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DPYDD
MCID: DHY002
MIFTS: 58

Dihydropyrimidine Dehydrogenase Deficiency (DPYDD)

Categories: Blood diseases, Bone diseases, Cancer diseases, Genetic diseases, Mental diseases, Metabolic diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Dihydropyrimidine Dehydrogenase Deficiency

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MalaCards integrated aliases for Dihydropyrimidine Dehydrogenase Deficiency:

Name: Dihydropyrimidine Dehydrogenase Deficiency 56 12 74 52 25 58 73 36 29 6 43 15 39 71
Dpd Deficiency 56 52 25 73
Hereditary Thymine-Uraciluria 52 25 73
Familial Pyrimidinemia 52 58 73
Dihydropyrimidinuria 25 73 71
5-Fluorouracil Toxicity 56 13
Dpyd Deficiency 56 73
Dihydrouracil Dehydrogenase Deficiency 12
Thymine-Uraciluria, Hereditary 56
Pyrimidinemia, Familial 56
Familial Pyrimidinaemia 12
Pyrimidinemia Familial 74
Familial Pyrimidemia 25
Thymine-Uracilurea 12
Dpydd 73

Characteristics:

Orphanet epidemiological data:

58
dihydropyrimidine dehydrogenase deficiency
Age of onset: All ages; Age of death: normal life expectancy;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype
onset usually in infancy although later onset may occur
some individuals are asymptomatic
heterozygous mutation carriers show toxicity to 5-fluorouracil (5fu)


HPO:

31
dihydropyrimidine dehydrogenase deficiency:
Inheritance autosomal recessive inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Metabolic diseases Cancer diseases
Anatomical: Bone diseases Neuronal diseases Blood diseases Mental diseases
See all MalaCards categories (disease lists)
ICD10: 33
Orphanet: 58  
Rare systemic and rhumatological diseases
Inborn errors of metabolism


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Summaries for Dihydropyrimidine Dehydrogenase Deficiency

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Genetics Home Reference : 25 Dihydropyrimidine dehydrogenase deficiency is a disorder characterized by a wide range of severity, with neurological problems in some individuals and no signs or symptoms in others. In people with severe dihydropyrimidine dehydrogenase deficiency, the disorder becomes apparent in infancy. These affected individuals have neurological problems such as recurrent seizures (epilepsy), intellectual disability, a small head size (microcephaly), increased muscle tone (hypertonia), delayed development of motor skills such as walking, and autistic behaviors that affect communication and social interaction. Other affected individuals are asymptomatic, which means they do not have any signs or symptoms of the condition. Individuals with asymptomatic dihydropyrimidine dehydrogenase deficiency may be identified only by laboratory testing. People with dihydropyrimidine dehydrogenase deficiency, including those who otherwise exhibit no symptoms, are vulnerable to severe, potentially life-threatening toxic reactions to certain drugs called fluoropyrimidines that are used to treat cancer. Common examples of these drugs are 5-fluorouracil and capecitabine. These drugs are not broken down efficiently by people with dihydropyrimidine dehydrogenase deficiency and build up to toxic levels in the body (fluoropyrimidine toxicity). Severe inflammation and ulceration of the lining of the gastrointestinal tract (mucositis) may occur, which can lead to signs and symptoms including mouth sores, abdominal pain, bleeding, nausea, vomiting, and diarrhea. Fluoropyrimidine toxicity may also lead to low numbers of white blood cells (neutropenia), which increases the risk of infections. It can also be associated with low numbers of platelets in the blood (thrombocytopenia), which impairs blood clotting and may lead to abnormal bleeding (hemorrhage). Redness, swelling, numbness, and peeling of the skin on the palms and soles (hand-foot syndrome); shortness of breath; and hair loss may also occur.

MalaCards based summary : Dihydropyrimidine Dehydrogenase Deficiency, also known as dpd deficiency, is related to dihydropyrimidinase deficiency and pyrimidine metabolic disorder, and has symptoms including seizures and lethargy. An important gene associated with Dihydropyrimidine Dehydrogenase Deficiency is DPYD (Dihydropyrimidine Dehydrogenase), and among its related pathways/superpathways are Pyrimidine metabolism and Drug metabolism - other enzymes. The drugs Immunologic Factors and Immunosuppressive Agents have been mentioned in the context of this disorder. Affiliated tissues include testes, skin and colon, and related phenotypes are agenesis of corpus callosum and intellectual disability

Disease Ontology : 12 A purine-pyrimidine metabolic disorder that is an autosomal recessive metabolic disorder in which there is absent or significantly decreased activity of dihydropyrimidine dehydrogenase, an enzyme involved in the metabolism of uracil and thymine.

NIH Rare Diseases : 52 Dihydropyrimidine dehydrogenase (DPD) deficiency is a condition in which the body cannot break down the nucleotides , thymine and uracil . DPD deficiency can have a has a wide range of severity. Most people have no obvious signs or symptoms, but some develop serious neurological problems as infants. In infants with severe DPD deficiency, the signs and symptoms may include seizures , intellectual disability , microcephaly , increased muscle tone (hypertonia ), delayed motor skills, and autistic behavior. It is not clear why some individuals with DPD deficiency have symptoms and others don't. DPD deficiency is caused by mutations in the DPYD gene and is inherited in an autosomal recessive manner. Babies with the severe form of DPD deficiency may be diagnosed based on the symptoms, and additional laboratory testing. Treatment for the severe form is based on the symptoms. All individuals with the DPD deficiency, regardless of the presence or severity of symptoms, are at risk for severe, toxic reactions to drugs called fluoropyrimidines which are used to treat cancer . Individuals with no symptoms may be diagnosed only by laboratory testing or after exposure to fluoropyrimidines.

OMIM : 56 Dihyropyrimidine dehydrogenase deficiency shows large phenotypic variability, ranging from no symptoms to a convulsive disorder with motor and mental retardation in homozygous patients. In addition, homozygous and heterozygous mutation carriers can develop severe toxicity after the administration of the antineoplastic drug 5-fluorouracil (5FU), which is also catabolized by the DPYD enzyme. This is an example of a pharmacogenetic disorder (Van Kuilenburg et al., 1999). Since there is no correlation between genotype and phenotype in DPD deficiency, it appears that the deficiency is a necessary, but not sufficient, prerequisite for the development of clinical abnormalities (Van Kuilenburg et al., 1999; Enns et al., 2004). (274270)

KEGG : 36 Dihydropyrimidine dehydrogenase enzyme deficiency is a pharmacogenetic syndrome leading to severe side-effects in patients receiving therapies containing the anticancer drug 5-fluorouracil.

UniProtKB/Swiss-Prot : 73 Dihydropyrimidine dehydrogenase deficiency: A metabolic disorder with large phenotypic variability, ranging from no symptoms to a convulsive disorder with motor and mental retardation. It is characterized by persistent urinary excretion of excessive amounts of uracil, thymine and 5-hydroxymethyluracil. Patients suffering from this disease show a severe reaction to the anticancer drug 5-fluorouracil.

Wikipedia : 74 Dihydropyrimidine dehydrogenase deficiency is an autosomal recessive metabolic disorder in which there... more...

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Related Diseases for Dihydropyrimidine Dehydrogenase Deficiency

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Diseases related to Dihydropyrimidine Dehydrogenase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 69)
# Related Disease Score Top Affiliating Genes
1 dihydropyrimidinase deficiency 32.9 DPYS DPYD ADSL
2 pyrimidine metabolic disorder 30.0 TYMP DPYS DPYD
3 neutropenia 29.7 UGT1A1 TYMS DPYD
4 rectum cancer 29.7 TYMS TYMP DPYD
5 gilbert syndrome 28.9 UGT1A8 UGT1A6 UGT1A1
6 autosomal recessive disease 10.5
7 mucositis 10.5
8 colorectal cancer 10.3
9 alacrima, achalasia, and mental retardation syndrome 10.3
10 breast cancer 10.3
11 microcephaly 10.3
12 thrombocytopenia 10.3
13 stomatitis 10.3
14 carbonic anhydrase va deficiency, hyperammonemia due to 10.2
15 beta-ureidopropionase deficiency 10.2 DPYS DPYD
16 enterocolitis 10.2
17 exanthem 10.2
18 diarrhea 10.2
19 hypotonia 10.2
20 macroglossia 10.2 DPYD COL11A1
21 echolalia 10.1 DPYD-IT1 DPYD-AS2 DPYD-AS1
22 angelman syndrome 10.0
23 ocular motor apraxia 10.0
24 yemenite deaf-blind hypopigmentation syndrome 10.0
25 brittle bone disorder 10.0
26 gastric cancer 10.0
27 aspiration pneumonia 10.0
28 anaplastic large cell lymphoma 10.0
29 cortical blindness 10.0
30 cicatricial ectropion 10.0
31 ectropion 10.0
32 epilepsy 10.0
33 ascending colon cancer 10.0
34 focal epilepsy 10.0
35 keratopathy 10.0
36 acute kidney failure 10.0
37 gastric adenocarcinoma 10.0
38 gastroesophageal junction adenocarcinoma 10.0
39 gangliosidosis 10.0
40 cerebral atrophy 10.0
41 encephalopathy 10.0
42 hypertonia 10.0
43 purine-pyrimidine metabolic disorder 10.0 DPYD-IT1 DPYD ADSL
44 factor vii deficiency 10.0
45 pancreatic cancer 10.0
46 pancytopenia 10.0
47 lynch syndrome 10.0
48 pancreatic adenocarcinoma 10.0
49 epicardium cancer 9.8 UGT1A8 UGT1A1
50 esophageal cancer 9.8

Graphical network of the top 20 diseases related to Dihydropyrimidine Dehydrogenase Deficiency:



Diseases related to Dihydropyrimidine Dehydrogenase Deficiency
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Symptoms & Phenotypes for Dihydropyrimidine Dehydrogenase Deficiency

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Human phenotypes related to Dihydropyrimidine Dehydrogenase Deficiency:

31 (show all 21)
# Description HPO Frequency HPO Source Accession
1 agenesis of corpus callosum 31 occasional (7.5%) HP:0001274
2 intellectual disability 31 HP:0001249
3 muscular hypotonia 31 HP:0001252
4 delayed speech and language development 31 HP:0000750
5 microcephaly 31 HP:0000252
6 optic atrophy 31 HP:0000648
7 hypertonia 31 HP:0001276
8 failure to thrive 31 HP:0001508
9 nystagmus 31 HP:0000639
10 autism 31 HP:0000717
11 growth delay 31 HP:0001510
12 motor delay 31 HP:0001270
13 microphthalmia 31 HP:0000568
14 lethargy 31 HP:0001254
15 cerebral atrophy 31 HP:0002059
16 hyperactivity 31 HP:0000752
17 generalized hypotonia 31 HP:0001290
18 tetraplegia 31 HP:0002445
19 coloboma 31 HP:0000589
20 seizure 31 HP:0001250
21 reduced dihydropyrimidine dehydrogenase level 31 HP:0003654

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
seizures
hypertonia
lethargy
cerebral atrophy
tetraplegia
more
Head And Neck Eyes:
optic atrophy
nystagmus
microphthalmia
coloboma
abnormal ocular movements

Neurologic Behavioral Psychiatric Manifestations:
autism
hyperactivity

Head And Neck Head:
microcephaly

Growth Other:
failure to thrive
growth retardation

Laboratory Abnormalities:
increased urinary uracil
increased urinary thymine
decreased or absent dihydropyrimidine dehydrogenase activity

Clinical features from OMIM:

274270

UMLS symptoms related to Dihydropyrimidine Dehydrogenase Deficiency:


seizures, lethargy
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Drugs & Therapeutics for Dihydropyrimidine Dehydrogenase Deficiency

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Drugs for Dihydropyrimidine Dehydrogenase Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 28)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Immunologic Factors Phase 4
2 Immunosuppressive Agents Phase 4
3
Fluorouracil Approved Phase 2 51-21-8 3385
4
Levoleucovorin Approved, Investigational Phase 2 68538-85-2
5
leucovorin Approved Phase 2 58-05-9 6006 143
6
Oxaliplatin Approved, Investigational Phase 2 61825-94-3 43805 6857599 5310940 9887054
7
Irinotecan Approved, Investigational Phase 2 97682-44-5, 100286-90-6 60838
8
Capecitabine Approved, Investigational Phase 1, Phase 2 154361-50-9 60953
9
Epirubicin Approved Phase 1, Phase 2 56420-45-2 41867
10
Carboplatin Approved Phase 1, Phase 2 41575-94-4 10339178 38904 498142
11
Folic acid Approved, Nutraceutical, Vet_approved Phase 2 59-30-3 6037
12 Antidotes Phase 2
13 Micronutrients Phase 2
14 Trace Elements Phase 2
15 Vitamins Phase 2
16 Vitamin B Complex Phase 2
17 Hematinics Phase 2
18 Folate Phase 2
19 topoisomerase I inhibitors Phase 2
20 Nutrients Phase 2
21 Folfirinox Phase 2
22 Vitamin B9 Phase 2
23 Protective Agents Phase 2
24 Antimetabolites Phase 1, Phase 2
25 Anti-Bacterial Agents Phase 1, Phase 2
26 Antibiotics, Antitubercular Phase 1, Phase 2
27
Lithium carbonate Approved 554-13-2
28 Cola

Interventional clinical trials:

(show all 11)
# Name Status NCT ID Phase Drugs
1 Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients With the Aim of Reducing Toxicity Not yet recruiting NCT04269369 Phase 4 5-Fluorouracil
2 Phase-2 Study Evaluating Overall Response Rate (Efficacy) and Autonomy Daily Living Preservation (Tolerance) of "FOLFIRINOX " Pharmacogenetic Dose Adjusted, in Elderly Patients (70 yo. or Older) With a Metastatic Pancreatic Adenocarcinoma. Active, not recruiting NCT02143219 Phase 2 Oxaliplatine;Folinic acid;Irinotecan;5-FU
3 Combined Phase I/II Study of Epirubicin (Pharmorubicin®), Carboplatin (Paraplatin®) and Capecitabine (Xeloda®) (ECC) in the Treatment of Unresectable Locally Advanced or Metastatic Gastric/Gastroesophageal Junction Cancer With Pharmacogenetic Correlates Terminated NCT00130936 Phase 1, Phase 2 Epirubicin;Carboplatin;Capecitabine
4 A Food Effect and QTc Study of Perifosine in Patients With Advanced Malignancies Completed NCT01224730 Phase 1 perifosine
5 Thymidylate Synthase Polymorphisms as a Predictor of Toxicity to 5-Fluorouracil Based Chemotherapy in Stage III Colon Cancer Unknown status NCT00131599 5FU/LV
6 An Open-Label Protocol for the Use of Uridine Triacetate as an Antidote to Treat Patients at Excess Risk of 5-Fluorouracil Toxicity Due to Overdosage or Impaired Elimination Approved for marketing NCT01432301 uridine triacetate
7 Safety, Feasibility and Cost-effectiveness of Genotype-directed Individualized Dosing of Fluoropyrimidines Completed NCT02324452 Fluoropyrimidine (capecitabine or 5-fluorouracil)
8 Multicentric Pilot Study of Dihydropyrimidine Dehydrogenase (DPD) Deficiency for Predicting Capecitabine Toxicity in Breast Cancer Patients Completed NCT00953537 capecitabine
9 Improving the Safety of Fluoropyrimidine-based Chemotherapy by Combined DPYD Genotype-guided and DPD Phenotype-guided Dose Individualization: The ALPE2U Study Recruiting NCT04194957 Fluoropyrimidine (capecitabine or 5-fluorouracil);Fluoropyrimidine (capecitabine or 5-fluorouracil);Fluoropyrimidine (capecitabine or 5-fluorouracil)
10 The Medical-financial Evaluation of Pre-therapeutic Screening by a Joint Phenotypic-pharmacogenetic Approach for Metabolic Fluoropyrimidine Enzyme Deficiency in Terms of Serious Toxicity Risk Prevention : a Multicentric Case Study Terminated NCT01547923
11 Thymidylate Synthase Polymorphisms as a Predictor of Toxicity to Capecitabine Based Adjuvant Chemotherapy in Colon Cancer Treatment Terminated NCT00126867

Search NIH Clinical Center for Dihydropyrimidine Dehydrogenase Deficiency

Cochrane evidence based reviews: dihydropyrimidine dehydrogenase deficiency

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Genetic Tests for Dihydropyrimidine Dehydrogenase Deficiency

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Genetic tests related to Dihydropyrimidine Dehydrogenase Deficiency:

# Genetic test Affiliating Genes
1 Dihydropyrimidine Dehydrogenase Deficiency 29
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Anatomical Context for Dihydropyrimidine Dehydrogenase Deficiency

About this section

MalaCards organs/tissues related to Dihydropyrimidine Dehydrogenase Deficiency:

40
Testes, Skin, Colon, Breast, Bone, Liver, Bone Marrow
Sources

Publications for Dihydropyrimidine Dehydrogenase Deficiency

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Articles related to Dihydropyrimidine Dehydrogenase Deficiency:

(show top 50) (show all 307)
# Title Authors PMID Year
1
Analysis of severely affected patients with dihydropyrimidine dehydrogenase deficiency reveals large intragenic rearrangements of DPYD and a de novo interstitial deletion del(1)(p13.3p21.3). 6 56 61
19296131 2009
2
Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency. 61 56 6
10071185 1999
3
Molecular basis of the human dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity. 56 6 61
8698850 1996
4
Heterozygosity for a point mutation in an invariant splice donor site of dihydropyrimidine dehydrogenase and severe 5-fluorouracil related toxicity. 6 56
9470816 1997
5
Identification of a four-base deletion (delTCAT296-299) in the dihydropyrimidine dehydrogenase gene with variable clinical expression. 56 6
9254861 1997
6
Human polymorphism in drug metabolism: mutation in the dihydropyrimidine dehydrogenase gene results in exon skipping and thymine uracilurea. 56 6
7832988 1995
7
Clinical and biochemical findings in six patients with pyrimidine degradation defects. 56 6
8051923 1994
8
Head imaging abnormalities in dihydropyrimidine dehydrogenase deficiency. 61 56
15303009 2004
9
Dihydropyrimidine dehydrogenase deficiency and fluorouracil-related toxicity. 61 56
10027340 1999
10
Dihydropyrimidine dehydrogenase deficiency: a novel mutation and expression of missense mutations in E. coli. 61 6
9686374 1998
11
Dihydropyrimidine dehydrogenase (DPD) deficiency: identification and expression of missense mutations C29R, R886H and R235W. 61 6
9439663 1997
12
A point mutation in an invariant splice donor site leads to exon skipping in two unrelated Dutch patients with dihydropyrimidine dehydrogenase deficiency. 61 6
8892022 1996
13
Severe 5-fluorouracil toxicity secondary to dihydropyrimidine dehydrogenase deficiency. A potentially more common pharmacogenetic syndrome. 56 61
1648430 1991
14
A new case of dihydropyrimidine dehydrogenase deficiency. 56 61
2109146 1990
15
Dihydropyrimidine dehydrogenase deficiency leading to thymine-uraciluria. An inborn error of pyrimidine metabolism. 56 61
3930854 1985
16
Dihydropyrimidine dehydrogenase deficiency--a further case. 61 56
3930855 1985
17
Dihydropyrimidine dehydrogenase deficiency leading to thymine-uraciluria. An inborn error of pyrimidine metabolism. 61 56
6488556 1984
18
Population and family studies of dihydropyrimidinuria: prevalence, inheritance mode, and risk of fluorouracil toxicity. 56
9714435 1998
19
Identification of novel point mutations in the dihydropyrimidine dehydrogenase gene. 6
9266349 1997
20
Possible prediction of adverse reactions to pyrimidine chemotherapy from urinary pyrimidine levels and a case of asymptomatic adult dihydropyrimidinuria. 56
9816152 1996
21
Dihydropyrimidinuria without clinical symptoms. 56
8892031 1996
22
Influence of sex and age on fluorouracil clearance. 56
1607921 1992
23
Familial deficiency of dihydropyrimidine dehydrogenase. Biochemical basis for familial pyrimidinemia and severe 5-fluorouracil-induced toxicity. 56
3335642 1988
24
Familial pyrimidinemia and pyrimidinuria associated with severe fluorouracil toxicity. 56
2989687 1985
25
Elevated urine, blood and cerebrospinal fluid levels of uracil and thymine in a child with dihydrothymine dehydrogenase deficiency. 56
6467612 1984
26
New defects of pyrimidine metabolism. 56
6720361 1984
27
Urinary excretion of thymine and uracil in a two-year-old child with a malignant tumor of the brain. 56
287571 1979
28
New DPYD variants causing DPD deficiency in patients treated with fluoropyrimidine. 61
32529295 2020
29
5-Fluorouracil-induced hyperammonaemic encephalopathy: A French national survey. 61
32120273 2020
30
Automatic quantification of uracil and dihydrouracil in plasma. 61
32169798 2020
31
Delaying Centrifugation and Freezing by Adding a Dihydropyrimidine Dehydrogenase Inhibitor Such as Gimeracil to Blood Sample Is Not a Valid Option to Simplify the Preanalytic Step for the Screening of Dihydropyrimidine Dehydrogenase Deficiency Using Uracilemia. 61
31855974 2020
32
Fluoropyrimidine-induced toxicity and DPD deficiency.. A case report of early onset, lethal capecitabine-induced toxicity and mini review of the literature. Uridine triacetate: Efficacy and safety as an antidote. Is it accessible outside USA? 61
31382864 2020
33
A Simple and Rapid UPLC-UV Method for Detecting DPD Deficiency in Patients With Cancer. 61
32058656 2020
34
Toxicities associated with chemotherapy regimens containing a fluoropyrimidine: A real-life evaluation in France. 61
31715555 2020
35
Letter to the Editor: Murphy C, Byrne S, Ahmed G, Kenny A, Gallagher J, Harvey H, O'Farrell, Bird B. Cost Implication of Reactive Versus Prospective Testing for DPD Deficiency in Patients with Colorectal Cancer: A Single Institution Experience. Dose Response. 2018; 16(4). 61
31802994 2019
36
Response to Letter: Cost Implications of Reactive Versus Prospective Testing for Dihydropyrimidine Dehydrogenase Deficiency in Patients With Colorectal Cancer: A Single-Institution Experience. 61
31802992 2019
37
[Dihydropyrimidine dehydrogenase deficiency screening for management of patients receiving a fluoropyrimidine: Results of two national practice surveys addressed to clinicians and biologists]. 61
31253356 2019
38
The Prevalence of DPYD*9A(c.85T>C) Genotype and the Genotype-Phenotype Correlation in Patients with Gastrointestinal Malignancies Treated With Fluoropyrimidines: Updated Analysis. 61
31160238 2019
39
Lethal toxicities after capecitabine intake in a previously 5-FU-treated patient: why dose matters with dihydropryimidine dehydrogenase deficiency. 61
31486738 2019
40
DPYD and Fluorouracil-Based Chemotherapy: Mini Review and Case Report. 61
31052357 2019
41
Effectiveness and safety of reduced-dose fluoropyrimidine therapy in patients carrying the DPYD*2A variant: A matched pair analysis. 61
30485432 2019
42
Capecitabine-induced cerebellar toxicity and TYMS pharmacogenetics. 61
30875351 2019
43
The clinical relevance of multiple DPYD polymorphisms on patients candidate for fluoropyrimidine based-chemotherapy. An Italian case-control study. 61
30858516 2019
44
5-Fluorouracil rechallenge after 5-fluorouracil-induced hyperammonemic encephalopathy. 61
30531368 2019
45
Three different polymorphisms of the DPYD gene associated with severe toxicity following administration of 5-FU: a case report. 61
30898145 2019
46
Long noncoding RNA LINC00261 induces chemosensitization to 5-fluorouracil by mediating methylation-dependent repression of DPYD in human esophageal cancer. 61
30226808 2019
47
Cytomegalovirus enterocolitis in a patient with dihydropyrimidine dehydrogenase deficiency after capecitabine treatment: A case report. 61
30831507 2019
48
Successful use of uridine triacetate (Vistogard) three weeks after capecitabine in a patient with homozygous dihydropyrimidine dehydrogenase mutation: A case report and review of the literature. 61
28950804 2019
49
Dihydropyrimidine Dehydrogenase Deficiency: Homozygosity for an Extremely Rare Variant in DPYD due to Uniparental Isodisomy of Chromosome 1. 61
30349988 2019
50
Rare Dihydropyrimidine Dehydrogenase Variants and Toxicity by Floropyrimidines: A Case Report. 61
30915274 2019
Sources

Variations for Dihydropyrimidine Dehydrogenase Deficiency

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ClinVar genetic disease variations for Dihydropyrimidine Dehydrogenase Deficiency:

6 (show top 50) (show all 178) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 DPYD DPYD, 4-BP DEL, 296TCATdeletion Pathogenic 434
2 DPYD DPYD, 1-BP DEL, 1897Cdeletion Pathogenic 436
3 DPYD NM_001160301.1(DPYD):c.127_134del (p.Lys42_Arg43insTer)deletion Pathogenic/Likely pathogenic 502676 rs1207177925 1:98348836-98348843 1:97883280-97883287
4 DPYD NM_000110.3(DPYD):c.763-2A>GSNV Pathogenic/Likely pathogenic 552475 rs1300669537 1:98144740-98144740 1:97679184-97679184
5 DPYD NM_000110.3(DPYD):c.2275C>T (p.Arg759Ter)SNV Pathogenic/Likely pathogenic 370760 rs759372918 1:97770839-97770839 1:97305283-97305283
6 DPYD NM_000110.3(DPYD):c.661G>T (p.Glu221Ter)SNV Pathogenic/Likely pathogenic 370661 rs146170505 1:98164926-98164926 1:97699370-97699370
7 DPYD NM_001160301.1(DPYD):c.208C>T (p.Arg70Ter)SNV Pathogenic/Likely pathogenic 370660 rs141597515 1:98293695-98293695 1:97828139-97828139
8 DPYD NM_001160301.1(DPYD):c.150+2T>ASNV Likely pathogenic 370330 rs1057516405 1:98348818-98348818 1:97883262-97883262
9 DPYD NM_001160301.1(DPYD):c.3G>A (p.Met1Ile)SNV Likely pathogenic 370476 rs768020954 1:98386476-98386476 1:97920920-97920920
10 DPYD NM_000110.4(DPYD):c.557A>G (p.Tyr186Cys)SNV drug response 100113 rs115232898 1:98165030-98165030 1:97699474-97699474
11 DPYD NM_000110.3(DPYD):c.523del (p.Ser175fs)deletion Likely pathogenic 371088 rs1057516997 1:98165064-98165064 1:97699508-97699508
12 DPYD NM_001160301.1(DPYD):c.483+1G>TSNV Likely pathogenic 370782 rs1057516763 1:98187065-98187065 1:97721509-97721509
13 DPYD NM_001160301.1(DPYD):c.322-1G>CSNV Likely pathogenic 370259 rs1057516356 1:98187228-98187228 1:97721672-97721672
14 DPYD NM_001160301.1(DPYD):c.232A>T (p.Arg78Ter)SNV Likely pathogenic 370260 rs776692894 1:98293671-98293671 1:97828115-97828115
15 DPYD NM_000110.3(DPYD):c.2058+1G>CSNV Likely pathogenic 370923 rs769167857 1:97839116-97839116 1:97373560-97373560
16 DPYD NM_000110.3(DPYD):c.2039dup (p.Met680fs)duplication Likely pathogenic 371596 rs1057517396 1:97839135-97839136 1:97373579-97373580
17 DPYD NM_000110.3(DPYD):c.2003del (p.Asn668fs)deletion Likely pathogenic 371160 rs1057517055 1:97839172-97839172 1:97373616-97373616
18 DPYD NM_000110.3(DPYD):c.1970del (p.Ser657fs)deletion Likely pathogenic 370712 rs1057516710 1:97847953-97847953 1:97382397-97382397
19 DPYD NM_000110.3(DPYD):c.1863G>A (p.Trp621Ter)SNV Likely pathogenic 370307 rs1057516388 1:97915657-97915657 1:97450101-97450101
20 DPYD NM_000110.3(DPYD):c.1831G>T (p.Glu611Ter)SNV Likely pathogenic 370668 rs1057516671 1:97915689-97915689 1:97450133-97450133
21 DPYD NM_000110.3(DPYD):c.1727del (p.Phe576fs)deletion Likely pathogenic 370256 rs764584080 1:97981295-97981295 1:97515739-97515739
22 DPYD NM_000110.3(DPYD):c.1681C>T (p.Arg561Ter)SNV Likely pathogenic 371053 rs1057516968 1:97981341-97981341 1:97515785-97515785
23 DPYD NM_000110.3(DPYD):c.1671del (p.Ser558fs)deletion Likely pathogenic 371114 rs1057517018 1:97981351-97981351 1:97515795-97515795
24 DPYD NM_000110.3(DPYD):c.1524+1G>ASNV Likely pathogenic 371253 rs1057517126 1:98015115-98015115 1:97549559-97549559
25 DPYD NM_000110.3(DPYD):c.1518del (p.Lys505_Tyr506insTer)deletion Likely pathogenic 370593 rs1057516615 1:98015122-98015122 1:97549566-97549566
26 DPYD NM_000110.3(DPYD):c.1379dup (p.Leu461fs)duplication Likely pathogenic 371469 rs779948148 1:98015260-98015261 1:97549704-97549705
27 DPYD NM_000110.3(DPYD):c.1340-2A>GSNV Likely pathogenic 370715 rs1057516713 1:98015302-98015302 1:97549746-97549746
28 DPYD NM_000110.3(DPYD):c.1339+1G>TSNV Likely pathogenic 370261 rs1057516357 1:98039315-98039315 1:97573759-97573759
29 DPYD NM_000110.3(DPYD):c.1316del (p.Gly439fs)deletion Likely pathogenic 370780 rs1057516761 1:98039339-98039339 1:97573783-97573783
30 DPYD NM_000110.3(DPYD):c.1311del (p.Phe438fs)deletion Likely pathogenic 371335 rs1057517189 1:98039344-98039344 1:97573788-97573788
31 DPYD NM_000110.3(DPYD):c.1109_1110delTAshort repeat Likely pathogenic 370309 rs749571474 1:98058792-98058793 1:97593236-97593237
32 DPYD NM_000110.3(DPYD):c.910del (p.Tyr304fs)deletion Likely pathogenic 370713 rs1057516711 1:98060663-98060663 1:97595107-97595107
33 DPYD NM_000110.3(DPYD):c.851-1G>CSNV Likely pathogenic 370698 rs1057516696 1:98060723-98060723 1:97595167-97595167
34 DPYD NM_000110.3(DPYD):c.762+2T>CSNV Likely pathogenic 371177 rs1057517065 1:98157271-98157271 1:97691715-97691715
35 DPYD NM_000110.3(DPYD):c.680+1G>ASNV Likely pathogenic 371334 rs867460475 1:98164906-98164906 1:97699350-97699350
36 DPYD NM_000110.4(DPYD):c.703C>T (p.Arg235Trp)SNV drug response 298300 rs1801266 1:98157332-98157332 1:97691776-97691776
37 DPYD NM_000110.3(DPYD):c.2589dup (p.Pro864fs)duplication Likely pathogenic 371510 rs1057517327 1:97658657-97658658 1:97193101-97193102
38 DPYD NM_000110.3(DPYD):c.2554C>T (p.Gln852Ter)SNV Likely pathogenic 371437 rs1057517271 1:97658693-97658693 1:97193137-97193137
39 DPYD NM_000110.3(DPYD):c.2335_2338delinsGC (p.Thr779fs)indel Likely pathogenic 370465 rs1057516510 1:97700512-97700515 1:97234956-97234959
40 DPYD NM_000110.3(DPYD):c.2754del (p.Pro919fs)deletion Likely pathogenic 370956 rs1057516894 1:97564057-97564057 1:97098501-97098501
41 DPYD NM_000110.3(DPYD):c.2748del (p.Arg916fs)deletion Likely pathogenic 371384 rs1057517230 1:97564063-97564063 1:97098507-97098507
42 DPYD NM_000110.3(DPYD):c.2680A>T (p.Lys894Ter)SNV Likely pathogenic 370928 rs1057516873 1:97564131-97564131 1:97098575-97098575
43 DPYD NM_000110.3(DPYD):c.2622+1G>ASNV Likely pathogenic 371215 rs1057517095 1:97658624-97658624 1:97193068-97193068
44 DPYD NM_000110.3(DPYD):c.2286_2287insA (p.Gly763fs)insertion Likely pathogenic 370868 rs1057516828 1:97770827-97770828 1:97305271-97305272
45 DPYD NM_000110.4(DPYD):c.2846A>T (p.Asp949Val)SNV drug response 88974 rs67376798 1:97547947-97547947 1:97082391-97082391
46 DPYD NM_000110.4(DPYD):c.1679T>G (p.Ile560Ser)SNV drug response 88975 rs55886062 1:97981343-97981343 1:97515787-97515787
47 DPYD NM_000110.3(DPYD):c.2043_2058del (p.Leu682fs)deletion Likely pathogenic 188871 rs773499329 1:97839117-97839132 1:97373561-97373576
48 DPYD NM_001160301.1(DPYD):c.61C>T (p.Arg21Ter)SNV Likely pathogenic 188848 rs72549310 1:98348909-98348909 1:97883353-97883353
49 DPYD NM_001160301.1(DPYD):c.295_298TCAT[1] (p.Phe100fs)short repeat drug response 495550 rs72549309 1:98205967-98205970 1:97740411-97740414
50 DPYD NM_000110.3(DPYD):c.2579del (p.Gln860fs)deletion Likely pathogenic 551707 rs746991079 1:97658668-97658668 1:97193112-97193112

UniProtKB/Swiss-Prot genetic disease variations for Dihydropyrimidine Dehydrogenase Deficiency:

73
# Symbol AA change Variation ID SNP ID
1 DPYD p.Cys29Arg VAR_005173 rs1801265
2 DPYD p.Arg235Trp VAR_005174 rs1801266
3 DPYD p.Arg886His VAR_005177 rs1801267

Copy number variations for Dihydropyrimidine Dehydrogenase Deficiency from CNVD:

7
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 20881 1 155000000 156500000 Copy number DPYD Dihydropyrimidine dehydrogenase deficiency
Sources

Expression for Dihydropyrimidine Dehydrogenase Deficiency

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Search GEO for disease gene expression data for Dihydropyrimidine Dehydrogenase Deficiency.
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Pathways for Dihydropyrimidine Dehydrogenase Deficiency

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Pathways related to Dihydropyrimidine Dehydrogenase Deficiency according to KEGG:

36
# Name Kegg Source Accession
1 Pyrimidine metabolism hsa00240
2 Drug metabolism - other enzymes hsa00983

Pathways related to Dihydropyrimidine Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

(show all 16)
# Super pathways Score Top Affiliating Genes
1
Metabolism 65
Show member pathways
 13.81 UGT1A8 UGT1A6 UGT1A1 TYMS TYMP DPYS
2
Metabolism of nucleotides 65
Show member pathways
 12.44 TYMS TYMP DPYS DPYD ADSL
3
Drug metabolism - cytochrome P450 36
Show member pathways
 12.36 UGT1A8 UGT1A6 UGT1A1 TYMP DPYS DPYD
4
Porphyrin and chlorophyll metabolism 36
Show member pathways
 12.08 UGT1A8 UGT1A6 UGT1A1
5
Bile secretion 36
11.61 UGT1A8 UGT1A6 UGT1A1
6
Acetaminophen Pathway (therapeutic doses), Pharmacokinetics 60
Show member pathways
 11.53 UGT1A8 UGT1A6 UGT1A1
7
Steroid hormone biosynthesis 36
Show member pathways
 11.44 UGT1A8 UGT1A6 UGT1A1
8
Irinotecan Pathway, Pharmacokinetics 60
Show member pathways
 11.35 UGT1A8 UGT1A6 UGT1A1
9
Aryl Hydrocarbon Receptor Pathway 1
11.24 UGT1A6 UGT1A1
10
Alanine, aspartate and glutamate metabolism 36
11.09 ADSL ABAT
11
Constitutive Androstane Receptor Pathway 1
11.03 UGT1A6 UGT1A1
12
Estrogen metabolism 1
Show member pathways
 11.03 UGT1A8 UGT1A6 UGT1A1
13
beta-Alanine metabolism (KEGG) 36
Show member pathways
 10.96 DPYS DPYD ABAT
14
Fluoropyrimidine Activity 1
Show member pathways
 10.8 TYMS TYMP DPYS DPYD
15
Pantothenate and CoA biosynthesis 36
10.77 DPYS DPYD
16
Beta-alanine metabolism (TR) 22
Show member pathways
 10.39 DPYS DPYD ABAT
Sources

GO Terms for Dihydropyrimidine Dehydrogenase Deficiency

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Biological processes related to Dihydropyrimidine Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 response to ethanol GO:0045471 9.67 UGT1A1 TYMS ABAT
2 response to starvation GO:0042594 9.54 UGT1A1 ADSL
3 retinoic acid metabolic process GO:0042573 9.52 UGT1A8 UGT1A1
4 cellular glucuronidation GO:0052695 9.51 UGT1A6 UGT1A1
5 pyrimidine nucleobase catabolic process GO:0006208 9.48 DPYS DPYD
6 flavone metabolic process GO:0051552 9.46 UGT1A8 UGT1A1
7 pyrimidine nucleobase metabolic process GO:0006206 9.43 TYMS TYMP
8 thymine catabolic process GO:0006210 9.4 DPYS DPYD
9 negative regulation of steroid metabolic process GO:0045939 9.37 UGT1A8 UGT1A1
10 xenobiotic glucuronidation GO:0052697 9.33 UGT1A8 UGT1A6 UGT1A1
11 uracil metabolic process GO:0019860 9.32 TYMS DPYS
12 uracil catabolic process GO:0006212 9.26 DPYS DPYD
13 pyrimidine nucleoside catabolic process GO:0046135 9.13 TYMP DPYS DPYD
14 flavonoid glucuronidation GO:0052696 8.8 UGT1A8 UGT1A6 UGT1A1

Molecular functions related to Dihydropyrimidine Dehydrogenase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transferase activity GO:0016740 9.91 UGT1A8 UGT1A6 UGT1A1 TYMS TYMP ABAT
2 protein homodimerization activity GO:0042803 9.77 UGT1A8 UGT1A6 UGT1A1 TYMP DPYD
3 transferase activity, transferring glycosyl groups GO:0016757 9.62 UGT1A8 UGT1A6 UGT1A1 TYMP
4 enzyme inhibitor activity GO:0004857 9.46 UGT1A8 UGT1A1
5 transferase activity, transferring hexosyl groups GO:0016758 9.43 UGT1A8 UGT1A6 UGT1A1
6 steroid binding GO:0005496 9.4 UGT1A8 UGT1A1
7 uracil binding GO:0002058 9.16 DPYS DPYD
8 glucuronosyltransferase activity GO:0015020 9.13 UGT1A8 UGT1A6 UGT1A1
9 retinoic acid binding GO:0001972 8.8 UGT1A8 UGT1A6 UGT1A1
Sources

Sources for Dihydropyrimidine Dehydrogenase Deficiency

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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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