Mutagenetix > Incidental Mutation

Incidental Mutation 'R4898:Sirt1'

375930

Institutional Source

Beutler Lab

Gene Symbol

Sirt1

Ensembl Gene

ENSMUSG00000020063

Gene Name

sirtuin 1

Synonyms

Sir2alpha, Sir2

MMRRC Submission

042502-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4898 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

63154784-63174814 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 63157783 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Phenylalanine at position 505 (I505F)

Ref Sequence

ENSEMBL: ENSMUSP00000101082 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000020257] [ENSMUST00000020258] [ENSMUST00000105442] [ENSMUST00000120239] [ENSMUST00000146028] [ENSMUST00000177694] [ENSMUST00000219577]

AlphaFold

Q923E4

Predicted Effect

probably benign
Transcript: ENSMUST00000020257
AA Change: I544F

PolyPhen 2 Score 0.229 (Sensitivity: 0.91; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000020257
Gene: ENSMUSG00000020063
AA Change: I544F

Domain	Start	End	E-Value	Type
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

Domain	Start	End	E-Value	Type
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: I505F

PolyPhen 2 Score 0.355 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000101082
Gene: ENSMUSG00000020063
AA Change: I505F

Domain	Start	End	E-Value	Type
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: I544F

PolyPhen 2 Score 0.229 (Sensitivity: 0.91; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000112595
Gene: ENSMUSG00000020063
AA Change: I544F

Domain	Start	End	E-Value	Type
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

Domain	Start	End	E-Value	Type
Pfam:SIR2	83	140	1.9e-15	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000148516

Predicted Effect

probably benign
Transcript: ENSMUST00000177694

SMART Domains

Protein: ENSMUSP00000137565
Gene: ENSMUSG00000020063

Domain	Start	End	E-Value	Type
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

Predicted Effect

probably benign
Transcript: ENSMUST00000219577

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000219789

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 96.8%
20x: 93.9%

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: 116 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcc6	T	C	7: 45,639,111 (GRCm39)	Y944C	probably damaging	Het
Acacb	T	C	5: 114,370,999 (GRCm39)	V1747A	probably benign	Het
Acad8	C	T	9: 26,889,698 (GRCm39)	R332H	probably damaging	Het
Acrbp	A	C	6: 125,027,501 (GRCm39)	T50P	probably damaging	Het
Ahctf1	G	T	1: 179,583,077 (GRCm39)	N1500K	probably benign	Het
Aoc1l3	A	G	6: 48,964,651 (GRCm39)	T220A	possibly damaging	Het
Arfgef1	A	G	1: 10,229,798 (GRCm39)	I1301T	possibly damaging	Het
Arhgef15	T	C	11: 68,842,171 (GRCm39)	S478G	probably benign	Het
Armh1	T	C	4: 117,094,977 (GRCm39)	D21G	probably damaging	Het
Atp13a4	A	T	16: 29,227,779 (GRCm39)	L1045*	probably null	Het
Atp2a3	T	A	11: 72,873,506 (GRCm39)	L793H	probably damaging	Het
B4galnt4	C	A	7: 140,648,173 (GRCm39)	P563Q	probably benign	Het
Bcl2a1b	A	T	9: 89,081,713 (GRCm39)	K94*	probably null	Het
Bod1	T	A	11: 31,616,853 (GRCm39)	Q136L	possibly damaging	Het
C2cd3	A	G	7: 100,055,166 (GRCm39)	K443R	probably damaging	Het
Cadps	A	G	14: 12,411,588 (GRCm38)	V1250A	possibly damaging	Het
Car12	T	A	9: 66,671,600 (GRCm39)	Y332*	probably null	Het
Ccdc186	A	T	19: 56,790,432 (GRCm39)		probably null	Het
Cdh6	T	C	15: 13,034,774 (GRCm39)	T629A	probably damaging	Het
Cep112	T	A	11: 108,397,471 (GRCm39)	D353E	probably damaging	Het
Cep152	T	C	2: 125,428,301 (GRCm39)	S777G	probably benign	Het
Clec4b2	A	C	6: 123,181,163 (GRCm39)	K183Q	probably benign	Het
Cngb3	T	C	4: 19,395,926 (GRCm39)	Y323H	probably benign	Het
Cnp	G	T	11: 100,467,202 (GRCm39)	E48D	probably benign	Het
Ctrb1	T	A	8: 112,413,783 (GRCm39)	I194F	probably benign	Het
Cyp2d11	T	A	15: 82,275,224 (GRCm39)	D241V	probably benign	Het
D5Ertd579e	T	A	5: 36,772,285 (GRCm39)	E703D	probably damaging	Het
Dlg1	T	C	16: 31,676,764 (GRCm39)	V731A	probably damaging	Het
Dlgap5	T	C	14: 47,651,276 (GRCm39)	S86G	probably benign	Het
Dock3	A	G	9: 106,807,266 (GRCm39)	F1354L	probably damaging	Het
Dock3	C	A	9: 106,870,171 (GRCm39)	V638F	possibly damaging	Het
Eif3c	A	T	7: 126,156,626 (GRCm39)	M407K	probably benign	Het
Eif4a3l1	A	T	6: 136,305,737 (GRCm39)	Q66L	possibly damaging	Het
Epha4	T	A	1: 77,366,712 (GRCm39)	K578*	probably null	Het
Erc2	C	T	14: 27,375,285 (GRCm39)	L168F	probably damaging	Het
Esyt2	A	G	12: 116,305,708 (GRCm39)	I313V	probably benign	Het
Far1	T	A	7: 113,167,432 (GRCm39)	Y506N	probably damaging	Het
Fbxw26	T	A	9: 109,547,037 (GRCm39)	N463Y	possibly damaging	Het
Fgg	A	G	3: 82,915,847 (GRCm39)	D96G	probably benign	Het
Gfer	A	G	17: 24,914,274 (GRCm39)	S130P	probably damaging	Het
Hdac10	A	T	15: 89,012,650 (GRCm39)	M1K	probably null	Het
Hsd3b1	A	T	3: 98,760,642 (GRCm39)	S110R	probably benign	Het
Ints15	A	G	5: 143,287,592 (GRCm39)	S438P	probably benign	Het
Itga6	T	C	2: 71,668,717 (GRCm39)	L552P	possibly damaging	Het
Klk14	G	A	7: 43,341,501 (GRCm39)	C51Y	probably damaging	Het
Lama2	TTTGCGCATT	TTT	10: 26,919,639 (GRCm39)		probably null	Het
Llgl1	C	T	11: 60,600,394 (GRCm39)	P581L	probably benign	Het
Lrrc8a	A	G	2: 30,147,214 (GRCm39)	K676R	probably benign	Het
Lrrc8b	A	T	5: 105,628,080 (GRCm39)	Y142F	probably benign	Het
Lyz2	T	A	10: 117,114,614 (GRCm39)	D105V	possibly damaging	Het
Mamdc4	T	C	2: 25,460,035 (GRCm39)	D76G	probably damaging	Het
Map7d1	T	C	4: 126,127,018 (GRCm39)	K731E	unknown	Het
Mgam	A	C	6: 40,619,988 (GRCm39)	I26L	probably benign	Het
Mmp13	A	T	9: 7,272,953 (GRCm39)	E104D	probably benign	Het
Morc2a	C	T	11: 3,626,664 (GRCm39)	R241*	probably null	Het
Mtfmt	C	A	9: 65,359,386 (GRCm39)	H354N	probably benign	Het
Myh3	T	C	11: 66,990,233 (GRCm39)	I1626T	probably benign	Het
Ndst1	A	T	18: 60,825,059 (GRCm39)	V753D	probably benign	Het
Neurl4	A	G	11: 69,793,997 (GRCm39)	D151G	probably damaging	Het
Nlrx1	T	C	9: 44,168,194 (GRCm39)	S568G	probably benign	Het
Or10g3b	G	C	14: 52,586,999 (GRCm39)	P168R	probably damaging	Het
Or2t45	T	C	11: 58,669,132 (GRCm39)	Y60H	possibly damaging	Het
Or2t46	T	G	11: 58,472,546 (GRCm39)	L292R	probably damaging	Het
Or4c52	T	C	2: 89,845,762 (GRCm39)	F163L	probably damaging	Het
Or52s1	A	G	7: 102,861,747 (GRCm39)	I216V	probably damaging	Het
Or6c66	A	T	10: 129,461,468 (GRCm39)	I154N	probably benign	Het
Or8b42	A	T	9: 38,342,111 (GRCm39)	M178L	probably benign	Het
Osbpl7	A	G	11: 96,950,976 (GRCm39)	I608V	probably damaging	Het
Pard3b	T	C	1: 61,807,159 (GRCm39)	I58T	probably damaging	Het
Pcare	A	G	17: 72,058,066 (GRCm39)	M537T	probably damaging	Het
Pcdhga1	A	C	18: 37,795,407 (GRCm39)	E137A	possibly damaging	Het
Pde6c	G	A	19: 38,139,072 (GRCm39)	V301I	possibly damaging	Het
Pdia5	G	C	16: 35,230,786 (GRCm39)	N338K	possibly damaging	Het
Pex11g	T	C	8: 3,514,042 (GRCm39)	Y40C	probably damaging	Het
Plekhg3	A	G	12: 76,610,899 (GRCm39)	Y183C	probably damaging	Het
Pole	A	C	5: 110,438,090 (GRCm39)		probably null	Het
Ppfia1	A	G	7: 144,045,313 (GRCm39)	L948P	probably damaging	Het
Prdm2	A	T	4: 142,860,761 (GRCm39)	V843E	probably damaging	Het
Prss56	C	A	1: 87,115,708 (GRCm39)	F527L	probably damaging	Het
Psmd11	T	C	11: 80,329,146 (GRCm39)	L88P	probably damaging	Het
Ptx3	G	C	3: 66,132,412 (GRCm39)	G311A	probably damaging	Het
Rars1	A	T	11: 35,699,385 (GRCm39)	L636H	probably damaging	Het
Rnft2	A	G	5: 118,375,507 (GRCm39)	S81P	probably benign	Het
Rufy4	T	C	1: 74,186,822 (GRCm39)	C537R	probably damaging	Het
Rxra	T	A	2: 27,631,195 (GRCm39)	I142N	probably damaging	Het
Scin	T	C	12: 40,154,931 (GRCm39)	M221V	probably benign	Het
Sfmbt2	G	A	2: 10,584,069 (GRCm39)	V809I	possibly damaging	Het
Six5	T	C	7: 18,829,096 (GRCm39)	Y179H	probably damaging	Het
Slc12a4	A	C	8: 106,671,241 (GRCm39)	M982R	probably damaging	Het
Slco4c1	T	A	1: 96,765,237 (GRCm39)	L404F	probably damaging	Het
Smn1	T	C	13: 100,268,931 (GRCm39)	L259P	probably damaging	Het
Sorl1	T	G	9: 41,952,935 (GRCm39)	D702A	probably damaging	Het
Spta1	A	G	1: 174,065,400 (GRCm39)	E1983G	possibly damaging	Het
Srsf1	T	A	11: 87,940,788 (GRCm39)		probably null	Het
Stard9	C	T	2: 120,536,900 (GRCm39)	R4224*	probably null	Het
Sybu	T	G	15: 44,538,895 (GRCm39)	M383L	probably benign	Het
Tbx15	A	C	3: 99,259,583 (GRCm39)	N485H	possibly damaging	Het
Tcerg1l	A	T	7: 137,819,786 (GRCm39)	F485I	probably damaging	Het
Tdrd7	C	A	4: 46,005,616 (GRCm39)	T474N	possibly damaging	Het
Thada	A	T	17: 84,755,470 (GRCm39)		probably null	Het
Tnik	A	T	3: 28,704,235 (GRCm39)	I1020F	probably damaging	Het
Tnxb	A	G	17: 34,914,566 (GRCm39)	D1884G	possibly damaging	Het
Tprn	T	C	2: 25,158,845 (GRCm39)	M623T	probably damaging	Het
Trdn	T	A	10: 33,350,413 (GRCm39)	Y661N	probably damaging	Het
Ttc41	T	C	10: 86,612,056 (GRCm39)	S1110P	possibly damaging	Het
Ttc6	A	C	12: 57,707,026 (GRCm39)	R644S	probably benign	Het
Ttyh1	A	T	7: 4,136,735 (GRCm39)	M448L	probably benign	Het
Unc79	G	T	12: 103,128,079 (GRCm39)	C2250F	probably damaging	Het
Ush2a	A	G	1: 188,358,805 (GRCm39)	I2110M	probably benign	Het
Uvssa	G	T	5: 33,571,257 (GRCm39)	E634*	probably null	Het
Vac14	A	C	8: 111,372,440 (GRCm39)	T384P	probably benign	Het
Wdr11	A	G	7: 129,235,445 (GRCm39)	E1169G	probably benign	Het
Zfp36l1	T	A	12: 80,157,298 (GRCm39)	T28S	probably benign	Het
Zfp715	A	T	7: 42,949,106 (GRCm39)	Y285N	possibly damaging	Het
Zfp91	A	T	19: 12,747,424 (GRCm39)	D566E	probably damaging	Het
Zgrf1	G	A	3: 127,396,085 (GRCm39)	V544M	probably damaging	Het

Other mutations in Sirt1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
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'- CTATTAGGCCAGCATTTTCTCACTG -3'
(R):5'- GGCTAGGTGGTGAATATGCC -3'

Sequencing Primer
(F):5'- CTCACTGTTTCTGCAACTGAAG -3'
(R):5'- CTAGGTGGTGAATATGCCAAACTTTG -3'

Posted On

2016-03-17