Incidental Mutation 'R4378:Sirt1'
ID 325202
Institutional Source Beutler Lab
Gene Symbol Sirt1
Ensembl Gene ENSMUSG00000020063
Gene Name sirtuin 1
Synonyms Sir2alpha, Sir2
MMRRC Submission 041121-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4378 (G1)
Quality Score 98
Status Not validated
Chromosome 10
Chromosomal Location 63154784-63174814 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to T at 63174728 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Alanine to Threonine at position 8 (A8T)
Ref Sequence ENSEMBL: ENSMUSP00000101082 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000020257] [ENSMUST00000105442] [ENSMUST00000120239] [ENSMUST00000146028] [ENSMUST00000177694]
AlphaFold Q923E4
Predicted Effect unknown
Transcript: ENSMUST00000020257
AA Change: A8T
SMART Domains Protein: ENSMUSP00000020257
Gene: ENSMUSG00000020063
AA Change: A8T

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: ENSMUST00000105442
AA Change: A8T

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000101082
Gene: ENSMUSG00000020063
AA Change: A8T

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 unknown
Transcript: ENSMUST00000120239
AA Change: A8T
SMART Domains Protein: ENSMUSP00000112595
Gene: ENSMUSG00000020063
AA Change: A8T

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 noncoding transcript
Transcript: ENSMUST00000131371
Predicted Effect probably benign
Transcript: ENSMUST00000146028
SMART Domains Protein: ENSMUSP00000117819
Gene: ENSMUSG00000020063

DomainStartEndE-ValueType
Pfam:SIR2 83 140 1.9e-15 PFAM
Predicted Effect unknown
Transcript: ENSMUST00000177694
AA Change: A8T
SMART Domains Protein: ENSMUSP00000137565
Gene: ENSMUSG00000020063
AA Change: A8T

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: 99.2%
  • 3x: 98.6%
  • 10x: 97.1%
  • 20x: 94.8%
Validation Efficiency 96% (47/49)
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: 43 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca13 A G 11: 9,243,644 (GRCm39) K1836E probably benign Het
Adora1 A G 1: 134,130,948 (GRCm39) F241S probably damaging Het
Akt1s1 C T 7: 44,503,384 (GRCm39) T168M probably damaging Het
Amigo1 C T 3: 108,099,069 (GRCm39) probably benign Het
Amigo2 A G 15: 97,143,859 (GRCm39) F188L possibly damaging Het
Armc2 T C 10: 41,869,078 (GRCm39) T29A possibly damaging Het
Axl G A 7: 25,458,262 (GRCm39) A822V probably benign Het
Borcs5 T C 6: 134,621,292 (GRCm39) V21A probably benign Het
Cdc42ep3 A G 17: 79,642,408 (GRCm39) S171P probably benign Het
Cmas T C 6: 142,718,011 (GRCm39) probably benign Het
Cyp4f40 A G 17: 32,887,003 (GRCm39) N158S probably null Het
Dnah6 G T 6: 73,095,009 (GRCm39) N2139K probably benign Het
Elmo1 A T 13: 20,557,286 (GRCm39) H409L possibly damaging Het
Exoc1l A G 5: 76,648,380 (GRCm39) K62R probably damaging Het
Exoc4 T A 6: 33,792,622 (GRCm39) V584E probably damaging Het
Gm9116 A G 3: 93,817,786 (GRCm39) noncoding transcript Het
Gxylt2 A G 6: 100,710,161 (GRCm39) S101G probably benign Het
Hsph1 C A 5: 149,559,472 (GRCm39) E24* probably null Het
Ighv1-56 C T 12: 115,206,568 (GRCm39) E50K probably benign Het
Kirrel1 C T 3: 86,996,458 (GRCm39) M380I probably null Het
Lrriq1 A T 10: 103,038,225 (GRCm39) D859E probably damaging Het
Mapk7 G A 11: 61,384,493 (GRCm39) S71L probably damaging Het
Nars1 A G 18: 64,634,424 (GRCm39) Y500H probably damaging Het
Or1j1 T C 2: 36,702,481 (GRCm39) M208V probably benign Het
Or5d20-ps1 G T 2: 87,931,829 (GRCm39) N167K unknown Het
Phc1 T C 6: 122,311,966 (GRCm39) N64S possibly damaging Het
Ppp4r3b T A 11: 29,159,450 (GRCm39) N180K possibly damaging Het
Primpol G A 8: 47,029,218 (GRCm39) probably benign Het
Prtg T C 9: 72,750,042 (GRCm39) S149P possibly damaging Het
Qrich2 T C 11: 116,337,741 (GRCm39) S1916G probably damaging Het
Rps6ka5 A T 12: 100,564,196 (GRCm39) Y218N probably damaging Het
Setbp1 T C 18: 78,899,833 (GRCm39) D1278G possibly damaging Het
Sobp C T 10: 42,897,300 (GRCm39) V762I probably damaging Het
Sptan1 T C 2: 29,915,581 (GRCm39) S1994P probably damaging Het
Taok3 T C 5: 117,347,636 (GRCm39) I87T probably damaging Het
Tecta T C 9: 42,278,004 (GRCm39) Y1168C probably damaging Het
Trhr A G 15: 44,061,023 (GRCm39) Y181C probably damaging Het
Ube4b C T 4: 149,468,255 (GRCm39) D174N probably damaging Het
Ubr4 C T 4: 139,137,751 (GRCm39) H1067Y possibly damaging Het
Vmn2r86 A G 10: 130,288,469 (GRCm39) I344T possibly damaging Het
Vmn2r88 T A 14: 51,650,746 (GRCm39) L153* probably null Het
Zfp516 T A 18: 83,005,305 (GRCm39) D736E probably benign Het
Zfp612 G T 8: 110,815,683 (GRCm39) V258F 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
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'- TCGTCGTCGAAGTCGTCAG -3'
(R):5'- GAGCCCCTGAGGTAAAAGC -3'

Sequencing Primer
(F):5'- AGGCCGGACCCATTGTCTC -3'
(R):5'- CCCTGAGGTAAAAGCCGACTTG -3'
Posted On 2015-07-06