Incidental Mutation 'R7151:Sirt1'
ID 554143
Institutional Source Beutler Lab
Gene Symbol Sirt1
Ensembl Gene ENSMUSG00000020063
Gene Name sirtuin 1
Synonyms Sir2alpha, Sir2
MMRRC Submission 045253-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R7151 (G1)
Quality Score 225.009
Status Not validated
Chromosome 10
Chromosomal Location 63154784-63174814 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 63159775 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Leucine to Glutamine at position 435 (L435Q)
Ref Sequence ENSEMBL: ENSMUSP00000020257 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000020257] [ENSMUST00000105442] [ENSMUST00000120239] [ENSMUST00000146028] [ENSMUST00000177694]
AlphaFold Q923E4
Predicted Effect probably damaging
Transcript: ENSMUST00000020257
AA Change: L435Q

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000020257
Gene: ENSMUSG00000020063
AA Change: L435Q

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 damaging
Transcript: ENSMUST00000105442
AA Change: L396Q

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000101082
Gene: ENSMUSG00000020063
AA Change: L396Q

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 damaging
Transcript: ENSMUST00000120239
AA Change: L435Q

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000112595
Gene: ENSMUSG00000020063
AA Change: L435Q

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 probably damaging
Transcript: ENSMUST00000177694
AA Change: L435Q

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000137565
Gene: ENSMUSG00000020063
AA Change: L435Q

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: 100.0%
  • 3x: 99.9%
  • 10x: 99.6%
  • 20x: 98.7%
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: 74 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
6330409D20Rik T A 2: 32,630,618 (GRCm39) Q52L unknown Het
Acsl1 A G 8: 46,966,634 (GRCm39) D202G probably damaging Het
Adam3 A T 8: 25,185,271 (GRCm39) C476S probably damaging Het
Adam34 T A 8: 44,104,499 (GRCm39) E382V probably benign Het
Akap5 G A 12: 76,375,023 (GRCm39) V152I probably benign Het
Aldh5a1 C T 13: 25,121,382 (GRCm39) W57* probably null Het
Angptl2 C T 2: 33,133,922 (GRCm39) Q415* probably null Het
Bnc1 G T 7: 81,623,055 (GRCm39) T724N possibly damaging Het
Brca2 T C 5: 150,464,901 (GRCm39) V1555A probably benign Het
Btn1a1 T A 13: 23,643,483 (GRCm39) D322V probably damaging Het
Chsy3 T A 18: 59,542,357 (GRCm39) D498E possibly damaging Het
Ddx24 T C 12: 103,390,347 (GRCm39) T215A probably benign Het
Dhx57 A T 17: 80,580,476 (GRCm39) V492E probably damaging Het
Dnhd1 G A 7: 105,359,234 (GRCm39) R3523Q probably benign Het
Dock3 T A 9: 106,841,916 (GRCm39) D971V possibly damaging Het
Ercc8 T C 13: 108,323,816 (GRCm39) probably null Het
Erich5 T A 15: 34,471,095 (GRCm39) L108Q probably damaging Het
F5 A T 1: 164,029,230 (GRCm39) Y1743F probably damaging Het
Gale T C 4: 135,694,503 (GRCm39) V243A probably damaging Het
Gspt1 T A 16: 11,071,692 (GRCm39) Q57L probably benign Het
Gtf3a C A 5: 146,888,085 (GRCm39) Q129K probably benign Het
Heyl T C 4: 123,140,254 (GRCm39) V271A probably benign Het
Hsd17b4 T C 18: 50,261,437 (GRCm39) F7L probably damaging Het
Hspa12a T C 19: 58,810,594 (GRCm39) T150A probably benign Het
Ift140 T A 17: 25,274,699 (GRCm39) D790E probably damaging Het
Igkv4-69 T A 6: 69,260,917 (GRCm39) Y70F probably damaging Het
Il1rap T C 16: 26,530,878 (GRCm39) Y405H probably damaging Het
Insyn2a A C 7: 134,520,374 (GRCm39) I52S probably damaging Het
Irf2bpl G T 12: 86,930,127 (GRCm39) P182Q probably benign Het
Itm2b C A 14: 73,605,829 (GRCm39) probably benign Het
Kcnc2 T C 10: 112,294,414 (GRCm39) V106A possibly damaging Het
Krt87 C A 15: 101,387,529 (GRCm39) D170Y probably damaging Het
Lca5 T A 9: 83,280,693 (GRCm39) Y369F probably benign Het
Mgat5 T A 1: 127,373,999 (GRCm39) D466E probably damaging Het
Mier3 C T 13: 111,851,302 (GRCm39) P428L probably benign Het
Myo6 T C 9: 80,152,418 (GRCm39) Y167H unknown Het
Neu2 A G 1: 87,524,297 (GRCm39) E94G probably benign Het
Nlrp9a A T 7: 26,256,672 (GRCm39) K97* probably null Het
Npdc1 A G 2: 25,299,120 (GRCm39) M306V probably damaging Het
Odf2l A T 3: 144,832,827 (GRCm39) N95I probably benign Het
Or10j3 A G 1: 173,031,633 (GRCm39) K237E probably damaging Het
Or13d1 G T 4: 52,970,665 (GRCm39) V15L probably benign Het
Or5t16 A G 2: 86,819,385 (GRCm39) V45A probably benign Het
Or7g21 A G 9: 19,033,037 (GRCm39) Y259C possibly damaging Het
P2ry12 A G 3: 59,125,127 (GRCm39) F183L probably benign Het
Proser3 A G 7: 30,239,749 (GRCm39) F452L possibly damaging Het
Ptgfrn G T 3: 100,987,511 (GRCm39) Y117* probably null Het
Rab3gap2 G T 1: 184,980,250 (GRCm39) V360F probably benign Het
Rp1l1 A T 14: 64,266,475 (GRCm39) D687V possibly damaging Het
Rxfp2 T G 5: 149,966,572 (GRCm39) N103K probably benign Het
Scfd2 T A 5: 74,558,326 (GRCm39) Q517L possibly damaging Het
Scnn1b G A 7: 121,517,109 (GRCm39) A582T probably damaging Het
Serpinb6e T C 13: 34,021,818 (GRCm39) E170G probably damaging Het
Serpinb8 T A 1: 107,533,527 (GRCm39) V194E probably damaging Het
Sgcz T A 8: 38,006,833 (GRCm39) H191L possibly damaging Het
Sorcs1 G A 19: 50,301,420 (GRCm39) P315S probably damaging Het
Spdef T A 17: 27,939,134 (GRCm39) S71C possibly damaging Het
Spta1 T A 1: 174,025,317 (GRCm39) H727Q probably damaging Het
Srsf1 C T 11: 87,940,084 (GRCm39) Q199* probably null Het
Stard9 A T 2: 120,526,623 (GRCm39) D960V probably benign Het
Tcp10c A T 17: 13,576,166 (GRCm39) I49F possibly damaging Het
Tgm2 T C 2: 157,971,315 (GRCm39) N308S possibly damaging Het
Tiam2 A G 17: 3,498,660 (GRCm39) D812G probably benign Het
Tph1 A T 7: 46,311,541 (GRCm39) V67D possibly damaging Het
Trps1 C T 15: 50,685,793 (GRCm39) R794H possibly damaging Het
Ttn C T 2: 76,683,505 (GRCm39) A906T Het
Vmn1r124 G A 7: 20,994,184 (GRCm39) P120L probably benign Het
Vmn2r92 A T 17: 18,387,005 (GRCm39) T115S probably benign Het
Wdr11 A G 7: 129,208,376 (GRCm39) D377G probably damaging Het
Wdr55 G T 18: 36,895,989 (GRCm39) A251S possibly damaging Het
Zbtb7b C T 3: 89,288,209 (GRCm39) R203H probably benign Het
Zfp109 A T 7: 23,929,231 (GRCm39) H67Q probably benign Het
Zfp462 G A 4: 55,051,271 (GRCm39) C2248Y probably damaging Het
Zyg11b T C 4: 108,102,119 (GRCm39) H534R possibly 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
R1653:Sirt1 UTSW 10 63,157,588 (GRCm39) missense probably benign
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
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'- GCATGCGTCAAACAGTTTTGC -3'
(R):5'- ACCTGGGCTACTTGACTTTCATG -3'

Sequencing Primer
(F):5'- GTCCCATTCCCATACCAAAATGTC -3'
(R):5'- CTACTTGACTTTCATGTTTTGTGCAG -3'
Posted On 2019-05-15