Incidental Mutation 'IGL02106:Sirt1'
ID 279992
Institutional Source Australian Phenomics Network (link to record)
Gene Symbol Sirt1
Ensembl Gene ENSMUSG00000020063
Gene Name sirtuin 1
Synonyms Sir2alpha, Sir2
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # IGL02106
Quality Score
Status
Chromosome 10
Chromosomal Location 63154784-63174814 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to T at 63171608 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Arginine to Glutamine at position 191 (R191Q)
Ref Sequence ENSEMBL: ENSMUSP00000137565 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000020257] [ENSMUST00000105442] [ENSMUST00000120239] [ENSMUST00000146028] [ENSMUST00000177694]
AlphaFold Q923E4
Predicted Effect probably damaging
Transcript: ENSMUST00000020257
AA Change: R191Q

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000020257
Gene: ENSMUSG00000020063
AA Change: R191Q

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: R152Q

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000101082
Gene: ENSMUSG00000020063
AA Change: R152Q

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: R191Q

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000112595
Gene: ENSMUSG00000020063
AA Change: R191Q

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 damaging
Transcript: ENSMUST00000146028
AA Change: R21Q

PolyPhen 2 Score 0.978 (Sensitivity: 0.76; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000117819
Gene: ENSMUSG00000020063
AA Change: R21Q

DomainStartEndE-ValueType
Pfam:SIR2 83 140 1.9e-15 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000177694
AA Change: R191Q

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000137565
Gene: ENSMUSG00000020063
AA Change: R191Q

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
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: 44 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Bcl9l A G 9: 44,420,496 (GRCm39) N1264D probably benign Het
Bmyc A G 2: 25,597,082 (GRCm39) K49E probably damaging Het
Cdc45 C T 16: 18,617,479 (GRCm39) M200I probably benign Het
Ceacam2 A G 7: 25,230,166 (GRCm39) S147P probably benign Het
Cep152 G T 2: 125,444,856 (GRCm39) probably null Het
Cnbd1 G T 4: 18,894,993 (GRCm39) P250T possibly damaging Het
Col6a4 A G 9: 105,940,304 (GRCm39) C1209R possibly damaging Het
Coro1c T C 5: 113,990,334 (GRCm39) T116A probably benign Het
Ddx46 A G 13: 55,825,416 (GRCm39) probably benign Het
Dnaaf5 T C 5: 139,137,268 (GRCm39) I207T probably damaging Het
Erap1 A G 13: 74,794,758 (GRCm39) D139G probably benign Het
Fbxw22 A T 9: 109,231,087 (GRCm39) I121N possibly damaging Het
Fcmr T C 1: 130,802,872 (GRCm39) S162P probably benign Het
Gadl1 A G 9: 115,766,225 (GRCm39) probably benign Het
Gli2 T A 1: 118,764,465 (GRCm39) S1229C probably benign Het
Gm10717 A T 9: 3,026,287 (GRCm39) Y195F probably damaging Het
Gne T C 4: 44,037,306 (GRCm39) N692D probably damaging Het
Knl1 A G 2: 118,902,489 (GRCm39) T1397A possibly damaging Het
Lama3 C A 18: 12,601,371 (GRCm39) A1016E probably damaging Het
Lhfpl2 A G 13: 94,328,419 (GRCm39) D160G probably benign Het
Lmtk2 T A 5: 144,112,769 (GRCm39) V1163E probably benign Het
Lrrtm2 G T 18: 35,345,868 (GRCm39) S478* probably null Het
Nfatc2ip T C 7: 125,989,736 (GRCm39) probably null Het
Nlrp12 A G 7: 3,282,574 (GRCm39) I775T probably benign Het
Npr1 A G 3: 90,372,165 (GRCm39) F216L probably benign Het
Or4m1 A T 14: 50,557,617 (GRCm39) L225H probably damaging Het
Or5ac24 T A 16: 59,165,387 (GRCm39) N226Y probably benign Het
Or5b99 G T 19: 12,976,929 (GRCm39) S193I possibly damaging Het
Pkd1l1 C A 11: 8,783,800 (GRCm39) G2052C probably damaging Het
Ppp1r16b A G 2: 158,588,451 (GRCm39) N112S possibly damaging Het
Prr11 A G 11: 86,994,141 (GRCm39) probably benign Het
Scap A G 9: 110,210,724 (GRCm39) probably benign Het
Slc38a6 A C 12: 73,397,320 (GRCm39) S321R possibly damaging Het
Sp140 T C 1: 85,570,940 (GRCm39) V460A probably benign Het
Spdye4c A T 2: 128,434,586 (GRCm39) K54N possibly damaging Het
Spta1 T A 1: 174,030,860 (GRCm39) N947K probably benign Het
Srgap1 A G 10: 121,621,598 (GRCm39) V965A possibly damaging Het
Tmem209 A C 6: 30,508,659 (GRCm39) probably null Het
Trim37 A T 11: 87,092,230 (GRCm39) K123* probably null Het
Trio T C 15: 27,744,244 (GRCm39) T2563A possibly damaging Het
Utrn A T 10: 12,289,717 (GRCm39) S734T possibly damaging Het
Vars2 A G 17: 35,975,513 (GRCm39) probably benign Het
Xrn1 G A 9: 95,859,858 (GRCm39) E417K probably benign Het
Yeats2 T A 16: 20,011,970 (GRCm39) V515E possibly damaging Het
Other mutations in Sirt1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02057:Sirt1 APN 10 63,160,982 (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
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
Posted On 2015-04-16