DPYD R29C - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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(DPYD Arg29Cys)

Short summary

This variant is also known as DPYD*9A, and is associated with Dihydropyrimidine dehydrogenase deficiency and impaired clearance of 5-fluorouracil with potential toxic consequence.

Variant evidence
Computational 1

NBLOSUM=5, this gene is associated with this disease, position not conserved.
PolyPhen2: Benign, score 0.072
SIFT: Affect protein function 0.01
GVGD: GV 28.82; GD 169.74; Class C45
Variant Effect Predictor (Ensembl):
Mutation Tasting Prediction: Polymorphism, P value: 0.580684; protein features (might be) affected.

See Vreken P et al. 1997 (9439663), unpublished research (below).

Functional 1

E. coli

See Vreken P et al. 1997 (9439663).

Case/Control -
Familial -
Clinical importance
Severity 5

Potentially lethal in homozygous and toxic in heterozygous individuals.

See Vreken P et al. 1997 (9439663), Zhang H et al. 2007 (17848752).

Treatability 4

Use alternate chemotherapy protocol or lower dosage to compensate for lower drug clearance.

See Zhang H et al. 2007 (17848752).

Penetrance -


Insufficiently evaluated pharmacogenetic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern


Summary of published research, and additional commentary


Allele frequency

  • A @ chr1:98348885: 71.4% (7680/10758) in EVS
  • A @ chr1:98121472: 71.9% (92/128) in GET-Evidence
  • Frequency shown in summary reports: 71.4% (7680/10758)


Vreken P, Van Kuilenburg AB, Meinsma R, van Gennip AH. Dihydropyrimidine dehydrogenase (DPD) deficiency: identification and expression of missense mutations C29R, R886H and R235W. Hum Genet. 1997 Dec;101(3):333-8. PubMed PMID: 9439663.

This variant was identified in three individuals with Dihydropyrimidine dehydrogenase (DPD) deficiency as part of two different compound heterozygotes (with either IVS14 (del(exon14)) or R886H). In a functional assay this variant alone was sufficient to abolish expression of function enzyme in E. coli. This position is not conserved. They note the potential lethal effect of 5-fluoruracil on homozygous individuals and toxic effect on heterozygous individuals.

McLeod HL, Collie-Duguid ES, Vreken P, Johnson MR, Wei X, Sapone A, Diasio RB, Fernandez-Salguero P, van Kuilenberg AB, van Gennip AH, Gonzalez FJ. Nomenclature for human DPYD alleles. Pharmacogenetics. 1998 Dec;8(6):455-9. PubMed PMID: 9918128.

This variant is named DPYD*9A

Collie-Duguid ES, Etienne MC, Milano G, McLeod HL. Known variant DPYD alleles do not explain DPD deficiency in cancer patients. Pharmacogenetics. 2000 Apr;10(3):217-23. PubMed PMID: 10803677.

In a study of 37 individuals for variants associated with DPD deficiency, it was noted that these variants (including our variant) do not sufficiently explains enzyme levels and two individuals with normal enzyme levels were found to be homozygous for this variant.

van Kuilenburg AB, Haasjes J, Richel DJ, Zoetekouw L, Van Lenthe H, De Abreu RA, Maring JG, Vreken P, van Gennip AH. Clinical implications of dihydropyrimidine dehydrogenase (DPD) deficiency in patients with severe 5-fluorouracil-associated toxicity: identification of new mutations in the DPD gene. Clin Cancer Res. 2000 Dec;6(12):4705-12. PubMed PMID: 11156223.

The authors report evidence contrary to that of Collie-Duguid et al., and find that C29R mutations do contribute to 5FU toxicity.

Zhang H, Li YM, Zhang H, Jin X. DPYD*5 gene mutation contributes to the reduced DPYD enzyme activity and chemotherapeutic toxicity of 5-FU: results from genotyping study on 75 gastric carcinoma and colon carcinoma patients. Med Oncol. 2007;24(2):251-8. PubMed PMID: 17848752.

An analysis of 75 individuals undergoing chemotherapy with 5FU found that the 7 individuals heterozygous for this variant had significantly increased incidence of middle-severe nausea and vomiting than the wildtype.




hu034DB1 - CGI sample GS00253-DNA_A02_200_37
hom A @ chr1:98348885


hu04FD18 - CGI sample GS00253-DNA_F01_200_37
hom A @ chr1:98348885


hu0D879F - CGI sample GS00253-DNA_G01_200_37
het A @ chr1:98348885















hu43860C - CGI sample GS00253-DNA_A01_200_37
het A @ chr1:98348885




hu604D39 - CGI sample GS00253-DNA_B02_200_37
hom A @ chr1:98348885







hu9385BA - CGI sample GS00253-DNA_E01_200_37
hom A @ chr1:98348885





huAE6220 - CGI sample GS00253-DNA_H01_200_37
hom A @ chr1:98348885




huBEDA0B - CGI sample GS00253-DNA_C01_200_37
hom A @ chr1:98348885


huC30901 - CGI sample GS00253-DNA_B01_200_37
hom A @ chr1:98348885





huE80E3D - CGI sample GS00253-DNA_D01_200_37
hom A @ chr1:98348885




GS06985 - var-GS06985-1100-36-ASM
hom A @ chr1:98121473


GS06994 - var-GS06994-1100-36-ASM
hom A @ chr1:98121473


GS07357 - var-GS07357-1100-36-ASM
het A @ chr1:98121473


GS10851 - var-GS10851-1100-36-ASM
het A @ chr1:98121473


GS12004 - var-GS12004-1100-36-ASM
hom A @ chr1:98121473


GS18501 - var-GS18501-1100-36-ASM
het A @ chr1:98121473


GS18502 - var-GS18502-1100-36-ASM
het A @ chr1:98121473


GS18504 - var-GS18504-1100-36-ASM
hom A @ chr1:98121473


GS18508 - var-GS18508-1100-36-ASM
hom A @ chr1:98121473


GS18517 - var-GS18517-1100-36-ASM
hom A @ chr1:98121473


GS18526 - var-GS18526-1100-36-ASM
hom A @ chr1:98121473


GS18537 - var-GS18537-1100-36-ASM
hom A @ chr1:98121473


GS18555 - var-GS18555-1100-36-ASM
hom A @ chr1:98121473


GS18558 - var-GS18558-1100-36-ASM
hom A @ chr1:98121473


GS18940 - var-GS18940-1100-36-ASM
hom A @ chr1:98121473


GS18942 - var-GS18942-1100-36-ASM
hom A @ chr1:98121473


GS18947 - var-GS18947-1100-36-ASM
hom A @ chr1:98121473


GS18956 - var-GS18956-1100-36-ASM
hom A @ chr1:98121473


GS19017 - var-GS19017-1100-36-ASM
het A @ chr1:98121473


GS19020 - var-GS19020-1100-36-ASM
het A @ chr1:98121473


GS19025 - var-GS19025-1100-36-ASM
hom A @ chr1:98121473


GS19129 - var-GS19129-1100-36-ASM
het A @ chr1:98121473


GS19239 - var-GS19239-1100-36-ASM
het A @ chr1:98121473


GS19648 - var-GS19648-1100-36-ASM
hom A @ chr1:98121473


GS19649 - var-GS19649-1100-36-ASM
hom A @ chr1:98121473


GS19669 - var-GS19669-1100-36-ASM
het A @ chr1:98121473


GS19670 - var-GS19670-1100-36-ASM
hom A @ chr1:98121473


GS19704 - var-GS19704-1100-36-ASM
hom A @ chr1:98121473


GS19735 - var-GS19735-1100-36-ASM
hom A @ chr1:98121473


GS19834 - var-GS19834-1100-36-ASM
het A @ chr1:98121473


GS20509 - var-GS20509-1100-36-ASM
het A @ chr1:98121473


GS21767 - var-GS21767-1100-36-ASM
het A @ chr1:98121473


Other external references

  • rs1801265
    Web search results (21 hits -- see all)
  • Pharma DMET - SNPedia
    ... del DPYD DPYD_>(V335L) DPYD*11_(V335L) noncore snp DPYD DPYD_1679T>G(I560S) DPYD ... DPYD DPYD_37594C>T(R29C) DPYD_37594C>T(R29C) core snp rs1801265 DPYD ...

Other in silico analyses

  • NBLOSUM100 score = 8
  • GET-Evidence autoscore = 2

Edit history

Gene search

"GENE" or "GENE A123C":

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