Incidental Mutation 'R1731:Myocd'
| ID |
199332 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Myocd
|
| Ensembl Gene |
ENSMUSG00000020542 |
| Gene Name |
myocardin |
| Synonyms |
Srfcp |
| MMRRC Submission |
039763-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R1731 (G1)
|
| Quality Score |
225 |
|
Status
|
Not validated
|
| Chromosome |
11 |
| Chromosomal Location |
65067387-65160815 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to A
at 65091714 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Asparagine to Isoleucine
at position 76
(N76I)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000098603
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000101042]
[ENSMUST00000102635]
[ENSMUST00000108695]
|
| AlphaFold |
Q8VIM5 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000101042
AA Change: N76I
PolyPhen 2
Score 0.304 (Sensitivity: 0.90; Specificity: 0.89)
|
| SMART Domains |
Protein: ENSMUSP00000098603
Gene: ENSMUSG00000020542
AA Change: N76I
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
19 |
32 |
N/A |
INTRINSIC |
|
low complexity region
|
119 |
132 |
N/A |
INTRINSIC |
|
SCOP:d1lsha3
|
140 |
221 |
4e-3 |
SMART |
|
SAP
|
252 |
286 |
1.29e-8 |
SMART |
|
low complexity region
|
326 |
343 |
N/A |
INTRINSIC |
|
low complexity region
|
371 |
383 |
N/A |
INTRINSIC |
|
coiled coil region
|
396 |
435 |
N/A |
INTRINSIC |
|
low complexity region
|
557 |
573 |
N/A |
INTRINSIC |
|
low complexity region
|
615 |
629 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000102635
AA Change: N204I
PolyPhen 2
Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)
|
| SMART Domains |
Protein: ENSMUSP00000099695
Gene: ENSMUSG00000020542
AA Change: N204I
| Domain | Start | End | E-Value | Type |
|---|
|
RPEL
|
18 |
43 |
4e-1 |
SMART |
|
RPEL
|
62 |
87 |
9.26e0 |
SMART |
|
RPEL
|
106 |
131 |
1.15e-6 |
SMART |
|
low complexity region
|
147 |
160 |
N/A |
INTRINSIC |
|
low complexity region
|
247 |
260 |
N/A |
INTRINSIC |
|
SCOP:d1lsha3
|
268 |
349 |
4e-3 |
SMART |
|
SAP
|
380 |
414 |
1.29e-8 |
SMART |
|
low complexity region
|
454 |
471 |
N/A |
INTRINSIC |
|
low complexity region
|
499 |
511 |
N/A |
INTRINSIC |
|
coiled coil region
|
524 |
563 |
N/A |
INTRINSIC |
|
low complexity region
|
695 |
709 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000108695
AA Change: N204I
PolyPhen 2
Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)
|
| SMART Domains |
Protein: ENSMUSP00000104335
Gene: ENSMUSG00000020542
AA Change: N204I
| Domain | Start | End | E-Value | Type |
|---|
|
RPEL
|
18 |
43 |
4e-1 |
SMART |
|
RPEL
|
62 |
87 |
9.26e0 |
SMART |
|
RPEL
|
106 |
131 |
1.15e-6 |
SMART |
|
low complexity region
|
147 |
160 |
N/A |
INTRINSIC |
|
low complexity region
|
247 |
260 |
N/A |
INTRINSIC |
|
SCOP:d1lsha3
|
268 |
349 |
5e-3 |
SMART |
|
SAP
|
380 |
414 |
1.29e-8 |
SMART |
|
low complexity region
|
454 |
471 |
N/A |
INTRINSIC |
|
low complexity region
|
499 |
511 |
N/A |
INTRINSIC |
|
coiled coil region
|
524 |
563 |
N/A |
INTRINSIC |
|
low complexity region
|
685 |
701 |
N/A |
INTRINSIC |
|
low complexity region
|
743 |
757 |
N/A |
INTRINSIC |
|
| Predicted Effect |
unknown
Transcript: ENSMUST00000144399
AA Change: N78I
|
| SMART Domains |
Protein: ENSMUSP00000115572
Gene: ENSMUSG00000020542
AA Change: N78I
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
22 |
35 |
N/A |
INTRINSIC |
|
low complexity region
|
122 |
135 |
N/A |
INTRINSIC |
|
low complexity region
|
160 |
195 |
N/A |
INTRINSIC |
|
| Coding Region Coverage |
- 1x: 97.5%
- 3x: 96.9%
- 10x: 95.3%
- 20x: 92.4%
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a nuclear protein, which is expressed in heart, aorta, and in smooth muscle cell-containing tissues. It functions as a transcriptional co-activator of serum response factor (SRF) and modulates expression of cardiac and smooth muscle-specific SRF-target genes, and thus may play a crucial role in cardiogenesis and differentiation of the smooth muscle cell lineage. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]
PHENOTYPE: Mice homozygous for a null mutation exhibit embryonic lethality and fail to form vascular smooth muscle. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 68 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Adam7 |
T |
A |
14: 68,762,805 (GRCm39) |
Y140F |
probably damaging |
Het |
| Adgrl4 |
T |
G |
3: 151,246,623 (GRCm39) |
I641S |
possibly damaging |
Het |
| Aqp9 |
A |
G |
9: 71,030,250 (GRCm39) |
I205T |
possibly damaging |
Het |
| Arap3 |
C |
T |
18: 38,122,965 (GRCm39) |
V512I |
probably benign |
Het |
| Atf2 |
C |
T |
2: 73,675,853 (GRCm39) |
G123E |
probably damaging |
Het |
| Baz1a |
T |
C |
12: 54,965,330 (GRCm39) |
D708G |
possibly damaging |
Het |
| Calcrl |
A |
G |
2: 84,175,512 (GRCm39) |
|
probably null |
Het |
| Capzb |
T |
A |
4: 139,007,341 (GRCm39) |
W110R |
probably damaging |
Het |
| Casp8ap2 |
A |
T |
4: 32,641,442 (GRCm39) |
N832I |
possibly damaging |
Het |
| Cecr2 |
T |
A |
6: 120,735,141 (GRCm39) |
H764Q |
possibly damaging |
Het |
| Cep131 |
T |
C |
11: 119,967,742 (GRCm39) |
|
probably null |
Het |
| Ces2e |
T |
C |
8: 105,656,208 (GRCm39) |
V173A |
probably damaging |
Het |
| Clstn3 |
T |
C |
6: 124,408,591 (GRCm39) |
D944G |
probably benign |
Het |
| Cyb5rl |
C |
A |
4: 106,938,110 (GRCm39) |
A189E |
probably damaging |
Het |
| Cyp2c40 |
A |
G |
19: 39,801,133 (GRCm39) |
S41P |
probably damaging |
Het |
| Dscam |
A |
G |
16: 96,621,076 (GRCm39) |
L544P |
probably damaging |
Het |
| Epha2 |
A |
G |
4: 141,049,063 (GRCm39) |
K640E |
possibly damaging |
Het |
| Erap1 |
T |
A |
13: 74,814,241 (GRCm39) |
C8* |
probably null |
Het |
| Fat3 |
A |
G |
9: 15,907,233 (GRCm39) |
V2923A |
probably benign |
Het |
| Fat4 |
A |
T |
3: 38,945,459 (GRCm39) |
I1451F |
probably damaging |
Het |
| Fcsk |
A |
T |
8: 111,621,455 (GRCm39) |
I163N |
probably damaging |
Het |
| Fzd6 |
G |
A |
15: 38,894,722 (GRCm39) |
G296D |
probably damaging |
Het |
| Gm3486 |
T |
A |
14: 41,206,492 (GRCm39) |
M194L |
probably benign |
Het |
| Gm5592 |
C |
T |
7: 40,937,837 (GRCm39) |
A373V |
probably damaging |
Het |
| Hectd3 |
T |
A |
4: 116,853,652 (GRCm39) |
|
probably null |
Het |
| Hira |
T |
A |
16: 18,751,764 (GRCm39) |
V521E |
probably benign |
Het |
| Hsd17b6 |
A |
G |
10: 127,830,348 (GRCm39) |
L141S |
possibly damaging |
Het |
| Idua |
A |
G |
5: 108,829,538 (GRCm39) |
D467G |
probably benign |
Het |
| Ikzf4 |
G |
A |
10: 128,470,401 (GRCm39) |
P373L |
probably benign |
Het |
| Kcng1 |
T |
C |
2: 168,110,609 (GRCm39) |
E185G |
probably benign |
Het |
| Krt84 |
G |
A |
15: 101,434,398 (GRCm39) |
S523F |
possibly damaging |
Het |
| Lpcat4 |
T |
C |
2: 112,074,188 (GRCm39) |
L250P |
probably damaging |
Het |
| Lrrc49 |
A |
G |
9: 60,528,914 (GRCm39) |
Y281H |
probably damaging |
Het |
| Mta2 |
C |
A |
19: 8,925,088 (GRCm39) |
|
probably null |
Het |
| Myo15b |
T |
C |
11: 115,782,386 (GRCm39) |
I372T |
possibly damaging |
Het |
| Nav2 |
T |
A |
7: 49,197,922 (GRCm39) |
Y1123N |
probably damaging |
Het |
| Otogl |
A |
T |
10: 107,652,972 (GRCm39) |
C1127S |
probably damaging |
Het |
| Pcdhb8 |
A |
G |
18: 37,488,891 (GRCm39) |
K190E |
probably damaging |
Het |
| Pcnx1 |
A |
G |
12: 82,037,478 (GRCm39) |
H1918R |
probably damaging |
Het |
| Pde2a |
T |
A |
7: 101,150,867 (GRCm39) |
Y272N |
probably damaging |
Het |
| Phldb3 |
T |
C |
7: 24,318,660 (GRCm39) |
V313A |
probably benign |
Het |
| Plch2 |
C |
T |
4: 155,091,451 (GRCm39) |
V116I |
possibly damaging |
Het |
| Plod2 |
G |
A |
9: 92,466,657 (GRCm39) |
|
probably null |
Het |
| Ppfibp2 |
T |
C |
7: 107,339,796 (GRCm39) |
Y730H |
probably damaging |
Het |
| Ptprh |
T |
C |
7: 4,604,912 (GRCm39) |
E44G |
probably benign |
Het |
| Rab11fip1 |
T |
C |
8: 27,642,438 (GRCm39) |
E787G |
probably damaging |
Het |
| Rabep2 |
T |
A |
7: 126,043,444 (GRCm39) |
L448Q |
probably damaging |
Het |
| Rbfox3 |
A |
G |
11: 118,387,762 (GRCm39) |
|
probably null |
Het |
| Rgma |
T |
C |
7: 73,059,160 (GRCm39) |
V88A |
probably damaging |
Het |
| Rif1 |
GCCACCA |
GCCA |
2: 52,000,336 (GRCm39) |
|
probably benign |
Het |
| Rnf125 |
A |
G |
18: 21,110,873 (GRCm39) |
T44A |
probably benign |
Het |
| Rusc2 |
G |
T |
4: 43,426,046 (GRCm39) |
A1384S |
probably benign |
Het |
| Selp |
T |
A |
1: 163,969,009 (GRCm39) |
C536* |
probably null |
Het |
| Serpinb3c |
G |
A |
1: 107,199,504 (GRCm39) |
T339I |
probably damaging |
Het |
| Slc4a5 |
C |
T |
6: 83,273,617 (GRCm39) |
R986C |
probably damaging |
Het |
| Slc8b1 |
T |
C |
5: 120,659,180 (GRCm39) |
I208T |
probably benign |
Het |
| Sp3 |
G |
A |
2: 72,776,999 (GRCm39) |
H533Y |
probably damaging |
Het |
| Speer1e |
T |
A |
5: 11,233,080 (GRCm39) |
N14K |
probably damaging |
Het |
| Tiam2 |
A |
G |
17: 3,568,698 (GRCm39) |
R1615G |
probably damaging |
Het |
| Tie1 |
T |
C |
4: 118,333,460 (GRCm39) |
E802G |
probably damaging |
Het |
| Tinagl1 |
A |
G |
4: 130,061,842 (GRCm39) |
V164A |
probably benign |
Het |
| Vmn1r68 |
A |
G |
7: 10,261,802 (GRCm39) |
Y99H |
probably damaging |
Het |
| Vmn1r87 |
T |
A |
7: 12,865,703 (GRCm39) |
T195S |
possibly damaging |
Het |
| Vmn2r56 |
T |
C |
7: 12,466,972 (GRCm39) |
T21A |
probably benign |
Het |
| Zfp108 |
C |
A |
7: 23,957,964 (GRCm39) |
H34Q |
possibly damaging |
Het |
| Zfp267 |
T |
A |
3: 36,218,620 (GRCm39) |
F214L |
probably benign |
Het |
| Zfp456 |
C |
T |
13: 67,514,674 (GRCm39) |
S344N |
probably benign |
Het |
| Zscan22 |
T |
C |
7: 12,640,907 (GRCm39) |
C384R |
probably damaging |
Het |
|
| Other mutations in Myocd |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00092:Myocd
|
APN |
11 |
65,071,770 (GRCm39) |
critical splice acceptor site |
probably null |
|
|
IGL00481:Myocd
|
APN |
11 |
65,077,980 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL00857:Myocd
|
APN |
11 |
65,069,662 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
IGL01012:Myocd
|
APN |
11 |
65,075,451 (GRCm39) |
missense |
possibly damaging |
0.51 |
|
IGL01570:Myocd
|
APN |
11 |
65,091,633 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL01865:Myocd
|
APN |
11 |
65,091,723 (GRCm39) |
missense |
probably benign |
0.30 |
|
IGL01938:Myocd
|
APN |
11 |
65,077,914 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02324:Myocd
|
APN |
11 |
65,069,484 (GRCm39) |
missense |
probably benign |
0.01 |
|
IGL02598:Myocd
|
APN |
11 |
65,074,296 (GRCm39) |
missense |
probably benign |
0.31 |
|
IGL02886:Myocd
|
APN |
11 |
65,069,569 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL03008:Myocd
|
APN |
11 |
65,078,392 (GRCm39) |
missense |
probably damaging |
0.98 |
|
IGL03034:Myocd
|
APN |
11 |
65,109,511 (GRCm39) |
missense |
probably benign |
0.00 |
|
harvey
|
UTSW |
11 |
65,069,856 (GRCm39) |
splice site |
probably null |
|
|
irma
|
UTSW |
11 |
65,087,220 (GRCm39) |
missense |
probably benign |
0.02 |
|
myra
|
UTSW |
11 |
65,069,685 (GRCm39) |
missense |
probably benign |
0.10 |
|
Nate
|
UTSW |
11 |
65,123,914 (GRCm39) |
splice site |
probably null |
|
|
R0838_Myocd_053
|
UTSW |
11 |
65,069,758 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0078:Myocd
|
UTSW |
11 |
65,078,290 (GRCm39) |
missense |
possibly damaging |
0.96 |
|
R0097:Myocd
|
UTSW |
11 |
65,069,840 (GRCm39) |
missense |
possibly damaging |
0.67 |
|
R0097:Myocd
|
UTSW |
11 |
65,069,840 (GRCm39) |
missense |
possibly damaging |
0.67 |
|
R0234:Myocd
|
UTSW |
11 |
65,078,066 (GRCm39) |
missense |
probably benign |
0.01 |
|
R0234:Myocd
|
UTSW |
11 |
65,078,066 (GRCm39) |
missense |
probably benign |
0.01 |
|
R0453:Myocd
|
UTSW |
11 |
65,087,051 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0523:Myocd
|
UTSW |
11 |
65,071,728 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0838:Myocd
|
UTSW |
11 |
65,069,758 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0899:Myocd
|
UTSW |
11 |
65,086,018 (GRCm39) |
missense |
possibly damaging |
0.50 |
|
R1167:Myocd
|
UTSW |
11 |
65,087,203 (GRCm39) |
missense |
possibly damaging |
0.77 |
|
R1472:Myocd
|
UTSW |
11 |
65,078,330 (GRCm39) |
missense |
probably benign |
0.01 |
|
R1508:Myocd
|
UTSW |
11 |
65,075,342 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R1620:Myocd
|
UTSW |
11 |
65,087,220 (GRCm39) |
missense |
probably benign |
0.02 |
|
R1630:Myocd
|
UTSW |
11 |
65,087,220 (GRCm39) |
missense |
probably benign |
0.02 |
|
R1740:Myocd
|
UTSW |
11 |
65,109,347 (GRCm39) |
splice site |
probably benign |
|
|
R1769:Myocd
|
UTSW |
11 |
65,069,527 (GRCm39) |
missense |
probably benign |
0.01 |
|
R1823:Myocd
|
UTSW |
11 |
65,069,496 (GRCm39) |
missense |
probably benign |
0.00 |
|
R1968:Myocd
|
UTSW |
11 |
65,091,733 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1997:Myocd
|
UTSW |
11 |
65,095,147 (GRCm39) |
nonsense |
probably null |
|
|
R2018:Myocd
|
UTSW |
11 |
65,077,854 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2105:Myocd
|
UTSW |
11 |
65,109,484 (GRCm39) |
nonsense |
probably null |
|
|
R2314:Myocd
|
UTSW |
11 |
65,091,633 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4330:Myocd
|
UTSW |
11 |
65,114,590 (GRCm39) |
missense |
probably benign |
0.12 |
|
R4331:Myocd
|
UTSW |
11 |
65,114,590 (GRCm39) |
missense |
probably benign |
0.12 |
|
R4603:Myocd
|
UTSW |
11 |
65,078,571 (GRCm39) |
missense |
possibly damaging |
0.82 |
|
R4619:Myocd
|
UTSW |
11 |
65,069,254 (GRCm39) |
utr 3 prime |
probably benign |
|
|
R4631:Myocd
|
UTSW |
11 |
65,069,685 (GRCm39) |
missense |
probably benign |
0.10 |
|
R4865:Myocd
|
UTSW |
11 |
65,069,856 (GRCm39) |
splice site |
probably null |
|
|
R4974:Myocd
|
UTSW |
11 |
65,074,299 (GRCm39) |
missense |
possibly damaging |
0.78 |
|
R4976:Myocd
|
UTSW |
11 |
65,112,876 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5478:Myocd
|
UTSW |
11 |
65,123,914 (GRCm39) |
splice site |
probably null |
|
|
R5499:Myocd
|
UTSW |
11 |
65,069,575 (GRCm39) |
missense |
possibly damaging |
0.62 |
|
R6052:Myocd
|
UTSW |
11 |
65,087,082 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6356:Myocd
|
UTSW |
11 |
65,109,396 (GRCm39) |
splice site |
probably null |
|
|
R7144:Myocd
|
UTSW |
11 |
65,109,474 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7261:Myocd
|
UTSW |
11 |
65,078,422 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R7354:Myocd
|
UTSW |
11 |
65,078,319 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7461:Myocd
|
UTSW |
11 |
65,109,429 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7613:Myocd
|
UTSW |
11 |
65,109,429 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7718:Myocd
|
UTSW |
11 |
65,109,452 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7956:Myocd
|
UTSW |
11 |
65,160,494 (GRCm39) |
missense |
possibly damaging |
0.50 |
|
R8345:Myocd
|
UTSW |
11 |
65,077,958 (GRCm39) |
nonsense |
probably null |
|
|
R8975:Myocd
|
UTSW |
11 |
65,069,287 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9051:Myocd
|
UTSW |
11 |
65,077,795 (GRCm39) |
missense |
probably benign |
|
|
R9400:Myocd
|
UTSW |
11 |
65,086,934 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9469:Myocd
|
UTSW |
11 |
65,087,220 (GRCm39) |
missense |
probably benign |
0.02 |
|
R9565:Myocd
|
UTSW |
11 |
65,078,209 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9567:Myocd
|
UTSW |
11 |
65,078,410 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9585:Myocd
|
UTSW |
11 |
65,095,192 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9710:Myocd
|
UTSW |
11 |
65,087,167 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9768:Myocd
|
UTSW |
11 |
65,078,217 (GRCm39) |
missense |
probably damaging |
1.00 |
|
X0057:Myocd
|
UTSW |
11 |
65,074,271 (GRCm39) |
missense |
possibly damaging |
0.87 |
|
Z1186:Myocd
|
UTSW |
11 |
65,075,418 (GRCm39) |
missense |
probably benign |
|
|
Z1187:Myocd
|
UTSW |
11 |
65,075,418 (GRCm39) |
missense |
probably benign |
|
|
Z1188:Myocd
|
UTSW |
11 |
65,075,418 (GRCm39) |
missense |
probably benign |
|
|
Z1189:Myocd
|
UTSW |
11 |
65,075,418 (GRCm39) |
missense |
probably benign |
|
|
Z1190:Myocd
|
UTSW |
11 |
65,075,418 (GRCm39) |
missense |
probably benign |
|
|
Z1191:Myocd
|
UTSW |
11 |
65,075,418 (GRCm39) |
missense |
probably benign |
|
|
Z1192:Myocd
|
UTSW |
11 |
65,075,418 (GRCm39) |
missense |
probably benign |
|
|
| Predicted Primers |
PCR Primer
(F):5'- AAGCTCTGCTTCGCATGGCTTC -3'
(R):5'- GGTGACCAGATGTCCCAATTTGCTC -3'
Sequencing Primer
(F):5'- TTCAGGGAGCCTAGCCTCAG -3'
(R):5'- TGTCCCAATTTGCTCAGATCAAAC -3'
|
| Posted On |
2014-05-23 |
Incidental Mutation