MTHFR

Summary

MTHFR (methylenetetrahydrofolate reductase, HGNC:7436) is a protein-coding gene on chromosome 1p36.22, encoding Methylenetetrahydrofolate reductase (NADPH) (P42898). Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine. In precision oncology, MTHFR A222V confers sensitivity to Fluorouracil in Rectum Cancer (CIViC Level B); 1 further curated variant–drug associations are listed below.

The protein encoded by this gene catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Genetic variation in this gene influences susceptibility to occlusive vascular disease, neural tube defects, colon cancer and acute leukemia, and mutations in this gene are associated with methylenetetrahydrofolate reductase deficiency.

Source: NCBI Gene 4524 — RefSeq curated summary.

At a glance

• Gene–disease (curated): homocystinuria due to methylene tetrahydrofolate reductase deficiency (Definitive, ClinGen)
• GWAS associations: 65
• Clinical variants (ClinVar): 985 total — 77 pathogenic, 87 likely-pathogenic
• Phenotypes (HPO): 90
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_005957

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7436
Approved symbol	MTHFR
Name	methylenetetrahydrofolate reductase
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000177000
Ensembl biotype	protein_coding
OMIM	607093
Entrez	4524

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 17 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000376486, ENST00000376583, ENST00000376585, ENST00000376590, ENST00000376592, ENST00000413656, ENST00000418034, ENST00000423400, ENST00000431243, ENST00000641407, ENST00000641437, ENST00000641446, ENST00000641721, ENST00000641747, ENST00000641759, ENST00000641805, ENST00000641820, ENST00000641909, ENST00000642002, ENST00000911084, ENST00000911085, ENST00000911086, ENST00000911087, ENST00000970341, ENST00000970342, ENST00000970343

RefSeq mRNA: 3 — MANE Select: NM_005957 NM_001330358, NM_001410750, NM_005957

CCDS: CCDS137, CCDS81262, CCDS90864

Canonical transcript exons

ENST00000376590 — 12 exons

Exon	Start	End
ENSE00001225788	11791207	11791326
ENSE00001225797	11792278	11792379
ENSE00001225805	11793907	11794089
ENSE00001225813	11794358	11794538
ENSE00001225817	11794729	11794863
ENSE00001225825	11795098	11795348
ENSE00001225832	11796206	11796399
ENSE00001225838	11800212	11800322
ENSE00001225848	11801161	11801399
ENSE00001470707	11805888	11805964
ENSE00001471053	11785723	11790898
ENSE00003529876	11802881	11803129

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 95.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.6919 / max 204.8865, expressed in 1794 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10320	4.5007	1313
10325	3.2690	1107
10326	2.8867	636
10324	1.4123	748
10323	1.2691	666
10321	0.5810	252
10317	0.3944	64
10319	0.3684	149
10316	0.0104	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	95.76	gold quality
sural nerve	UBERON:0015488	92.03	gold quality
apex of heart	UBERON:0002098	90.33	gold quality
right atrium auricular region	UBERON:0006631	89.88	gold quality
right ovary	UBERON:0002118	89.00	gold quality
granulocyte	CL:0000094	88.88	gold quality
cardiac atrium	UBERON:0002081	88.45	gold quality
mucosa of stomach	UBERON:0001199	88.24	gold quality
left ovary	UBERON:0002119	87.76	gold quality
heart left ventricle	UBERON:0002084	87.67	gold quality
cardiac ventricle	UBERON:0002082	87.64	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.52	gold quality
monocyte	CL:0000576	87.06	gold quality
adrenal tissue	UBERON:0018303	86.98	gold quality
heart	UBERON:0000948	86.97	gold quality
left uterine tube	UBERON:0001303	86.88	gold quality
tibial nerve	UBERON:0001323	86.59	gold quality
visceral pleura	UBERON:0002401	86.53	gold quality
mononuclear cell	CL:0000842	86.47	gold quality
upper lobe of left lung	UBERON:0008952	86.38	gold quality
leukocyte	CL:0000738	86.36	gold quality
cauda epididymis	UBERON:0004360	86.16	gold quality
right lobe of thyroid gland	UBERON:0001119	86.05	gold quality
adenohypophysis	UBERON:0002196	86.05	gold quality
pituitary gland	UBERON:0000007	85.91	gold quality
upper lobe of lung	UBERON:0008948	85.89	gold quality
gastrocnemius	UBERON:0001388	85.80	gold quality
muscle of leg	UBERON:0001383	85.71	gold quality
thyroid gland	UBERON:0002046	85.42	gold quality
body of stomach	UBERON:0001161	85.39	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	70.92
E-ANND-3	yes	10.78
E-GEOD-124858	no	21.04

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): JUN, MYC, NFE2L2

miRNA regulators (miRDB)

159 targeting MTHFR, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 14)

• role in in utero viability (PMID:11590551)
• Results indicate that MTHFR polymorphism may be a risk factor for CVD in patients on hemodialysis, and MTHFR VV genotype and gender may be strong determinants of the plasma homocysteine level. (PMID:11744804)
• association between left ventricular hypertrophy and the C825T allele of the G-protein beta3 subunit gene in Arabs. (G PROTEIN BETA3) (PMID:11768721)
• frequent 5,10-methylenetetrahydrofolate reductase C677T polymorphism is associated with a common haplotype in whites, Japanese, and Africans (PMID:11781870)
• The 677C–>T mutation of MTHFR was present in 26.1% of adults with idiopathic osteonecrosis of the femur head and appears to have a role in the complex pathophysiology of the disease. (PMID:11801474)
• polymorphism and ischemic stroke: sex difference in Japanese. 51.47, P=0.0091). T/T mutation appears to be restricted to women. (PMID:11870335)
• A significant association between the MTHFR TT genotype and spontaneous cervical artery dissection was observed (PMID:11872884)
• MTHFR gene mutations may affect vitamin B12 and homocysteine metabolism in Brazilian children with neural tube defects (PMID:11880124)
• polymorphisms are not risk factors for venous thromboembolism [methionine synthase and methylenetrahydrofolate reductase] (PMID:11920232)
• Polymorphisms in MTHFR is associated with the efficacy and toxicity of methotrexate used for the treatment of rhematoid arthritis (PMID:11927833)
• A common mutation in the 5,10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status. (PMID:11929966)
• high prevalence of mutated MTHFR genotypes in spontaneously aborted embryos (PMID:11938441)
• prevalence of the C677T mutation in the methylenetetrahydrofolate reductase gene (PMID:11940092)
• Homocysteine (tHcy) levels and methylenetetrahydrofolate reductase (MTHFR) genotype are primary risk factors for coronary heart disease (CHD). (PMID:11947914)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mthfr	ENSDARG00000053087
mus_musculus	Mthfr	ENSMUSG00000029009
rattus_norvegicus	Mthfr	ENSRNOG00000008553
drosophila_melanogaster	CG7560	FBGN0036157
caenorhabditis_elegans		WBGENE00015512

Paralogs (4): MTR (ENSG00000116984), UROD (ENSG00000126088), BHMT2 (ENSG00000132840), BHMT (ENSG00000145692)

Protein

Protein identifiers

Methylenetetrahydrofolate reductase (NADPH) — P42898 (reviewed: P42898)

All UniProt accessions (9): A0A1B0GXD9, A0A286YF17, A0A286YF47, A0A286YFD0, P42898, F8W9T8, L7P8G6, Q5SNW5, Q5SNW7

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine. Represents a key regulatory connection between the folate and methionine cycles.

Subunit / interactions. Homodimer.

Post-translational modifications. Phosphorylation of an N-terminal serine-rich phosphorylation region increases sensitivity to S-adenosylmethionine and inhibition.

Disease relevance. Homocystinuria due to deficiency of N(5,10)-methylenetetrahydrofolate reductase activity (MTHFRD) [MIM:236250] An autosomal recessive inborn error of folate metabolism. Clinical severity is variable, ranging from severe neurologic features to absence of symptoms. Clinical features include homocysteinuria, homocysteinemia, developmental delay, severe intellectual disability, perinatal death, psychiatric disturbances, and later-onset neurodegenerative disorders. The disease is caused by variants affecting the gene represented in this entry. Ischemic stroke (ISCHSTR) [MIM:601367] A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. Disease susceptibility is associated with variants affecting the gene represented in this entry. Neural tube defects, folate-sensitive (NTDFS) [MIM:601634] The most common NTDs are open spina bifida (myelomeningocele) and anencephaly. Disease susceptibility is associated with variants affecting the gene represented in this entry. Schizophrenia (SCZD) [MIM:181500] A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Activity regulation. Allosterically regulated by S-adenosylmethionine (SAM).

Domain organisation. Contains a serine-rich phosphorylation region at the N-terminal and an eukaryote-only S-adenosylmethionine (SAM)-binding domain at the C-terminal. Through asymmetric homodimerization, the two regions are positioned next to each other and N-terminal phosphorylation increases sensitivity to SAM binding and inhibition.

Pathway. One-carbon metabolism; tetrahydrofolate interconversion.

Polymorphism. Genetic variation in MTHFR influences susceptibility to occlusive vascular disease, neural tube defects (NTD), colon cancer and acute leukemia.

Similarity. Belongs to the methylenetetrahydrofolate reductase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P42898-1	1	yes
P42898-2	2

RefSeq proteins (3): NP_001317287, NP_001397679, NP_005948* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003171	Mehydrof_redctse-like	Domain
IPR004621	Fadh2_euk	Domain
IPR029041	FAD-linked_oxidoreductase-like	Homologous_superfamily
IPR053806	MTHFR_C	Domain

Pfam: PF02219, PF21895

Enzyme classification (BRENDA):

• EC 1.5.1.20 — methylenetetrahydrofolate reductase [NAD(P)H] (BRENDA: 69 organisms, 134 substrates, 59 inhibitors, 64 Km, 25 kcat entries)
• EC 1.5.1.53 — methylenetetrahydrofolate reductase (NADPH) (BRENDA: 4 organisms, 12 substrates, 19 inhibitors, 26 Km, 3 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
5,10-METHYLENETETRAHYDROFOLATE	0.0005–0.287	18
NADH	0.0027–0.585	14
5,10-METHYLENETETRAHYDROFOLATE	0.0082–0.152	11
NADPH	0.0073–0.049	10
NADPH	0.011–0.0355	8
5-METHYLTETRAHYDROFOLATE	0.019–0.16	6
METHYLENETETRAHYDROFOLATE	0.0004–0.187	6
NADH	0.1–3.76	4
(+)-5-METHYL-5,6,7,8-TETRAHYDROPTEROYLPENTAGLUTA	0.003	1
(6R)-5,10-METHYLENETETRAHYDROFOLATE	0.18	1
5-METHYLTETRAHYDROPTEROYLHEXAGLUTAMATE	0.0019	1
5-METHYLTETRAHYDROPTEROYLMONOGLUTAMATE	0.033	1
BENZYL VIOLOGEN	11.1	1
5-METHYLTETRAHYDROFOLATE	0.038	1
DIHYDROBIOPTERIN	0.03	1

Catalyzed reactions (Rhea), 1 shown:

• (6S)-5-methyl-5,6,7,8-tetrahydrofolate + NADP(+) = (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NADPH + H(+) (RHEA:19817)

UniProt features (160 total): sequence variant 65, helix 29, strand 20, binding site 19, modified residue 16, turn 4, mutagenesis site 2, chain 1, region of interest 1, compositionally biased region 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6FCX	X-RAY DIFFRACTION	2.5
8QA4	ELECTRON MICROSCOPY	2.8
8QA6	ELECTRON MICROSCOPY	2.91
8QA5	ELECTRON MICROSCOPY	3.14

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42898-F1	89.13	0.76

Functional residue map

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

Catalytic / active sites (1): 63 (proton donor/acceptor)

Ligand- & substrate-binding residues (19): 174–175; 197; 201–204; 210; 217; 228; 321; 325; 456; 461–464; 481–485; 560 …

Post-translational modifications (16): 9, 10, 18, 20, 21, 23, 25, 26, 29, 30, 34, 90, 94, 103, 394, 451

Mutagenesis-validated functional residues (2):

Position	Phenotype
368	no effect on s-adenosylmethionine-binding.
463	loss of s-adenosylmethionine-binding.

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: 411 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_RESPONSE_TO_PEPTIDE, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_AMINO_ACID_BIOSYNTHETIC_PROCESS, GOBP_NEURAL_TUBE_DEVELOPMENT, GOBP_ASPARTATE_FAMILY_AMINO_ACID_BIOSYNTHETIC_PROCESS, GGGTGGRR_PAX4_03, GOBP_MORPHOGENESIS_OF_EMBRYONIC_EPITHELIUM, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS

GO Biological Process (14): response to hypoxia (GO:0001666), neural tube closure (GO:0001843), L-methionine metabolic process (GO:0006555), obsolete methionine biosynthetic process (GO:0009086), response to xenobiotic stimulus (GO:0009410), response to vitamin B2 (GO:0033274), tetrahydrofolate interconversion (GO:0035999), response to amino acid (GO:0043200), S-adenosylmethionine metabolic process (GO:0046500), homocysteine metabolic process (GO:0050667), response to folic acid (GO:0051593), response to interleukin-1 (GO:0070555), heterochromatin organization (GO:0070828), tetrahydrofolate metabolic process (GO:0046653)

GO Molecular Function (10): methylenetetrahydrofolate reductase [NAD(P)H] activity (GO:0004489), protein-containing complex binding (GO:0044877), flavin adenine dinucleotide binding (GO:0050660), NADP binding (GO:0050661), FAD binding (GO:0071949), modified amino acid binding (GO:0072341), methylenetetrahydrofolate reductase (NADPH) activity (GO:0106313), catalytic activity (GO:0003824), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (1): cytosol (GO:0005829)

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
binding	3
sulfur amino acid metabolic process	2
response to vitamin	2
response to nitrogen compound	2
response to oxygen-containing compound	2
response to stress	1
response to decreased oxygen levels	1
primary neural tube formation	1
tube closure	1
L-amino acid metabolic process	1
proteinogenic amino acid metabolic process	1
response to chemical	1
one-carbon metabolic process	1
tetrahydrofolate metabolic process	1
response to acid chemical	1
sulfur compound metabolic process	1
non-proteinogenic amino acid metabolic process	1
response to cytokine	1
chromatin organization	1
folic acid-containing compound metabolic process	1
oxidoreductase activity, acting on the CH-NH group of donors, NAD or NADP as acceptor	1
nucleotide binding	1
anion binding	1
adenyl nucleotide binding	1
flavin adenine dinucleotide binding	1
methylenetetrahydrofolate reductase [NAD(P)H] activity	1
molecular_function	1
catalytic activity	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

3350 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTHFR	MTR	Q99707	978
MTHFR	MTRR	Q9UBK8	978
MTHFR	H7C2H4	H7C2H4	959
MTHFR	P0DN79	P0DN79	953
MTHFR	F2	P00734	935
MTHFR	MTHFD1	P11586	932
MTHFR	TYMS	P04818	916
MTHFR	SHMT1	P34896	913
MTHFR	BHMT	Q93088	850
MTHFR	DHFR	P00374	844
MTHFR	APOE	P02649	843
MTHFR	CTH	P32929	838
MTHFR	F5	P12259	822
MTHFR	ACE	P12821	818
MTHFR	CLCN6	P51797	814
MTHFR	SLC19A1	P41440	814

IntAct

63 interactions, top by confidence:

A	B	Type	Score
BCL2L11	BCL2	psi-mi:“MI:0914”(association)	0.930
ANKLE2	PPP2R1A	psi-mi:“MI:0914”(association)	0.850
PRPF31	PRPF4	psi-mi:“MI:0914”(association)	0.640
SMPD2	MTHFR	psi-mi:“MI:0914”(association)	0.560
SMPD2	MTHFR	psi-mi:“MI:0915”(physical association)	0.560
GNAI1	GNAT3	psi-mi:“MI:0914”(association)	0.530
PCDHB16	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
EPHA1	EXOC5	psi-mi:“MI:0914”(association)	0.530
HSD3B2	NARS1	psi-mi:“MI:0914”(association)	0.530
GDF10	LRP4	psi-mi:“MI:0914”(association)	0.530
ZNF556	LRP4	psi-mi:“MI:0914”(association)	0.530
KCNV2	HSPA8	psi-mi:“MI:0914”(association)	0.530
TIGD6	MTHFR	psi-mi:“MI:0914”(association)	0.530
SPATA19	MTHFR	psi-mi:“MI:0914”(association)	0.530
GNAZ	MTHFR	psi-mi:“MI:0914”(association)	0.530
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
JUN		psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
DCLRE1C	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
GNAZ	FAM171A2	psi-mi:“MI:0914”(association)	0.350
CDCA8	DCLK1	psi-mi:“MI:0914”(association)	0.350
TMEM223	SDCBP	psi-mi:“MI:0914”(association)	0.350
ZNF263	PPP1R12A	psi-mi:“MI:0914”(association)	0.350

BioGRID (79): MTHFR (Affinity Capture-MS), MTHFR (Affinity Capture-MS), MTHFR (Affinity Capture-MS), MTHFR (Affinity Capture-MS), MTHFR (Affinity Capture-MS), MTHFR (Affinity Capture-MS), MTHFR (Affinity Capture-MS), MTHFR (Affinity Capture-MS), MTHFR (Affinity Capture-MS), MTHFR (Affinity Capture-MS), MTHFR (Affinity Capture-MS), MTHFR (Affinity Capture-MS), MTHFR (Affinity Capture-MS), MTHFR (Affinity Capture-MS), MTHFR (Affinity Capture-MS)

ESM2 similar proteins: A0A1S4BZI5, A0A1S4CB73, B0F481, D2HRF1, F4I933, F4IY62, F4JKB6, F4JVN6, O23324, O23553, O80585, O82043, O82768, P10349, P30706, P36428, P42898, Q01292, Q05758, Q0J6P7, Q10S55, Q2QTL0, Q39639, Q42713, Q43307, Q43822, Q43870, Q5I598, Q5U2Z5, Q60HE5, Q66GI4, Q75HE6, Q7Z3D6, Q80YD1, Q8BH86, Q8H0W0, Q8K224, Q8RWG3, Q8VYL1, Q944I4

Diamond homologs: O54235, O67422, O74927, O80585, P0AEZ1, P0AEZ2, P11003, P42898, P45208, P46151, P53128, P57154, P71319, Q10258, Q5I598, Q60HE5, Q75HE6, Q89B13, Q8KA62, Q9JZQ3, Q9SE60, Q9SE94, Q9WU20, Q17693

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
JUN	up-regulates	MTHFR
CyclinB/CDK1	“down-regulates activity”	MTHFR	phosphorylation
MTHFR	up-regulates	Chromatine_condensation
MTHFR	“down-regulates quantity”	(6R)-5,10-methylenetetrahydrofolate(2-)	“chemical modification”
MTHFR	“up-regulates quantity”	(6S)-5-methyltetrahydrofolate(2-)	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
potassium ion transmembrane transport	7	13.8×	5e-04

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	77
Likely pathogenic	87
Uncertain significance	238
Likely benign	438
Benign	39

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1034230	NM_005957.5(MTHFR):c.552del (p.Ser184fs)	Pathogenic
1068573	NM_005957.5(MTHFR):c.1114_1115del (p.Lys372fs)	Pathogenic
1070453	NM_005957.5(MTHFR):c.191del (p.Phe64fs)	Pathogenic
1072666	NM_005957.5(MTHFR):c.1304_1305del (p.Phe435fs)	Pathogenic
1073018	NM_005957.5(MTHFR):c.1063_1075del (p.Pro355fs)	Pathogenic
1073673	NM_005957.5(MTHFR):c.1144del (p.Asp382fs)	Pathogenic
1363312	NM_005957.5(MTHFR):c.1768del (p.Leu590fs)	Pathogenic
1370847	NM_005957.5(MTHFR):c.1712del (p.Gln571fs)	Pathogenic
1452438	NM_005957.5(MTHFR):c.1552del (p.Ser518fs)	Pathogenic
1453807	NM_005957.5(MTHFR):c.495G>A (p.Trp165Ter)	Pathogenic
1455384	NM_005957.5(MTHFR):c.451A>T (p.Lys151Ter)	Pathogenic
1455663	NM_005957.5(MTHFR):c.1852del (p.Leu618fs)	Pathogenic
1456126	NC_000001.10:g.(?11850365)(11852446_?)del	Pathogenic
1457543	NM_005957.5(MTHFR):c.1262G>A (p.Trp421Ter)	Pathogenic
1459913	NC_000001.10:g.(?11850365)(11856466_?)del	Pathogenic
1460266	NC_000001.10:g.(?11850365)(11851393_?)del	Pathogenic
1686637	NM_005957.5(MTHFR):c.1657G>T (p.Glu553Ter)	Pathogenic
187868	NM_005957.5(MTHFR):c.176G>C (p.Trp59Ser)	Pathogenic
187874	NM_005957.5(MTHFR):c.388T>C (p.Cys130Arg)	Pathogenic
187877	NM_005957.5(MTHFR):c.587G>A (p.Gly196Asp)	Pathogenic
187879	NM_005957.5(MTHFR):c.673A>C (p.Ile225Leu)	Pathogenic
187882	NM_005957.5(MTHFR):c.764G>T (p.Gly255Val)	Pathogenic
187885	NM_005957.5(MTHFR):c.780+1G>T	Pathogenic
187887	NM_005957.5(MTHFR):c.1042C>T (p.Pro348Ser)	Pathogenic
187891	NM_005957.5(MTHFR):c.1167-2del	Pathogenic
187895	NM_005957.5(MTHFR):c.1530+2T>C	Pathogenic
187899	NM_005957.5(MTHFR):c.1724T>G (p.Val575Gly)	Pathogenic
187903	NM_005957.5(MTHFR):c.1797_1798delinsGT (p.Tyr599_Glu600delinsTer)	Pathogenic
187904	NM_005957.5(MTHFR):c.1808C>G (p.Ser603Cys)	Pathogenic
187905	NM_005957.5(MTHFR):c.1883T>C (p.Leu628Pro)	Pathogenic

SpliceAI

3063 predictions. Top by Δscore:

Variant	Effect	Δscore
1:11787492:GA:G	donor_gain	1.0000
1:11787494:G:GG	donor_gain	1.0000
1:11790690:T:TA	donor_gain	1.0000
1:11791201:CTTTA:C	donor_loss	1.0000
1:11791202:TTTA:T	donor_loss	1.0000
1:11791203:TTAC:T	donor_loss	1.0000
1:11791204:TA:T	donor_loss	1.0000
1:11791205:A:AT	donor_loss	1.0000
1:11791206:C:CT	donor_loss	1.0000
1:11791209:T:A	donor_gain	1.0000
1:11791325:CC:C	acceptor_gain	1.0000
1:11791326:CC:C	acceptor_gain	1.0000
1:11792274:CTA:C	donor_loss	1.0000
1:11792275:TACCT:T	donor_loss	1.0000
1:11792276:A:AT	donor_loss	1.0000
1:11792277:CCT:C	donor_gain	1.0000
1:11792316:A:AC	donor_gain	1.0000
1:11792317:C:CC	donor_gain	1.0000
1:11792319:T:TA	donor_gain	1.0000
1:11792375:TAGGC:T	acceptor_gain	1.0000
1:11792377:GGC:G	acceptor_gain	1.0000
1:11792378:GC:G	acceptor_gain	1.0000
1:11792378:GCCTG:G	acceptor_loss	1.0000
1:11792379:CC:C	acceptor_gain	1.0000
1:11792380:C:CC	acceptor_gain	1.0000
1:11792380:CT:C	acceptor_loss	1.0000
1:11792381:T:A	acceptor_loss	1.0000
1:11793966:T:TA	donor_gain	1.0000
1:11793967:C:A	donor_gain	1.0000
1:11794090:C:A	acceptor_loss	1.0000

AlphaMissense

4325 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:11791278:A:G	W561R	0.999
1:11791278:A:T	W561R	0.999
1:11791283:A:T	V559D	0.999
1:11791286:G:T	A558D	0.999
1:11793939:A:G	W500R	0.999
1:11793939:A:T	W500R	0.999
1:11790789:A:G	L621P	0.998
1:11793907:C:A	K510N	0.998
1:11793907:C:G	K510N	0.998
1:11793937:C:A	W500C	0.998
1:11793937:C:G	W500C	0.998
1:11794074:A:G	W455R	0.998
1:11794074:A:T	W455R	0.998
1:11794730:A:G	W389R	0.998
1:11794730:A:T	W389R	0.998
1:11794754:A:G	W381R	0.998
1:11794754:A:T	W381R	0.998
1:11794796:A:G	W367R	0.998
1:11794796:A:T	W367R	0.998
1:11790868:A:G	W595R	0.997
1:11790868:A:T	W595R	0.997
1:11790880:A:G	W591R	0.997
1:11790880:A:T	W591R	0.997
1:11791222:G:C	S579R	0.997
1:11791222:G:T	S579R	0.997
1:11791224:T:G	S579R	0.997
1:11794538:C:A	W389C	0.997
1:11794538:C:G	W389C	0.997
1:11791267:G:C	F564L	0.996
1:11791267:G:T	F564L	0.996

dbSNP variants (sampled 300 via entrez): RS1000347359 (1:11785349 C>T), RS1000393582 (1:11786723 C>A,T), RS1000610447 (1:11785668 C>A), RS1000680496 (1:11787086 G>A), RS1000738509 (1:11790847 C>A), RS1001032431 (1:11802497 T>G), RS1001108743 (1:11807224 G>C,T), RS1001126997 (1:11807480 T>G), RS1001128797 (1:11785452 G>A), RS1001229566 (1:11795696 C>G,T), RS1001336782 (1:11801608 G>A), RS1001565583 (1:11786302 A>G), RS1001575872 (1:11795330 G>T), RS1001620552 (1:11791647 G>C), RS1001699129 (1:11790217 G>A)

Disease associations

OMIM: gene MIM:607093 | disease phenotypes: MIM:236250, MIM:601634, MIM:209850, MIM:181500, MIM:188050, MIM:606764

GenCC curated gene-disease

Disease	Classification	Inheritance
homocystinuria due to methylene tetrahydrofolate reductase deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
homocystinuria due to methylene tetrahydrofolate reductase deficiency	Definitive	AR

Mondo (12): homocystinuria due to methylene tetrahydrofolate reductase deficiency (MONDO:0009353), neural tube defects, folate-sensitive (MONDO:0011120), autism (MONDO:0005260), schizophrenia (MONDO:0005090), thrombophilia due to thrombin defect (MONDO:0008559), vascular dementia (MONDO:0004648), prostate cancer (MONDO:0008315), neural tube defect (MONDO:0018075), gastrointestinal stromal tumor (MONDO:0011719), methotrexate toxicity (MONDO:0034212), schizophrenia, susceptibility to (MONDO:0100182), intellectual disability (MONDO:0001071)

Orphanet (10): Homocystinuria due to methylene tetrahydrofolate reductase deficiency (Orphanet:395), Spina bifida and other spinal dysraphisms (Orphanet:823), Familial prostate cancer (Orphanet:1331), Neural tube defect (Orphanet:3388), Orofacial clefting syndrome (Orphanet:139039), Gastrointestinal stromal tumor (Orphanet:44890), Methotrexate toxicity (Orphanet:565782), Rare genetic intellectual disability (Orphanet:183757), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

90 total (30 of 90 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000369	Low-set ears
HP:0000478	Abnormality of the eye
HP:0000520	Proptosis
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000708	Atypical behavior
HP:0000709	Psychosis
HP:0000725	Psychotic episodes
HP:0000738	Hallucinations
HP:0000746	Delusion
HP:0000776	Congenital diaphragmatic hernia
HP:0000835	Adrenal hypoplasia
HP:0000929	Abnormal skull morphology
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001254	Lethargy
HP:0001263	Global developmental delay
HP:0001268	Mental deterioration
HP:0001269	Hemiparesis
HP:0001274	Agenesis of corpus callosum
HP:0001288	Gait disturbance
HP:0001297	Stroke
HP:0001298	Encephalopathy
HP:0001324	Muscle weakness
HP:0001328	Specific learning disability

GWAS associations

65 associations (top):

Study	Trait	p-value
GCST000367_1	Homocysteine levels	8.000000e-35
GCST000395_2	Systolic blood pressure	2.000000e-13
GCST000445_2	Atrial fibrillation	6.000000e-07
GCST000483_1	Folate pathway vitamin levels	6.000000e-10
GCST001236_11	Blood pressure	2.000000e-16
GCST002087_1	Homocysteine levels	4.000000e-104
GCST002087_14	Homocysteine levels	3.000000e-21
GCST004776_9	Systolic blood pressure	1.000000e-16
GCST004777_45	Diastolic blood pressure	3.000000e-18
GCST004923_1	Tuberculosis	1.000000e-11
GCST005196_178	Coronary artery disease	2.000000e-07
GCST005207_1	Midregional pro atrial natriuretic peptide levels	4.000000e-13
GCST005575_25	Moyamoya disease	2.000000e-19
GCST005772_1	Diastolic blood pressure	3.000000e-09
GCST006021_17	Systolic blood pressure	8.000000e-17
GCST006054_1	High altitude adaptation	6.000000e-09
GCST006137_3	Serum folate levels	4.000000e-19
GCST006169_21	Diastolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	3.000000e-09
GCST006187_2	Diastolic blood pressure (cigarette smoking interaction)	9.000000e-40
GCST006187_3	Diastolic blood pressure (cigarette smoking interaction)	2.000000e-29
GCST006188_17	Systolic blood pressure (cigarette smoking interaction)	5.000000e-43
GCST006188_18	Systolic blood pressure (cigarette smoking interaction)	9.000000e-35
GCST006190_19	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	6.000000e-16
GCST006190_26	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-17
GCST006190_6	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	6.000000e-10
GCST006190_75	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	5.000000e-14
GCST006192_1	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	9.000000e-20
GCST006192_61	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-17
GCST006192_77	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	4.000000e-14
GCST006192_88	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	6.000000e-18

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004578	homocysteine measurement
EFO:0006335	systolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0006336	diastolic blood pressure
EFO:0008468	midregional pro atrial natriuretic peptide measurement
EFO:0009105	high altitude adaptation
EFO:0006527	smoking status measurement
EFO:0005763	pulse pressure measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D015140	Dementia, Vascular	C10.228.140.300.400; C10.228.140.300.510.800.500; C10.228.140.380.230; C10.228.140.695.500; C14.907.137.126.372.500; C14.907.253.560.350.500; F03.615.400.350
D046152	Gastrointestinal Stromal Tumors	C04.557.450.565.370; C06.301.371.308; C06.405.249.308
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009436	Neural Tube Defects	C10.500.680; C16.131.666.680
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C537357	Methylenetetrahydrofolate reductase deficiency (supp.)
C536409	Neural tube defect, folate-sensitive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

Clinical evidence (CIViC)

Drug × variant × indication: 2 predictive associations from 2 curated evidence items; also 1 predisposing.

Variant	Therapy	Indication	Effect	Level	CIViC
MTHFR A222V	Fluorouracil	Rectum Cancer	Sensitivity/Response	CIViC B	EID1757
MTHFR A222V	Fluorouracil	Stomach Cancer	Sensitivity/Response	CIViC B	EID669

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

PharmGKB clinical annotations

34 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1476413	Efficacy	3	methotrexate	Rheumatoid arthritis
rs17421511	Efficacy	3	methotrexate	Rheumatoid arthritis
rs1801131	Toxicity	3	nitrous oxide
rs1801131	Efficacy	4	methotrexate	Acute lymphoblastic leukemia
rs1801131	Toxicity	4	methotrexate	Acute lymphoblastic leukemia;Burkitt Lymphoma;Lymphoma;T-Cell;Non-Hodgkin Lymphoma
rs1801131	Toxicity	3	clozapine;olanzapine	Schizoaffective disorder;Schizophrenia
rs1801131	Efficacy	3	methotrexate	Rheumatoid arthritis
rs1801131	Efficacy	3	bevacizumab;carboplatin;cisplatin;cyanocobalamin;folic acid;pemetrexed	Neoplasms
rs1801131	Efficacy	3	l-methylfolate;Vitamin B-complex;Incl. Combinations	Major Depressive Disorder
rs1801131	Toxicity	3	capecitabine;fluorouracil;leucovorin;oxaliplatin	Neoplasms
rs1801131	Efficacy	3	capecitabine;fluorouracil;leucovorin;oxaliplatin	Neoplasms
rs1801131	Toxicity	3	methotrexate	Rheumatoid arthritis
rs1801131	Dosage	4	methotrexate	Acute lymphoblastic leukemia
rs1801133	Toxicity	3	antipsychotics	Schizophrenia
rs1801133	Toxicity	3	cisplatin;doxorubicin;methotrexate	Nephrotoxicity;Osteosarcoma
rs1801133	Toxicity	2A	methotrexate	Arthritis;Psoriatic;Drug Toxicity;Juvenile Rheumatoid Arthritis;Rheumatoid arthritis
rs1801133	Toxicity	3	phenobarbital;phenytoin	Epilepsy;Psychotic Disorder
rs1801133	Toxicity	3	cisplatin;oxaliplatin;Platinum compounds	Neoplasms
rs1801133	Metabolism/PK	3	methotrexate	Acute lymphoblastic leukemia;Burkitt Lymphoma;Leukemia;Lymphoma;Lymphoma;T-Cell
rs1801133	Efficacy	3	folic acid;vitamin b-complex;plain
rs1801133	Metabolism/PK	3	folic acid
rs1801133	Efficacy	3	methotrexate	Acute lymphoblastic leukemia
rs1801133	Efficacy	3	methotrexate	Chronic myelogenous leukemia;BCR-ABL1 positive;Graft vs Host Disease;Leukemia
rs1801133	Toxicity	4	mercaptopurine	Acute lymphoblastic leukemia
rs1801133	Toxicity	4	capecitabine;fluorouracil	Neoplasms
rs1801133	Toxicity	2A	methotrexate	Acute lymphoblastic leukemia;Drug Toxicity;Leukopenia;Lymphoma;Mucositis;Myelosuppression;Neoplasms;Neutropenia;Osteosarcoma;Primary central nervous system lymphoma;Thrombocytopenia;Toxic liver disease
rs1801133	Toxicity	3	nitrous oxide
rs1801133	Efficacy	3	pravastatin	Coronary Artery Disease;Myocardial Infarction
rs1801133	Efficacy	3	disulfiram	Cocaine dependence
rs1801133	Efficacy	3	benazepril	Hypertension
rs1801133	Efficacy	3	pemetrexed	Mesothelioma;Non-Small Cell Lung Carcinoma
rs1801133	Efficacy	3	l-methylfolate;Vitamin B-complex;Incl. Combinations	Major Depressive Disorder
rs1801133	Efficacy	3	fluorouracil;leucovorin;oxaliplatin	Colonic Neoplasms
rs4846051	Toxicity	3	methotrexate	Drug Toxicity;Rheumatoid arthritis

PharmGKB variants

8 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1476413	MTHFR	3	0.00	1	methotrexate
rs1801131	C1orf167, CLCN6, MTHFR	3	4.75	11	methotrexate;nitrous oxide;bevacizumab;carboplatin;cisplatin;cyanocobalamin;folic acid;pemetrexed;capecitabine;fluorouracil;leucovorin;oxaliplatin;clozapine;olanzapine;l-methylfolate;Vitamin B-complex;Incl. Combinations
rs1801133	CLCN6, MTHFR	2A	22.75	20	methotrexate;antipsychotics;nitrous oxide;capecitabine;fluorouracil;pravastatin;disulfiram;folic acid;vitamin b-complex;plain;benazepril;cisplatin;oxaliplatin;Platinum compounds
rs2274976	MTHFR		0.00	0
rs3737967	C1orf167, MTHFR		0.00	0
rs4846051	MTHFR	3	1.50	1	methotrexate
rs17367504	CLCN6, MTHFR		0.00	0
rs17421511	MTHFR	3	0.00	1	methotrexate

PharmGKB dosing guidelines

3 guidelines.

Source	Drug	Guideline	Dosing?	Recommendation?
DPWG	folic acid	Annotation of DPWG Guideline for folic acid and MTHFR
DPWG	methotrexate	Annotation of DPWG Guideline for methotrexate and MTHFR
RNPGx	methotrexate	Annotation of RNPGx Guideline for methotrexate and ABCB1, MTHFR, SLC19A1, SLCO1B1

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Methotrexate	affects abundance, affects response to substance, decreases expression, increases expression, affects metabolic processing (+3 more)	14
Folic Acid	affects expression, affects cotreatment, affects methylation, decreases reaction, increases activity (+5 more)	11
Fluorouracil	affects cotreatment, increases metabolic processing, affects response to substance, increases response to substance	8
Arsenic	affects response to substance, increases response to substance, affects methylation, affects metabolic processing	6
Homocysteine	decreases methylation, increases reaction, decreases reaction, increases expression, increases abundance (+1 more)	5
5-methyltetrahydrofolate	increases chemical synthesis	2
5,10-methylenetetrahydrofolic acid	increases metabolic processing, increases reduction	2
sodium arsenite	decreases expression	2
benazepril	affects response to substance	2
(+)-JQ1 compound	decreases expression, increases expression	2
Acetaminophen	increases expression, decreases expression	2
Nickel	increases expression	2
Pesticides	affects methylation, affects response to substance	2
Tretinoin	decreases expression, increases expression	2
Valproic Acid	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
afuresertib	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
7-hydroxymethotrexate	decreases response to substance	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
ferrous chloride	decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
corosolic acid	decreases expression	1
abrine	increases expression	1
bisphenol S	decreases methylation	1

Cellosaurus cell lines

42 cell lines: 25 finite cell line, 13 transformed cell line, 3 cancer cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_4W10	GM16028	Transformed cell line	Female
CVCL_7453	GM06160	Transformed cell line	Male
CVCL_7533	GM13591	Transformed cell line	Female
CVCL_B3VN	WG0354	Finite cell line	Female
CVCL_B3VP	WG0355	Finite cell line	Female
CVCL_B3VQ	WG0458	Finite cell line	Male
CVCL_B3VR	WG0670	Finite cell line	Female
CVCL_B3VS	WG0735	Finite cell line	Female
CVCL_B3VT	WG1396	Finite cell line	Female
CVCL_B3VV	WG1767	Finite cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
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