Incidental Mutation 'D4043:Ago3'
ID 259
Institutional Source Beutler Lab
Gene Symbol Ago3
Ensembl Gene ENSMUSG00000028842
Gene Name argonaute RISC catalytic subunit 3
Synonyms eIF2C3, C130014L07Rik, argonaute 3
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # D4043 (G3) of strain 483
Quality Score
Status Validated
Chromosome 4
Chromosomal Location 126225497-126323349 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 126244796 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Glutamic Acid at position 630 (V630E)
Ref Sequence ENSEMBL: ENSMUSP00000066633 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000069097] [ENSMUST00000127831] [ENSMUST00000132123]
AlphaFold Q8CJF9
Predicted Effect probably damaging
Transcript: ENSMUST00000069097
AA Change: V630E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000066633
Gene: ENSMUSG00000028842
AA Change: V630E

DomainStartEndE-ValueType
Pfam:ArgoN 20 167 9.4e-26 PFAM
DUF1785 176 228 3.48e-25 SMART
PAZ 236 371 4.18e-4 SMART
Pfam:ArgoL2 376 421 1.3e-14 PFAM
Pfam:ArgoMid 430 512 1.4e-34 PFAM
Piwi 518 819 2.96e-136 SMART
Blast:Piwi 826 852 5e-7 BLAST
Predicted Effect probably benign
Transcript: ENSMUST00000127831
SMART Domains Protein: ENSMUSP00000118577
Gene: ENSMUSG00000028842

DomainStartEndE-ValueType
Piwi 1 125 9.56e-1 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000132123
SMART Domains Protein: ENSMUSP00000116204
Gene: ENSMUSG00000028842

DomainStartEndE-ValueType
Piwi 1 140 1.41e-19 SMART
Meta Mutation Damage Score 0.9735 question?
Coding Region Coverage
  • 1x: 88.8%
  • 3x: 72.5%
Validation Efficiency 88% (220/249)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the Argonaute family of proteins which play a role in RNA interference. The encoded protein is highly basic, contains a PAZ domain and a PIWI domain, and may play a role in short-interfering-RNA-mediated gene silencing. This gene is located on chromosome 1 in a tandem cluster of closely related family members including argonaute 4 and eukaryotic translation initiation factor 2C, 1. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
Allele List at MGI

All alleles(22) : Gene trapped(22)

Other mutations in this stock
Total: 25 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adam29 A T 8: 56,325,496 (GRCm39) C319* probably null Het
Adgrg1 T C 8: 95,731,857 (GRCm39) probably null Homo
Armc8 G T 9: 99,366,029 (GRCm39) N628K probably benign Het
Cfap96 A G 8: 46,409,440 (GRCm39) V293A probably damaging Het
Chd7 A G 4: 8,862,650 (GRCm39) D2579G probably damaging Het
Duox1 G A 2: 122,175,276 (GRCm39) C1358Y probably benign Het
Ftsj3 C A 11: 106,145,634 (GRCm39) M66I possibly damaging Homo
Iqub C T 6: 24,505,750 (GRCm39) E53K possibly damaging Het
Kirrel1 T A 3: 86,990,510 (GRCm39) T771S probably benign Het
Lrrc66 A T 5: 73,764,869 (GRCm39) S725T probably benign Het
Mael T C 1: 166,064,455 (GRCm39) I104M probably benign Homo
Mkks C T 2: 136,716,530 (GRCm39) V457I probably benign Het
Nadk2 T A 15: 9,103,473 (GRCm39) probably benign Homo
Npas1 T C 7: 16,197,169 (GRCm39) probably null Het
Ocrl T C X: 47,025,200 (GRCm39) V359A probably benign Homo
Or8k27 G A 2: 86,275,564 (GRCm39) T254M probably damaging Het
Pde6b C T 5: 108,573,222 (GRCm39) R531* probably null Het
Polr1a G A 6: 71,918,401 (GRCm39) C653Y possibly damaging Het
Rbm26 A G 14: 105,389,976 (GRCm39) V216A possibly damaging Het
Rin2 C A 2: 145,664,283 (GRCm39) H52Q possibly damaging Het
Ssc5d C T 7: 4,946,982 (GRCm39) T1112I possibly damaging Het
Sv2c C T 13: 96,224,989 (GRCm39) V107M probably benign Het
Tasor A G 14: 27,193,949 (GRCm39) I1050V probably benign Het
Tulp3 G A 6: 128,301,113 (GRCm39) S366L probably benign Het
Zfp831 T A 2: 174,487,059 (GRCm39) V578E probably benign Homo
Other mutations in Ago3
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00090:Ago3 APN 4 126,265,334 (GRCm39) missense probably damaging 1.00
IGL01826:Ago3 APN 4 126,297,075 (GRCm39) missense probably damaging 1.00
IGL02285:Ago3 APN 4 126,244,670 (GRCm39) missense possibly damaging 0.88
IGL02869:Ago3 APN 4 126,261,580 (GRCm39) splice site probably benign
IGL03068:Ago3 APN 4 126,311,171 (GRCm39) missense probably damaging 0.99
R0506:Ago3 UTSW 4 126,311,045 (GRCm39) missense possibly damaging 0.79
R0545:Ago3 UTSW 4 126,311,025 (GRCm39) missense probably damaging 1.00
R0764:Ago3 UTSW 4 126,248,885 (GRCm39) missense possibly damaging 0.82
R1445:Ago3 UTSW 4 126,265,580 (GRCm39) missense probably benign
R1706:Ago3 UTSW 4 126,264,085 (GRCm39) missense probably damaging 1.00
R1909:Ago3 UTSW 4 126,240,530 (GRCm39) missense probably damaging 1.00
R1944:Ago3 UTSW 4 126,247,520 (GRCm39) missense probably damaging 1.00
R1974:Ago3 UTSW 4 126,240,544 (GRCm39) missense probably damaging 1.00
R2239:Ago3 UTSW 4 126,262,315 (GRCm39) missense probably damaging 1.00
R2380:Ago3 UTSW 4 126,262,315 (GRCm39) missense probably damaging 1.00
R2424:Ago3 UTSW 4 126,298,040 (GRCm39) missense probably damaging 1.00
R2571:Ago3 UTSW 4 126,257,604 (GRCm39) missense probably damaging 1.00
R3121:Ago3 UTSW 4 126,311,165 (GRCm39) missense probably benign
R3122:Ago3 UTSW 4 126,311,165 (GRCm39) missense probably benign
R4022:Ago3 UTSW 4 126,262,386 (GRCm39) missense probably benign 0.31
R4079:Ago3 UTSW 4 126,247,473 (GRCm39) critical splice donor site probably null
R4272:Ago3 UTSW 4 126,248,884 (GRCm39) missense possibly damaging 0.95
R4533:Ago3 UTSW 4 126,239,356 (GRCm39) missense probably damaging 1.00
R4575:Ago3 UTSW 4 126,240,475 (GRCm39) missense probably benign 0.06
R4656:Ago3 UTSW 4 126,257,545 (GRCm39) nonsense probably null
R4782:Ago3 UTSW 4 126,241,665 (GRCm39) splice site probably null
R4783:Ago3 UTSW 4 126,262,296 (GRCm39) missense probably benign 0.31
R4784:Ago3 UTSW 4 126,262,296 (GRCm39) missense probably benign 0.31
R4785:Ago3 UTSW 4 126,262,296 (GRCm39) missense probably benign 0.31
R4799:Ago3 UTSW 4 126,241,665 (GRCm39) splice site probably null
R5013:Ago3 UTSW 4 126,262,391 (GRCm39) missense probably benign 0.18
R5180:Ago3 UTSW 4 126,261,544 (GRCm39) missense probably benign 0.01
R5692:Ago3 UTSW 4 126,248,862 (GRCm39) splice site probably null
R5801:Ago3 UTSW 4 126,265,561 (GRCm39) missense possibly damaging 0.53
R5955:Ago3 UTSW 4 126,248,843 (GRCm39) missense probably damaging 1.00
R6730:Ago3 UTSW 4 126,265,338 (GRCm39) missense probably null 0.04
R7077:Ago3 UTSW 4 126,265,325 (GRCm39) missense probably null 0.01
R7123:Ago3 UTSW 4 126,248,798 (GRCm39) critical splice donor site probably null
R7125:Ago3 UTSW 4 126,264,145 (GRCm39) missense probably null 0.89
R7354:Ago3 UTSW 4 126,311,099 (GRCm39) missense possibly damaging 0.72
R7472:Ago3 UTSW 4 126,239,310 (GRCm39) missense probably damaging 1.00
R7522:Ago3 UTSW 4 126,257,600 (GRCm39) missense probably benign 0.00
R7863:Ago3 UTSW 4 126,243,990 (GRCm39) missense possibly damaging 0.53
R8163:Ago3 UTSW 4 126,262,377 (GRCm39) missense probably benign 0.10
R8225:Ago3 UTSW 4 126,247,532 (GRCm39) missense probably damaging 1.00
R8266:Ago3 UTSW 4 126,270,721 (GRCm39) nonsense probably null
R8269:Ago3 UTSW 4 126,270,721 (GRCm39) nonsense probably null
R8343:Ago3 UTSW 4 126,270,721 (GRCm39) nonsense probably null
R8344:Ago3 UTSW 4 126,270,721 (GRCm39) nonsense probably null
R8345:Ago3 UTSW 4 126,270,721 (GRCm39) nonsense probably null
R8547:Ago3 UTSW 4 126,264,109 (GRCm39) missense probably null 0.82
R8948:Ago3 UTSW 4 126,244,115 (GRCm39) critical splice acceptor site probably null
R8962:Ago3 UTSW 4 126,241,595 (GRCm39) missense probably damaging 1.00
R8989:Ago3 UTSW 4 126,298,191 (GRCm39) missense probably damaging 1.00
R9110:Ago3 UTSW 4 126,248,829 (GRCm39) missense probably damaging 1.00
R9356:Ago3 UTSW 4 126,264,144 (GRCm39) missense probably damaging 1.00
T0722:Ago3 UTSW 4 126,298,098 (GRCm39) missense probably benign
T0722:Ago3 UTSW 4 126,298,089 (GRCm39) missense probably benign 0.21
T0722:Ago3 UTSW 4 126,298,056 (GRCm39) missense probably benign
T0722:Ago3 UTSW 4 126,298,103 (GRCm39) missense probably benign 0.00
T0975:Ago3 UTSW 4 126,298,103 (GRCm39) missense probably benign 0.00
T0975:Ago3 UTSW 4 126,298,098 (GRCm39) missense probably benign
T0975:Ago3 UTSW 4 126,298,056 (GRCm39) missense probably benign
Nature of Mutation
DNA sequencing using the SOLiD technique identified a T to A transversion at position 2145 of the Eif2c3 transcript in exon 15 of 19 total exons. Multiple transcripts of the Eif2c3 gene are displayed on Ensembl and Vega. The mutated nucleotide causes a valine to glutamic acid substitution at amino acid 630 of the encoded protein.  The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
The Eif2c3 gene encodes an 860 amino acid member of the argonaute family required for RNA-mediated gene silencing. The protein binds to short RNAs such as microRNAs (miRNAs), and represses the translation of mRNAs that are complementary to the miRNAs. A PAZ domain is located at residues 236-349, and an RNA-binding Piwi domain is located at residues 518-819 (Uniprot Q8CJF9).  
 
The V630E change is located in the Piwi domain, and is predicted to be probably damaging by the PolyPhen program.
Posted On 2010-08-09