Incidental Mutation 'F6893:Dpyd'
ID 204
Institutional Source Beutler Lab
Gene Symbol Dpyd
Ensembl Gene ENSMUSG00000033308
Gene Name dihydropyrimidine dehydrogenase
Synonyms E330028L06Rik, DPD
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # F6893 (G3) of strain busy
Quality Score
Status Validated
Chromosome 3
Chromosomal Location 118355778-119226573 bp(+) (GRCm39)
Type of Mutation critical splice donor site (2 bp from exon)
DNA Base Change (assembly) T to A at 118597783 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000039429 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000039177]
AlphaFold Q8CHR6
Predicted Effect probably null
Transcript: ENSMUST00000039177
SMART Domains Protein: ENSMUSP00000039429
Gene: ENSMUSG00000033308

DomainStartEndE-ValueType
Pfam:Fer4_20 55 168 4.6e-35 PFAM
Pfam:Pyr_redox_2 188 499 1.5e-15 PFAM
Pfam:NAD_binding_8 193 249 5.5e-8 PFAM
Pfam:DHO_dh 532 838 8.1e-36 PFAM
Pfam:Dus 617 822 7.5e-8 PFAM
Pfam:Fer4_10 945 997 7.4e-9 PFAM
Pfam:Fer4_21 946 1004 1.3e-26 PFAM
Meta Mutation Damage Score 0.9491 question?
Coding Region Coverage
  • 1x: 88.7%
  • 3x: 74.0%
Validation Efficiency 88% (165/188)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a pyrimidine catabolic enzyme and the initial and rate-limiting factor in the pathway of uracil and thymidine catabolism. Mutations in this gene result in dihydropyrimidine dehydrogenase deficiency, an error in pyrimidine metabolism associated with thymine-uraciluria and an increased risk of toxicity in cancer patients receiving 5-fluorouracil chemotherapy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]
Allele List at MGI

All alleles(1) : Targeted, other(1)

Other mutations in this stock
Total: 35 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca14 G A 7: 119,924,261 (GRCm39) V1638M probably damaging Het
Agrn C T 4: 156,258,636 (GRCm39) R972Q probably benign Het
Anxa3 T C 5: 96,972,853 (GRCm39) probably benign Het
Bpifa6 G T 2: 153,829,078 (GRCm39) D202Y probably damaging Het
Ccdc15 G A 9: 37,226,936 (GRCm39) T346I probably damaging Homo
Celsr3 G A 9: 108,712,266 (GRCm39) R1731H probably benign Het
Ces4a A G 8: 105,873,859 (GRCm39) R443G possibly damaging Het
Chd2 T C 7: 73,157,620 (GRCm39) Q175R possibly damaging Het
Dscam G T 16: 96,857,660 (GRCm39) H117N possibly damaging Het
F13a1 A G 13: 37,155,999 (GRCm39) Y205H probably damaging Het
Fat3 A C 9: 15,918,085 (GRCm39) L1446R probably damaging Homo
Golga4 T C 9: 118,382,525 (GRCm39) L515S probably damaging Het
Hoxb1 A T 11: 96,256,728 (GRCm39) T26S probably benign Het
Igsf10 T G 3: 59,238,481 (GRCm39) T567P probably damaging Het
Lamb2 T C 9: 108,359,755 (GRCm39) V365A probably benign Het
Mepe A G 5: 104,485,242 (GRCm39) I127M possibly damaging Het
Mpi A T 9: 57,453,832 (GRCm39) M230K probably benign Homo
Myh4 A G 11: 67,146,283 (GRCm39) D1447G probably null Homo
Or1f19 A G 16: 3,411,027 (GRCm39) I256V possibly damaging Het
Or1j4 A G 2: 36,740,819 (GRCm39) T254A probably benign Het
Panx2 T C 15: 88,952,213 (GRCm39) Y227H probably damaging Homo
Pdzd7 A G 19: 45,025,173 (GRCm39) W441R probably damaging Het
Poldip2 A G 11: 78,410,020 (GRCm39) I267M probably damaging Homo
Pros1 T A 16: 62,745,002 (GRCm39) V539E probably damaging Het
Sacs T C 14: 61,450,425 (GRCm39) M4157T probably benign Het
Slc45a3 A G 1: 131,909,075 (GRCm39) E424G probably benign Homo
Slc9a1 A G 4: 133,149,457 (GRCm39) E761G probably benign Homo
Stab2 G A 10: 86,691,035 (GRCm39) P2178L probably damaging Het
Syt4 C T 18: 31,577,274 (GRCm39) V27I possibly damaging Homo
Thumpd1 T A 7: 119,319,799 (GRCm39) K56* probably null Het
Tpr A G 1: 150,269,313 (GRCm39) K19E possibly damaging Homo
Ttll10 A G 4: 156,132,775 (GRCm39) I74T probably benign Het
Txnrd1 C T 10: 82,702,823 (GRCm39) Q95* probably null Homo
Zc3h7b A G 15: 81,662,872 (GRCm39) E421G possibly damaging Homo
Zc3hc1 G T 6: 30,387,525 (GRCm39) D51E probably benign Homo
Other mutations in Dpyd
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00418:Dpyd APN 3 118,737,891 (GRCm39) missense probably damaging 1.00
IGL00508:Dpyd APN 3 118,858,636 (GRCm39) missense probably benign 0.06
IGL02113:Dpyd APN 3 118,792,868 (GRCm39) missense probably benign 0.06
IGL02177:Dpyd APN 3 118,858,559 (GRCm39) missense possibly damaging 0.76
IGL03001:Dpyd APN 3 118,710,891 (GRCm39) missense probably benign 0.07
IGL03106:Dpyd APN 3 118,988,783 (GRCm39) missense probably benign 0.03
IGL03399:Dpyd APN 3 119,108,426 (GRCm39) missense probably damaging 0.98
F5770:Dpyd UTSW 3 118,690,775 (GRCm39) nonsense probably null
R0014:Dpyd UTSW 3 118,935,584 (GRCm39) missense probably damaging 1.00
R0081:Dpyd UTSW 3 118,737,904 (GRCm39) missense probably benign 0.00
R0267:Dpyd UTSW 3 118,710,921 (GRCm39) missense probably benign
R0349:Dpyd UTSW 3 118,710,748 (GRCm39) nonsense probably null
R0387:Dpyd UTSW 3 119,220,875 (GRCm39) missense probably benign 0.21
R0523:Dpyd UTSW 3 118,692,852 (GRCm39) missense probably benign
R0555:Dpyd UTSW 3 119,225,191 (GRCm39) missense probably damaging 1.00
R0652:Dpyd UTSW 3 119,220,924 (GRCm39) missense probably damaging 1.00
R0741:Dpyd UTSW 3 118,468,154 (GRCm39) missense possibly damaging 0.79
R1313:Dpyd UTSW 3 118,692,810 (GRCm39) splice site probably benign
R1554:Dpyd UTSW 3 118,858,695 (GRCm39) splice site probably null
R1610:Dpyd UTSW 3 118,858,655 (GRCm39) missense probably benign
R1710:Dpyd UTSW 3 118,404,092 (GRCm39) critical splice acceptor site probably null
R1861:Dpyd UTSW 3 118,710,780 (GRCm39) missense probably damaging 1.00
R2103:Dpyd UTSW 3 118,858,601 (GRCm39) missense probably benign 0.02
R2130:Dpyd UTSW 3 118,468,217 (GRCm39) missense probably benign
R2131:Dpyd UTSW 3 118,468,217 (GRCm39) missense probably benign
R2882:Dpyd UTSW 3 118,858,679 (GRCm39) missense probably damaging 0.99
R3771:Dpyd UTSW 3 119,205,927 (GRCm39) critical splice donor site probably null
R3978:Dpyd UTSW 3 118,690,738 (GRCm39) critical splice acceptor site probably benign
R3978:Dpyd UTSW 3 118,690,737 (GRCm39) critical splice acceptor site probably benign
R4030:Dpyd UTSW 3 118,690,815 (GRCm39) missense probably benign 0.03
R4065:Dpyd UTSW 3 118,690,738 (GRCm39) critical splice acceptor site probably benign
R4066:Dpyd UTSW 3 118,690,738 (GRCm39) critical splice acceptor site probably benign
R4234:Dpyd UTSW 3 119,225,233 (GRCm39) missense probably damaging 1.00
R4502:Dpyd UTSW 3 118,591,186 (GRCm39) missense probably damaging 1.00
R4638:Dpyd UTSW 3 119,059,726 (GRCm39) missense probably benign 0.03
R4980:Dpyd UTSW 3 118,710,767 (GRCm39) missense probably damaging 0.99
R5262:Dpyd UTSW 3 118,591,071 (GRCm39) nonsense probably null
R5348:Dpyd UTSW 3 118,575,592 (GRCm39) missense probably benign
R5587:Dpyd UTSW 3 118,858,600 (GRCm39) missense probably damaging 1.00
R5611:Dpyd UTSW 3 118,987,942 (GRCm39) missense probably benign
R5665:Dpyd UTSW 3 118,710,741 (GRCm39) missense probably damaging 1.00
R5716:Dpyd UTSW 3 118,692,828 (GRCm39) missense probably damaging 1.00
R5786:Dpyd UTSW 3 119,220,886 (GRCm39) missense probably damaging 0.97
R6046:Dpyd UTSW 3 119,225,224 (GRCm39) missense probably benign 0.01
R6404:Dpyd UTSW 3 119,059,606 (GRCm39) missense probably benign 0.02
R6703:Dpyd UTSW 3 118,690,849 (GRCm39) splice site probably null
R7037:Dpyd UTSW 3 118,692,938 (GRCm39) missense probably benign 0.00
R7215:Dpyd UTSW 3 119,059,681 (GRCm39) missense probably benign 0.11
R7301:Dpyd UTSW 3 118,692,933 (GRCm39) missense possibly damaging 0.90
R7336:Dpyd UTSW 3 118,858,570 (GRCm39) missense probably damaging 1.00
R7714:Dpyd UTSW 3 118,597,780 (GRCm39) missense probably benign 0.01
R8238:Dpyd UTSW 3 118,988,842 (GRCm39) splice site probably null
R8306:Dpyd UTSW 3 119,205,822 (GRCm39) missense probably benign
R8315:Dpyd UTSW 3 119,108,534 (GRCm39) missense probably benign 0.09
R8321:Dpyd UTSW 3 118,575,573 (GRCm39) missense possibly damaging 0.84
R8342:Dpyd UTSW 3 119,108,452 (GRCm39) missense possibly damaging 0.60
R8735:Dpyd UTSW 3 118,935,565 (GRCm39) missense possibly damaging 0.74
R8750:Dpyd UTSW 3 118,935,585 (GRCm39) missense probably damaging 1.00
R8874:Dpyd UTSW 3 118,792,981 (GRCm39) missense probably damaging 1.00
R8910:Dpyd UTSW 3 118,404,167 (GRCm39) missense probably benign 0.17
R8973:Dpyd UTSW 3 119,108,582 (GRCm39) critical splice donor site probably null
R9070:Dpyd UTSW 3 118,792,892 (GRCm39) missense probably damaging 0.98
R9132:Dpyd UTSW 3 118,710,897 (GRCm39) missense probably damaging 1.00
R9198:Dpyd UTSW 3 118,553,303 (GRCm39) critical splice acceptor site probably null
R9260:Dpyd UTSW 3 119,108,447 (GRCm39) missense possibly damaging 0.95
R9307:Dpyd UTSW 3 119,108,560 (GRCm39) missense probably benign
V7581:Dpyd UTSW 3 118,690,775 (GRCm39) nonsense probably null
V7582:Dpyd UTSW 3 118,690,775 (GRCm39) nonsense probably null
V7583:Dpyd UTSW 3 118,690,775 (GRCm39) nonsense probably null
Nature of Mutation

DNA sequencing using the SOLiD technique identified a T to A transversion at base pair 118507052 in the Genbank genomic region NC_000069 (Build 37.1) for the Dpyd gene on Chromosome 3 (GTGAGTACGA ->GAGAGTACGA). The mutation is located within intron 7 from the ATG exon, two nucleotides from the previous exon. The Dpyd transcript contains 23 total exons. Multiple transcripts of the Dpyd gene are displayed on Ensembl. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction
The Dpyd gene encodes the 1025 amino acid dihydropyrimidine dehydrogenase (DPD). DPD is involved in pyrimidine base degradation, and catalyzes the reduction of uracil and thymine using NADP+.   The enzyme has three iron-sulfur (4Fe-4S) binding domains at amino acids 69-100, 944-976, and 978-1007 (Uniprot Q8CHR6). 
Posted On 2010-05-03