q91WF0

Diamond homologs: A0RIH3, A1A8J4, A4IQS0, A4SER8, A5FNE3, A5FRF1, A5UAS4, A5UHL4, A6GZM5, A6Q2W6, A6Q815, A7GSJ9, A7MJZ6, A7ZIT8, A7ZXI3, A8AJS4, A8ESH8, A8FF15, A9AGS9, A9VGW3, B0USU2, B1IZ72, B1LKE8, B1XGC7, B1YLQ1, B2TTB0, B2V9R3, B3QUL4, B5YPP4, B6I0H4, B7HB52, B7HNU4, B7IXH2, B7JM32, B7L7F6, B7LJI7, B7M4N2, B7ME52, B7MRJ2, B7N983

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MTHFD2L	“up-regulates quantity”	(6R)-5,10-methenyltetrahydrofolate	“chemical modification”
MTHFD2L	“up-regulates quantity”	10-formyltetrahydrofolate(2-)	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

55 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	44
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
685523	GRCh37/hg19 4q13.3-21.1(chr4:71561780-78304341)x1	Pathogenic

SpliceAI

2457 predictions. Top by Δscore:

Variant	Effect	Δscore
4:74158282:GTACG:G	donor_loss	1.0000
4:74174504:A:AG	acceptor_gain	1.0000
4:74174505:G:GA	acceptor_gain	1.0000
4:74174662:GAA:G	donor_gain	1.0000
4:74174669:A:G	donor_gain	1.0000
4:74199788:TTTCA:T	acceptor_loss	1.0000
4:74199789:TTCAG:T	acceptor_loss	1.0000
4:74199790:TCAG:T	acceptor_loss	1.0000
4:74199791:CAGA:C	acceptor_loss	1.0000
4:74199792:A:AG	acceptor_gain	1.0000
4:74199793:G:GG	acceptor_gain	1.0000
4:74199793:GACC:G	acceptor_gain	1.0000
4:74201241:A:AG	acceptor_gain	1.0000
4:74201258:TTAA:T	acceptor_loss	1.0000
4:74201259:TAAG:T	acceptor_loss	1.0000
4:74201260:AAG:A	acceptor_gain	1.0000
4:74201261:A:G	acceptor_gain	1.0000
4:74201261:AGG:A	acceptor_loss	1.0000
4:74201262:G:GG	acceptor_gain	1.0000
4:74201367:GGAG:G	donor_gain	1.0000
4:74201368:GAGG:G	donor_gain	1.0000
4:74201369:AGGTA:A	donor_loss	1.0000
4:74201370:GGTA:G	donor_loss	1.0000
4:74201371:G:GA	donor_loss	1.0000
4:74201372:T:G	donor_loss	1.0000
4:74225295:A:AG	acceptor_gain	1.0000
4:74225296:TTCCA:T	acceptor_loss	1.0000
4:74225297:TCCA:T	acceptor_loss	1.0000
4:74225298:CCA:C	acceptor_loss	1.0000
4:74225299:CA:C	acceptor_loss	1.0000

AlphaMissense

1889 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:74199841:G:C	D167H	0.994
4:74199851:G:A	G170E	0.993
4:74225307:G:C	A240P	0.993
4:74301730:T:A	V322D	0.993
4:74174613:T:C	L84P	0.992
4:74281535:G:C	D306H	0.992
4:74174668:G:C	K102N	0.991
4:74174668:G:T	K102N	0.991
4:74225308:C:A	A240E	0.991
4:74225383:T:A	I265K	0.991
4:74174645:A:C	S95R	0.989
4:74174647:C:A	S95R	0.989
4:74174647:C:G	S95R	0.989
4:74175377:G:A	G142D	0.989
4:74175386:T:A	V145D	0.989
4:74199867:T:A	N175K	0.989
4:74199867:T:G	N175K	0.989
4:74174658:T:A	V99D	0.988
4:74201304:T:C	S216P	0.988
4:74281473:T:A	V285E	0.988
4:74281537:T:A	D306E	0.988
4:74281537:T:G	D306E	0.988
4:74201293:T:A	V212E	0.987
4:74281455:T:A	V279D	0.987
4:74175332:T:C	L127P	0.986
4:74199848:A:T	D169V	0.986
4:74199880:T:C	C180R	0.986
4:74199920:C:A	A193D	0.986
4:74281533:G:A	G305E	0.986
4:74199914:C:A	A191D	0.985

dbSNP variants (sampled 300 via entrez): RS1000012892 (4:74177749 A>C,G), RS1000032595 (4:74187564 A>G), RS1000046553 (4:74198005 C>G,T), RS1000091544 (4:74262576 C>A), RS1000108080 (4:74183419 T>C,G), RS1000125713 (4:74175593 G>T), RS1000151660 (4:74141605 C>G,T), RS1000179489 (4:74214619 A>C,G), RS1000196093 (4:74129281 C>G), RS1000209653 (4:74124782 C>A,T), RS1000224126 (4:74233844 A>G), RS1000234959 (4:74254611 G>A,C), RS1000236452 (4:74272001 C>T), RS1000240018 (4:74239177 C>A,G), RS1000291514 (4:74184698 C>G)

Disease associations

OMIM: gene MIM:614047 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001533_8	Immune reponse to smallpox (secreted IL-1beta)	7.000000e-09
GCST001533_9	Immune reponse to smallpox (secreted IL-1beta)	7.000000e-09
GCST002896_46	Cholesterol, total	2.000000e-17
GCST002898_43	LDL cholesterol	2.000000e-12
GCST005973_26	White blood cell count	9.000000e-25
GCST005974_13	Neutrophil count	2.000000e-28

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105963 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, decreases methylation	7
trichostatin A	increases expression, affects cotreatment	3
Tetrachlorodibenzodioxin	affects expression, decreases expression	3
Cyclosporine	increases expression	3
Aflatoxin B1	affects expression, decreases expression, decreases methylation	3
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases abundance, increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
cupric chloride	increases expression	1
pentanal	decreases expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
NSC 689534	affects binding, increases expression	1
Temozolomide	decreases expression	1
Vorinostat	affects cotreatment, increases expression	1
Arsenic	increases expression, increases abundance	1
Atrazine	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4022809	Binding	Inhibition of MTHFD2L (unknown origin) using NAD/5,10-methylene THF as substrate after 2 hrs by HPLC method	Discovery of N-(6-Fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)-5-[(3R)-3-hydroxypyrrolidin-1-yl]thiophene-2-sulfonamide (LSN 3213128), a Potent and Selective Nonclassical Antifolate Aminoimidazole-4-carboxamide Ribonucleotide Formyltransferase (AICARFT) Inhibitor Effective at Tumor Suppression in a Cancer Xenograft Model. — J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.