Incidental Mutation 'R7596:Cad'
ID 587712
Institutional Source Beutler Lab
Gene Symbol Cad
Ensembl Gene ENSMUSG00000013629
Gene Name carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase
Synonyms 2410008J01Rik
MMRRC Submission 045671-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.968) question?
Stock # R7596 (G1)
Quality Score 225.009
Status Validated
Chromosome 5
Chromosomal Location 31212124-31235823 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 31226392 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Valine at position 1145 (I1145V)
Ref Sequence ENSEMBL: ENSMUSP00000013773 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000013773] [ENSMUST00000200953] [ENSMUST00000201182] [ENSMUST00000201838] [ENSMUST00000202795]
AlphaFold B2RQC6
Predicted Effect probably benign
Transcript: ENSMUST00000013773
AA Change: I1145V

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000013773
Gene: ENSMUSG00000013629
AA Change: I1145V

DomainStartEndE-ValueType
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 benign
Transcript: ENSMUST00000200953
AA Change: I1082V

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000144307
Gene: ENSMUSG00000013629
AA Change: I1082V

DomainStartEndE-ValueType
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 probably benign
Transcript: ENSMUST00000201182
AA Change: I1145V

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000144684
Gene: ENSMUSG00000013629
AA Change: I1145V

DomainStartEndE-ValueType
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 benign
Transcript: ENSMUST00000201838
SMART Domains Protein: ENSMUSP00000144127
Gene: ENSMUSG00000013629

DomainStartEndE-ValueType
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 probably benign
Transcript: ENSMUST00000202795
AA Change: I1145V

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000144009
Gene: ENSMUSG00000013629
AA Change: I1145V

DomainStartEndE-ValueType
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
Meta Mutation Damage Score 0.0898 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.7%
  • 20x: 98.9%
Validation Efficiency 95% (53/56)
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: 56 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
2310034C09Rik G A 16: 88,556,224 (GRCm39) S146N probably damaging Het
Adam26b A C 8: 43,973,237 (GRCm39) D588E probably benign Het
Ankrd13b C A 11: 77,363,140 (GRCm39) R547L probably benign Het
Bckdk G T 7: 127,505,572 (GRCm39) E232* probably null Het
C8a T C 4: 104,711,064 (GRCm39) K244E possibly damaging Het
Cd28 C A 1: 60,802,487 (GRCm39) H135Q possibly damaging Het
Ceacam19 A G 7: 19,615,812 (GRCm39) I209T possibly damaging Het
Cecr2 A G 6: 120,739,167 (GRCm39) N1298S probably benign Het
Cpne5 C T 17: 29,445,191 (GRCm39) D38N possibly damaging Het
Dcn A T 10: 97,345,871 (GRCm39) I228F probably damaging Het
Gm5591 T G 7: 38,219,608 (GRCm39) I422L probably benign Het
Gnptab T G 10: 88,279,232 (GRCm39) F1201V probably damaging Het
Hc A G 2: 34,890,859 (GRCm39) V1319A probably damaging Het
Htr3b T C 9: 48,847,361 (GRCm39) N385D probably benign Het
Ikbip A T 10: 90,918,891 (GRCm39) probably benign Het
Kcnk1 T C 8: 126,722,350 (GRCm39) L51P probably damaging Het
Lcn2 A G 2: 32,275,721 (GRCm39) Y160H probably damaging Het
Lig1 T C 7: 13,039,923 (GRCm39) S712P probably damaging Het
Lrrc19 T G 4: 94,531,592 (GRCm39) M7L probably benign Het
Lrrc4b C T 7: 44,111,310 (GRCm39) T394M probably damaging Het
Map7 A G 10: 20,153,927 (GRCm39) N681S unknown Het
Mdga2 A T 12: 66,552,897 (GRCm39) M912K probably damaging Het
Mlst8 C T 17: 24,697,084 (GRCm39) probably null Het
Ms4a13 A T 19: 11,147,329 (GRCm39) V195D unknown Het
Muc4 C G 16: 32,575,221 (GRCm39) Q1269E probably benign Het
Nr4a2 G C 2: 56,998,243 (GRCm39) F574L probably damaging Het
Nup107 T C 10: 117,613,065 (GRCm39) N288D probably damaging Het
Or11g26 A T 14: 50,753,002 (GRCm39) T114S probably benign Het
Or13a1 T A 6: 116,471,158 (GRCm39) V196D probably benign Het
Or5b3 C T 19: 13,388,511 (GRCm39) H193Y probably benign Het
Pcolce A G 5: 137,605,087 (GRCm39) probably null Het
Pik3cg A G 12: 32,254,740 (GRCm39) F416L probably damaging Het
Podnl1 A G 8: 84,853,024 (GRCm39) I65V Het
Prpf8 T C 11: 75,382,330 (GRCm39) F387S probably benign Het
Rev3l A G 10: 39,697,534 (GRCm39) Y677C probably damaging Het
Rhpn1 A G 15: 75,584,162 (GRCm39) T430A probably benign Het
Rnf187 T C 11: 58,829,241 (GRCm39) R124G possibly damaging Het
Rpl9-ps6 C T 19: 32,443,783 (GRCm39) V57I probably benign Het
Samhd1 A T 2: 156,943,754 (GRCm39) F587I probably damaging Het
Slc30a6 A G 17: 74,722,664 (GRCm39) T244A probably benign Het
Slc35f4 T A 14: 49,543,666 (GRCm39) Y310F probably damaging Het
Smarcc2 A G 10: 128,318,662 (GRCm39) Y648C probably damaging Het
Smc5 A C 19: 23,191,533 (GRCm39) V889G probably damaging Het
Sp110 G A 1: 85,506,813 (GRCm39) R417C probably benign Het
Spopfm2 T A 3: 94,083,737 (GRCm39) T25S probably benign Het
Tango2 A G 16: 18,120,574 (GRCm39) V229A probably damaging Het
Tnks1bp1 A G 2: 84,893,057 (GRCm39) T995A probably benign Het
Trio A T 15: 27,749,912 (GRCm39) I2263N probably damaging Het
Ttc28 T C 5: 111,427,990 (GRCm39) F1829L probably damaging Het
Ttn A G 2: 76,638,923 (GRCm39) S13920P probably damaging Het
Ube2b T C 11: 51,877,570 (GRCm39) N133S probably damaging Het
Ubn1 T A 16: 4,899,422 (GRCm39) H1055Q probably benign Het
Ubtf G A 11: 102,197,533 (GRCm39) T705M unknown Het
Vmn2r109 A T 17: 20,760,942 (GRCm39) M805K probably damaging Het
Vsig10 T C 5: 117,472,848 (GRCm39) V147A possibly damaging Het
Zbtb16 C A 9: 48,743,704 (GRCm39) V203L possibly damaging Het
Other mutations in Cad
AlleleSourceChrCoordTypePredicted EffectPPH 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
R5630:Cad UTSW 5 31,217,917 (GRCm39) missense probably damaging 1.00
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
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'- ACCCCGTAGTCATCTCCAAG -3'
(R):5'- CAGATTGAAGGGTCCTGTAACC -3'

Sequencing Primer
(F):5'- GTCATCTCCAAGTTCATTCAGGAAGC -3'
(R):5'- AAGGGTCCTGTAACCTGTAGCTC -3'
Posted On 2019-10-24