Mutagenetix > Incidental Mutation

Incidental Mutation 'R7365:Sirt1'

571727

Institutional Source

Beutler Lab

Gene Symbol

Sirt1

Ensembl Gene

ENSMUSG00000020063

Gene Name

sirtuin 1

Synonyms

Sir2alpha, Sir2

MMRRC Submission

045449-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7365 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

63154784-63174814 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 63157782 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Threonine at position 544 (I544T)

Ref Sequence

ENSEMBL: ENSMUSP00000020257 (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: I544T

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000020257
Gene: ENSMUSG00000020063
AA Change: I544T

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: I505T

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

SMART Domains

Protein: ENSMUSP00000101082
Gene: ENSMUSG00000020063
AA Change: I505T

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: I544T

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000112595
Gene: ENSMUSG00000020063
AA Change: I544T

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

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

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.8%
20x: 99.3%

Validation Efficiency

100% (96/96)

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: 96 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700123K08Rik	T	C	5: 138,561,198 (GRCm39)	S155G	probably benign	Het
Abcc4	T	C	14: 118,865,066 (GRCm39)	N320S	probably damaging	Het
Akr1c19	G	A	13: 4,287,069 (GRCm39)	R96H	probably benign	Het
Ankrd17	T	C	5: 90,439,010 (GRCm39)	D451G	possibly damaging	Het
Ano8	T	A	8: 71,937,754 (GRCm39)	D36V	probably damaging	Het
Aqp3	A	G	4: 41,098,003 (GRCm39)	V36A	probably benign	Het
Atf7ip	A	G	6: 136,537,708 (GRCm39)	T314A	probably benign	Het
Atp2c1	A	T	9: 105,300,198 (GRCm39)	D700E	probably damaging	Het
Axin2	G	A	11: 108,830,202 (GRCm39)	V341M	possibly damaging	Het
Bin3	A	G	14: 70,371,976 (GRCm39)	Q139R	probably damaging	Het
Brca2	A	G	5: 150,455,802 (GRCm39)	D181G	probably damaging	Het
Capn3	A	G	2: 120,325,295 (GRCm39)	E466G	probably damaging	Het
Ccdc14	T	A	16: 34,543,989 (GRCm39)	Y830*	probably null	Het
Cdk12	T	C	11: 98,111,910 (GRCm39)	F723L	unknown	Het
Cep89	G	A	7: 35,129,353 (GRCm39)	R630H	probably damaging	Het
Cip2a	T	A	16: 48,822,016 (GRCm39)	S215T	probably benign	Het
Clca3a2	T	A	3: 144,804,545 (GRCm39)	I61F	probably damaging	Het
Clca4b	T	C	3: 144,628,529 (GRCm39)	T393A	not run	Het
Cldn5	G	A	16: 18,595,845 (GRCm39)	A34T	probably damaging	Het
Cobll1	A	T	2: 64,928,717 (GRCm39)	S870T	probably damaging	Het
Col12a1	T	C	9: 79,613,642 (GRCm39)	K68E	probably damaging	Het
Crnn	A	T	3: 93,055,841 (GRCm39)	Q209L	probably damaging	Het
Cwf19l1	A	T	19: 44,120,579 (GRCm39)	F45I	probably damaging	Het
Cyfip2	T	A	11: 46,098,267 (GRCm39)	K1052*	probably null	Het
D930020B18Rik	G	A	10: 121,503,716 (GRCm39)		probably null	Het
Dcc	G	A	18: 71,959,194 (GRCm39)	P193S	probably damaging	Het
Dda1	T	A	8: 71,927,137 (GRCm39)	C48S	probably benign	Het
Disc1	A	G	8: 125,881,780 (GRCm39)	R572G	probably damaging	Het
Dnah7a	A	T	1: 53,536,297 (GRCm39)	M2582K	probably benign	Het
Dsel	C	T	1: 111,789,303 (GRCm39)	G411S	probably damaging	Het
Dynlrb2	T	C	8: 117,241,696 (GRCm39)	V80A	probably benign	Het
Eif3a	A	T	19: 60,755,082 (GRCm39)	D1033E	unknown	Het
Enam	C	A	5: 88,649,347 (GRCm39)	H285Q	possibly damaging	Het
Ep400	T	C	5: 110,867,480 (GRCm39)	D980G	unknown	Het
Epha7	C	T	4: 28,871,937 (GRCm39)	S422L	probably benign	Het
Erc2	A	C	14: 27,762,346 (GRCm39)	D703A	probably damaging	Het
Ezh2	G	T	6: 47,510,692 (GRCm39)	S639*	probably null	Het
Fbn1	G	A	2: 125,193,969 (GRCm39)	H1333Y	probably damaging	Het
Flad1	A	G	3: 89,315,972 (GRCm39)	S197P	possibly damaging	Het
Foxl3	A	G	5: 138,806,736 (GRCm39)	H82R	probably damaging	Het
Gfm2	G	T	13: 97,279,529 (GRCm39)	C26F	probably benign	Het
Golga2	C	T	2: 32,193,013 (GRCm39)	Q444*	probably null	Het
Gp5	A	T	16: 30,127,426 (GRCm39)	V416D	probably damaging	Het
Gpat2	A	G	2: 127,268,901 (GRCm39)		probably null	Het
Gpr137c	A	G	14: 45,516,471 (GRCm39)	D353G	probably damaging	Het
Hoxa13	A	C	6: 52,236,862 (GRCm39)	W133G	probably damaging	Het
Hydin	A	T	8: 111,327,905 (GRCm39)	K4804M	probably damaging	Het
Hydin	A	T	8: 111,284,294 (GRCm39)	I3189F	probably damaging	Het
Ice2	T	C	9: 69,307,794 (GRCm39)	F26S	probably damaging	Het
Ints11	T	C	4: 155,956,687 (GRCm39)		probably null	Het
Ipo5	A	G	14: 121,157,497 (GRCm39)	I112V	probably benign	Het
Itgax	T	A	7: 127,734,481 (GRCm39)	S346R	probably damaging	Het
Kcnj13	T	A	1: 87,316,739 (GRCm39)	M125L	probably damaging	Het
Lmbrd1	T	A	1: 24,783,948 (GRCm39)	V359E	possibly damaging	Het
Lrrc7	T	G	3: 157,903,798 (GRCm39)	K287N	probably damaging	Het
Mau2	C	T	8: 70,481,884 (GRCm39)	A191T	possibly damaging	Het
Mkx	C	A	18: 7,000,747 (GRCm39)	R65L	possibly damaging	Het
Mroh4	T	A	15: 74,482,220 (GRCm39)	K746*	probably null	Het
Myh4	A	G	11: 67,133,674 (GRCm39)	T238A	probably damaging	Het
Nlrp9c	T	A	7: 26,070,822 (GRCm39)	N920Y	possibly damaging	Het
Nr4a3	T	G	4: 48,051,290 (GRCm39)	S15A	possibly damaging	Het
Ntn4	T	C	10: 93,480,666 (GRCm39)	L130P	probably damaging	Het
Or2ag13	A	G	7: 106,313,171 (GRCm39)	V239A	probably benign	Het
Or4a68	A	G	2: 89,270,542 (GRCm39)	V27A	probably benign	Het
Or4f59	A	T	2: 111,873,359 (GRCm39)	V6E	possibly damaging	Het
Or56a42-ps1	T	A	7: 104,777,552 (GRCm39)	I21F	probably benign	Het
Or8d23	A	T	9: 38,842,072 (GRCm39)	I202F	probably damaging	Het
Otog	T	C	7: 45,947,732 (GRCm39)	L110P	probably damaging	Het
Platr25	G	A	13: 62,848,719 (GRCm39)	H48Y	probably benign	Het
Plcxd2	T	C	16: 45,800,789 (GRCm39)	E145G	probably damaging	Het
Pltp	A	T	2: 164,696,242 (GRCm39)	N143K	probably damaging	Het
Pnpt1	T	C	11: 29,111,334 (GRCm39)	Y735H	probably damaging	Het
Prom1	A	G	5: 44,178,173 (GRCm39)	Y520H	probably damaging	Het
Rag2	A	G	2: 101,461,118 (GRCm39)	Y476C	probably damaging	Het
Rdh16f2	A	G	10: 127,712,893 (GRCm39)	Y297C	probably damaging	Het
Ryr1	T	C	7: 28,785,180 (GRCm39)	E1844G	probably benign	Het
Ryr2	A	G	13: 11,655,161 (GRCm39)	C3679R	probably damaging	Het
Slc26a10	A	T	10: 127,012,716 (GRCm39)	I382N	possibly damaging	Het
Sox2	C	A	3: 34,705,121 (GRCm39)	P186Q	possibly damaging	Het
Spata31e5	A	T	1: 28,819,233 (GRCm39)	M16K	probably benign	Het
Tnpo3	A	G	6: 29,556,995 (GRCm39)	L752P	probably damaging	Het
Top2b	T	A	14: 16,416,649 (GRCm38)	N1136K	probably benign	Het
Tpsg1	G	T	17: 25,592,184 (GRCm39)	G86V	probably damaging	Het
Ttf2	C	A	3: 100,870,618 (GRCm39)	D152Y	possibly damaging	Het
Txndc15	T	C	13: 55,862,601 (GRCm39)	L4P	unknown	Het
Unc5a	T	C	13: 55,144,386 (GRCm39)	V237A	possibly damaging	Het
Urb1	CACTTAC	CAC	16: 90,569,461 (GRCm39)		probably benign	Het
Vav3	C	A	3: 109,535,415 (GRCm39)	P616T	possibly damaging	Het
Vmn2r15	T	A	5: 109,441,105 (GRCm39)	D251V	probably benign	Het
Vmn2r15	A	G	5: 109,445,388 (GRCm39)	L12S	probably benign	Het
Wfs1	A	C	5: 37,125,076 (GRCm39)	I605S	probably benign	Het
Wif1	G	A	10: 120,919,814 (GRCm39)	R187Q	possibly damaging	Het
Yipf1	A	G	4: 107,207,738 (GRCm39)		probably null	Het
Zdhhc20	G	T	14: 58,111,377 (GRCm39)	F74L	possibly damaging	Het
Zfp507	T	C	7: 35,475,843 (GRCm39)	T303A	unknown	Het
Zfp763	A	T	17: 33,252,352 (GRCm39)		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
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
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'- TAGGCCAGCATTTTCTCACTG -3'
(R):5'- CATAGGCTAGGTGGTGAATATGC -3'

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

Posted On

2019-09-13