Mutagenetix > Incidental Mutation

Incidental Mutation 'R4776:Sirt1'

367945

Institutional Source

Beutler Lab

Gene Symbol

Sirt1

Ensembl Gene

ENSMUSG00000020063

Gene Name

sirtuin 1

Synonyms

Sir2alpha, Sir2

MMRRC Submission

042413-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4776 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

63154784-63174814 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 63171501 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Lysine to Glutamic Acid at position 227 (K227E)

Ref Sequence

ENSEMBL: ENSMUSP00000137565 (fasta)

Gene Model

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

AlphaFold

Q923E4

Predicted Effect

probably benign
Transcript: ENSMUST00000020257
AA Change: K227E

PolyPhen 2 Score 0.175 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000020257
Gene: ENSMUSG00000020063
AA Change: K227E

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: ENSMUST00000105442
AA Change: K188E

PolyPhen 2 Score 0.143 (Sensitivity: 0.92; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000101082
Gene: ENSMUSG00000020063
AA Change: K188E

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: K227E

PolyPhen 2 Score 0.175 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000112595
Gene: ENSMUSG00000020063
AA Change: K227E

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

noncoding transcript
Transcript: ENSMUST00000131371

Predicted Effect

probably benign
Transcript: ENSMUST00000146028
AA Change: K57E

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000117819
Gene: ENSMUSG00000020063
AA Change: K57E

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

Predicted Effect

probably benign
Transcript: ENSMUST00000177694
AA Change: K227E

PolyPhen 2 Score 0.175 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000137565
Gene: ENSMUSG00000020063
AA Change: K227E

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

Meta Mutation Damage Score

0.0664

Coding Region Coverage

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

Validation Efficiency

98% (94/96)

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: 90 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2610028H24Rik	A	T	10: 76,293,346 (GRCm39)	M156L	probably benign	Het
4930470P17Rik	C	T	2: 170,421,644 (GRCm39)	A79T	unknown	Het
4930522L14Rik	A	G	5: 109,884,739 (GRCm39)	I373T	probably benign	Het
Amotl1	G	A	9: 14,504,669 (GRCm39)	Q217*	probably null	Het
Ankrd28	A	T	14: 31,454,011 (GRCm39)	C254S	probably damaging	Het
Ap2a1	A	G	7: 44,550,970 (GRCm39)		probably benign	Het
Arfgef3	A	T	10: 18,529,995 (GRCm39)	S245T	probably benign	Het
Atp1b2	A	T	11: 69,492,387 (GRCm39)	D224E	probably damaging	Het
Bmal1	A	T	7: 112,884,244 (GRCm39)	K94I	probably damaging	Het
Boc	G	A	16: 44,308,084 (GRCm39)	R924W	probably damaging	Het
Btbd8	C	A	5: 107,658,317 (GRCm39)	A1117E	probably damaging	Het
Car14	C	T	3: 95,806,185 (GRCm39)	G292D	probably benign	Het
Cenpb	T	C	2: 131,020,103 (GRCm39)		probably benign	Het
Ces1b	A	T	8: 93,789,658 (GRCm39)	D423E	possibly damaging	Het
Cfap54	T	A	10: 92,808,556 (GRCm39)	N1373I	possibly damaging	Het
Chrdl2	T	C	7: 99,655,748 (GRCm39)		probably benign	Het
Cic	T	G	7: 24,982,308 (GRCm39)	S12A	possibly damaging	Het
Csmd2	A	T	4: 128,336,685 (GRCm39)	Q1421L	probably benign	Het
D630039A03Rik	T	C	4: 57,910,452 (GRCm39)	H120R	possibly damaging	Het
Dicer1	T	A	12: 104,658,705 (GRCm39)	D1779V	probably damaging	Het
Dock9	G	T	14: 121,847,509 (GRCm39)	H1016N	possibly damaging	Het
Dxo	T	C	17: 35,057,974 (GRCm39)	L352P	probably damaging	Het
Eif2b5	T	A	16: 20,318,983 (GRCm39)	F78I	probably damaging	Het
Eri2	A	G	7: 119,384,169 (GRCm39)		probably benign	Het
Fbxw7	T	G	3: 84,832,996 (GRCm39)	L13V	possibly damaging	Het
Fgf7	T	A	2: 125,877,703 (GRCm39)	C23*	probably null	Het
Fubp1	T	A	3: 151,927,705 (GRCm39)		probably null	Het
Gm2663	A	T	6: 40,972,887 (GRCm39)	I240N	probably damaging	Het
Gnb1l	C	T	16: 18,366,846 (GRCm39)	Q140*	probably null	Het
Gnptab	G	A	10: 88,272,390 (GRCm39)	R1010Q	probably damaging	Het
Gtf2h1	G	A	7: 46,472,302 (GRCm39)	W544*	probably null	Het
Gucy2c	C	T	6: 136,699,512 (GRCm39)	E586K	probably damaging	Het
Hc	T	A	2: 34,929,746 (GRCm39)	E232V	probably benign	Het
Ifi207	T	A	1: 173,557,622 (GRCm39)	D372V	unknown	Het
Igkv8-28	A	T	6: 70,121,102 (GRCm39)	V15E	probably benign	Het
Il1rap	A	G	16: 26,511,549 (GRCm39)	S198G	possibly damaging	Het
Lct	A	G	1: 128,228,124 (GRCm39)	I1123T	probably damaging	Het
Lhcgr	T	C	17: 89,050,125 (GRCm39)	E467G	probably damaging	Het
Macf1	C	T	4: 123,369,808 (GRCm39)	R86K	probably benign	Het
Maml3	T	A	3: 51,763,953 (GRCm39)	Q337L	probably benign	Het
Marchf10	T	A	11: 105,280,863 (GRCm39)	D474V	probably benign	Het
Marchf2	G	T	17: 33,928,890 (GRCm39)	T2K	probably damaging	Het
Mast1	A	G	8: 85,663,822 (GRCm39)		probably null	Het
Med12l	T	C	3: 59,140,633 (GRCm39)	I868T	probably damaging	Het
Msrb1	T	C	17: 24,959,147 (GRCm39)	S100P	probably damaging	Het
Nlrp4c	T	C	7: 6,069,125 (GRCm39)	L342P	probably benign	Het
Nrxn3	T	A	12: 90,298,730 (GRCm39)	V417E	possibly damaging	Het
Ntng1	T	A	3: 109,842,029 (GRCm39)	D248V	probably damaging	Het
Oaz3	T	C	3: 94,342,305 (GRCm39)	Q117R	probably benign	Het
Or2a56	A	G	6: 42,932,455 (GRCm39)	I8V	probably benign	Het
Or4f58	A	G	2: 111,851,276 (GRCm39)	Y308H	probably benign	Het
Or52e2	A	G	7: 102,804,621 (GRCm39)	L111P	probably benign	Het
Osbpl3	A	C	6: 50,277,953 (GRCm39)	S767A	probably benign	Het
Pafah1b1	A	T	11: 74,576,697 (GRCm39)		probably benign	Het
Pard6b	A	G	2: 167,940,708 (GRCm39)	T232A	probably damaging	Het
Paxip1	A	T	5: 27,970,204 (GRCm39)	C596S	probably damaging	Het
Pnpla6	T	C	8: 3,573,818 (GRCm39)	V422A	probably benign	Het
Psmd6	A	T	14: 14,120,932 (GRCm38)		probably benign	Het
Relch	T	A	1: 105,647,260 (GRCm39)	Y683*	probably null	Het
Rock2	T	A	12: 17,027,741 (GRCm39)	C1353S	probably damaging	Het
Rpl31-ps17	C	T	12: 54,748,397 (GRCm39)		noncoding transcript	Het
Sel1l	T	A	12: 91,780,667 (GRCm39)	H658L	probably damaging	Het
Sh3yl1	T	A	12: 30,990,313 (GRCm39)	L105Q	probably damaging	Het
Shroom3	G	T	5: 93,090,945 (GRCm39)	V1151F	probably damaging	Het
Slc25a34	A	T	4: 141,350,899 (GRCm39)	F37I	possibly damaging	Het
Slc39a5	T	A	10: 128,232,918 (GRCm39)	I378F	probably damaging	Het
Smarcad1	A	T	6: 65,075,808 (GRCm39)	D731V	probably null	Het
Sox6	T	G	7: 115,140,905 (GRCm39)	K483N	probably damaging	Het
Sp140	T	A	1: 85,538,549 (GRCm39)	D95E	possibly damaging	Het
Srgap1	G	T	10: 121,628,256 (GRCm39)	D882E	probably benign	Het
Syne4	T	C	7: 30,016,258 (GRCm39)		probably benign	Het
Tasor2	A	G	13: 3,620,391 (GRCm39)	F2170S	probably damaging	Het
Tec	T	C	5: 72,926,119 (GRCm39)	Y289C	probably benign	Het
Tmem102	A	T	11: 69,695,628 (GRCm39)	Y115N	probably damaging	Het
Tns2	C	T	15: 102,017,369 (GRCm39)	R281C	probably damaging	Het
Trav17	T	A	14: 54,044,097 (GRCm39)	M1K	probably null	Het
Trdn	T	A	10: 33,275,078 (GRCm39)		probably null	Het
Trp53	A	T	11: 69,477,747 (GRCm39)	I8F	probably benign	Het
Ttn	T	A	2: 76,585,006 (GRCm39)	D22064V	probably damaging	Het
Ube3c	G	A	5: 29,837,836 (GRCm39)		probably null	Het
Ulk1	C	T	5: 110,936,813 (GRCm39)		probably null	Het
Upp1	T	C	11: 9,085,976 (GRCm39)	V271A	probably damaging	Het
Vmn2r4	T	C	3: 64,296,082 (GRCm39)	E901G	probably damaging	Het
Vmn2r96	G	A	17: 18,817,770 (GRCm39)	G449D	probably damaging	Het
Vps37b	T	C	5: 124,144,675 (GRCm39)	K165E	probably damaging	Het
Vwf	A	T	6: 125,543,268 (GRCm39)	I185F	possibly damaging	Het
Wasf2	A	G	4: 132,912,315 (GRCm39)	T56A	probably benign	Het
Zdhhc23	C	G	16: 43,793,952 (GRCm39)	D241H	possibly damaging	Het
Zfp276	T	C	8: 123,981,623 (GRCm39)	S57P	probably benign	Het
Zxdc	A	G	6: 90,347,500 (GRCm39)	H287R	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
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'- TATGAACAAAGGCTACATCAAGAGC -3'
(R):5'- CAGATCTTGTTAGGGATATGACATG -3'

Sequencing Primer
(F):5'- CTACATCAAGAGCAGAAAAAGTTAGC -3'
(R):5'- GAATTGATGTGAGTCTTTCTTCCC -3'

Posted On

2015-12-29