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THPM1
MCID: THP004
MIFTS: 47

Thiopurines, Poor Metabolism of, 1 (THPM1)

Categories: Blood diseases, Bone diseases, Cancer diseases, Genetic diseases, Immune diseases, Metabolic diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Thiopurines, Poor Metabolism of, 1

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MalaCards integrated aliases for Thiopurines, Poor Metabolism of, 1:

Name: Thiopurines, Poor Metabolism of, 1 56
Thiopurine S-Methyltransferase Deficiency 56 12 25 36 15 39
Thiopurine Methyltransferase Deficiency 25 29 6
Tpmt Deficiency 56 12 25
Thiopurine S-Methyltransferase Deficiency; Tpmtd 56
Thiopurine S Methyltranferase Deficiency 71
Poor Metabolism of Thiopurines-1 12
Poor Metabolism of Thiopurines 25
Thpm1 56
Tpmtd 56

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
increased susceptibility to toxic effects of treatment with 6-mercaptopurine (6mp), 6-thioguanine (6tg), and azathioprine (aza)
heterozygotes may also show increased susceptibility to toxic effects of thiopurine treatment


HPO:

31
thiopurines, poor metabolism of, 1:
Inheritance autosomal recessive inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases Metabolic diseases Cancer diseases
Anatomical: Bone diseases Immune diseases Blood diseases
See all MalaCards categories (disease lists)


External Ids:

Disease Ontology 12 DOID:0080172
OMIM 56 610460
OMIM Phenotypic Series 56 PS610460
KEGG 36 H00964
MedGen 41 C0342801
SNOMED-CT via HPO 68 191124002 258211005 34093004
UMLS 71 C0342801
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Summaries for Thiopurines, Poor Metabolism of, 1

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Genetics Home Reference : 25 Thiopurine S-methyltransferase (TPMT) deficiency is a condition characterized by significantly reduced activity of an enzyme that helps the body process drugs called thiopurines. These drugs, which include 6-thioguanine, 6-mercaptopurine, and azathioprine, inhibit (suppress) the body's immune system. Thiopurine drugs are used to treat some autoimmune disorders, including Crohn disease and rheumatoid arthritis, which occur when the immune system malfunctions. These drugs are also used to treat several forms of cancer, particularly cancers of blood-forming tissue (leukemias) and cancers of immune system cells (lymphomas). Additionally, thiopurine drugs are used in organ transplant recipients to help prevent the immune system from attacking the transplanted organ. A potential complication of treatment with thiopurine drugs is damage to the bone marrow (hematopoietic toxicity). Although this complication can occur in anyone who takes these drugs, people with TPMT deficiency are at highest risk. Bone marrow normally makes several types of blood cells, including red blood cells, which carry oxygen; white blood cells, which help protect the body from infection; and platelets, which are involved in blood clotting. Damage to the bone marrow results in myelosuppression, a condition in which the bone marrow is unable to make enough of these cells. A shortage of red blood cells (anemia) can cause pale skin (pallor), weakness, shortness of breath, and extreme tiredness (fatigue). Low numbers of white blood cells (neutropenia) can lead to frequent and potentially life-threatening infections. A shortage of platelets (thrombocytopenia) can cause easy bruising and bleeding. Many healthcare providers recommend that patients' TPMT activity levels be tested before thiopurine drugs are prescribed. In people who are found to have reduced enzyme activity, the drugs may be given at a significantly lower dose or different medications can be used to reduce the risk of hematopoietic toxicity. TPMT deficiency does not appear to cause any health problems other than those associated with thiopurine drug treatment.

MalaCards based summary : Thiopurines, Poor Metabolism of, 1, also known as thiopurine s-methyltransferase deficiency, is related to neutropenia and thiopurine s methyltranferase deficiency. An important gene associated with Thiopurines, Poor Metabolism of, 1 is TPMT (Thiopurine S-Methyltransferase), and among its related pathways/superpathways are Drug metabolism - other enzymes and Metabolism. The drugs Azathioprine and Immunologic Factors have been mentioned in the context of this disorder. Affiliated tissues include bone marrow, bone and skin, and related phenotypes are abnormality of metabolism/homeostasis and abnormality of blood and blood-forming tissues

Disease Ontology : 12 An inherited metabolic disease that is characterized by significantly reduced activity of an enzyme that helps the body process drugs called thiopurines.

OMIM : 56 THPM1 is an autosomal recessive trait associated with severe hematopoietic toxicity when patients are treated with standard doses of the antineoplastic agents 6-mercaptopurine (6MP) or 6-thioguanine (6TG), or the immunosuppressant azathioprine (AZA) (Lennard et al., 1989). The thiopurines are prodrugs that require extensive metabolism in order to exert their cytotoxic action. Azathioprine is nonenzymatically reduced to 6MP. 6MP and 6TG are activated by HPRT (308000) and subsequent steps to form cytotoxic thioguanine nucleotides (TGNs) which are incorporated into DNA and/or RNA, causing DNA-protein cross-links, single-strand breaks, interstrand cross-links, and sister chromatid exchange. TPMT functions mainly to inactivate these drugs; thus, a deficiency of TPMT results in increased conversion to toxic TGNs, which can result in myelosuppression (Coulthard and Hogarth, 2005). However, 6MP is unique in that it can also be converted via TPMT into a methyl-thioinosine 5-prime monophosphate (MeTIMP), a metabolite that inhibits de novo purine synthesis and likely contributes to the cytotoxic effect of 6MP (Vogt et al., 1993; Krynetski et al., 1995; Coulthard and Hogarth, 2005). (610460)

KEGG : 36 Thiopurine S-methyltransferase deficiency (TPMT deficiency) is inherited severe intolerance to thiopurine toxicity, caused by mutation in the TPMT gene. TPMT is part of a cascade of enzymes responsible for the metabolism of thiopurine drugs including azathioprine, mercaptopurine, and thioguanine.

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Related Diseases for Thiopurines, Poor Metabolism of, 1

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Diseases in the Thiopurines, Poor Metabolism of, 1 family:

Thiopurines, Poor Metabolism of, 2

Diseases related to Thiopurines, Poor Metabolism of, 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 47)
# Related Disease Score Top Affiliating Genes
1 neutropenia 29.6 UGT1A1 TPMT ITPA CYP3A5
2 thiopurine s methyltranferase deficiency 12.1
3 thiopurines, poor metabolism of, 2 11.3
4 inflammatory bowel disease 10.4
5 crohn's disease 10.4
6 pancytopenia 10.3
7 autoimmune hepatitis 10.3
8 nodular regenerative hyperplasia 10.2 TPMT ITPA
9 autoimmune disease 10.2
10 leukemia, acute myeloid 10.2
11 leukemia, acute lymphoblastic 10.2
12 aspergillosis 10.2
13 crohn's colitis 10.2
14 ulcerative colitis 10.2
15 myeloid leukemia 10.2
16 abacavir allergy 10.1 VKORC1 SLCO1B1
17 beta-thalassemia 10.1
18 thalassemia 10.1
19 leukemia 10.1
20 diarrhea 10.1
21 sclerosing cholangitis 10.1
22 thrombocytopenia 10.1
23 hepatitis 10.1
24 liver disease 10.1
25 cholangitis 10.1
26 cholestasis, progressive familial intrahepatic, 2 10.0 SLCO1B1 ABCC4
27 dermatitis, atopic 10.0
28 dermatitis 10.0
29 severe cutaneous adverse reaction 9.9 VKORC1 TPMT CYP2D6
30 epicardium cancer 9.9 UGT1A8 UGT1A1
31 dubin-johnson syndrome 9.8 SLCO1B1 ABCC4
32 drug-induced hepatitis 9.7 UGT1A1 CYP2D6
33 multiple chemical sensitivity 9.7 UGT1A1 CYP3A5 CYP2D6
34 acetaminophen metabolism 9.6 UGT1A6 UGT1A1 CYP2D6
35 bilirubin, serum level of, quantitative trait locus 1 9.5 UGT1A8 UGT1A6 UGT1A1
36 glucosephosphate dehydrogenase deficiency 9.5 UGT1A8 UGT1A1 SLCO1B1 CYP2D6
37 cardiomyopathy, dilated, with hypergonadotropic hypogonadism 9.5 UGT1A8 UGT1A6 UGT1A1
38 crigler-najjar syndrome, type i 9.5 UGT1A8 UGT1A6 UGT1A1
39 crigler-najjar syndrome, type ii 9.5 UGT1A8 UGT1A6 UGT1A1
40 kernicterus 9.5 UGT1A8 UGT1A6 UGT1A1
41 dihydropyrimidine dehydrogenase deficiency 9.5 UGT1A8 UGT1A6 UGT1A1
42 cholelithiasis 9.5 UGT1A8 UGT1A6 UGT1A1
43 sickle cell anemia 9.4 UGT1A8 UGT1A6 UGT1A1
44 inherited metabolic disorder 9.3 UGT1A8 UGT1A6 UGT1A1
45 pigmentation disease 9.3 UGT1A8 UGT1A6 UGT1A1 SLCO1B1
46 gilbert syndrome 9.3 UGT1A8 UGT1A6 UGT1A1 SLCO1B1
47 bilirubin metabolic disorder 9.1 UGT1A8 UGT1A6 UGT1A1 SLCO1B1 ABCC4

Graphical network of the top 20 diseases related to Thiopurines, Poor Metabolism of, 1:



Diseases related to Thiopurines, Poor Metabolism of, 1
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Symptoms & Phenotypes for Thiopurines, Poor Metabolism of, 1

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Human phenotypes related to Thiopurines, Poor Metabolism of, 1:

31
# Description HPO Frequency HPO Source Accession
1 abnormality of metabolism/homeostasis 31 HP:0001939
2 abnormality of blood and blood-forming tissues 31 HP:0001871

Symptoms via clinical synopsis from OMIM:

56
Hematology:
myelosuppression develops on standard doses of thiopurine drugs
hematopoietic toxicity develops on standard doses of thiopurine drugs

Laboratory Abnormalities:
decreased activity of thiopurine s-methyltransferase
decreased metabolism of thiopurine drugs
increased toxic thioguanine nucleotides (tgns) on standard doses of thiopurine drugs

Clinical features from OMIM:

610460
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Drugs & Therapeutics for Thiopurines, Poor Metabolism of, 1

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Drugs for Thiopurines, Poor Metabolism of, 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Azathioprine Approved 446-86-6 2265
2 Immunologic Factors
3 Immunosuppressive Agents
4 Antirheumatic Agents
5 Antimetabolites

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Functional Pharmacogenomics of Childhood Acute Lymphoblastic Leukemia in Taiwan Unknown status NCT00526084
2 Correlation of Genetic Polymorphism of Two Azathioprine Metabolizing Enzymes and Their Correlation to Clinical Adverse Effects Completed NCT00525473 Azathioprine

Search NIH Clinical Center for Thiopurines, Poor Metabolism of, 1

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Genetic Tests for Thiopurines, Poor Metabolism of, 1

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Genetic tests related to Thiopurines, Poor Metabolism of, 1:

# Genetic test Affiliating Genes
1 Thiopurine Methyltransferase Deficiency 29 TPMT
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Anatomical Context for Thiopurines, Poor Metabolism of, 1

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MalaCards organs/tissues related to Thiopurines, Poor Metabolism of, 1:

40
Bone Marrow, Bone, Skin, Testes, Heart, Kidney, Myeloid
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Publications for Thiopurines, Poor Metabolism of, 1

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Articles related to Thiopurines, Poor Metabolism of, 1:

(show all 41)
# Title Authors PMID Year
1
Severe azathioprine-induced myelotoxicity in a kidney transplant patient with thiopurine S-methyltransferase-deficient genotype (TPMT*3A/*3C). 56 6
15819814 2005
2
A single point mutation leading to loss of catalytic activity in human thiopurine S-methyltransferase. 56 6
7862671 1995
3
Altered mercaptopurine metabolism, toxic effects, and dosage requirement in a thiopurine methyltransferase-deficient child with acute lymphocytic leukemia. 6 56
1960624 1991
4
Preponderance of thiopurine S-methyltransferase deficiency and heterozygosity among patients intolerant to mercaptopurine or azathioprine. 61 56
11304783 2001
5
Thiopurine S-methyltransferase deficiency: two nucleotide transitions define the most prevalent mutant allele associated with loss of catalytic activity in Caucasians. 6 61
8644731 1996
6
Explaining TPMT genotype/phenotype discrepancy by haplotyping of TPMT*3A and identification of a novel sequence variant, TPMT*23. 6
17885628 2007
7
Molecular analysis of thiopurine S-methyltransferase alleles in Taiwan aborigines and Taiwanese. 6
16476125 2006
8
The thiopurines: an update. 56
16267626 2005
9
Human thiopurine S-methyltransferase pharmacogenetics: variant allozyme misfolding and aggresome formation. 6
15967990 2005
10
Thiopurine methyltransferase (TPMT) genotype and early treatment response to mercaptopurine in childhood acute lymphoblastic leukemia. 56
15784872 2005
11
Thiopurine S-methyltransferase: a genetic polymorphism that affects a small number of drugs in a big way. 56
12172209 2002
12
Azathioprine therapy and adverse drug reactions in patients with inflammatory bowel disease: impact of thiopurine S-methyltransferase polymorphism. 56
12172211 2002
13
Genetic analysis of thiopurine methyltransferase polymorphism in a Japanese population. 6
10751626 2000
14
Thiopurine methyltransferase pharmacogenetics: alternative molecular diagnosis and preliminary data from Northern Portugal. 56
10376773 1999
15
The frequency and distribution of thiopurine methyltransferase alleles in Caucasian and Asian populations. 6
10208641 1999
16
Thiopurine methyltransferase alleles in British and Ghanaian populations. 6
9931345 1999
17
Polymorphism of the thiopurine S-methyltransferase gene in African-Americans. 6
9931346 1999
18
Thiopurine methyltransferase genotype predicts therapy-limiting severe toxicity from azathioprine. 56
9841604 1998
19
Azathioprine-induced severe pancytopenia due to a homozygous two-point mutation of the thiopurine methyltransferase gene in a patient with juvenile HLA-B27-associated spondylarthritis. 6
9336428 1997
20
Human thiopurine methyltransferase pharmacogenetics: gene sequence polymorphisms. 6
9246020 1997
21
Enhanced proteolysis of thiopurine S-methyltransferase (TPMT) encoded by mutant alleles in humans (TPMT*3A, TPMT*2): mechanisms for the genetic polymorphism of TPMT activity. 6
9177237 1997
22
Thiopurine methyltransferase pharmacogenetics: human gene cloning and characterization of a common polymorphism. 6
8561894 1996
23
Congenital thiopurine methyltransferase deficiency and 6-mercaptopurine toxicity during treatment for acute lymphoblastic leukaemia. 56
8257179 1993
24
The importance of methylthio-IMP for methylmercaptopurine ribonucleoside (Me-MPR) cytotoxicity in Molt F4 human malignant T-lymphoblasts. 56
7683208 1993
25
Azathioprine-induced myelosuppression in thiopurine methyltransferase deficient heart transplant recipient. 56
8094196 1993
26
Genetic variation in response to 6-mercaptopurine for childhood acute lymphoblastic leukaemia. 56
1973780 1990
27
Pharmacogenetics of acute azathioprine toxicity: relationship to thiopurine methyltransferase genetic polymorphism. 56
2758725 1989
28
Thiopurine pharmacogenetics in leukemia: correlation of erythrocyte thiopurine methyltransferase activity and 6-thioguanine nucleotide concentrations. 56
3467886 1987
29
Early Assessment of Thiopurine Metabolites Identifies Patients at Risk of Thiopurine-induced Leukopenia in Inflammatory Bowel Disease. 61
27402913 2017
30
Update on thiopurine pharmacogenetics in inflammatory bowel disease. 61
26067482 2015
31
Evidence for a functional genetic polymorphism of the Rho-GTPase Rac1. Implication in azathioprine response? 61
21372752 2011
32
Thiopurine S-methyltransferase deficiency associated with a novel mutation. 61
20186941 2010
33
Transporter-mediated protection against thiopurine-induced hematopoietic toxicity. 61
18593894 2008
34
Azathioprine-associated acute myeloid leukemia in a patient with Crohn's disease and thiopurine S-methyltransferase deficiency. 61
17696202 2008
35
Association of inosine triphosphatase 94C>A and thiopurine S-methyltransferase deficiency with adverse events and study drop-outs under azathioprine therapy in a prospective Crohn disease study. 61
16214825 2005
36
[Pharmacogenetics: Important aspects for dermatology]. 61
15645192 2005
37
Allelic variants of the thiopurine S-methyltransferase deficiency in patients with ulcerative colitis and in healthy controls. 61
11007234 2000
38
Molecular diagnosis of thiopurine S-methyltransferase deficiency. 61
9412292 1997
39
Acute lymphoblastic leukemia. 61
9286287 1997
40
Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. 61
9103127 1997
41
Thiopurine S-methyltransferase activity in a Chinese population. 61
8330462 1993
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Variations for Thiopurines, Poor Metabolism of, 1

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ClinVar genetic disease variations for Thiopurines, Poor Metabolism of, 1:

6 (show all 50) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TPMT NM_000367.4(TPMT):c.719A>G (p.Tyr240Cys)SNV Likely benign, other 12725 rs1142345 6:18130918-18130918 6:18130687-18130687
2 TPMT NM_000367.4(TPMT):c.460G>A (p.Ala154Thr)SNV Likely benign, other 37126 rs1800460 6:18139228-18139228 6:18138997-18138997
3 TPMT NM_000367.4(TPMT):c.626-1G>ASNV drug response 12723 rs1800584 6:18131012-18131012 6:18130781-18130781
4 TPMT NM_000367.4(TPMT):c.644G>A (p.Arg215His)SNV drug response 12726 rs56161402 6:18130993-18130993 6:18130762-18130762
5 TPMT NM_000367.4(TPMT):c.500C>G (p.Ala167Gly)SNV drug response 12727 rs74423290 6:18134115-18134115 6:18133884-18133884
6 TPMT NM_000367.2(TPMT):c.238G>C (p.Ala80Pro)SNV drug response 12721 rs1800462 6:18143955-18143955 6:18143724-18143724
7 TPMT NM_000367.4(TPMT):c.-30T>ASNV Uncertain significance 356121 rs376768623 6:18149388-18149388 6:18149157-18149157
8 TPMT NM_000367.4(TPMT):c.*1658C>ASNV Uncertain significance 356091 rs886061257 6:18129241-18129241 6:18129010-18129010
9 TPMT NM_000367.4(TPMT):c.*501G>CSNV Uncertain significance 356107 rs886061262 6:18130398-18130398 6:18130167-18130167
10 TPMT NM_000367.4(TPMT):c.*414G>ASNV Uncertain significance 356108 rs528907381 6:18130485-18130485 6:18130254-18130254
11 TPMT NM_000367.4(TPMT):c.620T>G (p.Leu207Trp)SNV Uncertain significance 356112 rs761626260 6:18132369-18132369 6:18132138-18132138
12 TPMT NM_000367.4(TPMT):c.339C>T (p.Thr113=)SNV Uncertain significance 356116 rs17839843 6:18143854-18143854 6:18143623-18143623
13 TPMT NM_000367.4(TPMT):c.292G>T (p.Glu98Ter)SNV Uncertain significance 356118 rs72552739 6:18143901-18143901 6:18143670-18143670
14 TPMT NM_000367.4(TPMT):c.210C>T (p.Cys70=)SNV Uncertain significance 356119 rs186214874 6:18148077-18148077 6:18147846-18147846
15 TPMT NM_000367.4(TPMT):c.141-10T>CSNV Uncertain significance 356120 rs757278118 6:18148156-18148156 6:18147925-18147925
16 TPMT NM_000367.4(TPMT):c.-45+11T>CSNV Uncertain significance 356123 rs886061267 6:18155253-18155253 6:18155022-18155022
17 TPMT NM_000367.4(TPMT):c.-138deldeletion Uncertain significance 356125 rs543585967 6:18155357-18155357 6:18155126-18155126
18 TPMT NM_000367.4(TPMT):c.420-4G>ASNV Uncertain significance 143913 rs56019966 6:18139272-18139272 6:18139041-18139041
19 TPMT NM_000367.4(TPMT):c.*1873G>ASNV Uncertain significance 356086 rs886061255 6:18129026-18129026 6:18128795-18128795
20 TPMT NM_000367.4(TPMT):c.*1804G>TSNV Uncertain significance 356088 rs559243767 6:18129095-18129095 6:18128864-18128864
21 TPMT NM_000367.4(TPMT):c.*1778_*1781dupduplication Uncertain significance 356089 rs886061256 6:18129117-18129118 6:18128886-18128887
22 TPMT NM_000367.4(TPMT):c.*1757deldeletion Uncertain significance 356090 rs748123873 6:18129142-18129142 6:18128911-18128911
23 TPMT NM_000367.4(TPMT):c.*1522C>TSNV Uncertain significance 356094 rs116170115 6:18129377-18129377 6:18129146-18129146
24 TPMT NM_000367.4(TPMT):c.*1204G>ASNV Uncertain significance 356100 rs886061260 6:18129695-18129695 6:18129464-18129464
25 TPMT NM_000367.4(TPMT):c.*523G>ASNV Uncertain significance 356104 rs886061261 6:18130376-18130376 6:18130145-18130145
26 TPMT NM_000367.4(TPMT):c.*329A>GSNV Uncertain significance 356109 rs886061263 6:18130570-18130570 6:18130339-18130339
27 TPMT NM_000367.4(TPMT):c.375G>A (p.Ser125=)SNV Uncertain significance 356115 rs760980416 6:18139940-18139940 6:18139709-18139709
28 TPMT NM_000367.4(TPMT):c.-44-4G>ASNV Uncertain significance 356122 rs202034437 6:18149406-18149406 6:18149175-18149175
29 TPMT NM_000367.4(TPMT):c.-66C>TSNV Uncertain significance 356124 rs141028204 6:18155285-18155285 6:18155054-18155054
30 TPMT NM_000367.4(TPMT):c.*1820A>GSNV Uncertain significance 356087 rs1142374 6:18129079-18129079 6:18128848-18128848
31 TPMT NM_000367.4(TPMT):c.*1511G>ASNV Uncertain significance 356095 rs553500255 6:18129388-18129388 6:18129157-18129157
32 TPMT NM_000367.4(TPMT):c.*1305C>GSNV Uncertain significance 356096 rs144017186 6:18129594-18129594 6:18129363-18129363
33 TPMT NM_000367.4(TPMT):c.*1218G>ASNV Uncertain significance 356099 rs186206580 6:18129681-18129681 6:18129450-18129450
34 TPMT NM_000367.4(TPMT):c.*634dupduplication Uncertain significance 356103 rs760084154 6:18130264-18130265 6:18130033-18130034
35 TPMT NM_000367.4(TPMT):c.*515G>ASNV Uncertain significance 356105 rs145605593 6:18130384-18130384 6:18130153-18130153
36 TPMT NM_000367.4(TPMT):c.*60T>CSNV Uncertain significance 356110 rs886061264 6:18130839-18130839 6:18130608-18130608
37 TPMT NM_000367.4(TPMT):c.335T>A (p.Ile112Asn)SNV Uncertain significance 356117 rs886061266 6:18143858-18143858 6:18143627-18143627
38 TPMT NM_000367.4(TPMT):c.*2340T>CSNV Uncertain significance 356083 rs539430078 6:18128559-18128559 6:18128328-18128328
39 TPMT NM_000367.4(TPMT):c.*1590T>CSNV Uncertain significance 356093 rs886061258 6:18129309-18129309 6:18129078-18129078
40 TPMT NM_000367.4(TPMT):c.*1285G>ASNV Uncertain significance 356097 rs886061259 6:18129614-18129614 6:18129383-18129383
41 TPMT NM_000367.4(TPMT):c.*1221T>CSNV Uncertain significance 356098 rs146425737 6:18129678-18129678 6:18129447-18129447
42 TPMT NM_000367.4(TPMT):c.*1177G>ASNV Uncertain significance 356101 rs139793761 6:18129722-18129722 6:18129491-18129491
43 TPMT NM_000367.4(TPMT):c.*899_*902deldeletion Uncertain significance 356102 rs542619563 6:18129997-18130000 6:18129766-18129769
44 TPMT NM_000367.4(TPMT):c.*514C>TSNV Uncertain significance 356106 rs532306797 6:18130385-18130385 6:18130154-18130154
45 TPMT NM_000367.4(TPMT):c.*44G>ASNV Uncertain significance 356111 rs886061265 6:18130855-18130855 6:18130624-18130624
46 TPMT NM_000367.4(TPMT):c.580+14G>TSNV Likely benign 356113 rs2842949 6:18134021-18134021 6:18133790-18133790
47 TPMT NM_000367.4(TPMT):c.474= (p.Ile158=)SNV Likely benign 356114 rs2842934 6:18139214-18139214 6:18138983-18138983
48 TPMT NM_000367.4(TPMT):c.*1604G>ASNV Likely benign 356092 rs9465100 6:18129295-18129295 6:18129064-18129064
49 TPMT NM_000367.4(TPMT):c.*1900A>CSNV Likely benign 356085 rs1142378 6:18128999-18128999 6:18128768-18128768
50 TPMT NM_000367.4(TPMT):c.*2240A>TSNV Likely benign 356084 rs7886 6:18128659-18128659 6:18128428-18128428
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Expression for Thiopurines, Poor Metabolism of, 1

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Search GEO for disease gene expression data for Thiopurines, Poor Metabolism of, 1.
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Pathways for Thiopurines, Poor Metabolism of, 1

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Pathways related to Thiopurines, Poor Metabolism of, 1 according to KEGG:

36
# Name Kegg Source Accession
1 Drug metabolism - other enzymes hsa00983

Pathways related to Thiopurines, Poor Metabolism of, 1 according to GeneCards Suite gene sharing:

(show all 25)
# Super pathways Score Top Affiliating Genes
1
Metabolism 65
Show member pathways
 13.95 VKORC1 UGT1A8 UGT1A6 UGT1A1 TPMT SLCO1B1
2
Cytochrome P450 - arranged by substrate type 65
Show member pathways
 13.05 UGT1A8 UGT1A6 UGT1A1 TPMT CYP3A5 CYP2D6
3
Drug metabolism - cytochrome P450 36
Show member pathways
 12.71 UGT1A8 UGT1A6 UGT1A1 TPMT ITPA CYP3A5
4
Glucose / Energy Metabolism 4
12.38 UGT1A8 UGT1A6 UGT1A1 CYP2D6 ABCC4
5
Porphyrin and chlorophyll metabolism 36
Show member pathways
 12.15 UGT1A8 UGT1A6 UGT1A1
6
NRF2 pathway 1
11.95 UGT1A6 UGT1A1 ABCC4
7
Statin Pathway - Generalized, Pharmacokinetics 60
Show member pathways
 11.86 UGT1A1 SLCO1B1 CYP3A5 CYP2D6 ABCC4
8
Bile secretion 36
11.61 UGT1A8 UGT1A6 UGT1A1 SLCO1B1 ABCC4
9
Steroid hormone biosynthesis 36
Show member pathways
 11.6 UGT1A8 UGT1A6 UGT1A1 CYP3A5
10
Phenytoin Pathway, Pharmacokinetics 60
Show member pathways
 11.56 UGT1A6 UGT1A1 CYP3A5 CYP2D6
11
Ponatinib Pathway, Pharmacokinetics/Pharmacodynamics 60
Show member pathways
 11.46 UGT1A1 CYP3A5 CYP2D6
12
Acetaminophen Pathway (therapeutic doses), Pharmacokinetics 60
Show member pathways
 11.45 UGT1A8 UGT1A6 UGT1A1 CYP2D6 ABCC4
13
Tamoxifen metabolism 1
Show member pathways
 11.31 UGT1A8 CYP3A5 CYP2D6
14
Erlotinib Pathway, Pharmacokinetics 60
Show member pathways
 11.26 UGT1A1 CYP3A5 CYP2D6
15
Estrogen metabolism 1
Show member pathways
 11.23 UGT1A8 UGT1A6 UGT1A1
16
Carvedilol Pathway, Pharmacokinetics 60
Show member pathways
 11.23 UGT1A8 UGT1A1 SLCO1B1 CYP3A5 CYP2D6
17
Crizotinib Pathway, Pharmacokinetics/Pharmacodynamics 60
11.2 SLCO1B1 CYP3A5
18
Pazopanib Pathway, Pharmacokinetics 60
Show member pathways
 11.2 UGT1A1 SLCO1B1 CYP3A5 CYP2D6
19
Constitutive Androstane Receptor Pathway 1
11.19 UGT1A6 UGT1A1 CYP3A5
20
Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics 60
11.05 TPMT NUDT15 ITPA ABCC4
21
Methotrexate Pathway, Pharmacokinetics 60
Show member pathways
 10.91 SLCO1B1 ABCC4
22
Drug Induction of Bile Acid Pathway 1
10.83 SLCO1B1 ABCC4
23
Irinotecan Pathway, Pharmacokinetics 60
Show member pathways
 10.79 UGT1A8 UGT1A6 UGT1A1 SLCO1B1 CYP3A5
24
Lamotrigine Pathway, Pharmacokinetics and Pharmacodynamics 60
10.77 CYP2D6 ABCC4
25
Etoposide Pathway, Pharmacokinetics/Pharmacodynamics 60
10.76 UGT1A1 CYP3A5
Sources

GO Terms for Thiopurines, Poor Metabolism of, 1

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Cellular components related to Thiopurines, Poor Metabolism of, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum GO:0005783 9.63 VKORC1 UGT1A8 UGT1A6 UGT1A1 CYP3A5 CYP2D6
2 endoplasmic reticulum membrane GO:0005789 9.43 VKORC1 UGT1A8 UGT1A6 UGT1A1 CYP3A5 CYP2D6
3 intracellular membrane-bounded organelle GO:0043231 9.17 VKORC1 UGT1A8 UGT1A6 UGT1A1 PACSIN2 CYP3A5

Biological processes related to Thiopurines, Poor Metabolism of, 1 according to GeneCards Suite gene sharing:

(show all 20)
# Name GO ID Score Top Affiliating Genes
1 response to organic cyclic compound GO:0014070 9.74 VKORC1 UGT1A1 ABCC4
2 steroid metabolic process GO:0008202 9.71 UGT1A8 UGT1A1 CYP3A5 CYP2D6
3 xenobiotic metabolic process GO:0006805 9.7 UGT1A6 CYP3A5 CYP2D6
4 retinol metabolic process GO:0042572 9.59 CYP3A5 CYP2D6
5 response to organonitrogen compound GO:0010243 9.58 VKORC1 ABCC4
6 exogenous drug catabolic process GO:0042738 9.58 NUDT15 CYP2D6
7 oxidative demethylation GO:0070989 9.56 CYP3A5 CYP2D6
8 cellular glucuronidation GO:0052695 9.55 UGT1A6 UGT1A1
9 purine nucleotide catabolic process GO:0006195 9.54 NUDT15 ITPA
10 heterocycle metabolic process GO:0046483 9.51 UGT1A1 CYP2D6
11 retinoic acid metabolic process GO:0042573 9.5 UGT1A8 UGT1A1 CYP3A5
12 coumarin metabolic process GO:0009804 9.49 UGT1A8 CYP2D6
13 flavone metabolic process GO:0051552 9.48 UGT1A8 UGT1A1
14 drug catabolic process GO:0042737 9.46 CYP3A5 CYP2D6
15 alkaloid catabolic process GO:0009822 9.43 CYP3A5 CYP2D6
16 estrogen metabolic process GO:0008210 9.43 UGT1A1 CYP3A5 CYP2D6
17 negative regulation of steroid metabolic process GO:0045939 9.37 UGT1A8 UGT1A1
18 xenobiotic glucuronidation GO:0052697 9.33 UGT1A8 UGT1A6 UGT1A1
19 flavonoid glucuronidation GO:0052696 9.13 UGT1A8 UGT1A6 UGT1A1
20 drug metabolic process GO:0017144 8.92 VKORC1 UGT1A1 TPMT CYP2D6

Molecular functions related to Thiopurines, Poor Metabolism of, 1 according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 enzyme inhibitor activity GO:0004857 9.49 UGT1A8 UGT1A1
2 steroid hydroxylase activity GO:0008395 9.48 CYP3A5 CYP2D6
3 steroid binding GO:0005496 9.46 UGT1A8 UGT1A1
4 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen GO:0016712 9.43 CYP3A5 CYP2D6
5 NADH pyrophosphatase activity GO:0035529 9.4 NUDT15 ITPA
6 nucleotide diphosphatase activity GO:0004551 9.37 NUDT15 ITPA
7 transferase activity, transferring hexosyl groups GO:0016758 9.33 UGT1A8 UGT1A6 UGT1A1
8 nucleoside-triphosphate diphosphatase activity GO:0047429 9.32 NUDT15 ITPA
9 dTTP diphosphatase activity GO:0036218 9.26 NUDT15 ITPA
10 glucuronosyltransferase activity GO:0015020 9.13 UGT1A8 UGT1A6 UGT1A1
11 retinoic acid binding GO:0001972 8.8 UGT1A8 UGT1A6 UGT1A1
Sources

Sources for Thiopurines, Poor Metabolism of, 1

About this section
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
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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