Incidental Mutation 'R7171:Msh3'
| ID |
558300 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Msh3
|
| Ensembl Gene |
ENSMUSG00000014850 |
| Gene Name |
mutS homolog 3 |
| Synonyms |
Rep3, D13Em1, Rep-3 |
| MMRRC Submission |
045230-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly non essential
(E-score: 0.285)
|
| Stock # |
R7171 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
13 |
| Chromosomal Location |
92348387-92491515 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to G
at 92485806 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Threonine to Proline
at position 173
(T173P)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000140002
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000022220]
[ENSMUST00000185852]
[ENSMUST00000187424]
[ENSMUST00000187874]
[ENSMUST00000190393]
[ENSMUST00000191509]
[ENSMUST00000191550]
|
| AlphaFold |
no structure available at present |
| Predicted Effect |
|
| SMART Domains |
Protein: ENSMUSP00000022220
Gene: ENSMUSG00000014850
AA Change: T173P
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
4 |
19 |
N/A |
INTRINSIC |
|
low complexity region
|
24 |
40 |
N/A |
INTRINSIC |
|
Pfam:MutS_I
|
188 |
301 |
1.6e-35 |
PFAM |
|
Pfam:MutS_II
|
324 |
481 |
2.2e-36 |
PFAM |
|
MUTSd
|
513 |
828 |
7.62e-97 |
SMART |
|
MUTSac
|
847 |
1049 |
9.7e-122 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000185852
AA Change: T173P
PolyPhen 2
Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)
|
| SMART Domains |
Protein: ENSMUSP00000140002
Gene: ENSMUSG00000014850
AA Change: T173P
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
4 |
19 |
N/A |
INTRINSIC |
|
low complexity region
|
24 |
40 |
N/A |
INTRINSIC |
|
Pfam:MutS_I
|
188 |
301 |
7.2e-35 |
PFAM |
|
Pfam:MutS_II
|
324 |
481 |
2.2e-36 |
PFAM |
|
MUTSd
|
513 |
828 |
7.62e-97 |
SMART |
|
MUTSac
|
847 |
1049 |
9.7e-122 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000187424
|
| SMART Domains |
Protein: ENSMUSP00000139622
Gene: ENSMUSG00000014850
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
4 |
19 |
N/A |
INTRINSIC |
|
low complexity region
|
24 |
40 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000187874
|
| SMART Domains |
Protein: ENSMUSP00000139620
Gene: ENSMUSG00000014850
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
4 |
19 |
N/A |
INTRINSIC |
|
low complexity region
|
24 |
40 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000190393
AA Change: T173P
PolyPhen 2
Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
|
| SMART Domains |
Protein: ENSMUSP00000141163
Gene: ENSMUSG00000014850
AA Change: T173P
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
4 |
19 |
N/A |
INTRINSIC |
|
low complexity region
|
24 |
40 |
N/A |
INTRINSIC |
|
Pfam:MutS_I
|
188 |
241 |
6.4e-10 |
PFAM |
|
low complexity region
|
261 |
285 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000191509
|
| SMART Domains |
Protein: ENSMUSP00000141158
Gene: ENSMUSG00000014850
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
4 |
19 |
N/A |
INTRINSIC |
|
low complexity region
|
24 |
40 |
N/A |
INTRINSIC |
|
| Predicted Effect |
unknown
Transcript: ENSMUST00000191550
AA Change: R142S
|
| SMART Domains |
Protein: ENSMUSP00000140659
Gene: ENSMUSG00000014850
AA Change: R142S
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
4 |
19 |
N/A |
INTRINSIC |
|
low complexity region
|
24 |
40 |
N/A |
INTRINSIC |
|
| Meta Mutation Damage Score |
0.0576 |
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 100.0%
- 10x: 99.7%
- 20x: 98.9%
|
| Validation Efficiency |
100% (81/81) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene forms a heterodimer with MSH2 to form MutS beta, part of the post-replicative DNA mismatch repair system. MutS beta initiates mismatch repair by binding to a mismatch and then forming a complex with MutL alpha heterodimer. This gene contains a polymorphic 9 bp tandem repeat sequence in the first exon. The repeat is present 6 times in the reference genome sequence and 3-7 repeats have been reported. Defects in this gene are a cause of susceptibility to endometrial cancer. [provided by RefSeq, Mar 2011]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit a partial defect mismatch repair and development of intestinal tumors. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 81 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4930519P11Rik |
T |
C |
2: 154,454,897 (GRCm39) |
N154S |
unknown |
Het |
| Ank3 |
C |
T |
10: 69,828,311 (GRCm39) |
H2327Y |
|
Het |
| Ano6 |
A |
G |
15: 95,818,172 (GRCm39) |
Y305C |
probably damaging |
Het |
| Apc2 |
A |
G |
10: 80,151,170 (GRCm39) |
T2075A |
possibly damaging |
Het |
| Arl6 |
A |
G |
16: 59,443,455 (GRCm39) |
V93A |
possibly damaging |
Het |
| Bcas3 |
T |
C |
11: 85,474,763 (GRCm39) |
S790P |
probably damaging |
Het |
| Bcl9l |
C |
A |
9: 44,416,448 (GRCm39) |
H211N |
probably benign |
Het |
| Bptf |
G |
T |
11: 107,022,233 (GRCm39) |
D172E |
unknown |
Het |
| Card9 |
T |
G |
2: 26,249,496 (GRCm39) |
I22L |
possibly damaging |
Het |
| Catsperg1 |
C |
A |
7: 28,884,637 (GRCm39) |
G933V |
probably damaging |
Het |
| Catsperg2 |
T |
A |
7: 29,404,750 (GRCm39) |
H771L |
possibly damaging |
Het |
| Ccdc66 |
T |
C |
14: 27,215,229 (GRCm39) |
N281S |
possibly damaging |
Het |
| Cfap54 |
A |
T |
10: 92,612,072 (GRCm39) |
L3162H |
probably damaging |
Het |
| Clca4a |
A |
G |
3: 144,663,934 (GRCm39) |
L503P |
probably benign |
Het |
| Cpn1 |
T |
C |
19: 43,962,470 (GRCm39) |
N160D |
probably damaging |
Het |
| Ctsh |
T |
A |
9: 89,949,154 (GRCm39) |
I206K |
probably benign |
Het |
| Cyb561d1 |
G |
A |
3: 108,106,679 (GRCm39) |
T180M |
probably damaging |
Het |
| Dapk1 |
A |
T |
13: 60,909,599 (GRCm39) |
D1404V |
probably damaging |
Het |
| Dip2c |
G |
T |
13: 9,556,684 (GRCm39) |
R76L |
probably benign |
Het |
| Dnah7c |
T |
C |
1: 46,719,898 (GRCm39) |
I2783T |
probably damaging |
Het |
| E130308A19Rik |
T |
C |
4: 59,690,333 (GRCm39) |
Y56H |
probably damaging |
Het |
| Efemp2 |
G |
T |
19: 5,530,285 (GRCm39) |
A310S |
probably benign |
Het |
| Enpp5 |
G |
A |
17: 44,396,155 (GRCm39) |
G356S |
probably damaging |
Het |
| Faap24 |
G |
A |
7: 35,092,279 (GRCm39) |
Q213* |
probably null |
Het |
| Fam181b |
G |
A |
7: 92,729,943 (GRCm39) |
G239S |
possibly damaging |
Het |
| Fancm |
T |
C |
12: 65,148,394 (GRCm39) |
W670R |
probably damaging |
Het |
| Fcgbpl1 |
T |
A |
7: 27,853,944 (GRCm39) |
L1636* |
probably null |
Het |
| Fmnl1 |
T |
C |
11: 103,081,224 (GRCm39) |
Y357H |
probably damaging |
Het |
| Fryl |
A |
T |
5: 73,279,653 (GRCm39) |
V215E |
probably damaging |
Het |
| Fscn2 |
C |
A |
11: 120,253,335 (GRCm39) |
N267K |
probably damaging |
Het |
| Fsip2 |
T |
A |
2: 82,816,571 (GRCm39) |
Y4101* |
probably null |
Het |
| Gcn1 |
G |
A |
5: 115,728,352 (GRCm39) |
V738I |
probably benign |
Het |
| Gdf9 |
C |
T |
11: 53,328,366 (GRCm39) |
R441C |
probably damaging |
Het |
| Gipc3 |
C |
T |
10: 81,177,455 (GRCm39) |
G79E |
probably damaging |
Het |
| Gzmf |
T |
A |
14: 56,443,391 (GRCm39) |
I196L |
probably benign |
Het |
| Hectd1 |
A |
T |
12: 51,806,080 (GRCm39) |
V1852E |
probably damaging |
Het |
| Hip1r |
A |
T |
5: 124,134,007 (GRCm39) |
Q256L |
probably benign |
Het |
| Hmgxb4 |
T |
C |
8: 75,746,890 (GRCm39) |
S405P |
probably damaging |
Het |
| Il9r |
T |
A |
11: 32,142,671 (GRCm39) |
H294L |
probably benign |
Het |
| Kif12 |
G |
A |
4: 63,086,931 (GRCm39) |
T331I |
probably damaging |
Het |
| Krtap8-1 |
A |
T |
16: 89,284,794 (GRCm39) |
M1K |
probably null |
Het |
| Lamc2 |
A |
T |
1: 153,015,495 (GRCm39) |
C613S |
probably damaging |
Het |
| Lgr4 |
T |
A |
2: 109,831,314 (GRCm39) |
N314K |
probably benign |
Het |
| Lpcat2 |
T |
C |
8: 93,635,894 (GRCm39) |
I432T |
probably benign |
Het |
| Mfhas1 |
T |
C |
8: 36,056,146 (GRCm39) |
V207A |
probably benign |
Het |
| Mup15 |
T |
A |
4: 61,356,505 (GRCm39) |
M87L |
probably benign |
Het |
| N4bp2 |
T |
C |
5: 65,965,365 (GRCm39) |
V1138A |
probably benign |
Het |
| Noc2l |
T |
C |
4: 156,326,179 (GRCm39) |
V422A |
probably benign |
Het |
| Notch3 |
C |
T |
17: 32,377,936 (GRCm39) |
G74D |
probably damaging |
Het |
| Ocstamp |
T |
A |
2: 165,240,081 (GRCm39) |
K35I |
probably benign |
Het |
| Or12k7 |
T |
C |
2: 36,958,400 (GRCm39) |
F28L |
possibly damaging |
Het |
| Or52w1 |
A |
G |
7: 105,017,968 (GRCm39) |
H145R |
probably benign |
Het |
| Or5p58 |
A |
G |
7: 107,694,342 (GRCm39) |
V145A |
probably benign |
Het |
| Or9a2 |
T |
G |
6: 41,748,961 (GRCm39) |
T91P |
probably benign |
Het |
| Plekhh2 |
T |
A |
17: 84,829,216 (GRCm39) |
V29D |
probably damaging |
Het |
| Pof1b |
A |
G |
X: 111,554,042 (GRCm39) |
I544T |
probably benign |
Het |
| Rad54l2 |
C |
T |
9: 106,590,677 (GRCm39) |
R483H |
probably damaging |
Het |
| Rapgef6 |
T |
A |
11: 54,567,189 (GRCm39) |
D1128E |
possibly damaging |
Het |
| Rhbdl2 |
T |
A |
4: 123,708,049 (GRCm39) |
I86N |
possibly damaging |
Het |
| Rims1 |
C |
A |
1: 22,498,740 (GRCm39) |
R68L |
|
Het |
| Rnf157 |
A |
G |
11: 116,253,199 (GRCm39) |
F70L |
possibly damaging |
Het |
| Rtp3 |
C |
T |
9: 110,815,009 (GRCm39) |
C452Y |
unknown |
Het |
| S100a14 |
A |
T |
3: 90,435,069 (GRCm39) |
K27* |
probably null |
Het |
| Scai |
C |
T |
2: 38,996,948 (GRCm39) |
G282D |
possibly damaging |
Het |
| Sclt1 |
A |
T |
3: 41,672,195 (GRCm39) |
I132N |
probably benign |
Het |
| Serpinf1 |
T |
A |
11: 75,308,811 (GRCm39) |
Q2L |
possibly damaging |
Het |
| Skor2 |
T |
A |
18: 76,948,681 (GRCm39) |
V801E |
probably benign |
Het |
| Slc16a10 |
C |
G |
10: 39,913,255 (GRCm39) |
E484D |
probably benign |
Het |
| Slc1a5 |
T |
A |
7: 16,531,463 (GRCm39) |
D489E |
probably damaging |
Het |
| Slx4 |
C |
T |
16: 3,808,650 (GRCm39) |
R430H |
probably benign |
Het |
| Teddm1b |
A |
T |
1: 153,750,679 (GRCm39) |
I163F |
probably damaging |
Het |
| Tmem171 |
A |
T |
13: 98,828,744 (GRCm39) |
C135* |
probably null |
Het |
| Tmem82 |
C |
T |
4: 141,342,284 (GRCm39) |
R306H |
possibly damaging |
Het |
| Tmem94 |
T |
A |
11: 115,681,781 (GRCm39) |
|
probably null |
Het |
| Trpm2 |
A |
C |
10: 77,759,848 (GRCm39) |
L1096R |
probably damaging |
Het |
| Trrap |
T |
A |
5: 144,730,859 (GRCm39) |
L780Q |
probably damaging |
Het |
| Txlnb |
A |
G |
10: 17,718,732 (GRCm39) |
D521G |
probably benign |
Het |
| Usp7 |
T |
C |
16: 8,534,390 (GRCm39) |
D59G |
probably benign |
Het |
| Vcan |
G |
A |
13: 89,873,710 (GRCm39) |
T48I |
probably damaging |
Het |
| Vmn1r45 |
A |
G |
6: 89,910,316 (GRCm39) |
L218P |
probably damaging |
Het |
| Wdr25 |
A |
T |
12: 108,990,922 (GRCm39) |
T370S |
probably damaging |
Het |
|
| Other mutations in Msh3 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00895:Msh3
|
APN |
13 |
92,481,472 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL00983:Msh3
|
APN |
13 |
92,436,785 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01490:Msh3
|
APN |
13 |
92,436,813 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02072:Msh3
|
APN |
13 |
92,436,803 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02313:Msh3
|
APN |
13 |
92,485,820 (GRCm39) |
missense |
possibly damaging |
0.86 |
|
IGL02711:Msh3
|
APN |
13 |
92,487,819 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03108:Msh3
|
APN |
13 |
92,357,596 (GRCm39) |
splice site |
probably benign |
|
|
IGL03227:Msh3
|
APN |
13 |
92,422,468 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R0164:Msh3
|
UTSW |
13 |
92,485,717 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0164:Msh3
|
UTSW |
13 |
92,485,717 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0415:Msh3
|
UTSW |
13 |
92,483,294 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
R0457:Msh3
|
UTSW |
13 |
92,357,505 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0659:Msh3
|
UTSW |
13 |
92,481,604 (GRCm39) |
missense |
possibly damaging |
0.80 |
|
R0661:Msh3
|
UTSW |
13 |
92,481,604 (GRCm39) |
missense |
possibly damaging |
0.80 |
|
R0686:Msh3
|
UTSW |
13 |
92,487,939 (GRCm39) |
missense |
possibly damaging |
0.53 |
|
R0688:Msh3
|
UTSW |
13 |
92,487,939 (GRCm39) |
missense |
possibly damaging |
0.53 |
|
R0707:Msh3
|
UTSW |
13 |
92,483,848 (GRCm39) |
nonsense |
probably null |
|
|
R1605:Msh3
|
UTSW |
13 |
92,436,783 (GRCm39) |
missense |
probably null |
1.00 |
|
R1622:Msh3
|
UTSW |
13 |
92,481,462 (GRCm39) |
critical splice donor site |
probably null |
|
|
R1771:Msh3
|
UTSW |
13 |
92,349,004 (GRCm39) |
missense |
probably benign |
0.05 |
|
R1970:Msh3
|
UTSW |
13 |
92,386,328 (GRCm39) |
splice site |
probably benign |
|
|
R1971:Msh3
|
UTSW |
13 |
92,386,328 (GRCm39) |
splice site |
probably benign |
|
|
R1971:Msh3
|
UTSW |
13 |
92,359,784 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2894:Msh3
|
UTSW |
13 |
92,478,868 (GRCm39) |
missense |
probably benign |
0.16 |
|
R3837:Msh3
|
UTSW |
13 |
92,491,366 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4119:Msh3
|
UTSW |
13 |
92,490,519 (GRCm39) |
intron |
probably benign |
|
|
R4225:Msh3
|
UTSW |
13 |
92,422,431 (GRCm39) |
missense |
probably benign |
0.03 |
|
R4881:Msh3
|
UTSW |
13 |
92,402,549 (GRCm39) |
intron |
probably benign |
|
|
R5118:Msh3
|
UTSW |
13 |
92,445,942 (GRCm39) |
splice site |
probably benign |
|
|
R5209:Msh3
|
UTSW |
13 |
92,481,462 (GRCm39) |
critical splice donor site |
probably null |
|
|
R5817:Msh3
|
UTSW |
13 |
92,422,508 (GRCm39) |
missense |
possibly damaging |
0.86 |
|
R5849:Msh3
|
UTSW |
13 |
92,386,386 (GRCm39) |
missense |
possibly damaging |
0.81 |
|
R5851:Msh3
|
UTSW |
13 |
92,352,030 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5940:Msh3
|
UTSW |
13 |
92,386,351 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6004:Msh3
|
UTSW |
13 |
92,478,922 (GRCm39) |
critical splice acceptor site |
probably null |
|
|
R6363:Msh3
|
UTSW |
13 |
92,349,032 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6510:Msh3
|
UTSW |
13 |
92,489,772 (GRCm39) |
nonsense |
probably null |
|
|
R6654:Msh3
|
UTSW |
13 |
92,481,550 (GRCm39) |
missense |
probably benign |
0.01 |
|
R6853:Msh3
|
UTSW |
13 |
92,449,080 (GRCm39) |
critical splice donor site |
probably null |
|
|
R7022:Msh3
|
UTSW |
13 |
92,372,096 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7098:Msh3
|
UTSW |
13 |
92,410,619 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R7103:Msh3
|
UTSW |
13 |
92,411,308 (GRCm39) |
missense |
probably benign |
|
|
R7148:Msh3
|
UTSW |
13 |
92,491,330 (GRCm39) |
missense |
probably benign |
0.18 |
|
R7317:Msh3
|
UTSW |
13 |
92,422,512 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7369:Msh3
|
UTSW |
13 |
92,435,770 (GRCm39) |
missense |
probably benign |
0.15 |
|
R7586:Msh3
|
UTSW |
13 |
92,485,840 (GRCm39) |
utr 3 prime |
probably benign |
|
|
R7641:Msh3
|
UTSW |
13 |
92,349,011 (GRCm39) |
missense |
probably benign |
0.08 |
|
R7648:Msh3
|
UTSW |
13 |
92,410,536 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7674:Msh3
|
UTSW |
13 |
92,349,011 (GRCm39) |
missense |
probably benign |
0.08 |
|
R8125:Msh3
|
UTSW |
13 |
92,435,690 (GRCm39) |
missense |
probably benign |
|
|
R8252:Msh3
|
UTSW |
13 |
92,357,569 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8388:Msh3
|
UTSW |
13 |
92,359,784 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8442:Msh3
|
UTSW |
13 |
92,349,020 (GRCm39) |
missense |
probably benign |
0.00 |
|
R8735:Msh3
|
UTSW |
13 |
92,411,374 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R8986:Msh3
|
UTSW |
13 |
92,483,334 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9264:Msh3
|
UTSW |
13 |
92,485,812 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9326:Msh3
|
UTSW |
13 |
92,400,307 (GRCm39) |
missense |
probably benign |
0.15 |
|
R9457:Msh3
|
UTSW |
13 |
92,481,594 (GRCm39) |
missense |
probably benign |
0.04 |
|
R9459:Msh3
|
UTSW |
13 |
92,352,047 (GRCm39) |
missense |
possibly damaging |
0.91 |
|
R9648:Msh3
|
UTSW |
13 |
92,478,757 (GRCm39) |
missense |
probably benign |
0.00 |
|
S24628:Msh3
|
UTSW |
13 |
92,483,294 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
X0027:Msh3
|
UTSW |
13 |
92,410,578 (GRCm39) |
missense |
probably damaging |
0.98 |
|
X0063:Msh3
|
UTSW |
13 |
92,411,293 (GRCm39) |
nonsense |
probably null |
|
|
| Predicted Primers |
PCR Primer
(F):5'- AGTGCTTGGAAACACAACTTGTAAG -3'
(R):5'- CCCTCAGAATGCCTTTAGAAAC -3'
Sequencing Primer
(F):5'- CACCTTTAATCTCAGAACTTGGGGG -3'
(R):5'- AGAAACCGTTCTGTGTTGTCAC -3'
|
| Posted On |
2019-06-26 |
Incidental Mutation