Mutagenetix > Incidental Mutation

Incidental Mutation 'R5630:Cad'

442047

Institutional Source

Beutler Lab

Gene Symbol

Cad

Ensembl Gene

ENSMUSG00000013629

Gene Name

carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase

Synonyms

2410008J01Rik

MMRRC Submission

043281-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.968) question?

Stock #

R5630 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

31212124-31235823 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 31217917 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 401 (S401P)

Ref Sequence

ENSEMBL: ENSMUSP00000144009 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000013773] [ENSMUST00000200953] [ENSMUST00000201182] [ENSMUST00000201838] [ENSMUST00000202795]

AlphaFold

B2RQC6

Predicted Effect

possibly damaging
Transcript: ENSMUST00000013773
AA Change: S401P

PolyPhen 2 Score 0.919 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000013773
Gene: ENSMUSG00000013629
AA Change: S401P

Domain	Start	End	E-Value	Type
CPSase_sm_chain	1	139	8.81e-80	SMART
Pfam:GATase	179	356	4.7e-47	PFAM
low complexity region	397	407	N/A	INTRINSIC
Pfam:ATP-grasp_4	511	692	1.2e-15	PFAM
Pfam:CPSase_L_D2	514	718	1.8e-85	PFAM
Pfam:ATP-grasp	522	690	1.5e-9	PFAM
Pfam:Dala_Dala_lig_C	527	687	2.2e-10	PFAM
CPSase_L_D3	798	921	9.7e-59	SMART
Pfam:ATP-grasp_4	1044	1223	1.8e-23	PFAM
Pfam:CPSase_L_D2	1047	1250	3.1e-28	PFAM
Pfam:Dala_Dala_lig_C	1054	1242	2.3e-7	PFAM
Pfam:ATP-grasp	1055	1222	2.1e-12	PFAM
MGS	1327	1428	1.35e-7	SMART
Pfam:Amidohydro_1	1462	1730	7.4e-12	PFAM
low complexity region	1820	1839	N/A	INTRINSIC
low complexity region	1864	1880	N/A	INTRINSIC
Pfam:OTCace_N	1924	2065	1.9e-44	PFAM
Pfam:OTCace	2071	2221	7.6e-37	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000031049
AA Change: S401P

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000031049
Gene: ENSMUSG00000013629
AA Change: S401P

Domain	Start	End	E-Value	Type
CPSase_sm_chain	1	139	8.81e-80	SMART
Pfam:GATase	179	356	3.8e-48	PFAM
Pfam:CPSase_L_chain	392	509	2.1e-20	PFAM
Pfam:CPSase_L_D2	514	616	1.9e-34	PFAM
Pfam:ATP-grasp	522	626	1.7e-6	PFAM
Pfam:Dala_Dala_lig_C	524	624	2.7e-7	PFAM
Pfam:CPSase_L_D2	614	655	5.2e-15	PFAM
CPSase_L_D3	735	858	9.7e-59	SMART
Pfam:CPSase_L_chain	868	979	2.9e-20	PFAM
Pfam:ATP-grasp_4	981	1160	6.4e-24	PFAM
Pfam:CPSase_L_D2	984	1187	3.5e-28	PFAM
Pfam:Dala_Dala_lig_C	991	1179	1.2e-6	PFAM
Pfam:ATP-grasp	992	1159	1.6e-11	PFAM
MGS	1264	1365	1.35e-7	SMART
Pfam:Amidohydro_5	1374	1437	9.4e-7	PFAM
Pfam:Amidohydro_1	1399	1597	1.9e-12	PFAM
Pfam:Amidohydro_4	1401	1692	5.5e-15	PFAM
low complexity region	1757	1776	N/A	INTRINSIC
low complexity region	1801	1817	N/A	INTRINSIC
Pfam:OTCace_N	1861	2003	1.7e-48	PFAM
Pfam:OTCace	2008	2158	1.5e-42	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000200953
AA Change: S401P

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000144307
Gene: ENSMUSG00000013629
AA Change: S401P

Domain	Start	End	E-Value	Type
CPSase_sm_chain	1	139	8.81e-80	SMART
Pfam:GATase	179	356	4.5e-47	PFAM
low complexity region	397	407	N/A	INTRINSIC
Pfam:CPSase_L_D2	514	616	1.5e-34	PFAM
Pfam:Dala_Dala_lig_C	527	625	2.4e-7	PFAM
Pfam:CPSase_L_D2	614	655	4.9e-15	PFAM
CPSase_L_D3	735	858	9.7e-59	SMART
Pfam:ATP-grasp_4	981	1160	1.7e-23	PFAM
Pfam:CPSase_L_D2	984	1187	3e-28	PFAM
Pfam:Dala_Dala_lig_C	991	1179	2.3e-7	PFAM
Pfam:ATP-grasp	992	1159	2.1e-12	PFAM
MGS	1264	1365	1.35e-7	SMART
Pfam:Amidohydro_1	1399	1667	7.1e-12	PFAM
low complexity region	1757	1776	N/A	INTRINSIC
low complexity region	1801	1817	N/A	INTRINSIC
Pfam:OTCace_N	1861	2002	1.8e-44	PFAM
Pfam:OTCace	2008	2158	7.3e-37	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000201182
AA Change: S401P

PolyPhen 2 Score 0.919 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000144684
Gene: ENSMUSG00000013629
AA Change: S401P

Domain	Start	End	E-Value	Type
CPSase_sm_chain	1	139	8.81e-80	SMART
Pfam:GATase	179	356	4.5e-47	PFAM
low complexity region	397	407	N/A	INTRINSIC
Pfam:ATP-grasp_4	511	692	1.1e-15	PFAM
Pfam:CPSase_L_D2	514	718	1.7e-85	PFAM
Pfam:ATP-grasp	522	690	1.4e-9	PFAM
Pfam:Dala_Dala_lig_C	527	687	2.1e-10	PFAM
CPSase_L_D3	798	921	9.7e-59	SMART
Pfam:ATP-grasp_4	1044	1223	1.7e-23	PFAM
Pfam:CPSase_L_D2	1047	1250	3e-28	PFAM
Pfam:Dala_Dala_lig_C	1054	1242	2.3e-7	PFAM
Pfam:ATP-grasp	1055	1222	2.1e-12	PFAM
MGS	1327	1428	1.35e-7	SMART
Pfam:Amidohydro_1	1462	1730	7.1e-12	PFAM
low complexity region	1820	1839	N/A	INTRINSIC
low complexity region	1864	1880	N/A	INTRINSIC
Pfam:OTCace_N	1949	1994	1.4e-11	PFAM
Pfam:OTCace	2000	2150	7.3e-37	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000201838
AA Change: S401P

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000144127
Gene: ENSMUSG00000013629
AA Change: S401P

Domain	Start	End	E-Value	Type
CPSase_sm_chain	1	139	8.81e-80	SMART
Pfam:GATase	179	356	6.3e-48	PFAM
low complexity region	397	407	N/A	INTRINSIC
Pfam:ATP-grasp_4	511	692	1.9e-16	PFAM
Pfam:CPSase_L_D2	514	718	3.7e-86	PFAM
Pfam:ATP-grasp	522	690	2.5e-10	PFAM
Pfam:Dala_Dala_lig_C	526	687	4.2e-11	PFAM
CPSase_L_D3	798	921	9.7e-59	SMART
SCOP:d1a9xa3	935	964	1e-7	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000201844

Predicted Effect

probably damaging
Transcript: ENSMUST00000202795
AA Change: S401P

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000144009
Gene: ENSMUSG00000013629
AA Change: S401P

Domain	Start	End	E-Value	Type
CPSase_sm_chain	1	139	8.81e-80	SMART
Pfam:GATase	179	356	1.9e-47	PFAM
low complexity region	397	407	N/A	INTRINSIC
Pfam:ATP-grasp_4	511	692	5.9e-16	PFAM
Pfam:CPSase_L_D2	514	718	1.2e-85	PFAM
Pfam:ATP-grasp	522	690	7.3e-10	PFAM
Pfam:Dala_Dala_lig_C	527	687	1.3e-10	PFAM
CPSase_L_D3	798	921	9.7e-59	SMART
Pfam:ATP-grasp_4	1044	1223	8.9e-24	PFAM
Pfam:CPSase_L_D2	1047	1250	2.1e-28	PFAM
Pfam:Dala_Dala_lig_C	1054	1242	1.3e-7	PFAM
Pfam:ATP-grasp	1055	1222	1.1e-12	PFAM
MGS	1327	1428	1.35e-7	SMART
Pfam:Amidohydro_1	1462	1730	2.5e-11	PFAM
low complexity region	1820	1839	N/A	INTRINSIC
low complexity region	1864	1880	N/A	INTRINSIC
Pfam:OTCace_N	1970	2004	4.6e-11	PFAM
Pfam:OTCace	2010	2160	9.9e-37	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000202967

Coding Region Coverage

1x: 99.3%
3x: 98.7%
10x: 97.5%
20x: 95.8%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The de novo synthesis of pyrimidine nucleotides is required for mammalian cells to proliferate. This gene encodes a trifunctional protein which is associated with the enzymatic activities of the first 3 enzymes in the 6-step pathway of pyrimidine biosynthesis: carbamoylphosphate synthetase (CPS II), aspartate transcarbamoylase, and dihydroorotase. This protein is regulated by the mitogen-activated protein kinase (MAPK) cascade, which indicates a direct link between activation of the MAPK cascade and de novo biosynthesis of pyrimidine nucleotides. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

Allele List at MGI

Other mutations in this stock

Total: 46 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Ap3s2	A	T	7: 79,559,647 (GRCm39)	V94E	probably damaging	Het
Aven	T	A	2: 112,344,890 (GRCm39)	Y109*	probably null	Het
Ccdc122	A	T	14: 77,330,216 (GRCm39)	I189F	probably damaging	Het
Cdkal1	A	T	13: 29,961,198 (GRCm39)		probably null	Het
Clock	G	A	5: 76,378,185 (GRCm39)	P572S	probably benign	Het
Cnih4	C	G	1: 180,989,748 (GRCm39)	F120L	probably benign	Het
Cntnap5b	A	G	1: 99,999,794 (GRCm39)	D184G	probably damaging	Het
Cpa2	T	A	6: 30,550,731 (GRCm39)		probably null	Het
Cpne5	T	C	17: 29,445,190 (GRCm39)	D38G	probably damaging	Het
Dst	GGAATCGTGCACTCGAA	GGAA	1: 34,227,866 (GRCm39)		probably null	Het
E330034G19Rik	A	G	14: 24,358,336 (GRCm39)		probably benign	Het
Flrt1	A	T	19: 7,073,830 (GRCm39)	I239N	probably damaging	Het
Foxb1	T	A	9: 69,667,402 (GRCm39)	I43F	probably damaging	Het
Kcnq3	A	G	15: 65,896,971 (GRCm39)	W310R	probably damaging	Het
Klrb1a	A	T	6: 128,595,573 (GRCm39)	D60E	probably benign	Het
Lbr	A	G	1: 181,644,529 (GRCm39)		probably null	Het
Lsm8	T	A	6: 18,851,672 (GRCm39)	I41N	probably damaging	Het
Mroh7	T	C	4: 106,577,764 (GRCm39)	M305V	possibly damaging	Het
Npdc1	G	A	2: 25,298,957 (GRCm39)	D284N	probably damaging	Het
Or5p4	T	A	7: 107,680,323 (GRCm39)	F107L	probably benign	Het
Or8c10	T	C	9: 38,279,402 (GRCm39)	Y177H	probably damaging	Het
Or8g20	T	A	9: 39,396,247 (GRCm39)	M98L	probably benign	Het
Pcdhb5	A	T	18: 37,454,208 (GRCm39)	D196V	possibly damaging	Het
Pcmt1	A	G	10: 7,524,857 (GRCm39)	Y84H	probably damaging	Het
Pcnx2	A	T	8: 126,587,697 (GRCm39)	I877K	probably damaging	Het
Pcsk5	A	G	19: 17,553,195 (GRCm39)	Y662H	probably benign	Het
Prdx1	T	A	4: 116,556,414 (GRCm39)	D187E	probably benign	Het
Ranbp2	T	G	10: 58,314,898 (GRCm39)	Y1873D	probably damaging	Het
Rcor2	A	T	19: 7,248,416 (GRCm39)	R144W	probably damaging	Het
Rptor	T	G	11: 119,647,075 (GRCm39)	I222S	probably benign	Het
Rrp8	C	A	7: 105,382,608 (GRCm39)	R448L	possibly damaging	Het
Ryr2	A	T	13: 11,616,691 (GRCm39)	I3909N	probably damaging	Het
Scn2a	T	G	2: 65,556,709 (GRCm39)	V1147G	probably damaging	Het
Secisbp2l	C	T	2: 125,582,657 (GRCm39)	G933D	possibly damaging	Het
Smox	C	T	2: 131,366,786 (GRCm39)	Q582*	probably null	Het
Sqor	T	A	2: 122,651,277 (GRCm39)	L180H	possibly damaging	Het
Stox2	T	C	8: 47,644,925 (GRCm39)	D845G	probably damaging	Het
Szt2	T	C	4: 118,250,102 (GRCm39)	I469V	possibly damaging	Het
Tns2	C	T	15: 102,017,369 (GRCm39)	R281C	probably damaging	Het
Tox	C	CTGGAGT	4: 6,688,835 (GRCm39)		probably benign	Het
Trgc2	A	G	13: 19,489,279 (GRCm39)	F151S	possibly damaging	Het
Upf2	T	C	2: 6,032,112 (GRCm39)	V141A	probably damaging	Het
Usp54	A	G	14: 20,615,125 (GRCm39)	L772P	probably damaging	Het
Vmn2r83	A	T	10: 79,327,785 (GRCm39)	T798S	possibly damaging	Het
Wee1	TCCCC	TCCC	7: 109,723,776 (GRCm39)		probably null	Het
Zfp143	C	T	7: 109,687,980 (GRCm39)	T473I	probably damaging	Het

Other mutations in Cad

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00821:Cad	APN	5	31,218,828 (GRCm39)	missense	probably damaging	1.00
IGL00908:Cad	APN	5	31,216,398 (GRCm39)	missense	possibly damaging	0.93
IGL01068:Cad	APN	5	31,219,114 (GRCm39)	splice site	probably benign
IGL01638:Cad	APN	5	31,224,958 (GRCm39)	missense	probably damaging	1.00
IGL02483:Cad	APN	5	31,218,170 (GRCm39)	critical splice acceptor site	probably null
IGL02499:Cad	APN	5	31,226,948 (GRCm39)	missense	probably damaging	1.00
IGL02691:Cad	APN	5	31,212,638 (GRCm39)	missense	probably damaging	1.00
IGL03002:Cad	APN	5	31,212,330 (GRCm39)	missense	probably benign	0.00
PIT4696001:Cad	UTSW	5	31,229,438 (GRCm39)	missense	probably damaging	0.99
R0212:Cad	UTSW	5	31,235,454 (GRCm39)	missense	probably damaging	1.00
R0317:Cad	UTSW	5	31,229,665 (GRCm39)	missense	probably benign	0.01
R0335:Cad	UTSW	5	31,231,329 (GRCm39)	unclassified	probably benign
R0401:Cad	UTSW	5	31,231,330 (GRCm39)	unclassified	probably benign
R0445:Cad	UTSW	5	31,230,053 (GRCm39)	missense	probably benign	0.08
R0494:Cad	UTSW	5	31,234,856 (GRCm39)	unclassified	probably benign
R0532:Cad	UTSW	5	31,219,531 (GRCm39)	splice site	probably benign
R0539:Cad	UTSW	5	31,232,801 (GRCm39)	splice site	probably benign
R0578:Cad	UTSW	5	31,216,120 (GRCm39)	missense	probably benign	0.01
R0590:Cad	UTSW	5	31,219,575 (GRCm39)	missense	probably damaging	1.00
R0638:Cad	UTSW	5	31,235,032 (GRCm39)	missense	probably damaging	0.98
R0831:Cad	UTSW	5	31,224,944 (GRCm39)	missense	probably damaging	1.00
R1329:Cad	UTSW	5	31,216,926 (GRCm39)	missense	probably damaging	1.00
R1513:Cad	UTSW	5	31,226,106 (GRCm39)	missense	probably damaging	1.00
R1531:Cad	UTSW	5	31,233,563 (GRCm39)	missense	probably benign	0.14
R1763:Cad	UTSW	5	31,218,295 (GRCm39)	missense	probably damaging	1.00
R1785:Cad	UTSW	5	31,215,416 (GRCm39)	missense	probably damaging	1.00
R1786:Cad	UTSW	5	31,215,416 (GRCm39)	missense	probably damaging	1.00
R2131:Cad	UTSW	5	31,215,416 (GRCm39)	missense	probably damaging	1.00
R2165:Cad	UTSW	5	31,219,564 (GRCm39)	missense	probably damaging	1.00
R3103:Cad	UTSW	5	31,219,018 (GRCm39)	missense	possibly damaging	0.95
R3113:Cad	UTSW	5	31,231,481 (GRCm39)	missense	possibly damaging	0.50
R3762:Cad	UTSW	5	31,232,890 (GRCm39)	splice site	probably null
R3847:Cad	UTSW	5	31,218,994 (GRCm39)	missense	probably damaging	1.00
R3898:Cad	UTSW	5	31,231,366 (GRCm39)	missense	probably benign	0.06
R3943:Cad	UTSW	5	31,229,729 (GRCm39)	critical splice donor site	probably null
R4213:Cad	UTSW	5	31,229,688 (GRCm39)	missense	probably benign	0.01
R4458:Cad	UTSW	5	31,218,570 (GRCm39)	missense	probably damaging	1.00
R4562:Cad	UTSW	5	31,215,477 (GRCm39)	missense	possibly damaging	0.82
R4629:Cad	UTSW	5	31,227,639 (GRCm39)	missense	probably damaging	1.00
R4717:Cad	UTSW	5	31,224,030 (GRCm39)	critical splice acceptor site	probably null
R4811:Cad	UTSW	5	31,232,034 (GRCm39)	missense	probably benign	0.02
R5044:Cad	UTSW	5	31,212,365 (GRCm39)	missense	probably benign	0.00
R5660:Cad	UTSW	5	31,234,191 (GRCm39)	missense	probably damaging	1.00
R6008:Cad	UTSW	5	31,226,456 (GRCm39)	missense	probably damaging	1.00
R6029:Cad	UTSW	5	31,212,327 (GRCm39)	missense	possibly damaging	0.65
R6073:Cad	UTSW	5	31,219,906 (GRCm39)	missense	possibly damaging	0.84
R6240:Cad	UTSW	5	31,230,322 (GRCm39)	missense	probably benign	0.00
R6260:Cad	UTSW	5	31,224,144 (GRCm39)	missense	probably null
R7145:Cad	UTSW	5	31,224,956 (GRCm39)	missense	possibly damaging	0.89
R7303:Cad	UTSW	5	31,217,557 (GRCm39)	critical splice donor site	probably null
R7352:Cad	UTSW	5	31,215,422 (GRCm39)	missense	probably damaging	1.00
R7382:Cad	UTSW	5	31,233,173 (GRCm39)	missense	probably benign
R7387:Cad	UTSW	5	31,219,284 (GRCm39)	missense	probably damaging	1.00
R7455:Cad	UTSW	5	31,231,506 (GRCm39)	missense	probably damaging	0.99
R7596:Cad	UTSW	5	31,226,392 (GRCm39)	missense	probably benign
R7627:Cad	UTSW	5	31,217,508 (GRCm39)	missense	probably damaging	1.00
R7898:Cad	UTSW	5	31,218,829 (GRCm39)	missense	probably damaging	1.00
R8022:Cad	UTSW	5	31,226,150 (GRCm39)	missense	probably damaging	1.00
R8115:Cad	UTSW	5	31,218,271 (GRCm39)	missense	possibly damaging	0.82
R8511:Cad	UTSW	5	31,233,165 (GRCm39)	missense	probably benign	0.00
R8523:Cad	UTSW	5	31,215,450 (GRCm39)	missense	probably damaging	0.98
R8690:Cad	UTSW	5	31,232,500 (GRCm39)	missense	possibly damaging	0.58
R8697:Cad	UTSW	5	31,231,945 (GRCm39)	missense	probably benign	0.06
R8698:Cad	UTSW	5	31,234,819 (GRCm39)	missense	probably benign
R8699:Cad	UTSW	5	31,233,605 (GRCm39)	missense	possibly damaging	0.80
R8803:Cad	UTSW	5	31,226,908 (GRCm39)	missense	probably damaging	1.00
R9262:Cad	UTSW	5	31,225,009 (GRCm39)	missense	probably null
R9272:Cad	UTSW	5	31,218,576 (GRCm39)	missense	possibly damaging	0.91
R9287:Cad	UTSW	5	31,230,000 (GRCm39)	missense	possibly damaging	0.67
R9314:Cad	UTSW	5	31,234,988 (GRCm39)	missense	probably damaging	1.00
R9609:Cad	UTSW	5	31,228,018 (GRCm39)	critical splice donor site	probably null
R9665:Cad	UTSW	5	31,229,703 (GRCm39)	missense	probably benign	0.28
RF001:Cad	UTSW	5	31,217,556 (GRCm39)	critical splice donor site	probably benign
RF012:Cad	UTSW	5	31,217,556 (GRCm39)	critical splice donor site	probably benign
X0021:Cad	UTSW	5	31,225,475 (GRCm39)	missense	probably null	1.00
X0022:Cad	UTSW	5	31,229,661 (GRCm39)	missense	probably damaging	0.99
Z1177:Cad	UTSW	5	31,232,472 (GRCm39)	missense	probably benign	0.25
Z1177:Cad	UTSW	5	31,225,765 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TCTCTGTGCTTGCCTGGAAG -3'
(R):5'- TCTACAGAAGACAGGACTTAGGCAC -3'

Sequencing Primer
(F):5'- CCTGGAAGTGAGGGTCTAGTAC -3'
(R):5'- GAAGACAGGACTTAGGCACTTCTTC -3'

Posted On

2016-11-08