Incidental Mutation 'V7581:Trps1'
| ID |
152578 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Trps1
|
| Ensembl Gene |
ENSMUSG00000038679 |
| Gene Name |
transcriptional repressor GATA binding 1 |
| Synonyms |
D15Ertd586e, trichorhinophalangeal syndrome I (human) |
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
V7581 ()
of strain
stinger
|
| Quality Score |
225 |
|
Status
|
Not validated
|
| Chromosome |
15 |
| Chromosomal Location |
50518148-50753859 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 50694973 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Lysine to Glutamic Acid
at position 150
(K150E)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000139063
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000077935]
[ENSMUST00000165201]
[ENSMUST00000183421]
[ENSMUST00000183757]
[ENSMUST00000183997]
[ENSMUST00000184458]
[ENSMUST00000184885]
|
| AlphaFold |
no structure available at present |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000077935
AA Change: K437E
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000077089
Gene: ENSMUSG00000038679
AA Change: K437E
| Domain | Start | End | E-Value | Type |
|---|
|
ZnF_C2H2
|
222 |
247 |
1.41e0 |
SMART |
|
ZnF_C2H2
|
333 |
358 |
4.45e0 |
SMART |
|
ZnF_C2H2
|
434 |
459 |
1.31e2 |
SMART |
|
ZnF_C2H2
|
523 |
554 |
1.93e2 |
SMART |
|
low complexity region
|
597 |
602 |
N/A |
INTRINSIC |
|
ZnF_C2H2
|
614 |
637 |
8.67e-1 |
SMART |
|
ZnF_C2H2
|
666 |
689 |
2.29e0 |
SMART |
|
ZnF_C2H2
|
692 |
715 |
8.22e-2 |
SMART |
|
low complexity region
|
766 |
779 |
N/A |
INTRINSIC |
|
ZnF_GATA
|
890 |
940 |
3.95e-16 |
SMART |
|
low complexity region
|
1050 |
1062 |
N/A |
INTRINSIC |
|
ZnF_C2H2
|
1215 |
1237 |
4.34e0 |
SMART |
|
ZnF_C2H2
|
1243 |
1267 |
5.72e-1 |
SMART |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000165201
AA Change: K437E
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000129779
Gene: ENSMUSG00000038679
AA Change: K437E
| Domain | Start | End | E-Value | Type |
|---|
|
ZnF_C2H2
|
222 |
247 |
1.41e0 |
SMART |
|
ZnF_C2H2
|
333 |
358 |
4.45e0 |
SMART |
|
ZnF_C2H2
|
434 |
459 |
1.31e2 |
SMART |
|
ZnF_C2H2
|
523 |
554 |
1.93e2 |
SMART |
|
low complexity region
|
597 |
602 |
N/A |
INTRINSIC |
|
ZnF_C2H2
|
614 |
637 |
8.67e-1 |
SMART |
|
ZnF_C2H2
|
666 |
689 |
2.29e0 |
SMART |
|
ZnF_C2H2
|
692 |
715 |
8.22e-2 |
SMART |
|
low complexity region
|
766 |
779 |
N/A |
INTRINSIC |
|
ZnF_GATA
|
890 |
940 |
3.95e-16 |
SMART |
|
low complexity region
|
1050 |
1062 |
N/A |
INTRINSIC |
|
ZnF_C2H2
|
1215 |
1237 |
4.34e0 |
SMART |
|
ZnF_C2H2
|
1243 |
1267 |
5.72e-1 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000183421
|
| SMART Domains |
Protein: ENSMUSP00000138835
Gene: ENSMUSG00000038679
| Domain | Start | End | E-Value | Type |
|---|
|
ZnF_C2H2
|
26 |
49 |
8.22e-2 |
SMART |
|
low complexity region
|
100 |
113 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000183757
AA Change: K441E
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000139017
Gene: ENSMUSG00000038679
AA Change: K441E
| Domain | Start | End | E-Value | Type |
|---|
|
ZnF_C2H2
|
226 |
251 |
1.41e0 |
SMART |
|
ZnF_C2H2
|
337 |
362 |
4.45e0 |
SMART |
|
ZnF_C2H2
|
438 |
463 |
1.31e2 |
SMART |
|
ZnF_C2H2
|
527 |
558 |
1.93e2 |
SMART |
|
low complexity region
|
601 |
606 |
N/A |
INTRINSIC |
|
ZnF_C2H2
|
618 |
641 |
8.67e-1 |
SMART |
|
ZnF_C2H2
|
670 |
693 |
2.29e0 |
SMART |
|
ZnF_C2H2
|
696 |
719 |
8.22e-2 |
SMART |
|
low complexity region
|
770 |
783 |
N/A |
INTRINSIC |
|
ZnF_GATA
|
894 |
944 |
3.95e-16 |
SMART |
|
low complexity region
|
1054 |
1066 |
N/A |
INTRINSIC |
|
ZnF_C2H2
|
1219 |
1241 |
4.34e0 |
SMART |
|
ZnF_C2H2
|
1247 |
1271 |
5.72e-1 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000183997
|
| SMART Domains |
Protein: ENSMUSP00000139115
Gene: ENSMUSG00000038679
| Domain | Start | End | E-Value | Type |
|---|
|
ZnF_C2H2
|
226 |
251 |
1.41e0 |
SMART |
|
ZnF_C2H2
|
337 |
362 |
4.45e0 |
SMART |
|
ZnF_C2H2
|
470 |
493 |
2.29e0 |
SMART |
|
ZnF_C2H2
|
496 |
519 |
8.22e-2 |
SMART |
|
low complexity region
|
570 |
583 |
N/A |
INTRINSIC |
|
ZnF_GATA
|
705 |
755 |
3.95e-16 |
SMART |
|
low complexity region
|
865 |
877 |
N/A |
INTRINSIC |
|
ZnF_C2H2
|
1030 |
1052 |
4.34e0 |
SMART |
|
ZnF_C2H2
|
1058 |
1082 |
5.72e-1 |
SMART |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000184458
AA Change: K150E
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000139063
Gene: ENSMUSG00000038679
AA Change: K150E
| Domain | Start | End | E-Value | Type |
|---|
|
ZnF_C2H2
|
46 |
71 |
4.45e0 |
SMART |
|
ZnF_C2H2
|
147 |
172 |
1.31e2 |
SMART |
|
ZnF_C2H2
|
236 |
267 |
1.93e2 |
SMART |
|
low complexity region
|
310 |
315 |
N/A |
INTRINSIC |
|
ZnF_C2H2
|
327 |
350 |
8.67e-1 |
SMART |
|
ZnF_C2H2
|
379 |
402 |
2.29e0 |
SMART |
|
ZnF_C2H2
|
405 |
428 |
8.22e-2 |
SMART |
|
low complexity region
|
479 |
492 |
N/A |
INTRINSIC |
|
ZnF_GATA
|
603 |
653 |
3.95e-16 |
SMART |
|
low complexity region
|
763 |
775 |
N/A |
INTRINSIC |
|
ZnF_C2H2
|
928 |
950 |
4.34e0 |
SMART |
|
ZnF_C2H2
|
956 |
980 |
5.72e-1 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000184885
|
| SMART Domains |
Protein: ENSMUSP00000138905
Gene: ENSMUSG00000038679
| Domain | Start | End | E-Value | Type |
|---|
|
ZnF_C2H2
|
176 |
201 |
1.41e0 |
SMART |
|
ZnF_C2H2
|
287 |
312 |
4.45e0 |
SMART |
|
ZnF_C2H2
|
420 |
443 |
2.29e0 |
SMART |
|
ZnF_C2H2
|
446 |
469 |
8.22e-2 |
SMART |
|
low complexity region
|
520 |
533 |
N/A |
INTRINSIC |
|
ZnF_GATA
|
644 |
694 |
3.95e-16 |
SMART |
|
low complexity region
|
804 |
816 |
N/A |
INTRINSIC |
|
ZnF_C2H2
|
969 |
991 |
4.34e0 |
SMART |
|
ZnF_C2H2
|
997 |
1021 |
5.72e-1 |
SMART |
|
| Meta Mutation Damage Score |
0.4292 |
| Coding Region Coverage |
- 1x: 99.0%
- 3x: 98.2%
- 10x: 95.7%
- 20x: 90.5%
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a transcription factor that represses GATA-regulated genes and binds to a dynein light chain protein. Binding of the encoded protein to the dynein light chain protein affects binding to GATA consensus sequences and suppresses its transcriptional activity. Defects in this gene are a cause of tricho-rhino-phalangeal syndrome (TRPS) types I-III. [provided by RefSeq, Jul 2008]
PHENOTYPE: Newborn mice homozygous for a knock-out allele exhibit craniofacial and hair anomalies and die of respiratory failure due to thoracic spine and rib defects. Mice homozygous for a reporter allele show additional defects in chondrocyte proliferation and apoptosis as well as reduced nephron formation. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 46 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 9530002B09Rik |
A |
T |
4: 122,595,050 (GRCm39) |
H102L |
possibly damaging |
Het |
| Abcb10 |
GGCCATCG |
GG |
8: 124,696,500 (GRCm39) |
|
probably benign |
Het |
| Atp6v1h |
A |
G |
1: 5,194,666 (GRCm39) |
T282A |
possibly damaging |
Het |
| Clasp1 |
G |
A |
1: 118,509,078 (GRCm39) |
R1027Q |
probably damaging |
Het |
| D630003M21Rik |
T |
C |
2: 158,042,931 (GRCm39) |
T870A |
probably benign |
Het |
| Dnah12 |
T |
A |
14: 26,495,050 (GRCm39) |
N1369K |
possibly damaging |
Het |
| Dnajc22 |
T |
A |
15: 98,999,363 (GRCm39) |
Y183N |
probably damaging |
Het |
| Dpyd |
C |
T |
3: 118,690,775 (GRCm39) |
Q295* |
probably null |
Het |
| Dync2i1 |
A |
C |
12: 116,175,460 (GRCm39) |
S906A |
possibly damaging |
Het |
| Erv3 |
T |
C |
2: 131,697,846 (GRCm39) |
H171R |
possibly damaging |
Het |
| Fam221b |
T |
C |
4: 43,665,865 (GRCm39) |
T249A |
probably benign |
Het |
| Fcgr1 |
T |
C |
3: 96,191,592 (GRCm39) |
*405W |
probably null |
Het |
| Glrx3 |
A |
G |
7: 137,060,882 (GRCm39) |
H172R |
probably benign |
Het |
| Gm10770 |
T |
A |
2: 150,021,404 (GRCm39) |
K38* |
probably null |
Het |
| Gm4787 |
G |
A |
12: 81,424,341 (GRCm39) |
Q606* |
probably null |
Het |
| Hira |
G |
A |
16: 18,713,571 (GRCm39) |
A29T |
probably damaging |
Het |
| Hnrnpab |
A |
T |
11: 51,493,451 (GRCm39) |
N252K |
probably benign |
Het |
| Izumo4 |
A |
T |
10: 80,539,725 (GRCm39) |
T155S |
probably benign |
Het |
| Kcnb2 |
A |
G |
1: 15,780,315 (GRCm39) |
I396V |
probably benign |
Het |
| Klc1 |
A |
T |
12: 111,741,006 (GRCm39) |
I161F |
probably benign |
Het |
| Lpar5 |
C |
A |
6: 125,058,690 (GRCm39) |
A137E |
possibly damaging |
Het |
| Lrp4 |
C |
T |
2: 91,318,863 (GRCm39) |
S900L |
possibly damaging |
Het |
| Muc6 |
T |
G |
7: 141,233,880 (GRCm39) |
E808A |
probably benign |
Het |
| Or10j7 |
G |
T |
1: 173,011,531 (GRCm39) |
L157I |
probably benign |
Het |
| Or5p57 |
G |
T |
7: 107,665,885 (GRCm39) |
T40K |
probably benign |
Het |
| Otop3 |
T |
A |
11: 115,235,664 (GRCm39) |
L432Q |
probably damaging |
Het |
| Papln |
C |
T |
12: 83,825,608 (GRCm39) |
R608C |
possibly damaging |
Het |
| Pelp1 |
T |
A |
11: 70,288,976 (GRCm39) |
T257S |
probably damaging |
Het |
| Pik3cd |
A |
C |
4: 149,741,776 (GRCm39) |
L390R |
probably damaging |
Het |
| Ppwd1 |
A |
G |
13: 104,356,745 (GRCm39) |
Y257H |
probably damaging |
Het |
| Prkcb |
G |
T |
7: 122,127,699 (GRCm39) |
W274C |
probably damaging |
Het |
| Rbbp8nl |
T |
A |
2: 179,920,001 (GRCm39) |
T558S |
probably benign |
Het |
| Recql4 |
T |
C |
15: 76,590,369 (GRCm39) |
D705G |
possibly damaging |
Het |
| Slc30a4 |
T |
A |
2: 122,531,458 (GRCm39) |
M136L |
probably benign |
Het |
| Slc5a6 |
C |
T |
5: 31,199,957 (GRCm39) |
|
probably null |
Het |
| Spaca1 |
T |
C |
4: 34,039,311 (GRCm39) |
E192G |
probably damaging |
Het |
| Spata31 |
C |
A |
13: 65,069,462 (GRCm39) |
P537T |
probably benign |
Het |
| Tmc3 |
T |
C |
7: 83,271,713 (GRCm39) |
V955A |
probably benign |
Het |
| Tnrc6c |
G |
A |
11: 117,614,152 (GRCm39) |
R770H |
probably damaging |
Het |
| Toe1 |
A |
T |
4: 116,663,308 (GRCm39) |
N56K |
probably damaging |
Het |
| Tprkb |
A |
G |
6: 85,905,764 (GRCm39) |
K150E |
probably damaging |
Het |
| Tspyl3 |
A |
G |
2: 153,066,980 (GRCm39) |
V86A |
probably benign |
Het |
| Vmn2r68 |
C |
T |
7: 84,871,088 (GRCm39) |
V732I |
probably benign |
Het |
| Zfp292 |
C |
T |
4: 34,806,783 (GRCm39) |
C2087Y |
possibly damaging |
Het |
| Zfp933 |
G |
A |
4: 147,910,927 (GRCm39) |
A223V |
probably damaging |
Het |
| Zmynd8 |
G |
A |
2: 165,654,314 (GRCm39) |
R724* |
probably null |
Het |
|
| Other mutations in Trps1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00420:Trps1
|
APN |
15 |
50,710,266 (GRCm39) |
missense |
probably benign |
0.07 |
|
IGL00497:Trps1
|
APN |
15 |
50,524,703 (GRCm39) |
missense |
possibly damaging |
0.91 |
|
IGL00558:Trps1
|
APN |
15 |
50,524,481 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01325:Trps1
|
APN |
15 |
50,710,210 (GRCm39) |
missense |
probably benign |
0.40 |
|
IGL02132:Trps1
|
APN |
15 |
50,685,674 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02631:Trps1
|
APN |
15 |
50,709,417 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02740:Trps1
|
APN |
15 |
50,709,935 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02821:Trps1
|
APN |
15 |
50,524,273 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03096:Trps1
|
APN |
15 |
50,709,875 (GRCm39) |
missense |
probably benign |
|
|
F5770:Trps1
|
UTSW |
15 |
50,694,973 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0050:Trps1
|
UTSW |
15 |
50,628,921 (GRCm39) |
missense |
probably benign |
0.18 |
|
R0244:Trps1
|
UTSW |
15 |
50,528,139 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0377:Trps1
|
UTSW |
15 |
50,695,174 (GRCm39) |
nonsense |
probably null |
|
|
R0599:Trps1
|
UTSW |
15 |
50,695,256 (GRCm39) |
nonsense |
probably null |
|
|
R0848:Trps1
|
UTSW |
15 |
50,524,945 (GRCm39) |
missense |
possibly damaging |
0.54 |
|
R1744:Trps1
|
UTSW |
15 |
50,524,609 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1830:Trps1
|
UTSW |
15 |
50,524,532 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R2083:Trps1
|
UTSW |
15 |
50,685,701 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2167:Trps1
|
UTSW |
15 |
50,695,126 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R2267:Trps1
|
UTSW |
15 |
50,685,794 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2314:Trps1
|
UTSW |
15 |
50,524,742 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3735:Trps1
|
UTSW |
15 |
50,709,456 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R4133:Trps1
|
UTSW |
15 |
50,694,783 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4223:Trps1
|
UTSW |
15 |
50,710,044 (GRCm39) |
missense |
probably benign |
|
|
R4280:Trps1
|
UTSW |
15 |
50,709,478 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4566:Trps1
|
UTSW |
15 |
50,695,074 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4810:Trps1
|
UTSW |
15 |
50,685,692 (GRCm39) |
missense |
probably benign |
0.14 |
|
R4828:Trps1
|
UTSW |
15 |
50,524,073 (GRCm39) |
makesense |
probably null |
|
|
R4838:Trps1
|
UTSW |
15 |
50,690,712 (GRCm39) |
missense |
probably benign |
0.05 |
|
R4852:Trps1
|
UTSW |
15 |
50,709,705 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5001:Trps1
|
UTSW |
15 |
50,524,703 (GRCm39) |
missense |
possibly damaging |
0.91 |
|
R5311:Trps1
|
UTSW |
15 |
50,528,156 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5463:Trps1
|
UTSW |
15 |
50,695,286 (GRCm39) |
nonsense |
probably null |
|
|
R5677:Trps1
|
UTSW |
15 |
50,709,504 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5691:Trps1
|
UTSW |
15 |
50,690,700 (GRCm39) |
missense |
probably benign |
|
|
R6432:Trps1
|
UTSW |
15 |
50,694,793 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R6528:Trps1
|
UTSW |
15 |
50,685,823 (GRCm39) |
missense |
probably benign |
0.01 |
|
R6594:Trps1
|
UTSW |
15 |
50,694,351 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R6827:Trps1
|
UTSW |
15 |
50,685,959 (GRCm39) |
missense |
probably benign |
0.14 |
|
R6862:Trps1
|
UTSW |
15 |
50,695,001 (GRCm39) |
critical splice donor site |
probably null |
|
|
R6912:Trps1
|
UTSW |
15 |
50,685,694 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
R7151:Trps1
|
UTSW |
15 |
50,685,793 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R7846:Trps1
|
UTSW |
15 |
50,695,273 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R7857:Trps1
|
UTSW |
15 |
50,524,401 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7986:Trps1
|
UTSW |
15 |
50,753,019 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7986:Trps1
|
UTSW |
15 |
50,525,132 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8744:Trps1
|
UTSW |
15 |
50,524,642 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8838:Trps1
|
UTSW |
15 |
50,753,007 (GRCm39) |
missense |
probably benign |
0.01 |
|
R8859:Trps1
|
UTSW |
15 |
50,685,769 (GRCm39) |
missense |
possibly damaging |
0.77 |
|
R8935:Trps1
|
UTSW |
15 |
50,752,344 (GRCm39) |
nonsense |
probably null |
|
|
R9044:Trps1
|
UTSW |
15 |
50,686,003 (GRCm39) |
missense |
probably benign |
0.11 |
|
R9142:Trps1
|
UTSW |
15 |
50,524,658 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R9211:Trps1
|
UTSW |
15 |
50,694,840 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9283:Trps1
|
UTSW |
15 |
50,694,447 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9363:Trps1
|
UTSW |
15 |
50,524,676 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9402:Trps1
|
UTSW |
15 |
50,709,652 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9562:Trps1
|
UTSW |
15 |
50,524,657 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9647:Trps1
|
UTSW |
15 |
50,524,944 (GRCm39) |
missense |
probably benign |
0.09 |
|
R9803:Trps1
|
UTSW |
15 |
50,710,090 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
V7580:Trps1
|
UTSW |
15 |
50,694,973 (GRCm39) |
missense |
probably damaging |
1.00 |
|
V7583:Trps1
|
UTSW |
15 |
50,694,973 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- GTGGACCCACTACAATCACATCAGG -3'
(R):5'- GCAACATTTTCTTCAGACGCACCC -3'
Sequencing Primer
(F):5'- TCCCTTGCTGGGGAAGTC -3'
(R):5'- TCCTCCGAGGGTGTGAAAC -3'
|
| Posted On |
2014-01-29 |
Incidental Mutation