MCID: MTH086
MIFTS: 32

Methotrexate Toxicity

Categories: Rare diseases

Aliases & Classifications for Methotrexate Toxicity

MalaCards integrated aliases for Methotrexate Toxicity:

Name: Methotrexate Toxicity 58

Classifications:



External Ids:

Orphanet 58 ORPHA565782

Summaries for Methotrexate Toxicity

MalaCards based summary : Methotrexate Toxicity is related to mucositis and leukemia, acute lymphoblastic. An important gene associated with Methotrexate Toxicity is MTHFR (Methylenetetrahydrofolate Reductase), and among its related pathways/superpathways are Metabolism and Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds. The drugs Methotrexate and Levoleucovorin have been mentioned in the context of this disorder. Affiliated tissues include bone marrow and colon, and related phenotype is homeostasis/metabolism.

Related Diseases for Methotrexate Toxicity

Diseases related to Methotrexate Toxicity via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 136)
# Related Disease Score Top Affiliating Genes
1 mucositis 30.8 TYMS MTHFR ABCB1
2 leukemia, acute lymphoblastic 30.1 TYMS SLC19A1 MTHFR DHFR ABCB1
3 neutropenia 30.0 TYMS SLCO1B1 GPT ABCB1
4 down syndrome 30.0 SLC19A1 MTRR MTR MTHFR
5 homocysteinemia 29.9 SLC19A1 MTRR MTR MTHFR
6 childhood acute lymphocytic leukemia 29.9 TYMS SLC19A1 MTHFR DHFR ABCB1
7 vitamin b12 deficiency 29.9 MTR MTHFR GPT
8 megaloblastic anemia 29.3 SLC46A1 SLC19A1 MTRR MTR MTHFR DHFR
9 pustulosis of palm and sole 10.4
10 psoriasis 10.4
11 hemifacial spasm 10.3 TYMS MTHFR
12 rheumatoid arthritis 10.3
13 pancytopenia 10.3
14 sudden sensorineural hearing loss 10.3 MTR MTHFR
15 homocystinuria due to deficiency of n -methylenetetrahydrofolate reductase activity 10.3 MTR MTHFR
16 nondisjunction 10.3 MTRR MTHFR
17 methylmalonic aciduria and homocystinuria type cblg 10.3 MTRR MTR
18 methylmalonic aciduria and homocystinuria type cble 10.3 MTRR MTR
19 acute kidney failure 10.3
20 intracranial vasospasm 10.2 MTR MTHFR
21 lung non-squamous non-small cell carcinoma 10.2 TYMS DHFR
22 ophthalmia neonatorum 10.2 MTRR MTR
23 cutis laxa, autosomal dominant 3 10.2 MTR MTHFR DHFR
24 cutis laxa, autosomal dominant 2 10.2 MTR MTHFR DHFR
25 paralytic ileus 10.2 GPT ABCB1
26 arthritis 10.2
27 gastroesophageal adenocarcinoma 10.2 TYMS MTR MTHFR
28 adult acute lymphocytic leukemia 10.2 TYMS MTR MTHFR
29 cardia cancer 10.2 TYMS MTRR MTHFR
30 neural tube defects, folate-sensitive 10.2 MTRR MTR MTHFR
31 homocystinuria 10.1 MTRR MTR MTHFR
32 heterophyiasis 10.1 SELE GPT
33 juvenile rheumatoid arthritis 10.1
34 cleft lip/palate 10.1 MTRR MTR MTHFR
35 amino acid metabolic disorder 10.1 MTRR MTR MTHFR
36 choline deficiency disease 10.1 MTR MTHFR GPT
37 disorders of intracellular cobalamin metabolism 10.1 MTRR MTR
38 paraquat poisoning 10.1 SLC17A5 GPT
39 critical illness polyneuropathy 10.1 SELE GPT
40 parenteral nutrition-associated cholestasis 10.1 SLC17A5 GPT
41 methylmalonic acidemia 10.1 MTRR MTR MTHFR
42 urethritis 10.1 MTRR MTR
43 pyridoxine deficiency anemia 10.1 SLC17A5 GPT
44 physical disorder 10.1 MTRR MTR MTHFR
45 lymphoma, hodgkin, classic 10.1
46 osteogenic sarcoma 10.1
47 lymphoma, non-hodgkin, familial 10.1
48 stomatitis 10.1
49 48,xyyy 10.1
50 folate malabsorption, hereditary 10.1 SLC46A1 SLC19A1

Graphical network of the top 20 diseases related to Methotrexate Toxicity:



Diseases related to Methotrexate Toxicity

Symptoms & Phenotypes for Methotrexate Toxicity

MGI Mouse Phenotypes related to Methotrexate Toxicity:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.4 ABCB1 DHFR MTHFR MTR MTRR RFC1

Drugs & Therapeutics for Methotrexate Toxicity

Drugs for Methotrexate Toxicity (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 21)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Methotrexate Approved Phase 2 1959-05-2, 59-05-2 126941
2
Levoleucovorin Approved, Investigational Phase 1 68538-85-2 149436
3
leucovorin Approved Phase 1 58-05-9 6006
4
Folic acid Approved, Nutraceutical, Vet_approved Phase 1 59-30-3 6037
5 Nutrients Phase 1
6 Micronutrients Phase 1
7 Protective Agents Phase 1
8 Immunosuppressive Agents Phase 1
9 Vitamin B Complex Phase 1
10 Trace Elements Phase 1
11 Folic Acid Antagonists Phase 1
12 Vitamins Phase 1
13 Immunologic Factors Phase 1
14 Antimetabolites Phase 1
15 Folate Phase 1
16 Vitamin B9 Phase 1
17 Antirheumatic Agents Phase 1
18 Dermatologic Agents Phase 1
19 Antidotes Phase 1
20 Immunoglobulins Phase 1
21 Antibodies Phase 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 HM-178: Assessing Methods for Improvement in Methotrexate Toxicity Management and Detection of Central Nervous System Involvement of Aggressive Lymphoma Not yet recruiting NCT04668768 Phase 2 Glucarpidase
2 An Open-Label Study to Assess the Pharmacokinetics of Leucovorin in Patients Receiving High Dose Methotrexate, With or Without Voraxaze Treatment Completed NCT00634504 Phase 1 glucarpidase, high-dose methotrexate, leucovorin;high-dose methotrexate, leucovorin
3 A Trial of Carboxypeptidase-G2 (CPDG2) and Thymidine for the Management of Patients With Methotrexate Toxicity and Renal Dysfunction Completed NCT00001298 Phase 1 carboxypeptidase-G2
4 Individualized High Dose Methotrexate for the Treatment of Malignancies in Children and Adolescents With a Significant Risk for Methotrexate Toxicities Unknown status NCT02076997 Methotrexate
5 An Open-Label Treatment Protocol for the Use of Voraxaze as Adjunctive Treatment for Patients Experiencing or at Risk of Methotrexate Toxicity Approved for marketing NCT00481559 Voraxaze (glucarpidase)

Search NIH Clinical Center for Methotrexate Toxicity

Genetic Tests for Methotrexate Toxicity

Anatomical Context for Methotrexate Toxicity

MalaCards organs/tissues related to Methotrexate Toxicity:

40
Bone Marrow, Colon

Publications for Methotrexate Toxicity

Articles related to Methotrexate Toxicity:

(show top 50) (show all 337)
# Title Authors PMID Year
1
Potential contributors to low dose methotrexate toxicity in a patient with rheumatoid arthritis and pernicious anemia: case report. 61
33573706 2021
2
Lower Extremity Non-Blanchable Purpura Secondary to Methotrexate Toxicity: A Case Report. 61
32736973 2020
3
Cutaneous ulceration: A sign of methotrexate toxicity in oral cancer patient. 61
32273152 2020
4
Association between SLCO1A2 genetic variation and methotrexate toxicity in human rheumatoid arthritis treatment. 61
32304147 2020
5
Adverse effects with intravenous methotrexate in children with acute lymphoblastic leukemia/lymphoma: a retrospective study. 61
32647424 2020
6
Altered Folate Homeostasis in Children with Down Syndrome: A Potential Basis for Enhanced Methotrexate Toxicity. 61
32111377 2020
7
Use of Transient Elastography in Detection of Liver Fibrosis in Psoriasis Patients - A Cross- Sectional Study. 61
32695699 2020
8
Hemophagocytic Lymphohistiocytosis Complicating Methotrexate Toxicity. 61
32477983 2020
9
Methotrexate-Induced Pancytopenia and Mucositis Caused by Medication Error. 61
32863415 2020
10
Low-dose Methotrexate Toxicity in the Setting of Vancomycin-induced Acute Kidney Injury. 61
32775622 2020
11
Yet another case of acute methotrexate toxicity due to accidental overdose. 61
31979693 2020
12
The effect of asparaginase therapy on methotrexate toxicity and efficacy in children with acute lymphoblastic leukemia. 61
31120351 2019
13
[Severe methotrexate toxicity in elderly: 7 years experience]. 61
30992139 2019
14
Methotrexate Polyglutamate Values in Children and Adolescents With Acute Lymphoblastic Leukemia During Maintenance Therapy. 61
31259826 2019
15
Low-dose methotrexate toxicity. 61
30988043 2019
16
Mucocutaneous ulcers as forerunners of methotrexate toxicity. 61
30638290 2019
17
Renal clearance and intracellular half-life essentially determine methotrexate toxicity: A case series. 61
30581945 2019
18
DAMPAned Methotrexate: A Case Report and Review of the Management of Acute Methotrexate Toxicity. 61
31903191 2019
19
Acute Methotrexate Toxicity Due to Overdosing in Psoriasis: A Series of Seven Cases. 61
30775303 2019
20
Acute bone marrow suppression and gastrointestinal toxicity following acute oral methotrexate overdose. 61
29973099 2018
21
Leptotrichia trevisanii bacteremia in a woman with systemic lupus erythematosus receiving high-dose chemotherapy. 61
30547754 2018
22
Skin and mucosal ulcerations and acute kidney failure due to methotrexate toxicity in a patient with non-Hodgkin's lymphoma. 61
30829285 2018
23
Endogenous Metabolites-Mediated Communication Between OAT1/OAT3 and OATP1B1 May Explain the Association Between SLCO1B1 SNPs and Methotrexate Toxicity. 61
29285751 2018
24
A 2018 Approach to Combating Methotrexate Toxicity Folic Acid and Beyond. 61
31513516 2018
25
More than skin deep. 61
29861373 2018
26
Methotrexate Cutaneous Toxicity following a Single Dose of 10 mg in a Case of Chronic Plaque Psoriasis: A Possible Idiosyncratic Reaction. 61
30258802 2018
27
Use of MTHFR C677T polymorphism and plasma pharmacokinetics to predict methotrexate toxicity in patients with acute lymphoblastic leukemia. 61
29911750 2018
28
Association of hyperhomocysteinemia with genetic variants in key enzymes of homocysteine metabolism and methotrexate toxicity in rheumatoid arthritis patients. 61
29796841 2018
29
Concomitant use of low-dose methotrexate and NSAIDs and the risk of serious adverse events among patients with rheumatoid arthritis. 61
29797447 2018
30
Working Through the Paradox of Methotrexate Toxicity. 61
30031507 2018
31
Severe bone marrow suppression due to methotrexate toxicity following aceclofenac-induced acute kidney injury. 61
29871962 2018
32
Hypersegmented Neutrophils in Methotrexate Toxicity. 61
29269671 2018
33
Evaluating off-label uses of acetazolamide. 61
29626002 2018
34
Acute mucocutaneous methotrexate toxicity with marked tissue eosinophilia. 61
29627775 2018
35
Delayed Methotrexate Clearance Despite Carboxypeptidase-G2 (Glucarpidase) Administration in 2 Patients With Toxic Methotrexate Levels. 61
29240024 2018
36
[Apparent worsening of psoriasis lesions revealing methotrexate overdosage]. 61
28917574 2018
37
A Rapidly Fatal Case of Low-Dose Methotrexate Toxicity. 61
30008749 2018
38
Sunburn Recall Reaction and Mucositis Secondary to Methotrexate Toxicity. 61
30413231 2018
39
[4pp Mucocutaneous manifestations of methotrexate toxicity]. 61
29360079 2018
40
Evaluation, Identification, and Management of Acute Methotrexate Toxicity in High-dose Methotrexate Administration in Hematologic Malignancies. 61
29541561 2018
41
Effects of Infliximab against Methotrexate Toxicity in Splenic Tissue via the Regulation of CD3, CD68, and C200R in Rats. 61
31284287 2018
42
Association between SLC19A1 Gene Polymorphism and High Dose Methotrexate Toxicity in Childhood Acute Lymphoblastic Leukaemia and Non Hodgkin Malignant Lymphoma: Introducing a Haplotype based Approach. 61
29333125 2017
43
SLCO1B1 rs4149056 genetic polymorphism predicting methotrexate toxicity in Chinese patients with non-Hodgkin lymphoma. 61
29095107 2017
44
Impact of genetic variants of ATP binding cassette B1, AICAR transformylase/IMP cyclohydrolase, folyl-polyglutamatesynthetase, and methylenetetrahydrofolatereductase on methotrexate toxicity. 61
27751863 2017
45
Methotrexate toxicity: More than just reminders. 61
28651880 2017
46
Does daily folic acid supplementation reduce methotrexate efficacy? 61
29447631 2017
47
The Almost-Normal Liver Biopsy: Presentation, Clinical Associations, and Outcome. 61
28614198 2017
48
Investigating methotrexate toxicity within a randomized double-blinded, placebo-controlled trial: Rationale and design of the Cardiovascular Inflammation Reduction Trial-Adverse Events (CIRT-AE) Study. 61
28284844 2017
49
Acute methotrexate toxicity presenting with bullous lesions: an unusual presentation. 61
27975132 2017
50
Folate binding protein: therapeutic natural nanotechnology for folic acid, methotrexate, and leucovorin. 61
28155935 2017

Variations for Methotrexate Toxicity

Expression for Methotrexate Toxicity

Search GEO for disease gene expression data for Methotrexate Toxicity.

Pathways for Methotrexate Toxicity

Pathways related to Methotrexate Toxicity according to GeneCards Suite gene sharing:

(show all 18)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.88 TYMS SLCO1B1 SLC46A1 SLC19A1 MTRR MTR
2
Show member pathways
13.15 SLCO1B1 SLC46A1 SLC22A8 SLC22A6 SLC17A5 ABCB1
3
Show member pathways
12.41 SLC46A1 SLC19A1 MTRR MTR MTHFR DHFR
4
Show member pathways
11.97 SLC46A1 SLC19A1 MTRR MTR MTHFR DHFR
5
Show member pathways
11.9 SLCO1B1 SLC22A8 ABCB1
6
Show member pathways
11.81 TYMS MTRR MTR MTHFR DHFR
7
Show member pathways
11.79 SLCO1B1 SLC22A8 SLC22A6 ABCB1
8 11.63 SLCO1B1 SLC22A8 ABCB1
9
Show member pathways
11.53 TYMS MTHFR DHFR
10 10.96 SLC46A1 SLC19A1
11 10.88 MTRR MTR
12 10.88 SLC22A8 SLC22A6 ABCB1
13 10.85 TYMS SLC46A1 SLC19A1 MTHFR DHFR
14 10.77 SLCO1B1 ABCB1
15
Show member pathways
10.72 SLC22A8 SLC22A6 ABCB1
16 10.59 SLC22A8 SLC22A6
17
Show member pathways
10.4 SLCO1B1 SLC46A1 SLC22A8 SLC22A6 SLC19A1 ABCB1
18
Show member pathways
10.06 MTRR MTR

GO Terms for Methotrexate Toxicity

Cellular components related to Methotrexate Toxicity according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 apical plasma membrane GO:0016324 9.26 SLC46A1 SLC22A8 SLC19A1 ABCB1
2 basolateral plasma membrane GO:0016323 9.02 SLCO1B1 SLC46A1 SLC22A8 SLC22A6 SLC19A1

Biological processes related to Methotrexate Toxicity according to GeneCards Suite gene sharing:

(show all 21)
# Name GO ID Score Top Affiliating Genes
1 transmembrane transport GO:0055085 9.7 SLCO1B1 SLC46A1 SLC22A8 SLC22A6 SLC19A1 SLC17A5
2 regulation of transcription involved in G1/S transition of mitotic cell cycle GO:0000083 9.6 TYMS DHFR
3 anion transport GO:0006820 9.59 SLC22A6 SLC17A5
4 inorganic anion transport GO:0015698 9.58 SLC22A8 SLC22A6
5 cobalamin metabolic process GO:0009235 9.58 MTRR MTR
6 cellular amino acid biosynthetic process GO:0008652 9.58 MTRR MTR GPT
7 sodium-independent organic anion transport GO:0043252 9.57 SLCO1B1 SLC22A6
8 axon regeneration GO:0031103 9.56 MTR DHFR
9 tetrahydrofolate interconversion GO:0035999 9.55 TYMS MTHFR
10 response to folic acid GO:0051593 9.54 TYMS MTHFR
11 folic acid transport GO:0015884 9.52 SLC46A1 SLC19A1
12 homocysteine metabolic process GO:0050667 9.51 MTRR MTHFR
13 organic anion transport GO:0015711 9.5 SLCO1B1 SLC22A6 SLC19A1
14 methionine metabolic process GO:0006555 9.49 MTRR MTHFR
15 sulfur amino acid metabolic process GO:0000096 9.48 MTRR MTR
16 folate import across plasma membrane GO:1904447 9.46 SLC46A1 SLC19A1
17 response to methotrexate GO:0031427 9.43 SLC22A6 DHFR
18 methionine biosynthetic process GO:0009086 9.43 MTRR MTR MTHFR
19 methotrexate transport GO:0051958 9.37 SLC46A1 SLC19A1
20 tetrahydrofolate metabolic process GO:0046653 9.13 TYMS MTHFR DHFR
21 folic acid metabolic process GO:0046655 9.02 SLC46A1 SLC19A1 MTRR MTHFR DHFR

Molecular functions related to Methotrexate Toxicity according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 drug binding GO:0008144 9.51 TYMS DHFR
2 sodium-independent organic anion transmembrane transporter activity GO:0015347 9.49 SLCO1B1 SLC22A6
3 organic anion transmembrane transporter activity GO:0008514 9.48 SLC22A6 SLC19A1
4 translation repressor activity, mRNA regulatory element binding GO:0000900 9.46 TYMS DHFR
5 NADPH binding GO:0070402 9.43 MTRR DHFR
6 NADP binding GO:0050661 9.43 MTRR MTHFR DHFR
7 transmembrane transporter activity GO:0022857 9.43 SLCO1B1 SLC46A1 SLC22A8 SLC22A6 SLC17A5 ABCB1
8 sequence-specific mRNA binding GO:1990825 9.4 TYMS DHFR
9 inorganic anion exchanger activity GO:0005452 9.37 SLC22A8 SLC22A6
10 folic acid transmembrane transporter activity GO:0008517 9.32 SLC46A1 SLC19A1
11 methotrexate transmembrane transporter activity GO:0015350 9.16 SLC46A1 SLC19A1
12 folic acid binding GO:0005542 8.92 TYMS SLC46A1 SLC19A1 DHFR

Sources for Methotrexate Toxicity

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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