Incidental Mutation 'R9127:Rasgrp2'
| ID |
693371 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Rasgrp2
|
| Ensembl Gene |
ENSMUSG00000032946 |
| Gene Name |
RAS, guanyl releasing protein 2 |
| Synonyms |
Caldaggef1, CalDAG-GEFI |
| MMRRC Submission |
068926-MU
|
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
R9127 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
19 |
| Chromosomal Location |
6449370-6465246 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to T
at 6454438 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Glutamic Acid to Aspartic acid
at position 160
(E160D)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000041135
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000035716]
[ENSMUST00000113467]
[ENSMUST00000113468]
[ENSMUST00000113469]
[ENSMUST00000113471]
[ENSMUST00000113472]
[ENSMUST00000113475]
[ENSMUST00000113476]
[ENSMUST00000127021]
[ENSMUST00000138555]
[ENSMUST00000139522]
[ENSMUST00000146601]
[ENSMUST00000146831]
[ENSMUST00000150713]
[ENSMUST00000167240]
|
| AlphaFold |
Q9QUG9 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000035716
AA Change: E160D
PolyPhen 2
Score 0.914 (Sensitivity: 0.81; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000041135
Gene: ENSMUSG00000032946
AA Change: E160D
| Domain | Start | End | E-Value | Type |
|---|
|
RasGEFN
|
3 |
126 |
3.56e-29 |
SMART |
|
RasGEF
|
150 |
388 |
1.08e-100 |
SMART |
|
EFh
|
430 |
458 |
8.25e-3 |
SMART |
|
EFh
|
459 |
487 |
1.42e1 |
SMART |
|
C1
|
499 |
548 |
3.22e-14 |
SMART |
|
low complexity region
|
575 |
595 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000113467
|
| SMART Domains |
Protein: ENSMUSP00000109095
Gene: ENSMUSG00000032946
| Domain | Start | End | E-Value | Type |
|---|
|
Blast:RasGEFN
|
3 |
24 |
9e-8 |
BLAST |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000113468
|
| SMART Domains |
Protein: ENSMUSP00000109096
Gene: ENSMUSG00000032946
| Domain | Start | End | E-Value | Type |
|---|
|
RasGEFN
|
3 |
97 |
1.93e-7 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000113469
|
| SMART Domains |
Protein: ENSMUSP00000109097
Gene: ENSMUSG00000032946
| Domain | Start | End | E-Value | Type |
|---|
|
Blast:RasGEFN
|
3 |
24 |
1e-7 |
BLAST |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000113471
|
| SMART Domains |
Protein: ENSMUSP00000109099
Gene: ENSMUSG00000032946
| Domain | Start | End | E-Value | Type |
|---|
|
RasGEFN
|
3 |
126 |
7.2e-31 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000113472
|
| SMART Domains |
Protein: ENSMUSP00000109100
Gene: ENSMUSG00000032946
| Domain | Start | End | E-Value | Type |
|---|
|
RasGEFN
|
3 |
126 |
7.2e-31 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000113475
|
| SMART Domains |
Protein: ENSMUSP00000109103
Gene: ENSMUSG00000032946
| Domain | Start | End | E-Value | Type |
|---|
|
RasGEFN
|
3 |
126 |
7.2e-31 |
SMART |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000113476
AA Change: E160D
PolyPhen 2
Score 0.914 (Sensitivity: 0.81; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000109104
Gene: ENSMUSG00000032946
AA Change: E160D
| Domain | Start | End | E-Value | Type |
|---|
|
RasGEFN
|
3 |
126 |
3.56e-29 |
SMART |
|
RasGEF
|
150 |
388 |
1.08e-100 |
SMART |
|
EFh
|
430 |
458 |
8.25e-3 |
SMART |
|
EFh
|
459 |
487 |
1.42e1 |
SMART |
|
C1
|
499 |
548 |
3.22e-14 |
SMART |
|
low complexity region
|
575 |
595 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000127021
|
| SMART Domains |
Protein: ENSMUSP00000119740
Gene: ENSMUSG00000032946
| Domain | Start | End | E-Value | Type |
|---|
|
Blast:RasGEFN
|
3 |
24 |
1e-7 |
BLAST |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000138555
AA Change: E160D
PolyPhen 2
Score 0.914 (Sensitivity: 0.81; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000121635
Gene: ENSMUSG00000032946
AA Change: E160D
| Domain | Start | End | E-Value | Type |
|---|
|
RasGEFN
|
3 |
126 |
3.56e-29 |
SMART |
|
Pfam:RasGEF
|
151 |
231 |
1.6e-15 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000139522
|
| SMART Domains |
Protein: ENSMUSP00000123036
Gene: ENSMUSG00000032946
| Domain | Start | End | E-Value | Type |
|---|
|
RasGEFN
|
3 |
125 |
6.02e-27 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000146601
|
| SMART Domains |
Protein: ENSMUSP00000117681
Gene: ENSMUSG00000032946
| Domain | Start | End | E-Value | Type |
|---|
|
Blast:RasGEFN
|
3 |
58 |
1e-35 |
BLAST |
|
SCOP:d1bkds_
|
9 |
58 |
1e-8 |
SMART |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000146831
AA Change: E160D
PolyPhen 2
Score 0.914 (Sensitivity: 0.81; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000120630
Gene: ENSMUSG00000032946
AA Change: E160D
| Domain | Start | End | E-Value | Type |
|---|
|
RasGEFN
|
3 |
126 |
3.56e-29 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000150713
|
| SMART Domains |
Protein: ENSMUSP00000120949
Gene: ENSMUSG00000032946
| Domain | Start | End | E-Value | Type |
|---|
|
RasGEFN
|
3 |
95 |
6.73e-7 |
SMART |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000167240
AA Change: E160D
PolyPhen 2
Score 0.914 (Sensitivity: 0.81; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000129873
Gene: ENSMUSG00000032946
AA Change: E160D
| Domain | Start | End | E-Value | Type |
|---|
|
RasGEFN
|
3 |
126 |
3.56e-29 |
SMART |
|
RasGEF
|
150 |
388 |
1.08e-100 |
SMART |
|
EFh
|
430 |
458 |
8.25e-3 |
SMART |
|
EFh
|
459 |
487 |
1.42e1 |
SMART |
|
C1
|
499 |
548 |
3.22e-14 |
SMART |
|
low complexity region
|
575 |
595 |
N/A |
INTRINSIC |
|
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 100.0%
- 10x: 99.8%
- 20x: 99.3%
|
| Validation Efficiency |
100% (82/82) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a brain-enriched nucleotide exchanged factor that contains an N-terminal GEF domain, 2 tandem repeats of EF-hand calcium-binding motifs, and a C-terminal diacylglycerol/phorbol ester-binding domain. This protein can activate small GTPases, including RAS and RAP1/RAS3. The nucleotide exchange activity of this protein can be stimulated by calcium and diacylglycerol. Four alternatively spliced transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]
PHENOTYPE: Mice homozygous for a knock-out allele do not undergo spontaneous hemorrhaging but exhibit impaired platelet aggregation, resistance to collagen-induced thrombosis, and increased bleeding times after tail transection. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 82 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abca13 |
T |
G |
11: 9,242,080 (GRCm39) |
D1314E |
probably benign |
Het |
| Abcb1a |
A |
T |
5: 8,724,707 (GRCm39) |
R47W |
probably benign |
Het |
| Abcc6 |
T |
C |
7: 45,629,184 (GRCm39) |
N1354S |
probably damaging |
Het |
| Abracl |
T |
C |
10: 17,887,444 (GRCm39) |
Y61C |
probably damaging |
Het |
| Adamtsl1 |
A |
G |
4: 86,208,027 (GRCm39) |
T633A |
probably benign |
Het |
| Agap3 |
G |
A |
5: 24,681,439 (GRCm39) |
|
probably benign |
Het |
| Ago4 |
A |
T |
4: 126,400,904 (GRCm39) |
M647K |
probably damaging |
Het |
| Akap7 |
G |
T |
10: 25,155,676 (GRCm39) |
S72R |
unknown |
Het |
| Arhgef12 |
A |
G |
9: 42,885,870 (GRCm39) |
L1251S |
possibly damaging |
Het |
| Astn2 |
A |
T |
4: 66,322,164 (GRCm39) |
V145E |
unknown |
Het |
| Atxn2l |
A |
T |
7: 126,097,393 (GRCm39) |
S304R |
probably damaging |
Het |
| Cd226 |
A |
T |
18: 89,287,155 (GRCm39) |
I318F |
probably damaging |
Het |
| Cep250 |
C |
T |
2: 155,812,042 (GRCm39) |
A446V |
unknown |
Het |
| Cfap65 |
A |
T |
1: 74,958,510 (GRCm39) |
|
probably benign |
Het |
| Cfap96 |
T |
G |
8: 46,415,403 (GRCm39) |
D201A |
probably benign |
Het |
| Chtf8 |
A |
G |
8: 107,613,640 (GRCm39) |
V18A |
probably benign |
Het |
| Cit |
G |
T |
5: 116,074,896 (GRCm39) |
E683* |
probably null |
Het |
| Ckmt2 |
T |
C |
13: 92,007,337 (GRCm39) |
R286G |
probably damaging |
Het |
| Clec4a2 |
T |
A |
6: 123,116,218 (GRCm39) |
W128R |
probably damaging |
Het |
| Clec4n |
T |
G |
6: 123,212,447 (GRCm39) |
S88A |
probably damaging |
Het |
| Cndp2 |
G |
A |
18: 84,699,121 (GRCm39) |
A48V |
probably benign |
Het |
| Csmd1 |
T |
C |
8: 16,273,286 (GRCm39) |
T849A |
probably benign |
Het |
| Cts3 |
A |
T |
13: 61,715,235 (GRCm39) |
Y199* |
probably null |
Het |
| Dag1 |
A |
T |
9: 108,085,734 (GRCm39) |
L469* |
probably null |
Het |
| Dclre1c |
T |
C |
2: 3,439,125 (GRCm39) |
V225A |
|
Het |
| Dedd |
A |
G |
1: 171,166,409 (GRCm39) |
D115G |
probably damaging |
Het |
| Efcab3 |
T |
A |
11: 104,741,407 (GRCm39) |
V2166D |
probably benign |
Het |
| Eif2ak3 |
T |
A |
6: 70,860,704 (GRCm39) |
W427R |
probably damaging |
Het |
| Fbln2 |
T |
A |
6: 91,210,473 (GRCm39) |
V139D |
probably damaging |
Het |
| Fbn1 |
A |
T |
2: 125,223,985 (GRCm39) |
M588K |
possibly damaging |
Het |
| Gm17019 |
A |
T |
5: 15,081,113 (GRCm39) |
Y109* |
probably null |
Het |
| Gm32742 |
T |
A |
9: 51,056,015 (GRCm39) |
N1255Y |
probably damaging |
Het |
| Gm5431 |
T |
A |
11: 48,779,600 (GRCm39) |
K441* |
probably null |
Het |
| Golga2 |
A |
G |
2: 32,196,079 (GRCm39) |
D898G |
|
Het |
| Gramd4 |
G |
A |
15: 85,975,525 (GRCm39) |
R39H |
probably benign |
Het |
| Gucy1a2 |
A |
G |
9: 3,634,553 (GRCm39) |
N199S |
probably damaging |
Het |
| Heyl |
G |
A |
4: 123,139,885 (GRCm39) |
R148H |
probably damaging |
Het |
| Ifi208 |
A |
T |
1: 173,523,400 (GRCm39) |
M557L |
probably benign |
Het |
| Igf2r |
A |
G |
17: 12,958,238 (GRCm39) |
V145A |
probably damaging |
Het |
| Ighv1-4 |
A |
T |
12: 114,450,879 (GRCm39) |
Y76* |
probably null |
Het |
| Ikzf4 |
T |
C |
10: 128,468,487 (GRCm39) |
D664G |
unknown |
Het |
| Il1a |
T |
A |
2: 129,146,715 (GRCm39) |
Y126F |
possibly damaging |
Het |
| Lmf2 |
C |
A |
15: 89,239,771 (GRCm39) |
|
probably benign |
Het |
| Lyst |
T |
C |
13: 13,808,827 (GRCm39) |
S166P |
probably damaging |
Het |
| Mgat5 |
A |
C |
1: 127,294,197 (GRCm39) |
T180P |
probably benign |
Het |
| Mical2 |
A |
C |
7: 111,870,589 (GRCm39) |
K26T |
possibly damaging |
Het |
| Mov10 |
G |
T |
3: 104,711,659 (GRCm39) |
Y209* |
probably null |
Het |
| Nol8 |
T |
C |
13: 49,815,475 (GRCm39) |
Y528H |
probably benign |
Het |
| Numa1 |
T |
A |
7: 101,641,869 (GRCm39) |
S106T |
possibly damaging |
Het |
| Or1e1d-ps1 |
A |
T |
11: 73,819,167 (GRCm39) |
E39V |
probably damaging |
Het |
| Or4c124 |
G |
A |
2: 89,156,474 (GRCm39) |
Q17* |
probably null |
Het |
| Or5b107 |
A |
G |
19: 13,142,396 (GRCm39) |
N6S |
probably damaging |
Het |
| Or7g27 |
A |
G |
9: 19,250,026 (GRCm39) |
H90R |
probably benign |
Het |
| Pcdhb14 |
A |
G |
18: 37,582,091 (GRCm39) |
N399S |
probably damaging |
Het |
| Plcl2 |
T |
A |
17: 50,918,032 (GRCm39) |
S944T |
probably benign |
Het |
| Pml |
A |
T |
9: 58,127,660 (GRCm39) |
I695N |
probably benign |
Het |
| Ppard |
G |
T |
17: 28,505,349 (GRCm39) |
R12L |
unknown |
Het |
| Ppip5k1 |
C |
T |
2: 121,158,125 (GRCm39) |
|
probably null |
Het |
| Ppp1r3g |
T |
C |
13: 36,152,621 (GRCm39) |
S14P |
probably benign |
Het |
| Pramel55 |
A |
G |
5: 95,951,623 (GRCm39) |
Y470C |
probably damaging |
Het |
| Prrc2b |
C |
A |
2: 32,103,764 (GRCm39) |
R1081S |
probably damaging |
Het |
| Rb1cc1 |
G |
A |
1: 6,333,073 (GRCm39) |
V1331I |
probably damaging |
Het |
| Rnd3 |
A |
T |
2: 51,022,413 (GRCm39) |
S210T |
probably benign |
Het |
| Scaf11 |
T |
C |
15: 96,312,764 (GRCm39) |
T1426A |
probably benign |
Het |
| Sin3b |
C |
T |
8: 73,460,034 (GRCm39) |
T207I |
possibly damaging |
Het |
| Slc26a7 |
A |
T |
4: 14,593,873 (GRCm39) |
Y81N |
probably damaging |
Het |
| Slc28a3 |
C |
T |
13: 58,724,581 (GRCm39) |
M224I |
probably benign |
Het |
| Slc30a1 |
T |
C |
1: 191,639,342 (GRCm39) |
I75T |
probably damaging |
Het |
| Slc6a21 |
T |
A |
7: 44,929,674 (GRCm39) |
|
probably benign |
Het |
| Slco2a1 |
T |
A |
9: 102,945,243 (GRCm39) |
L206Q |
probably damaging |
Het |
| Spata31d1e |
A |
G |
13: 59,890,828 (GRCm39) |
S331P |
probably benign |
Het |
| Sptbn1 |
A |
G |
11: 30,104,356 (GRCm39) |
V116A |
probably damaging |
Het |
| Syngap1 |
G |
A |
17: 27,181,095 (GRCm39) |
D1008N |
probably damaging |
Het |
| Syt11 |
T |
C |
3: 88,669,643 (GRCm39) |
D83G |
probably benign |
Het |
| Syt14 |
G |
A |
1: 192,584,131 (GRCm39) |
T428I |
probably damaging |
Het |
| Taf15 |
T |
A |
11: 83,395,085 (GRCm39) |
Y338* |
probably null |
Het |
| Tfap4 |
A |
T |
16: 4,365,183 (GRCm39) |
M253K |
possibly damaging |
Het |
| Tnr |
T |
C |
1: 159,713,680 (GRCm39) |
S703P |
possibly damaging |
Het |
| Trrap |
G |
A |
5: 144,767,830 (GRCm39) |
D2577N |
probably benign |
Het |
| Uqcc6 |
A |
T |
10: 82,458,588 (GRCm39) |
M21K |
probably benign |
Het |
| Wdr20 |
C |
T |
12: 110,759,597 (GRCm39) |
S161L |
possibly damaging |
Het |
| Zfp503 |
C |
A |
14: 22,037,418 (GRCm39) |
V62L |
probably benign |
Het |
|
| Other mutations in Rasgrp2 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01013:Rasgrp2
|
APN |
19 |
6,454,413 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03053:Rasgrp2
|
APN |
19 |
6,457,362 (GRCm39) |
splice site |
probably benign |
|
|
afar
|
UTSW |
19 |
6,453,595 (GRCm39) |
critical splice donor site |
probably null |
|
|
thither
|
UTSW |
19 |
6,454,757 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1593:Rasgrp2
|
UTSW |
19 |
6,453,490 (GRCm39) |
missense |
possibly damaging |
0.77 |
|
R1604:Rasgrp2
|
UTSW |
19 |
6,457,087 (GRCm39) |
missense |
possibly damaging |
0.62 |
|
R2016:Rasgrp2
|
UTSW |
19 |
6,463,195 (GRCm39) |
missense |
probably benign |
0.01 |
|
R2017:Rasgrp2
|
UTSW |
19 |
6,463,195 (GRCm39) |
missense |
probably benign |
0.01 |
|
R2119:Rasgrp2
|
UTSW |
19 |
6,454,425 (GRCm39) |
missense |
probably benign |
0.00 |
|
R2120:Rasgrp2
|
UTSW |
19 |
6,454,425 (GRCm39) |
missense |
probably benign |
0.00 |
|
R2122:Rasgrp2
|
UTSW |
19 |
6,454,425 (GRCm39) |
missense |
probably benign |
0.00 |
|
R2124:Rasgrp2
|
UTSW |
19 |
6,454,425 (GRCm39) |
missense |
probably benign |
0.00 |
|
R3879:Rasgrp2
|
UTSW |
19 |
6,463,920 (GRCm39) |
missense |
probably benign |
0.07 |
|
R4049:Rasgrp2
|
UTSW |
19 |
6,454,757 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4655:Rasgrp2
|
UTSW |
19 |
6,454,876 (GRCm39) |
intron |
probably benign |
|
|
R5250:Rasgrp2
|
UTSW |
19 |
6,454,343 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5320:Rasgrp2
|
UTSW |
19 |
6,458,864 (GRCm39) |
splice site |
probably null |
|
|
R5620:Rasgrp2
|
UTSW |
19 |
6,455,031 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5933:Rasgrp2
|
UTSW |
19 |
6,452,543 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6155:Rasgrp2
|
UTSW |
19 |
6,452,531 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6157:Rasgrp2
|
UTSW |
19 |
6,452,531 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6867:Rasgrp2
|
UTSW |
19 |
6,463,213 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7237:Rasgrp2
|
UTSW |
19 |
6,454,838 (GRCm39) |
missense |
possibly damaging |
0.79 |
|
R7575:Rasgrp2
|
UTSW |
19 |
6,454,397 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R7659:Rasgrp2
|
UTSW |
19 |
6,451,857 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R7744:Rasgrp2
|
UTSW |
19 |
6,455,031 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7960:Rasgrp2
|
UTSW |
19 |
6,464,839 (GRCm39) |
missense |
probably benign |
|
|
R7975:Rasgrp2
|
UTSW |
19 |
6,458,589 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8415:Rasgrp2
|
UTSW |
19 |
6,454,781 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8470:Rasgrp2
|
UTSW |
19 |
6,453,595 (GRCm39) |
critical splice donor site |
probably null |
|
|
R8745:Rasgrp2
|
UTSW |
19 |
6,463,949 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8853:Rasgrp2
|
UTSW |
19 |
6,464,855 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R8897:Rasgrp2
|
UTSW |
19 |
6,453,100 (GRCm39) |
missense |
probably benign |
0.15 |
|
R9108:Rasgrp2
|
UTSW |
19 |
6,458,890 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9725:Rasgrp2
|
UTSW |
19 |
6,463,907 (GRCm39) |
missense |
probably benign |
0.07 |
|
R9725:Rasgrp2
|
UTSW |
19 |
6,454,694 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- ACTGCTTAGGATGGTGGCTC -3'
(R):5'- ATTTGATGAAACCGCCCAAC -3'
Sequencing Primer
(F):5'- CTCAAGTCAGTTTGAGTGGCATGTC -3'
(R):5'- TTAGCCCTTCCTGGAATC -3'
|
| Posted On |
2022-01-20 |
Incidental Mutation