Incidental Mutation 'F6893:Sacs'
ID185
Institutional Source Beutler Lab
Gene Symbol Sacs
Ensembl Gene ENSMUSG00000048279
Gene Namesacsin
SynonymsE130115J16Rik
Accession Numbers

Genbank: NM_172809; MGI: 1354724; Ensembl: ENSMUST00000119943

Is this an essential gene? Possibly non essential (E-score: 0.422) question?
Stock #F6893 (G3) of strain busy
Quality Score
Status Validated
Chromosome14
Chromosomal Location61138457-61240695 bp(+) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) T to C at 61212976 bp
ZygosityHeterozygous
Amino Acid Change Methionine to Threonine at position 4157 (M4157T)
Ref Sequence ENSEMBL: ENSMUSP00000113377 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000119943]
Predicted Effect probably benign
Transcript: ENSMUST00000119943
AA Change: M4157T

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000113377
Gene: ENSMUSG00000048279
AA Change: M4157T

DomainStartEndE-ValueType
internal_repeat_1 61 514 1.35e-52 PROSPERO
low complexity region 608 623 N/A INTRINSIC
low complexity region 664 673 N/A INTRINSIC
low complexity region 1019 1033 N/A INTRINSIC
low complexity region 1131 1145 N/A INTRINSIC
low complexity region 1526 1537 N/A INTRINSIC
low complexity region 2454 2463 N/A INTRINSIC
internal_repeat_1 2475 2934 1.35e-52 PROSPERO
low complexity region 3751 3760 N/A INTRINSIC
low complexity region 3997 4012 N/A INTRINSIC
low complexity region 4285 4300 N/A INTRINSIC
Blast:DnaJ 4304 4363 1e-31 BLAST
PDB:1IUR|A 4309 4376 5e-39 PDB
SCOP:d1gh6a_ 4317 4407 2e-3 SMART
HEPN 4454 4570 9.49e-24 SMART
Meta Mutation Damage Score 0.102 question?
Coding Region Coverage
  • 1x: 88.7%
  • 3x: 74.0%
Validation Efficiency 88% (165/188)
Allele List at MGI

All alleles(3) : Gene trapped(3)

Other mutations in this stock
Total: 35 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
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 R1729H 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
Dpyd T A 3: 118,804,134 probably null 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 L543S 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 Y235H 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
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 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 Sacs
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01540:Sacs APN 14 61191635 missense possibly damaging 0.64
IGL01839:Sacs APN 14 61183945 unclassified noncoding transcript
IGL02024:Sacs APN 14 61189678 missense probably damaging 0.96
IGL02247:Sacs APN 14 61192535 missense probably damaging 1.00
IGL03052:Sacs UTSW 14 61207858 missense probably damaging 0.99
R0090:Sacs UTSW 14 61205440 missense probably damaging 1.00
R0102:Sacs UTSW 14 61204568 missense probably damaging 1.00
R0102:Sacs UTSW 14 61204568 missense probably damaging 1.00
R0390:Sacs UTSW 14 61205640 missense possibly damaging 0.92
R0479:Sacs UTSW 14 61191479 missense probably damaging 0.99
R0556:Sacs UTSW 14 61183958 missense probably damaging 0.99
R0673:Sacs UTSW 14 61210215 missense possibly damaging 0.89
R0748:Sacs UTSW 14 61209265 missense probably damaging 0.99
R0931:Sacs UTSW 14 61203495 missense probably benign
R0972:Sacs UTSW 14 61211963 nonsense probably null
R1281:Sacs UTSW 14 61191801 missense probably benign 0.02
R1340:Sacs UTSW 14 61204509 missense probably damaging 0.98
R1351:Sacs UTSW 14 61202761 missense probably benign 0.00
R1499:Sacs UTSW 14 61213704 missense possibly damaging 0.70
R1538:Sacs UTSW 14 61210059 missense probably damaging 0.98
R1581:Sacs UTSW 14 61213679 missense probably damaging 0.96
R1599:Sacs UTSW 14 61203638 missense probably benign
R1631:Sacs UTSW 14 61210732 nonsense probably null
R1635:Sacs UTSW 14 61203828 missense probably damaging 0.98
R1655:Sacs UTSW 14 61191782 missense probably benign
R1660:Sacs UTSW 14 61209009 missense probably damaging 0.99
R1707:Sacs UTSW 14 61209762 missense probably benign 0.01
R1733:Sacs UTSW 14 61205454 missense probably damaging 1.00
R1772:Sacs UTSW 14 61210897 missense probably damaging 1.00
R1976:Sacs UTSW 14 61202895 missense probably benign
R2055:Sacs UTSW 14 61214049 missense probably damaging 0.97
R2083:Sacs UTSW 14 61206506 missense possibly damaging 0.69
R2091:Sacs UTSW 14 61191919 missense possibly damaging 0.95
R2105:Sacs UTSW 14 61173441 missense probably benign 0.00
R2109:Sacs UTSW 14 61173453 splice site probably null
R2117:Sacs UTSW 14 61213771 missense probably benign 0.01
R2122:Sacs UTSW 14 61212316 missense probably damaging 1.00
R2148:Sacs UTSW 14 61173378 missense probably damaging 0.97
R2151:Sacs UTSW 14 61209640 missense probably damaging 1.00
R2231:Sacs UTSW 14 61205929 missense probably null
R2248:Sacs UTSW 14 61212802 missense probably damaging 1.00
R2271:Sacs UTSW 14 61204660 missense probably benign 0.06
R2314:Sacs UTSW 14 61207759 missense probably benign 0.17
R2436:Sacs UTSW 14 61202905 missense possibly damaging 0.94
R2445:Sacs UTSW 14 61205206 missense probably damaging 1.00
R2512:Sacs UTSW 14 61203080 missense probably benign 0.00
R3434:Sacs UTSW 14 61212303 missense probably damaging 1.00
R3785:Sacs UTSW 14 61183961 missense probably damaging 1.00
R3786:Sacs UTSW 14 61183961 missense probably damaging 1.00
R3796:Sacs UTSW 14 61206121 missense possibly damaging 0.87
R3798:Sacs UTSW 14 61206121 missense possibly damaging 0.87
R3872:Sacs UTSW 14 61148068 missense probably benign 0.04
R3873:Sacs UTSW 14 61192286 missense possibly damaging 0.64
R3892:Sacs UTSW 14 61204387 missense probably damaging 0.98
R4184:Sacs UTSW 14 61213944 missense probably damaging 0.97
R4204:Sacs UTSW 14 61173443 missense possibly damaging 0.93
R4249:Sacs UTSW 14 61203457 missense probably benign 0.02
R4256:Sacs UTSW 14 61206337 missense probably damaging 1.00
R4370:Sacs UTSW 14 61212309 missense probably damaging 1.00
R4445:Sacs UTSW 14 61204686 missense probably benign 0.30
R4503:Sacs UTSW 14 61207603 missense probably damaging 1.00
R4548:Sacs UTSW 14 61191938 missense probably damaging 1.00
R4582:Sacs UTSW 14 61191698 missense probably damaging 1.00
R4613:Sacs UTSW 14 61211797 missense probably null
R4639:Sacs UTSW 14 61207268 missense probably benign 0.12
R4697:Sacs UTSW 14 61212747 missense probably benign 0.19
R4706:Sacs UTSW 14 61204273 missense probably damaging 1.00
R4717:Sacs UTSW 14 61212855 missense probably damaging 1.00
R4777:Sacs UTSW 14 61211809 missense probably damaging 1.00
R4888:Sacs UTSW 14 61212198 missense probably damaging 1.00
R4913:Sacs UTSW 14 61213797 missense probably benign 0.17
R4973:Sacs UTSW 14 61213122 missense probably damaging 1.00
R4986:Sacs UTSW 14 61213043 nonsense probably null
R5090:Sacs UTSW 14 61205253 missense probably damaging 1.00
R5243:Sacs UTSW 14 61205957 nonsense probably null
R5292:Sacs UTSW 14 61211983 missense probably damaging 1.00
R5308:Sacs UTSW 14 61192400 missense probably benign 0.21
R5337:Sacs UTSW 14 61193514 missense unknown
R5502:Sacs UTSW 14 61206100 missense probably damaging 1.00
R5586:Sacs UTSW 14 61206441 nonsense probably null
R5692:Sacs UTSW 14 61207839 missense probably benign 0.00
R5725:Sacs UTSW 14 61211110 missense probably damaging 1.00
R5854:Sacs UTSW 14 61211547 missense probably damaging 1.00
R5959:Sacs UTSW 14 61212400 missense probably damaging 0.99
R5960:Sacs UTSW 14 61208695 missense probably benign 0.30
R5968:Sacs UTSW 14 61189629 missense probably damaging 0.99
R5983:Sacs UTSW 14 61205199 missense probably damaging 1.00
R5992:Sacs UTSW 14 61205543 missense probably damaging 1.00
R6076:Sacs UTSW 14 61204536 nonsense probably null
R6175:Sacs UTSW 14 61212826 missense possibly damaging 0.82
R6347:Sacs UTSW 14 61211160 missense probably damaging 1.00
R6357:Sacs UTSW 14 61208824 missense possibly damaging 0.47
R6415:Sacs UTSW 14 61205359 missense not run
R6469:Sacs UTSW 14 61191248 missense probably damaging 1.00
R6503:Sacs UTSW 14 61211361 missense probably benign 0.00
R6523:Sacs UTSW 14 61202961 missense probably damaging 0.99
X0067:Sacs UTSW 14 61208019 missense probably damaging 1.00
Nature of Mutation
DNA sequencing using the SOLiD technique identified a T to C transition at position 12470 of the Sacs transcript using Ensembl record ENSMUST00000119943 in exon 9 of 9 total exons. Multiple transcripts of the Sacs gene are displayed on Ensembl. The mutated nucleotide causes a methionine to threonine substitution at amino acid 4157 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function & Prediction
If using the Ensembl record ENSMUST00000119943, the Sacs gene encodes a 4582 amino acid protein sacsin that may function in chaperone-mediated protein folding, and contains one protein-interacting J domain at residues 4309-4396 and one nucleotide-binding HEPN domain at residues 4454-4570 (Uniprot Q9JLC8). The NCBI record NM_172809 predicts a 768 amino acid protein that is identical with the first 731 amino acids of the longer protein, but does not contain the residue altered in busy mice (Uniprot B2RRL5). Humans with mutations in the SACS gene develop an early-onset neurodegenerative disease, spastic ataxia of the Charlevoix-Saguenay type (OMIM #270550).
 
The M4157T change is predicted to be benign by the PolyPhen program.
Posted OnMay 04, 2010