Mutagenetix > Incidental Mutation

Incidental Mutation 'R4133:Sirt1'

314751

Institutional Source

Beutler Lab

Gene Symbol

Sirt1

Ensembl Gene

ENSMUSG00000020063

Gene Name

sirtuin 1

Synonyms

Sir2alpha, Sir2

MMRRC Submission

041637-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4133 (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 63171438 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Valine at position 209 (I209V)

Ref Sequence

ENSEMBL: ENSMUSP00000101082 (fasta)

Gene Model

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

AlphaFold

Q923E4

Predicted Effect

probably null
Transcript: ENSMUST00000020257
AA Change: I248V

PolyPhen 2 Score 0.036 (Sensitivity: 0.94; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000020257
Gene: ENSMUSG00000020063
AA Change: I248V

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 null
Transcript: ENSMUST00000105442
AA Change: I209V

PolyPhen 2 Score 0.417 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000101082
Gene: ENSMUSG00000020063
AA Change: I209V

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 null
Transcript: ENSMUST00000120239
AA Change: I248V

PolyPhen 2 Score 0.036 (Sensitivity: 0.94; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000112595
Gene: ENSMUSG00000020063
AA Change: I248V

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

possibly damaging
Transcript: ENSMUST00000146028
AA Change: I78V

PolyPhen 2 Score 0.948 (Sensitivity: 0.79; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000117819
Gene: ENSMUSG00000020063
AA Change: I78V

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

Predicted Effect

probably null
Transcript: ENSMUST00000177694
AA Change: I248V

PolyPhen 2 Score 0.036 (Sensitivity: 0.94; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000137565
Gene: ENSMUSG00000020063
AA Change: I248V

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 null
Transcript: ENSMUST00000177694
AA Change: I248V

PolyPhen 2 Score 0.036 (Sensitivity: 0.94; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000137565
Gene: ENSMUSG00000020063
AA Change: I248V

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

0.2580

Coding Region Coverage

1x: 99.4%
3x: 98.7%
10x: 97.4%
20x: 95.5%

Validation Efficiency

97% (77/79)

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: 75 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700036A12Rik	T	A	9: 60,677,280 (GRCm39)		noncoding transcript	Het
Aldh3b1	A	G	19: 3,970,808 (GRCm39)	I184T	probably damaging	Het
Arhgap42	C	T	9: 9,011,300 (GRCm39)		probably benign	Het
Arhgef4	A	G	1: 34,845,185 (GRCm39)	D1463G	probably damaging	Het
Arpc5	A	G	1: 152,644,622 (GRCm39)	T52A	probably benign	Het
Asb6	A	G	2: 30,718,247 (GRCm39)		probably benign	Het
Ash1l	T	C	3: 88,889,567 (GRCm39)	V482A	probably benign	Het
Bop1	T	C	15: 76,338,535 (GRCm39)	N469S	probably benign	Het
Btaf1	T	A	19: 36,939,138 (GRCm39)	N266K	probably benign	Het
Btla	T	C	16: 45,059,661 (GRCm39)	Y122H	probably damaging	Het
Cacna1g	A	G	11: 94,323,370 (GRCm39)	M1278T	probably damaging	Het
Cdc42bpb	A	G	12: 111,287,976 (GRCm39)	S524P	probably benign	Het
Cep78	A	G	19: 15,946,519 (GRCm39)	S438P	probably damaging	Het
Clca4a	T	G	3: 144,675,113 (GRCm39)	E171D	probably benign	Het
Cldn6	A	T	17: 23,900,467 (GRCm39)	I144F	probably damaging	Het
Cpd	G	A	11: 76,705,644 (GRCm39)	Q363*	probably null	Het
Cpn1	G	A	19: 43,974,723 (GRCm39)	P2L	possibly damaging	Het
Ddx31	A	G	2: 28,748,864 (GRCm39)	D264G	probably damaging	Het
Ddx39b	C	T	17: 35,472,065 (GRCm39)	S368L	probably damaging	Het
Ddx60	A	G	8: 62,425,254 (GRCm39)	K681E	probably damaging	Het
Dennd1c	A	C	17: 57,383,980 (GRCm39)	W15G	possibly damaging	Het
Dgkd	T	G	1: 87,869,223 (GRCm39)		probably null	Het
Dnah7c	G	T	1: 46,705,150 (GRCm39)	A2388S	probably benign	Het
Etv4	C	A	11: 101,661,324 (GRCm39)	K442N	probably damaging	Het
Fam234a	T	C	17: 26,432,532 (GRCm39)	D539G	probably damaging	Het
Fancm	A	G	12: 65,167,304 (GRCm39)	T1538A	probably benign	Het
Fbn2	A	T	18: 58,229,034 (GRCm39)	N725K	possibly damaging	Het
Fcer2a	T	A	8: 3,741,130 (GRCm39)	N4I	possibly damaging	Het
Fgd5	T	C	6: 92,046,418 (GRCm39)	V1229A	probably damaging	Het
Garin4	A	T	1: 190,895,205 (GRCm39)	N479K	probably benign	Het
Gm5471	A	T	15: 44,835,297 (GRCm39)		noncoding transcript	Het
Gm5478	T	A	15: 101,553,080 (GRCm39)	I331F	probably damaging	Het
Gm6729	C	A	10: 86,377,030 (GRCm39)		noncoding transcript	Het
Hectd4	G	T	5: 121,415,897 (GRCm39)		probably null	Het
Hspb3	A	C	13: 113,800,027 (GRCm39)	M1R	probably null	Het
Igkv10-95	T	C	6: 68,657,601 (GRCm39)	V19A	probably damaging	Het
Il1rap	A	G	16: 26,541,636 (GRCm39)	S626G	probably benign	Het
Ints9	A	G	14: 65,228,003 (GRCm39)	H103R	probably benign	Het
Itga4	T	A	2: 79,152,996 (GRCm39)	D894E	probably damaging	Het
Khsrp	T	C	17: 57,332,605 (GRCm39)	H225R	probably benign	Het
Lama1	T	C	17: 68,057,650 (GRCm39)	Y575H	probably damaging	Het
Lama1	A	T	17: 68,119,481 (GRCm39)	I2653F	probably damaging	Het
Map4k5	A	T	12: 69,892,497 (GRCm39)	L144Q	probably damaging	Het
Mcm5	A	G	8: 75,842,482 (GRCm39)	Y252C	probably damaging	Het
Mmgt2	A	G	11: 62,555,877 (GRCm39)	E75G	probably damaging	Het
Mroh2a	A	T	1: 88,182,687 (GRCm39)	N1205I	possibly damaging	Het
Nckap5	A	G	1: 126,150,443 (GRCm39)	V162A	probably benign	Het
Nr3c2	T	C	8: 77,636,378 (GRCm39)	I493T	probably damaging	Het
Or2ag16	A	C	7: 106,352,286 (GRCm39)	L103R	probably damaging	Het
Or2t46	A	T	11: 58,471,901 (GRCm39)	Y77F	probably damaging	Het
Or9s15	T	C	1: 92,524,465 (GRCm39)	F75L	probably benign	Het
Papola	A	G	12: 105,765,917 (GRCm39)	T6A	possibly damaging	Het
Ppp1cc	G	A	5: 122,306,289 (GRCm39)	R36Q	probably benign	Het
Ptpro	G	T	6: 137,397,370 (GRCm39)	W81C	probably damaging	Het
Rasgrf2	A	G	13: 92,130,773 (GRCm39)	S162P	possibly damaging	Het
Rpusd2	T	C	2: 118,869,196 (GRCm39)	S540P	probably damaging	Het
Scn5a	T	A	9: 119,315,438 (GRCm39)	T1757S	probably damaging	Het
Setbp1	T	C	18: 78,900,206 (GRCm39)	I1154V	probably benign	Het
Slco6c1	T	A	1: 97,009,218 (GRCm39)	I406L	probably benign	Het
Smc2	A	G	4: 52,450,947 (GRCm39)	E255G	probably damaging	Het
Snap91	C	A	9: 86,659,102 (GRCm39)	G477V	probably damaging	Het
Speg	A	G	1: 75,404,548 (GRCm39)	Q2780R	probably benign	Het
Spmap2	T	C	10: 79,415,884 (GRCm39)	T236A	probably damaging	Het
Ssh2	A	G	11: 77,312,095 (GRCm39)	Y196C	probably damaging	Het
Ssxb9	A	T	X: 8,235,845 (GRCm39)	T18S	probably damaging	Het
Stxbp5l	T	C	16: 37,028,481 (GRCm39)	I527M	possibly damaging	Het
Tex10	T	C	4: 48,468,968 (GRCm39)	Y69C	probably damaging	Het
Thoc3	T	C	13: 54,616,361 (GRCm39)	D87G	probably benign	Het
Top2b	T	G	14: 16,409,189 (GRCm38)	I777M	probably damaging	Het
Trps1	T	C	15: 50,694,783 (GRCm39)	K213R	probably damaging	Het
Uggt1	A	T	1: 36,197,240 (GRCm39)	L1221Q	probably damaging	Het
Vmn2r3	T	A	3: 64,183,138 (GRCm39)	Y187F	probably damaging	Het
Washc2	G	A	6: 116,235,891 (GRCm39)	E1121K	probably damaging	Het
Zfx	T	C	X: 93,124,464 (GRCm39)	N360D	probably damaging	Het
Znhit3	A	G	11: 84,807,139 (GRCm39)	V10A	probably benign	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
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

Predicted Primers

PCR Primer
(F):5'- ACCATAATTCCACTTACCAATTGTTC -3'
(R):5'- CCGATCCTCGAACAATTCTTAAAG -3'

Sequencing Primer
(F):5'- CAAAGGCTACATCAAGAGC -3'
(R):5'- ATGATATGACGCTGTGGC -3'

Posted On

2015-05-14