MCID: MTH086
MIFTS: 34

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 leucovorin have been mentioned in the context of this disorder. Affiliated tissues include kidney, bone and bone marrow, 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 131)
# Related Disease Score Top Affiliating Genes
1 mucositis 30.7 TYMS MTHFR ABCB1
2 leukemia, acute lymphoblastic 30.0 TYMS SLC19A1 MTHFR DHFR ABCB1
3 down syndrome 29.7 SLC19A1 MTRR MTR MTHFR
4 homocysteinemia 29.7 SLC19A1 MTRR MTR MTHFR
5 megaloblastic anemia 28.9 SLC46A1 MTRR MTR MTHFR DHFR
6 obsolete: methotrexate toxicity or dose selection 12.4
7 methotrexate dose selection 10.4 SLC19A1 MTHFR
8 hemifacial spasm 10.4 TYMS MTHFR
9 pustulosis of palm and sole 10.4
10 psoriasis 10.4
11 homocystinuria due to deficiency of n -methylenetetrahydrofolate reductase activity 10.4 MTR MTHFR
12 nondisjunction 10.3 MTRR MTHFR
13 methylmalonic aciduria and homocystinuria type cblg 10.3 MTRR MTR
14 methylmalonic aciduria and homocystinuria type cble 10.3 MTRR MTR
15 paralytic ileus 10.3 GPT ABCB1
16 pancytopenia 10.2
17 acute kidney failure 10.2
18 heterophyiasis 10.2 SELE GPT
19 paraquat poisoning 10.2 SLC17A5 GPT
20 grange syndrome 10.2 SELE MTHFR
21 gastroesophageal adenocarcinoma 10.2 TYMS MTR MTHFR
22 placental abruption 10.2 SLC19A1 MTRR MTHFR
23 familial intrahepatic cholestasis 10.2 SLCO1B1 ABCB1
24 adult acute lymphocytic leukemia 10.2 TYMS MTR MTHFR
25 lymphocytic leukemia 10.2
26 choline deficiency disease 10.2 MTR MTHFR GPT
27 pyridoxine deficiency anemia 10.1 SLC17A5 GPT
28 cardia cancer 10.1 TYMS MTRR MTHFR
29 vitamin b12 deficiency 10.1 MTR MTHFR GPT
30 non-alcoholic steatohepatitis 10.1 SLC17A5 GPT
31 thiamine metabolism dysfunction syndrome 2 10.1 SLC46A1 SLC19A1
32 vitamin metabolic disorder 10.1 MTRR MTR MTHFR
33 neural tube defects, folate-sensitive 10.1 MTRR MTR MTHFR
34 homocystinuria 10.1 MTRR MTR MTHFR
35 neutropenia 10.1
36 kidney disease 10.1
37 juvenile rheumatoid arthritis 10.1
38 methylmalonic acidemia 10.1 MTRR MTR MTHFR
39 infantile liver failure syndrome 1 10.1 SLC17A5 GPT
40 disorders of intracellular cobalamin metabolism 10.1 MTRR MTR
41 amino acid metabolic disorder 10.1 MTRR MTR MTHFR
42 intrahepatic cholestasis of pregnancy 10.1 SLCO1B1 GPT ABCB1
43 fatty liver disease, nonalcoholic 1 10.1 SLC17A5 GPT
44 migraine with aura 10.0 MTRR MTR MTHFR
45 lymphoma, hodgkin, classic 10.0
46 osteogenic sarcoma 10.0
47 lymphoma, non-hodgkin, familial 10.0
48 stomatitis 10.0
49 phenylketonuria 10.0 MTRR MTR MTHFR
50 kwashiorkor 10.0 SLC17A5 GPT

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:

45
# 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 27)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Methotrexate Approved Phase 4 59-05-2, 1959-05-2 126941
2
leucovorin Approved Phase 4 58-05-9 6006 143
3
Folic acid Approved, Nutraceutical, Vet_approved Phase 4 59-30-3 6037
4 Immunosuppressive Agents Phase 4
5 Folic Acid Antagonists Phase 4
6 Vitamin B Complex Phase 4
7 Immunologic Factors Phase 4
8 Dermatologic Agents Phase 4
9 Folate Phase 4
10 Antimetabolites Phase 4
11 Antirheumatic Agents Phase 4
12 Vitamin B9 Phase 4
13 Hematinics Phase 4
14 Trace Elements Phase 4
15 Micronutrients Phase 4
16 Vitamins Phase 4
17 Nutrients Phase 4
18
Prednisone Approved, Vet_approved Phase 2 53-03-2 5865
19 glucocorticoids Phase 2
20 Anti-Inflammatory Agents Phase 2
21 Hormone Antagonists Phase 2
22 Antineoplastic Agents, Hormonal Phase 2
23 Hormones Phase 2
24 Antipsychotic Agents Phase 2
25 Antibodies Phase 1
26 Immunoglobulins Phase 1
27 Antibodies, Monoclonal

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Evaluating the Efficacy of Weekly Folic Acid in Pediatric Inflammatory Bowel Disease Patients on Methotrexate Recruiting NCT03860012 Phase 4 Folic Acid
2 Phase II Randomized Study of Glucocorticoids With or Without Methotrexate for Treatment of Giant Cell Arteritis Completed NCT00004686 Phase 2 methotrexate;prednisone
3 A Randomized Double Blind Parallel Trial Administering Methotrexate vs Placebo as add-on to Antipsychotics in Patients With Schizophrenia or Schizoaffecive Disorder Not yet recruiting NCT03369795 Phase 2 Methotrexate
4 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
5 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
6 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)
7 Exploratory Evaluation of Biomarkers Associated With Treatment Response to Cosentyx (Secukinumab) in Psoriasis Patients Completed NCT03149900 Secukinumab

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
Kidney, Bone, Bone Marrow, Liver, Skin, Brain, Colon

Publications for Methotrexate Toxicity

Articles related to Methotrexate Toxicity:

(show top 50) (show all 328)
# Title Authors PMID Year
1
The effect of asparaginase therapy on methotrexate toxicity and efficacy in children with acute lymphoblastic leukemia. 61
31120351 2019
2
[Severe methotrexate toxicity in elderly: 7 years experience]. 61
30992139 2019
3
Methotrexate-associated toxicity in children with Down syndrome and acute lymphoblastic leukemia during consolidation therapy with high dose methotrexate according to ALL-BFM treatment regimen. 61
31371414 2019
4
Methotrexate Polyglutamate Values in Children and Adolescents With Acute Lymphoblastic Leukemia During Maintenance Therapy. 61
31259826 2019
5
Low-dose methotrexate toxicity. 61
30988043 2019
6
Mucocutaneous ulcers as forerunners of methotrexate toxicity. 61
30638290 2019
7
Acute Methotrexate Toxicity Due to Overdosing in Psoriasis: A Series of Seven Cases. 61
30775303 2019
8
Renal clearance and intracellular half-life essentially determine methotrexate toxicity: A case series. 61
30581945 2019
9
Acute bone marrow suppression and gastrointestinal toxicity following acute oral methotrexate overdose. 61
29973099 2018
10
Leptotrichia trevisanii bacteremia in a woman with systemic lupus erythematosus receiving high-dose chemotherapy. 61
30547754 2018
11
Skin and mucosal ulcerations and acute kidney failure due to methotrexate toxicity in a patient with non-Hodgkin's lymphoma. 61
30829285 2018
12
Endogenous Metabolites-Mediated Communication Between OAT1/OAT3 and OATP1B1 May Explain the Association Between SLCO1B1 SNPs and Methotrexate Toxicity. 61
29285751 2018
13
A 2018 Approach to Combating Methotrexate Toxicity Folic Acid and Beyond. 61
31513516 2018
14
More than skin deep. 61
29861373 2018
15
Methotrexate Cutaneous Toxicity following a Single Dose of 10 mg in a Case of Chronic Plaque Psoriasis: A Possible Idiosyncratic Reaction. 61
30258802 2018
16
Concomitant use of low-dose methotrexate and NSAIDs and the risk of serious adverse events among patients with rheumatoid arthritis. 61
29797447 2018
17
Association of hyperhomocysteinemia with genetic variants in key enzymes of homocysteine metabolism and methotrexate toxicity in rheumatoid arthritis patients. 61
29796841 2018
18
Use of MTHFR C677T polymorphism and plasma pharmacokinetics to predict methotrexate toxicity in patients with acute lymphoblastic leukemia. 61
29911750 2018
19
Working Through the Paradox of Methotrexate Toxicity. 61
30031507 2018
20
Severe bone marrow suppression due to methotrexate toxicity following aceclofenac-induced acute kidney injury. 61
29871962 2018
21
Acute mucocutaneous methotrexate toxicity with marked tissue eosinophilia. 61
29627775 2018
22
Hypersegmented Neutrophils in Methotrexate Toxicity. 61
29269671 2018
23
Evaluating off-label uses of acetazolamide. 61
29626002 2018
24
Delayed Methotrexate Clearance Despite Carboxypeptidase-G2 (Glucarpidase) Administration in 2 Patients With Toxic Methotrexate Levels. 61
29240024 2018
25
[Apparent worsening of psoriasis lesions revealing methotrexate overdosage]. 61
28917574 2018
26
Sunburn Recall Reaction and Mucositis Secondary to Methotrexate Toxicity. 61
30413231 2018
27
A Rapidly Fatal Case of Low-Dose Methotrexate Toxicity. 61
30008749 2018
28
Effects of Infliximab against Methotrexate Toxicity in Splenic Tissue via the Regulation of CD3, CD68, and C200R in Rats. 61
31284287 2018
29
[4pp Mucocutaneous manifestations of methotrexate toxicity]. 61
29360079 2018
30
Evaluation, Identification, and Management of Acute Methotrexate Toxicity in High-dose Methotrexate Administration in Hematologic Malignancies. 61
29541561 2018
31
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
32
SLCO1B1 rs4149056 genetic polymorphism predicting methotrexate toxicity in Chinese patients with non-Hodgkin lymphoma. 61
29095107 2017
33
Methotrexate toxicity: More than just reminders. 61
28651880 2017
34
Impact of genetic variants of ATP binding cassette B1, AICAR transformylase/IMP cyclohydrolase, folyl-polyglutamatesynthetase, and methylenetetrahydrofolatereductase on methotrexate toxicity. 61
27751863 2017
35
Does daily folic acid supplementation reduce methotrexate efficacy? 61
29447631 2017
36
The Almost-Normal Liver Biopsy: Presentation, Clinical Associations, and Outcome. 61
28614198 2017
37
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
38
Acute methotrexate toxicity presenting with bullous lesions: an unusual presentation. 61
27975132 2017
39
Folate binding protein: therapeutic natural nanotechnology for folic acid, methotrexate, and leucovorin. 61
28155935 2017
40
Using a Bedside Algorithm to Individually Dose High-dose Methotrexate for Patients at Risk for Toxicity. 61
27820134 2017
41
Severe methotrexate toxicity after treatment for ectopic pregnancy: A case report. 61
28913127 2016
42
Methotrexate toxicity-response. 61
27101928 2016
43
Letter to the editor in response to the article "Clinical characteristics and risk factors for low dose methotrexate toxicity: a cohort of 28 patients" by Kivity S, Zafrir Y, Loebstein R, Pauzner R, Mouallem M, Mayan H, Autoimmun Rev. 2014 Nov.;13(11):1109-13: Height of MTX-PG levels in low-dose MTX-toxicity differs according to the time of onset. 61
27095131 2016
44
Sequential use of hemoperfusion and single-pass albumin dialysis can safely reverse methotrexate nephrotoxicity. 61
27335061 2016
45
Poster 62 Muscle Weakness, Dysarthria, and Dysphagia After Methotrexate Toxicity: A Case Report. 61
27672831 2016
46
Genetic Determinants of Methotrexate Toxicity in Tunisian Patients with Rheumatoid Arthritis: A Study of Polymorphisms Involved in the MTX Metabolic Pathway. 61
26077125 2016
47
Methotrexate-induced toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses. 61
27142726 2016
48
Management of non-tubal ectopic pregnancies at a large tertiary hospital. 61
27174395 2016
49
A decade of Australian methotrexate dosing errors. 61
27256650 2016
50
Precursor miR-499a Variant but not miR-196a2 is Associated with Rheumatoid Arthritis Susceptibility in an Egyptian Population. 61
27002721 2016

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
13.87 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
Show member pathways
11.55 TYMS MTHFR DHFR
9 11.51 SLCO1B1 SLC22A8 ABCB1
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 integral component of plasma membrane GO:0005887 9.63 SLCO1B1 SLC46A1 SLC22A6 SLC19A1 SLC17A5 SELE
2 apical plasma membrane GO:0016324 9.26 SLC46A1 SLC22A8 SLC19A1 ABCB1
3 basolateral plasma membrane GO:0016323 8.92 SLCO1B1 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 inorganic anion transport GO:0015698 9.6 SLC22A8 SLC22A6
3 regulation of transcription involved in G1/S transition of mitotic cell cycle GO:0000083 9.59 TYMS DHFR
4 anion transport GO:0006820 9.58 SLC22A6 SLC17A5
5 cobalamin metabolic process GO:0009235 9.58 MTRR MTR
6 sodium-independent organic anion transport GO:0043252 9.57 SLCO1B1 SLC22A6
7 organic anion transport GO:0015711 9.56 SLCO1B1 SLC22A6
8 axon regeneration GO:0031103 9.55 MTR DHFR
9 tetrahydrofolate interconversion GO:0035999 9.54 TYMS MTHFR
10 cellular amino acid biosynthetic process GO:0008652 9.54 MTRR MTR GPT
11 response to folic acid GO:0051593 9.52 TYMS MTHFR
12 homocysteine metabolic process GO:0050667 9.51 MTRR MTHFR
13 folic acid transport GO:0015884 9.49 SLC46A1 SLC19A1
14 methionine metabolic process GO:0006555 9.48 MTRR MTHFR
15 sulfur amino acid metabolic process GO:0000096 9.46 MTRR MTR
16 folate import across plasma membrane GO:1904447 9.43 SLC46A1 SLC19A1
17 methionine biosynthetic process GO:0009086 9.43 MTRR MTR MTHFR
18 response to methotrexate GO:0031427 9.4 SLC22A6 DHFR
19 methotrexate transport GO:0051958 9.32 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:

# Name GO ID Score Top Affiliating Genes
1 transmembrane transporter activity GO:0022857 9.65 SLC46A1 SLC22A8 SLC22A6
2 sodium-independent organic anion transmembrane transporter activity GO:0015347 9.46 SLCO1B1 SLC22A6
3 NADPH binding GO:0070402 9.43 MTRR DHFR
4 translation repressor activity, mRNA regulatory element binding GO:0000900 9.4 TYMS DHFR
5 sequence-specific mRNA binding GO:1990825 9.37 TYMS DHFR
6 NADP binding GO:0050661 9.33 MTRR MTHFR DHFR
7 inorganic anion exchanger activity GO:0005452 9.32 SLC22A8 SLC22A6
8 folic acid transmembrane transporter activity GO:0008517 9.26 SLC46A1 SLC19A1
9 methotrexate transmembrane transporter activity GO:0015350 8.96 SLC46A1 SLC19A1
10 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
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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