Mutagenetix > Incidental Mutation

Incidental Mutation 'R7773:Sirt1'

628428

Institutional Source

Beutler Lab

Gene Symbol

Sirt1

Ensembl Gene

ENSMUSG00000020063

Gene Name

sirtuin 1

Synonyms

Sir2alpha, Sir2

MMRRC Submission

045829-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7773 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

63154784-63174814 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 63162562 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Lysine to Methionine at position 137 (K137M)

Ref Sequence

ENSEMBL: ENSMUSP00000117819 (fasta)

Gene Model

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

AlphaFold

Q923E4

Predicted Effect

probably benign
Transcript: ENSMUST00000020257

SMART Domains

Protein: ENSMUSP00000020257
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	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

SMART Domains

Protein: ENSMUSP00000101082
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
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

SMART Domains

Protein: ENSMUSP00000112595
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	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

possibly damaging
Transcript: ENSMUST00000146028
AA Change: K137M

PolyPhen 2 Score 0.753 (Sensitivity: 0.85; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000117819
Gene: ENSMUSG00000020063
AA Change: K137M

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

Meta Mutation Damage Score

0.1795

Coding Region Coverage

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

Validation Efficiency

98% (55/56)

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: 59 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700006A11Rik	A	G	3: 124,206,180 (GRCm39)	I336T	probably benign	Het
4930519P11Rik	T	C	2: 154,455,107 (GRCm39)	Y84C	unknown	Het
4930568D16Rik	C	T	2: 35,244,606 (GRCm39)	G249S	probably damaging	Het
AAdacl4fm3	A	T	4: 144,430,047 (GRCm39)	L314Q	probably damaging	Het
Adprhl1	C	T	8: 13,298,682 (GRCm39)	V83I	probably damaging	Het
Agbl1	T	A	7: 76,348,585 (GRCm39)	V894E	unknown	Het
Amigo3	T	C	9: 107,931,867 (GRCm39)	L430P	probably benign	Het
Aoc1	A	G	6: 48,883,146 (GRCm39)	I341V	probably benign	Het
Bod1l	A	G	5: 41,990,055 (GRCm39)	S223P	probably benign	Het
Cacnb3	T	C	15: 98,537,819 (GRCm39)		probably null	Het
Ccdc63	G	T	5: 122,247,335 (GRCm39)	N503K	probably damaging	Het
Ccdc83	T	A	7: 89,879,120 (GRCm39)	I225F	probably damaging	Het
Cd200r1	A	G	16: 44,610,050 (GRCm39)	T90A	possibly damaging	Het
Cd8a	A	G	6: 71,350,799 (GRCm39)	N88S	probably benign	Het
Cep170	A	G	1: 176,567,642 (GRCm39)	V152A		Het
Chid1	T	C	7: 141,109,518 (GRCm39)	M123V	probably benign	Het
Cnnm4	T	C	1: 36,538,603 (GRCm39)	V595A	probably benign	Het
Coro7	A	G	16: 4,449,870 (GRCm39)	L630P	probably damaging	Het
Cpvl	A	G	6: 53,908,890 (GRCm39)		probably null	Het
Edem3	A	T	1: 151,687,347 (GRCm39)	K762*	probably null	Het
Elp6	T	A	9: 110,141,627 (GRCm39)		probably null	Het
Emilin3	A	T	2: 160,752,718 (GRCm39)	Y77*	probably null	Het
Fam234b	T	A	6: 135,220,912 (GRCm39)	I641N	probably benign	Het
Farsa	T	C	8: 85,590,781 (GRCm39)		probably null	Het
Foxf2	T	C	13: 31,811,182 (GRCm39)	S374P	probably benign	Het
Gm11596	A	T	11: 99,683,667 (GRCm39)	I151N	unknown	Het
Gm9817	C	T	13: 45,232,427 (GRCm39)	Q77*	probably null	Het
Gon4l	A	G	3: 88,803,102 (GRCm39)	K1238E	probably benign	Het
H13	A	G	2: 152,537,431 (GRCm39)	Y292C	probably damaging	Het
Hip1r	A	G	5: 124,139,504 (GRCm39)	N928S	probably benign	Het
Iqcf4	T	C	9: 106,445,812 (GRCm39)	N112D	probably benign	Het
Jak3	A	C	8: 72,131,686 (GRCm39)	T125P	probably benign	Het
Krt7	A	C	15: 101,311,913 (GRCm39)	K124Q	possibly damaging	Het
Ldc1	T	C	4: 130,114,169 (GRCm39)	N83D	probably damaging	Het
Lrrc66	G	A	5: 73,764,664 (GRCm39)	S793F	probably damaging	Het
Mycbp2	C	T	14: 103,485,840 (GRCm39)	V1074I	probably damaging	Het
Nckap5	T	C	1: 125,954,581 (GRCm39)	D657G	probably benign	Het
Nt5el	A	G	13: 105,218,793 (GRCm39)	I42M	probably damaging	Het
Or5b113	T	A	19: 13,342,598 (GRCm39)	V202E	probably benign	Het
Or8k21	T	C	2: 86,145,034 (GRCm39)	I199V	probably benign	Het
Osbpl7	A	G	11: 96,941,548 (GRCm39)	S24G	probably benign	Het
Pcm1	G	T	8: 41,762,610 (GRCm39)	E1385*	probably null	Het
Poc5	A	G	13: 96,547,143 (GRCm39)	T469A	probably damaging	Het
Ppp3ca	A	G	3: 136,596,222 (GRCm39)	T296A	probably benign	Het
Prl6a1	T	C	13: 27,502,125 (GRCm39)	I164T	probably damaging	Het
Psmd6	GCAGAGCGGGCAGGGCATCTCACTGACCCTGTCACCTACCCAGAGCGGGCAGGGCATCTCACTGACCCTGTCACCTACCCAGAGCGGGCAGGGCATCTCACTGACC	GCAGAGCGGGCAGGGCATCTCACTGACCCTGTCACCTACCCAGAGCGGGCAGGGCATCTCACTGACC	14: 14,119,882 (GRCm38)		probably null	Het
Rnf149	A	C	1: 39,604,299 (GRCm39)	M188R	possibly damaging	Het
Rpl10l	T	C	12: 66,331,041 (GRCm39)	I31V	probably benign	Het
Serinc5	T	C	13: 92,797,592 (GRCm39)	S32P	probably damaging	Het
Smc4	A	G	3: 68,923,496 (GRCm39)	Y251C	probably damaging	Het
Sod3	A	C	5: 52,525,643 (GRCm39)	E114A	possibly damaging	Het
Tgfbr3	A	G	5: 107,288,368 (GRCm39)	V431A	probably benign	Het
Tlr4	T	C	4: 66,757,836 (GRCm39)	S210P	probably damaging	Het
Trub2	G	T	2: 29,676,520 (GRCm39)	T70N	probably benign	Het
Tsga10	A	T	1: 37,874,323 (GRCm39)	C159S	unknown	Het
Vmn1r15	A	T	6: 57,235,644 (GRCm39)	I171F	probably benign	Het
Vmn2r50	T	A	7: 9,771,562 (GRCm39)	H713L	possibly damaging	Het
Zcchc14	T	C	8: 122,378,514 (GRCm39)	S43G	unknown	Het
Zfp638	T	C	6: 83,956,196 (GRCm39)	I1601T	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
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
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'- TTGATAAATATCAACCTGCTGGGAG -3'
(R):5'- AACACTATCAGGAGTTGTGAGG -3'

Sequencing Primer
(F):5'- TCAACCTGCTGGGAGTTTAAAGC -3'
(R):5'- ACTGGCTGCTCTTCCAAAGG -3'

Posted On

2020-04-06