Incidental Mutation 'R1653:Sirt1'
ID 188867
Institutional Source Beutler Lab
Gene Symbol Sirt1
Ensembl Gene ENSMUSG00000020063
Gene Name sirtuin 1
Synonyms Sir2alpha, Sir2
MMRRC Submission 039689-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R1653 (G1)
Quality Score 225
Status Not validated
Chromosome 10
Chromosomal Location 63154784-63174814 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 63157588 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Threonine to Alanine at position 609 (T609A)
Ref Sequence ENSEMBL: ENSMUSP00000112595 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000020257] [ENSMUST00000020258] [ENSMUST00000105442] [ENSMUST00000120239] [ENSMUST00000146028] [ENSMUST00000219577] [ENSMUST00000177694]
AlphaFold Q923E4
Predicted Effect probably benign
Transcript: ENSMUST00000020257
AA Change: T609A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000020257
Gene: ENSMUSG00000020063
AA Change: T609A

DomainStartEndE-ValueType
low complexity region 6 28 N/A INTRINSIC
low complexity region 46 94 N/A INTRINSIC
low complexity region 108 131 N/A INTRINSIC
low complexity region 136 148 N/A INTRINSIC
Pfam:SIR2 253 439 1.3e-62 PFAM
PDB:4KXQ|B 629 648 4e-6 PDB
low complexity region 649 667 N/A INTRINSIC
low complexity region 672 687 N/A INTRINSIC
low complexity region 702 713 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000020258
SMART Domains Protein: ENSMUSP00000020258
Gene: ENSMUSG00000020064

DomainStartEndE-ValueType
Pfam:RCC1 1 49 5.1e-11 PFAM
Pfam:RCC1_2 36 65 1.2e-9 PFAM
Pfam:RCC1 52 99 7.9e-16 PFAM
Pfam:RCC1_2 86 115 2.8e-11 PFAM
Pfam:RCC1 102 152 7.6e-18 PFAM
Pfam:RCC1_2 139 168 9.9e-14 PFAM
Pfam:RCC1 156 205 2.2e-15 PFAM
Pfam:RCC1_2 194 221 4.9e-10 PFAM
Pfam:RCC1 208 257 3.5e-17 PFAM
Pfam:RCC1 260 309 9.4e-14 PFAM
Pfam:RCC1 313 376 2.7e-8 PFAM
HECTc 720 1049 1.19e-135 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000105442
AA Change: T570A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000101082
Gene: ENSMUSG00000020063
AA Change: T570A

DomainStartEndE-ValueType
low complexity region 6 28 N/A INTRINSIC
low complexity region 46 94 N/A INTRINSIC
low complexity region 108 131 N/A INTRINSIC
Pfam:SIR2 214 400 4e-63 PFAM
PDB:4KXQ|B 590 609 3e-6 PDB
low complexity region 610 628 N/A INTRINSIC
low complexity region 633 648 N/A INTRINSIC
low complexity region 663 674 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000120239
AA Change: T609A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000112595
Gene: ENSMUSG00000020063
AA Change: T609A

DomainStartEndE-ValueType
low complexity region 6 28 N/A INTRINSIC
low complexity region 46 94 N/A INTRINSIC
low complexity region 108 131 N/A INTRINSIC
low complexity region 136 148 N/A INTRINSIC
Pfam:SIR2 253 439 6.5e-64 PFAM
PDB:4KXQ|B 629 648 4e-6 PDB
low complexity region 649 667 N/A INTRINSIC
low complexity region 672 687 N/A INTRINSIC
low complexity region 702 713 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000146028
SMART Domains Protein: ENSMUSP00000117819
Gene: ENSMUSG00000020063

DomainStartEndE-ValueType
Pfam:SIR2 83 140 1.9e-15 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000148516
Predicted Effect noncoding transcript
Transcript: ENSMUST00000219789
Predicted Effect probably benign
Transcript: ENSMUST00000219577
Predicted Effect probably benign
Transcript: ENSMUST00000177694
SMART Domains Protein: ENSMUSP00000137565
Gene: ENSMUSG00000020063

DomainStartEndE-ValueType
low complexity region 6 28 N/A INTRINSIC
low complexity region 46 94 N/A INTRINSIC
low complexity region 108 131 N/A INTRINSIC
low complexity region 136 148 N/A INTRINSIC
Pfam:SIR2 253 439 7.3e-63 PFAM
low complexity region 465 483 N/A INTRINSIC
low complexity region 488 503 N/A INTRINSIC
low complexity region 518 529 N/A INTRINSIC
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.4%
  • 10x: 96.4%
  • 20x: 92.7%
Validation Efficiency
MGI Phenotype FUNCTION: This gene encodes a member of the sirtuin family of proteins, characterized by their deacetylase activity and proposed role in longevity. The encoded protein regulates gene expression in a wide range of cell and tissue types through its NAD+-dependent deacetylation of histones, transcription factors and transcriptional coactivators. Brain-specific overexpression of this gene has been shown to result in increased median lifespan. Viability of homozygous knockout mice for this gene varies with strain background. Homozygous knockout mice of strains that do not exhibit embryonic lethality are sterile and have a reduced lifespan. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]
PHENOTYPE: Mice homozygous for a knock-out allele show embryonic and fetal lethality, abnormal embryogenesis, and abnormal cellular phenotypes of derived MEFs. Mice homozygous for other knock-out alleles may exhibit peri- and postnatal lethality and heart, mammary gland, eye, and reproductive system anomalies. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 51 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adam34 A T 8: 44,103,682 (GRCm39) C654* probably null Het
Adamts19 T A 18: 59,023,365 (GRCm39) N253K probably benign Het
Adgrb3 A G 1: 25,140,584 (GRCm39) L1162S probably benign Het
Ap2b1 T A 11: 83,237,657 (GRCm39) Y574N probably damaging Het
Atrn A G 2: 130,777,544 (GRCm39) I198V probably benign Het
Bcan T A 3: 87,901,503 (GRCm39) I400F probably damaging Het
Capn10 A G 1: 92,874,620 (GRCm39) Y617C probably damaging Het
Capn8 A G 1: 182,451,516 (GRCm39) N578D probably benign Het
Casd1 T C 6: 4,624,134 (GRCm39) L309P probably benign Het
Ccser1 T A 6: 61,288,449 (GRCm39) I204K probably benign Het
Cd276 T C 9: 58,444,732 (GRCm39) T80A probably benign Het
Cdh3 T C 8: 107,265,700 (GRCm39) S248P probably damaging Het
Celsr2 T C 3: 108,320,836 (GRCm39) T659A possibly damaging Het
Col6a4 C T 9: 105,949,608 (GRCm39) V676I probably damaging Het
Crmp1 T A 5: 37,443,812 (GRCm39) V575D probably damaging Het
Ep400 G A 5: 110,841,040 (GRCm39) Q1795* probably null Het
Gcnt3 A G 9: 69,942,359 (GRCm39) C70R probably damaging Het
Gm12258 T C 11: 58,749,113 (GRCm39) I96T possibly damaging Het
Gpr183 A G 14: 122,191,675 (GRCm39) F282S probably damaging Het
Igfals T C 17: 25,100,052 (GRCm39) V381A probably benign Het
Irs3 C A 5: 137,642,783 (GRCm39) L218F probably damaging Het
Kdm5b T C 1: 134,530,219 (GRCm39) F410S probably damaging Het
Klc4 T C 17: 46,942,785 (GRCm39) Y593C possibly damaging Het
Lce1h T A 3: 92,670,750 (GRCm39) Q134L unknown Het
Lyst T C 13: 13,809,811 (GRCm39) S494P probably damaging Het
Marchf3 A G 18: 56,944,967 (GRCm39) M42T probably benign Het
Myh7 A G 14: 55,228,246 (GRCm39) I250T probably benign Het
N4bp1 G T 8: 87,571,576 (GRCm39) H807Q probably benign Het
Ndn C T 7: 61,998,256 (GRCm39) P34L probably benign Het
Nfs1 C T 2: 155,967,256 (GRCm39) G44D probably damaging Het
Nrg1 C T 8: 32,308,681 (GRCm39) R445H probably damaging Het
Or14c43 T C 7: 86,115,420 (GRCm39) V267A probably benign Het
Or4e5 A T 14: 52,728,229 (GRCm39) F64Y probably damaging Het
Or56a5 T A 7: 104,793,077 (GRCm39) D141V possibly damaging Het
Pak5 C T 2: 135,958,807 (GRCm39) V94M probably damaging Het
Pdk1 G A 2: 71,719,339 (GRCm39) probably null Het
Sin3b G T 8: 73,468,147 (GRCm39) V290L probably benign Het
Skint5 A T 4: 113,347,875 (GRCm39) S1289T unknown Het
Slc32a1 A T 2: 158,456,809 (GRCm39) H488L probably benign Het
Slc35b3 A G 13: 39,139,774 (GRCm39) S18P probably benign Het
Spaca7 T A 8: 12,636,501 (GRCm39) I109K possibly damaging Het
Tmem204 A G 17: 25,299,501 (GRCm39) L6P possibly damaging Het
Tubgcp6 G A 15: 88,991,645 (GRCm39) R651C probably damaging Het
Vps13b T A 15: 35,607,418 (GRCm39) L1117* probably null Het
Wdcp T C 12: 4,901,815 (GRCm39) L557P probably damaging Het
Wwp2 T C 8: 108,210,042 (GRCm39) F140S possibly damaging Het
Zfp429 C T 13: 67,538,043 (GRCm39) R467H possibly damaging Het
Zfp747l1 G T 7: 126,983,652 (GRCm39) H483Q possibly damaging Het
Zfp839 T A 12: 110,821,684 (GRCm39) M166K probably benign Het
Zfyve9 G A 4: 108,517,774 (GRCm39) Q1106* probably null Het
Zrsr2-ps1 T A 11: 22,924,158 (GRCm39) C311S probably damaging Het
Other mutations in Sirt1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02057:Sirt1 APN 10 63,160,982 (GRCm39) missense probably damaging 1.00
IGL02106:Sirt1 APN 10 63,171,608 (GRCm39) missense probably damaging 1.00
PIT4283001:Sirt1 UTSW 10 63,157,565 (GRCm39) missense probably benign 0.02
R0658:Sirt1 UTSW 10 63,157,515 (GRCm39) unclassified probably benign
R0724:Sirt1 UTSW 10 63,159,752 (GRCm39) missense possibly damaging 0.82
R1831:Sirt1 UTSW 10 63,156,425 (GRCm39) missense probably benign 0.13
R4133:Sirt1 UTSW 10 63,171,438 (GRCm39) missense probably null 0.42
R4250:Sirt1 UTSW 10 63,172,877 (GRCm39) critical splice acceptor site probably null
R4378:Sirt1 UTSW 10 63,174,728 (GRCm39) missense probably benign 0.00
R4396:Sirt1 UTSW 10 63,157,777 (GRCm39) missense probably benign 0.00
R4776:Sirt1 UTSW 10 63,171,501 (GRCm39) missense probably benign 0.17
R4898:Sirt1 UTSW 10 63,157,783 (GRCm39) missense probably benign 0.35
R7151:Sirt1 UTSW 10 63,159,775 (GRCm39) missense probably damaging 1.00
R7365:Sirt1 UTSW 10 63,157,782 (GRCm39) missense probably benign
R7467:Sirt1 UTSW 10 63,157,929 (GRCm39) missense probably benign 0.00
R7773:Sirt1 UTSW 10 63,162,562 (GRCm39) missense possibly damaging 0.75
R8729:Sirt1 UTSW 10 63,156,705 (GRCm39) missense probably damaging 1.00
R8949:Sirt1 UTSW 10 63,161,964 (GRCm39) missense probably damaging 1.00
R9095:Sirt1 UTSW 10 63,158,077 (GRCm39) missense probably damaging 0.98
R9228:Sirt1 UTSW 10 63,172,857 (GRCm39) missense probably damaging 1.00
R9423:Sirt1 UTSW 10 63,158,025 (GRCm39) missense probably damaging 1.00
R9463:Sirt1 UTSW 10 63,171,487 (GRCm39) missense probably benign 0.17
R9759:Sirt1 UTSW 10 63,156,516 (GRCm39) missense probably benign 0.00
RF015:Sirt1 UTSW 10 63,172,795 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- TCTGGGGTACATCTTCAACCCTGAG -3'
(R):5'- AGGCTAGGTGGTGAATATGCCAAAC -3'

Sequencing Primer
(F):5'- CGGAGTAAAACCCACTTTTGG -3'
(R):5'- TTCGGAAGACTCAAGTTCACCTG -3'
Posted On 2014-05-09