Incidental Mutation 'R4396:Sirt1'
| ID |
325493 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Sirt1
|
| Ensembl Gene |
ENSMUSG00000020063 |
| Gene Name |
sirtuin 1 |
| Synonyms |
Sir2alpha, Sir2 |
| MMRRC Submission |
041129-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R4396 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
10 |
| Chromosomal Location |
63154784-63174814 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 63157777 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Threonine to Alanine
at position 546
(T546A)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000112595
(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: T546A
PolyPhen 2
Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
|
| SMART Domains |
Protein: ENSMUSP00000020257
Gene: ENSMUSG00000020063
AA Change: T546A
| 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: T507A
PolyPhen 2
Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
|
| SMART Domains |
Protein: ENSMUSP00000101082
Gene: ENSMUSG00000020063
AA Change: T507A
| 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: T546A
PolyPhen 2
Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
|
| SMART Domains |
Protein: ENSMUSP00000112595
Gene: ENSMUSG00000020063
AA Change: T546A
| 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
|
| Meta Mutation Damage Score |
0.0692 |
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.6%
- 10x: 97.1%
- 20x: 94.8%
|
| Validation Efficiency |
98% (52/53) |
| 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: 45 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Acsm2 |
T |
C |
7: 119,195,143 (GRCm39) |
F552L |
probably damaging |
Het |
| Actn2 |
A |
G |
13: 12,325,765 (GRCm39) |
L70P |
probably damaging |
Het |
| Btbd7 |
A |
G |
12: 102,751,552 (GRCm39) |
S1071P |
probably benign |
Het |
| Cd200r1 |
T |
A |
16: 44,586,417 (GRCm39) |
W16R |
probably benign |
Het |
| Cdhr2 |
A |
G |
13: 54,863,478 (GRCm39) |
N120D |
probably damaging |
Het |
| Col19a1 |
T |
C |
1: 24,549,947 (GRCm39) |
T317A |
unknown |
Het |
| Dab1 |
C |
T |
4: 104,588,948 (GRCm39) |
A524V |
probably benign |
Het |
| Dmbt1 |
T |
C |
7: 130,718,361 (GRCm39) |
L1683P |
probably damaging |
Het |
| Dynll1 |
A |
T |
5: 115,438,700 (GRCm39) |
C2S |
probably benign |
Het |
| Elp2 |
T |
A |
18: 24,742,707 (GRCm39) |
S80T |
probably damaging |
Het |
| Fat1 |
T |
A |
8: 45,405,383 (GRCm39) |
N711K |
probably damaging |
Het |
| Fzd3 |
A |
G |
14: 65,473,054 (GRCm39) |
I238T |
probably damaging |
Het |
| Galnt7 |
A |
T |
8: 57,991,215 (GRCm39) |
F432I |
probably damaging |
Het |
| Gemin5 |
T |
A |
11: 58,030,375 (GRCm39) |
T817S |
probably benign |
Het |
| Gm5414 |
T |
G |
15: 101,534,101 (GRCm39) |
E294A |
probably damaging |
Het |
| H2-T5 |
C |
A |
17: 36,472,861 (GRCm39) |
|
probably benign |
Het |
| Homer3 |
G |
A |
8: 70,742,793 (GRCm39) |
|
probably null |
Het |
| Kcnj4 |
C |
A |
15: 79,368,874 (GRCm39) |
A369S |
probably benign |
Het |
| Llgl1 |
T |
C |
11: 60,596,834 (GRCm39) |
V145A |
probably benign |
Het |
| Mdga1 |
T |
C |
17: 30,069,491 (GRCm39) |
D185G |
probably damaging |
Het |
| Mettl2 |
A |
G |
11: 105,017,604 (GRCm39) |
D38G |
probably damaging |
Het |
| Mfsd13a |
C |
T |
19: 46,360,431 (GRCm39) |
R328C |
probably damaging |
Het |
| Mpp4 |
T |
C |
1: 59,183,961 (GRCm39) |
I260V |
possibly damaging |
Het |
| Mtcl1 |
T |
C |
17: 66,651,220 (GRCm39) |
E1112G |
probably damaging |
Het |
| Mtus2 |
T |
A |
5: 148,140,748 (GRCm39) |
N871K |
possibly damaging |
Het |
| Mylk |
C |
T |
16: 34,732,645 (GRCm39) |
Q642* |
probably null |
Het |
| Naip6 |
C |
T |
13: 100,437,108 (GRCm39) |
A472T |
probably benign |
Het |
| Or4f57 |
A |
G |
2: 111,790,560 (GRCm39) |
I286T |
probably damaging |
Het |
| Pdzd2 |
A |
T |
15: 12,387,732 (GRCm39) |
D875E |
probably benign |
Het |
| Piezo1 |
G |
T |
8: 123,225,413 (GRCm39) |
T557K |
probably damaging |
Het |
| Plxna2 |
C |
T |
1: 194,431,625 (GRCm39) |
S538F |
probably damaging |
Het |
| Plxnb1 |
T |
C |
9: 108,929,291 (GRCm39) |
V49A |
possibly damaging |
Het |
| Pramel6 |
A |
T |
2: 87,338,874 (GRCm39) |
I25F |
probably damaging |
Het |
| Rreb1 |
C |
T |
13: 38,114,419 (GRCm39) |
Q593* |
probably null |
Het |
| Scn8a |
A |
G |
15: 100,870,711 (GRCm39) |
N254S |
probably damaging |
Het |
| Scnn1g |
T |
G |
7: 121,339,650 (GRCm39) |
S150A |
probably benign |
Het |
| Sec24a |
A |
G |
11: 51,605,991 (GRCm39) |
F686L |
possibly damaging |
Het |
| Tns2 |
C |
T |
15: 102,017,369 (GRCm39) |
R281C |
probably damaging |
Het |
| Traf5 |
A |
T |
1: 191,729,806 (GRCm39) |
V415E |
probably benign |
Het |
| Traip |
C |
G |
9: 107,836,686 (GRCm39) |
T110S |
probably benign |
Het |
| Treml2 |
T |
C |
17: 48,615,142 (GRCm39) |
V209A |
probably benign |
Het |
| Trpv5 |
T |
C |
6: 41,634,830 (GRCm39) |
S500G |
probably benign |
Het |
| Usp32 |
G |
A |
11: 84,944,801 (GRCm39) |
L296F |
probably benign |
Het |
| Vmn2r79 |
A |
G |
7: 86,651,099 (GRCm39) |
H166R |
possibly damaging |
Het |
| Zswim1 |
A |
G |
2: 164,667,369 (GRCm39) |
D207G |
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 |
|
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'- TTAGGCCAGCATTTTCTCACTG -3'
(R):5'- TCATAGGCTAGGTGGTGAATATGC -3'
Sequencing Primer
(F):5'- CTCACTGTTTCTGCAACTGAAG -3'
(R):5'- CTAGGTGGTGAATATGCCAAACTTTG -3'
|
| Posted On |
2015-07-06 |
Incidental Mutation