Mutagenetix > Incidental Mutation

Incidental Mutation 'F6893:Dpyd'

204

Institutional Source

Beutler Lab

Gene Symbol

Dpyd

Ensembl Gene

ENSMUSG00000033308

Gene Name

dihydropyrimidine dehydrogenase

Synonyms

DPD, E330028L06Rik

Accession Numbers

Genbank: NM_170778; MGI: 2139667

Is this an essential gene?

Non essential (E-score: 0.000) question?

Stock #

F6893 (G3) of strain busy

Quality Score

Status

Validated

Chromosome

Chromosomal Location

118562129-119432924 bp(+) (GRCm38)

Type of Mutation

critical splice donor site (2 bp from exon)

DNA Base Change (assembly)

T to A at 118804134 bp (GRCm38)

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

Domain	Start	End	E-Value	Type
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

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
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca14	G	A	7: 120,325,038	V1638M	probably damaging	Het
Agrn	C	T	4: 156,174,179	R972Q	probably benign	Het
Anxa3	T	C	5: 96,824,994		probably benign	Het
Bpifa6	G	T	2: 153,987,158	D202Y	probably damaging	Het
Ccdc15	G	A	9: 37,315,640	T346I	probably damaging	Homo
Celsr3	G	A	9: 108,835,067	R1731H	probably benign	Het
Ces4a	A	G	8: 105,147,227	R443G	possibly damaging	Het
Chd2	T	C	7: 73,507,872	Q175R	possibly damaging	Het
Dscam	G	T	16: 97,056,460	H117N	possibly damaging	Het
F13a1	A	G	13: 36,972,025	Y205H	probably damaging	Het
Fat3	A	C	9: 16,006,789	L1446R	probably damaging	Homo
Golga4	T	C	9: 118,553,457	L515S	probably damaging	Het
Hoxb1	A	T	11: 96,365,902	T26S	probably benign	Het
Igsf10	T	G	3: 59,331,060	T567P	probably damaging	Het
Lamb2	T	C	9: 108,482,556	V365A	probably benign	Het
Mepe	A	G	5: 104,337,376	I127M	possibly damaging	Het
Mpi	A	T	9: 57,546,549	M230K	probably benign	Homo
Myh4	A	G	11: 67,255,457	D1447G	probably null	Homo
Olfr161	A	G	16: 3,593,163	I256V	possibly damaging	Het
Olfr350	A	G	2: 36,850,807	T254A	probably benign	Het
Panx2	T	C	15: 89,068,010	Y227H	probably damaging	Homo
Pdzd7	A	G	19: 45,036,734	W441R	probably damaging	Het
Poldip2	A	G	11: 78,519,194	I267M	probably damaging	Homo
Pros1	T	A	16: 62,924,639	V539E	probably damaging	Het
Sacs	T	C	14: 61,212,976	M4157T	probably benign	Het
Slc45a3	A	G	1: 131,981,337	E424G	probably benign	Homo
Slc9a1	A	G	4: 133,422,146	E761G	probably benign	Homo
Stab2	G	A	10: 86,855,171	P2178L	probably damaging	Het
Syt4	C	T	18: 31,444,221	V27I	possibly damaging	Homo
Thumpd1	T	A	7: 119,720,576	K56*	probably null	Het
Tpr	A	G	1: 150,393,562	K19E	possibly damaging	Homo
Ttll10	A	G	4: 156,048,318	I74T	probably benign	Het
Txnrd1	C	T	10: 82,866,989	Q95*	probably null	Homo
Zc3h7b	A	G	15: 81,778,671	E421G	possibly damaging	Homo
Zc3hc1	G	T	6: 30,387,526	D51E	probably benign	Homo

Other mutations in Dpyd

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00418:Dpyd	APN	3	118944242	missense	probably damaging	1.00
IGL00508:Dpyd	APN	3	119064987	missense	probably benign	0.06
IGL02113:Dpyd	APN	3	118999219	missense	probably benign	0.06
IGL02177:Dpyd	APN	3	119064910	missense	possibly damaging	0.76
IGL03001:Dpyd	APN	3	118917242	missense	probably benign	0.07
IGL03106:Dpyd	APN	3	119195134	missense	probably benign	0.03
IGL03399:Dpyd	APN	3	119314777	missense	probably damaging	0.98
F5770:Dpyd	UTSW	3	118897126	nonsense	probably null
R0014:Dpyd	UTSW	3	119141935	missense	probably damaging	1.00
R0081:Dpyd	UTSW	3	118944255	missense	probably benign	0.00
R0267:Dpyd	UTSW	3	118917272	missense	probably benign
R0349:Dpyd	UTSW	3	118917099	nonsense	probably null
R0387:Dpyd	UTSW	3	119427226	missense	probably benign	0.21
R0523:Dpyd	UTSW	3	118899203	missense	probably benign
R0555:Dpyd	UTSW	3	119431542	missense	probably damaging	1.00
R0652:Dpyd	UTSW	3	119427275	missense	probably damaging	1.00
R0741:Dpyd	UTSW	3	118674505	missense	possibly damaging	0.79
R1313:Dpyd	UTSW	3	118899161	splice site	probably benign
R1554:Dpyd	UTSW	3	119065046	splice site	probably null
R1610:Dpyd	UTSW	3	119065006	missense	probably benign
R1710:Dpyd	UTSW	3	118610443	critical splice acceptor site	probably null
R1861:Dpyd	UTSW	3	118917131	missense	probably damaging	1.00
R2103:Dpyd	UTSW	3	119064952	missense	probably benign	0.02
R2130:Dpyd	UTSW	3	118674568	missense	probably benign
R2131:Dpyd	UTSW	3	118674568	missense	probably benign
R2882:Dpyd	UTSW	3	119065030	missense	probably damaging	0.99
R3771:Dpyd	UTSW	3	119412278	critical splice donor site	probably null
R3978:Dpyd	UTSW	3	118897088	critical splice acceptor site	probably benign
R3978:Dpyd	UTSW	3	118897089	critical splice acceptor site	probably benign
R4030:Dpyd	UTSW	3	118897166	missense	probably benign	0.03
R4065:Dpyd	UTSW	3	118897089	critical splice acceptor site	probably benign
R4066:Dpyd	UTSW	3	118897089	critical splice acceptor site	probably benign
R4234:Dpyd	UTSW	3	119431584	missense	probably damaging	1.00
R4502:Dpyd	UTSW	3	118797537	missense	probably damaging	1.00
R4638:Dpyd	UTSW	3	119266077	missense	probably benign	0.03
R4980:Dpyd	UTSW	3	118917118	missense	probably damaging	0.99
R5262:Dpyd	UTSW	3	118797422	nonsense	probably null
R5348:Dpyd	UTSW	3	118781943	missense	probably benign
R5587:Dpyd	UTSW	3	119064951	missense	probably damaging	1.00
R5611:Dpyd	UTSW	3	119194293	missense	probably benign
R5665:Dpyd	UTSW	3	118917092	missense	probably damaging	1.00
R5716:Dpyd	UTSW	3	118899179	missense	probably damaging	1.00
R5786:Dpyd	UTSW	3	119427237	missense	probably damaging	0.97
R6046:Dpyd	UTSW	3	119431575	missense	probably benign	0.01
R6404:Dpyd	UTSW	3	119265957	missense	probably benign	0.02
R6703:Dpyd	UTSW	3	118897200	splice site	probably null
R7037:Dpyd	UTSW	3	118899289	missense	probably benign	0.00
R7215:Dpyd	UTSW	3	119266032	missense	probably benign	0.11
R7301:Dpyd	UTSW	3	118899284	missense	possibly damaging	0.90
R7336:Dpyd	UTSW	3	119064921	missense	probably damaging	1.00
R7714:Dpyd	UTSW	3	118804131	missense	probably benign	0.01
R8238:Dpyd	UTSW	3	119195193	splice site	probably null
R8306:Dpyd	UTSW	3	119412173	missense	probably benign
R8315:Dpyd	UTSW	3	119314885	missense	probably benign	0.09
R8321:Dpyd	UTSW	3	118781924	missense	possibly damaging	0.84
R8342:Dpyd	UTSW	3	119314803	missense	possibly damaging	0.60
R8735:Dpyd	UTSW	3	119141916	missense	possibly damaging	0.74
R8750:Dpyd	UTSW	3	119141936	missense	probably damaging	1.00
R8874:Dpyd	UTSW	3	118999332	missense	probably damaging	1.00
R8910:Dpyd	UTSW	3	118610518	missense	probably benign	0.17
R8973:Dpyd	UTSW	3	119314933	critical splice donor site	probably null
R9070:Dpyd	UTSW	3	118999243	missense	probably damaging	0.98
R9132:Dpyd	UTSW	3	118917248	missense	probably damaging	1.00
R9198:Dpyd	UTSW	3	118759654	critical splice acceptor site	probably null
R9260:Dpyd	UTSW	3	119314798	missense	possibly damaging	0.95
R9307:Dpyd	UTSW	3	119314911	missense	probably benign
V7581:Dpyd	UTSW	3	118897126	nonsense	probably null
V7582:Dpyd	UTSW	3	118897126	nonsense	probably null
V7583:Dpyd	UTSW	3	118897126	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