Incidental Mutation 'R1482:Nbr1'
| ID |
164467 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Nbr1
|
| Ensembl Gene |
ENSMUSG00000017119 |
| Gene Name |
NBR1, autophagy cargo receptor |
| Synonyms |
|
| MMRRC Submission |
039535-MU
|
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
R1482 (G1)
|
| Quality Score |
225 |
|
Status
|
Not validated
|
| Chromosome |
11 |
| Chromosomal Location |
101442975-101472777 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
C to T
at 101463667 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Threonine to Isoleucine
at position 633
(T633I)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000102836
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000071537]
[ENSMUST00000103098]
[ENSMUST00000103099]
[ENSMUST00000107208]
[ENSMUST00000107212]
[ENSMUST00000107213]
[ENSMUST00000107218]
[ENSMUST00000123558]
|
| AlphaFold |
P97432 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000071537
AA Change: T633I
PolyPhen 2
Score 0.143 (Sensitivity: 0.92; Specificity: 0.86)
|
| SMART Domains |
Protein: ENSMUSP00000071467
Gene: ENSMUSG00000017119
AA Change: T633I
| Domain | Start | End | E-Value | Type |
|---|
|
PB1
|
4 |
86 |
2.05e-8 |
SMART |
|
ZnF_ZZ
|
212 |
257 |
1.21e-13 |
SMART |
|
coiled coil region
|
291 |
330 |
N/A |
INTRINSIC |
|
Pfam:N_BRCA1_IG
|
378 |
479 |
7.1e-34 |
PFAM |
|
low complexity region
|
507 |
518 |
N/A |
INTRINSIC |
|
coiled coil region
|
714 |
744 |
N/A |
INTRINSIC |
|
PDB:2MJ5|B
|
935 |
981 |
2e-24 |
PDB |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000103098
AA Change: T633I
PolyPhen 2
Score 0.342 (Sensitivity: 0.90; Specificity: 0.89)
|
| SMART Domains |
Protein: ENSMUSP00000099387
Gene: ENSMUSG00000017119
AA Change: T633I
| Domain | Start | End | E-Value | Type |
|---|
|
PB1
|
4 |
86 |
7.02e-16 |
SMART |
|
ZnF_ZZ
|
212 |
257 |
1.21e-13 |
SMART |
|
coiled coil region
|
291 |
330 |
N/A |
INTRINSIC |
|
PDB:4OLE|D
|
368 |
486 |
5e-77 |
PDB |
|
low complexity region
|
507 |
518 |
N/A |
INTRINSIC |
|
coiled coil region
|
714 |
744 |
N/A |
INTRINSIC |
|
PDB:2MJ5|B
|
935 |
981 |
2e-24 |
PDB |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000103099
AA Change: T633I
PolyPhen 2
Score 0.342 (Sensitivity: 0.90; Specificity: 0.89)
|
| SMART Domains |
Protein: ENSMUSP00000099388
Gene: ENSMUSG00000017119
AA Change: T633I
| Domain | Start | End | E-Value | Type |
|---|
|
PB1
|
4 |
86 |
7.02e-16 |
SMART |
|
ZnF_ZZ
|
212 |
257 |
1.21e-13 |
SMART |
|
coiled coil region
|
291 |
330 |
N/A |
INTRINSIC |
|
PDB:4OLE|D
|
368 |
486 |
5e-77 |
PDB |
|
low complexity region
|
507 |
518 |
N/A |
INTRINSIC |
|
coiled coil region
|
714 |
744 |
N/A |
INTRINSIC |
|
PDB:2MJ5|B
|
935 |
981 |
2e-24 |
PDB |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000107208
AA Change: T633I
PolyPhen 2
Score 0.143 (Sensitivity: 0.92; Specificity: 0.86)
|
| SMART Domains |
Protein: ENSMUSP00000102826
Gene: ENSMUSG00000017119
AA Change: T633I
| Domain | Start | End | E-Value | Type |
|---|
|
PB1
|
4 |
86 |
7.02e-16 |
SMART |
|
ZnF_ZZ
|
212 |
257 |
1.21e-13 |
SMART |
|
coiled coil region
|
291 |
330 |
N/A |
INTRINSIC |
|
PDB:4OLE|D
|
368 |
486 |
1e-77 |
PDB |
|
low complexity region
|
507 |
518 |
N/A |
INTRINSIC |
|
coiled coil region
|
714 |
744 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000107212
AA Change: T633I
PolyPhen 2
Score 0.143 (Sensitivity: 0.92; Specificity: 0.86)
|
| SMART Domains |
Protein: ENSMUSP00000102830
Gene: ENSMUSG00000017119
AA Change: T633I
| Domain | Start | End | E-Value | Type |
|---|
|
PB1
|
4 |
86 |
7.02e-16 |
SMART |
|
ZnF_ZZ
|
212 |
257 |
1.21e-13 |
SMART |
|
coiled coil region
|
291 |
330 |
N/A |
INTRINSIC |
|
PDB:4OLE|D
|
368 |
486 |
3e-77 |
PDB |
|
low complexity region
|
507 |
518 |
N/A |
INTRINSIC |
|
coiled coil region
|
689 |
719 |
N/A |
INTRINSIC |
|
PDB:2MJ5|B
|
910 |
956 |
2e-24 |
PDB |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000107213
AA Change: T596I
PolyPhen 2
Score 0.055 (Sensitivity: 0.94; Specificity: 0.84)
|
| SMART Domains |
Protein: ENSMUSP00000102831
Gene: ENSMUSG00000017119
AA Change: T596I
| Domain | Start | End | E-Value | Type |
|---|
|
PB1
|
4 |
86 |
7.02e-16 |
SMART |
|
ZnF_ZZ
|
212 |
257 |
1.21e-13 |
SMART |
|
coiled coil region
|
291 |
330 |
N/A |
INTRINSIC |
|
PDB:4OLE|D
|
368 |
486 |
2e-77 |
PDB |
|
low complexity region
|
507 |
518 |
N/A |
INTRINSIC |
|
coiled coil region
|
677 |
707 |
N/A |
INTRINSIC |
|
PDB:2MJ5|B
|
898 |
944 |
2e-24 |
PDB |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000107218
AA Change: T633I
PolyPhen 2
Score 0.342 (Sensitivity: 0.90; Specificity: 0.89)
|
| SMART Domains |
Protein: ENSMUSP00000102836
Gene: ENSMUSG00000017119
AA Change: T633I
| Domain | Start | End | E-Value | Type |
|---|
|
PB1
|
4 |
86 |
7.02e-16 |
SMART |
|
ZnF_ZZ
|
212 |
257 |
1.21e-13 |
SMART |
|
coiled coil region
|
291 |
330 |
N/A |
INTRINSIC |
|
PDB:4OLE|D
|
368 |
486 |
5e-77 |
PDB |
|
low complexity region
|
507 |
518 |
N/A |
INTRINSIC |
|
coiled coil region
|
714 |
744 |
N/A |
INTRINSIC |
|
PDB:2MJ5|B
|
935 |
981 |
2e-24 |
PDB |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000123558
AA Change: T633I
PolyPhen 2
Score 0.143 (Sensitivity: 0.92; Specificity: 0.86)
|
| SMART Domains |
Protein: ENSMUSP00000133619
Gene: ENSMUSG00000017119
AA Change: T633I
| Domain | Start | End | E-Value | Type |
|---|
|
PB1
|
4 |
86 |
7.02e-16 |
SMART |
|
ZnF_ZZ
|
212 |
257 |
1.21e-13 |
SMART |
|
coiled coil region
|
291 |
330 |
N/A |
INTRINSIC |
|
PDB:4OLE|D
|
368 |
486 |
2e-77 |
PDB |
|
low complexity region
|
507 |
518 |
N/A |
INTRINSIC |
|
coiled coil region
|
714 |
744 |
N/A |
INTRINSIC |
|
| Predicted Effect |
unknown
Transcript: ENSMUST00000149019
AA Change: T392I
|
| SMART Domains |
Protein: ENSMUSP00000119900
Gene: ENSMUSG00000017119
AA Change: T392I
| Domain | Start | End | E-Value | Type |
|---|
|
coiled coil region
|
50 |
89 |
N/A |
INTRINSIC |
|
Pfam:N_BRCA1_IG
|
138 |
239 |
2.3e-34 |
PFAM |
|
low complexity region
|
267 |
278 |
N/A |
INTRINSIC |
|
coiled coil region
|
473 |
500 |
N/A |
INTRINSIC |
|
PDB:2MJ5|B
|
659 |
705 |
1e-24 |
PDB |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000127871
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000172744
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000141170
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000149170
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000144517
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000174013
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000148805
|
| Coding Region Coverage |
- 1x: 98.8%
- 3x: 97.7%
- 10x: 93.8%
- 20x: 83.6%
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene was originally identified as an ovarian tumor antigen monitored in ovarian cancer. The encoded protein contains a B-box/coiled-coil motif, which is present in many genes with transformation potential. It functions as a specific autophagy receptor for the selective autophagic degradation of peroxisomes by forming intracellular inclusions with ubiquitylated autophagic substrates. This gene is located on a region of chromosome 17q21.1 that is in close proximity to the BRCA1 tumor suppressor gene. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2014]
PHENOTYPE: Homozygous mice of the genetic truncation allele had an age-dependent increase in bone mass and bone mineral density. Mice homozygous for a floxed allele activated in T cells exhibit decreased ovalbumin-induced inflammation and defective Th2 polarization. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 61 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 1810055G02Rik |
G |
A |
19: 3,767,192 (GRCm39) |
D260N |
probably benign |
Het |
| Ankef1 |
A |
T |
2: 136,392,078 (GRCm39) |
K422N |
possibly damaging |
Het |
| Anxa2 |
TCCC |
TCC |
9: 69,397,036 (GRCm39) |
|
probably null |
Het |
| Aqp6 |
A |
T |
15: 99,502,188 (GRCm39) |
*294C |
probably null |
Het |
| Baz2a |
T |
A |
10: 127,944,877 (GRCm39) |
M38K |
possibly damaging |
Het |
| Bcl2l14 |
A |
G |
6: 134,404,265 (GRCm39) |
D151G |
probably damaging |
Het |
| Cabp5 |
T |
A |
7: 13,132,267 (GRCm39) |
L12* |
probably null |
Het |
| Cachd1 |
T |
C |
4: 100,845,795 (GRCm39) |
V993A |
possibly damaging |
Het |
| Cd44 |
G |
A |
2: 102,661,728 (GRCm39) |
T306I |
probably damaging |
Het |
| Cdc20 |
A |
T |
4: 118,294,253 (GRCm39) |
N22K |
probably benign |
Het |
| Cdc6 |
T |
A |
11: 98,807,807 (GRCm39) |
D433E |
possibly damaging |
Het |
| Clhc1 |
A |
G |
11: 29,503,725 (GRCm39) |
D47G |
probably damaging |
Het |
| Csf2 |
T |
C |
11: 54,139,389 (GRCm39) |
K65E |
probably benign |
Het |
| Cul9 |
T |
C |
17: 46,819,473 (GRCm39) |
E2005G |
probably damaging |
Het |
| Dclk3 |
G |
T |
9: 111,296,888 (GRCm39) |
R144L |
possibly damaging |
Het |
| Dcpp2 |
C |
T |
17: 24,119,516 (GRCm39) |
T110I |
probably damaging |
Het |
| Disp1 |
A |
T |
1: 182,868,038 (GRCm39) |
F1461I |
possibly damaging |
Het |
| Dnah1 |
C |
T |
14: 31,016,831 (GRCm39) |
G1562D |
probably damaging |
Het |
| Ecpas |
T |
C |
4: 58,820,163 (GRCm39) |
K1217E |
possibly damaging |
Het |
| Exoc3l2 |
C |
A |
7: 19,229,284 (GRCm39) |
P234Q |
probably damaging |
Het |
| F2rl2 |
T |
C |
13: 95,838,047 (GRCm39) |
V364A |
probably benign |
Het |
| Fam151a |
T |
C |
4: 106,602,876 (GRCm39) |
L265P |
probably damaging |
Het |
| Fam151b |
T |
A |
13: 92,586,674 (GRCm39) |
Q253L |
probably benign |
Het |
| Fat1 |
G |
A |
8: 45,406,281 (GRCm39) |
V1011M |
probably benign |
Het |
| Fbxo6 |
G |
A |
4: 148,230,441 (GRCm39) |
R274* |
probably null |
Het |
| Fgd4 |
G |
T |
16: 16,302,337 (GRCm39) |
Q73K |
probably benign |
Het |
| Fth1 |
A |
G |
19: 9,962,217 (GRCm39) |
T154A |
probably benign |
Het |
| Hgs |
C |
A |
11: 120,370,866 (GRCm39) |
H572Q |
probably benign |
Het |
| Kcnk10 |
G |
A |
12: 98,456,207 (GRCm39) |
T208I |
probably damaging |
Het |
| Kdm5b |
G |
A |
1: 134,552,635 (GRCm39) |
V1204M |
probably damaging |
Het |
| Keg1 |
A |
C |
19: 12,696,185 (GRCm39) |
H166P |
probably damaging |
Het |
| Kifap3 |
A |
T |
1: 163,653,428 (GRCm39) |
N338I |
possibly damaging |
Het |
| Llcfc1 |
A |
T |
6: 41,662,218 (GRCm39) |
D74V |
probably damaging |
Het |
| Lman2 |
A |
G |
13: 55,499,218 (GRCm39) |
V219A |
possibly damaging |
Het |
| Mettl25 |
A |
G |
10: 105,662,451 (GRCm39) |
I173T |
possibly damaging |
Het |
| Mov10 |
G |
T |
3: 104,711,862 (GRCm39) |
P170Q |
probably damaging |
Het |
| Mtif2 |
G |
T |
11: 29,486,847 (GRCm39) |
A286S |
probably damaging |
Het |
| Mtmr10 |
A |
G |
7: 63,963,997 (GRCm39) |
Y244C |
probably damaging |
Het |
| Nbea |
A |
T |
3: 55,987,414 (GRCm39) |
C359S |
probably damaging |
Het |
| Nepn |
A |
T |
10: 52,276,512 (GRCm39) |
T22S |
probably damaging |
Het |
| Nup214 |
C |
T |
2: 31,924,478 (GRCm39) |
S1669F |
probably damaging |
Het |
| Oacyl |
T |
A |
18: 65,871,043 (GRCm39) |
L342M |
probably damaging |
Het |
| Or2ag17 |
A |
G |
7: 106,389,540 (GRCm39) |
F223L |
probably benign |
Het |
| Or52b2 |
T |
A |
7: 104,986,463 (GRCm39) |
R153S |
probably damaging |
Het |
| Or6c205 |
T |
A |
10: 129,087,012 (GRCm39) |
I203N |
possibly damaging |
Het |
| Or7e176 |
G |
A |
9: 20,172,020 (GRCm39) |
V295I |
possibly damaging |
Het |
| Oxnad1 |
T |
C |
14: 31,821,590 (GRCm39) |
|
probably null |
Het |
| Pard3b |
A |
T |
1: 62,205,526 (GRCm39) |
D440V |
probably damaging |
Het |
| Pou3f2 |
T |
G |
4: 22,486,960 (GRCm39) |
D391A |
possibly damaging |
Het |
| Ptprk |
T |
C |
10: 28,139,512 (GRCm39) |
V79A |
probably benign |
Het |
| Rwdd2a |
A |
G |
9: 86,456,331 (GRCm39) |
D169G |
probably damaging |
Het |
| Scn3b |
A |
C |
9: 40,190,792 (GRCm39) |
D74A |
probably damaging |
Het |
| Setbp1 |
C |
T |
18: 79,130,050 (GRCm39) |
D61N |
probably damaging |
Het |
| Setx |
T |
A |
2: 29,053,004 (GRCm39) |
D2089E |
probably damaging |
Het |
| Vmn2r69 |
C |
G |
7: 85,056,082 (GRCm39) |
W685C |
probably damaging |
Het |
| Vps8 |
A |
G |
16: 21,400,348 (GRCm39) |
Q1272R |
probably benign |
Het |
| Wnk4 |
T |
C |
11: 101,160,462 (GRCm39) |
F699L |
probably damaging |
Het |
| Zfp616 |
T |
A |
11: 73,974,803 (GRCm39) |
N448K |
possibly damaging |
Het |
| Zfp618 |
C |
A |
4: 63,033,685 (GRCm39) |
D307E |
possibly damaging |
Het |
| Zfp687 |
A |
G |
3: 94,914,844 (GRCm39) |
F1219S |
probably damaging |
Het |
| Zfpm2 |
T |
A |
15: 40,962,687 (GRCm39) |
D248E |
probably damaging |
Het |
|
| Other mutations in Nbr1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL02187:Nbr1
|
APN |
11 |
101,460,185 (GRCm39) |
missense |
possibly damaging |
0.91 |
|
IGL02192:Nbr1
|
APN |
11 |
101,460,417 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02259:Nbr1
|
APN |
11 |
101,468,816 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL02951:Nbr1
|
APN |
11 |
101,462,805 (GRCm39) |
critical splice donor site |
probably null |
|
|
IGL02994:Nbr1
|
APN |
11 |
101,447,053 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0087:Nbr1
|
UTSW |
11 |
101,455,519 (GRCm39) |
missense |
probably benign |
0.16 |
|
R0630:Nbr1
|
UTSW |
11 |
101,457,913 (GRCm39) |
unclassified |
probably benign |
|
|
R0723:Nbr1
|
UTSW |
11 |
101,467,145 (GRCm39) |
nonsense |
probably null |
|
|
R0733:Nbr1
|
UTSW |
11 |
101,467,197 (GRCm39) |
missense |
probably benign |
0.00 |
|
R1567:Nbr1
|
UTSW |
11 |
101,466,037 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R1570:Nbr1
|
UTSW |
11 |
101,455,656 (GRCm39) |
unclassified |
probably benign |
|
|
R1668:Nbr1
|
UTSW |
11 |
101,460,592 (GRCm39) |
missense |
probably benign |
0.00 |
|
R1759:Nbr1
|
UTSW |
11 |
101,450,369 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1903:Nbr1
|
UTSW |
11 |
101,465,978 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R1927:Nbr1
|
UTSW |
11 |
101,458,040 (GRCm39) |
missense |
possibly damaging |
0.78 |
|
R2131:Nbr1
|
UTSW |
11 |
101,457,017 (GRCm39) |
splice site |
probably null |
|
|
R2211:Nbr1
|
UTSW |
11 |
101,458,090 (GRCm39) |
critical splice donor site |
probably null |
|
|
R2255:Nbr1
|
UTSW |
11 |
101,463,643 (GRCm39) |
missense |
possibly damaging |
0.80 |
|
R4270:Nbr1
|
UTSW |
11 |
101,458,048 (GRCm39) |
missense |
possibly damaging |
0.87 |
|
R4271:Nbr1
|
UTSW |
11 |
101,458,048 (GRCm39) |
missense |
possibly damaging |
0.87 |
|
R4710:Nbr1
|
UTSW |
11 |
101,466,101 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4947:Nbr1
|
UTSW |
11 |
101,465,903 (GRCm39) |
missense |
probably benign |
0.06 |
|
R5468:Nbr1
|
UTSW |
11 |
101,463,290 (GRCm39) |
missense |
probably benign |
0.10 |
|
R5554:Nbr1
|
UTSW |
11 |
101,455,633 (GRCm39) |
missense |
probably benign |
0.34 |
|
R5771:Nbr1
|
UTSW |
11 |
101,450,364 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6119:Nbr1
|
UTSW |
11 |
101,457,938 (GRCm39) |
splice site |
probably null |
|
|
R6400:Nbr1
|
UTSW |
11 |
101,456,600 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6603:Nbr1
|
UTSW |
11 |
101,446,931 (GRCm39) |
unclassified |
probably benign |
|
|
R6943:Nbr1
|
UTSW |
11 |
101,468,777 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7347:Nbr1
|
UTSW |
11 |
101,460,147 (GRCm39) |
nonsense |
probably null |
|
|
R7472:Nbr1
|
UTSW |
11 |
101,462,765 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7501:Nbr1
|
UTSW |
11 |
101,457,026 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7709:Nbr1
|
UTSW |
11 |
101,447,067 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7744:Nbr1
|
UTSW |
11 |
101,460,210 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7795:Nbr1
|
UTSW |
11 |
101,460,154 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8865:Nbr1
|
UTSW |
11 |
101,455,520 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9377:Nbr1
|
UTSW |
11 |
101,456,590 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R9615:Nbr1
|
UTSW |
11 |
101,465,978 (GRCm39) |
missense |
probably benign |
0.02 |
|
R9667:Nbr1
|
UTSW |
11 |
101,451,261 (GRCm39) |
missense |
possibly damaging |
0.68 |
|
R9801:Nbr1
|
UTSW |
11 |
101,447,025 (GRCm39) |
missense |
probably damaging |
0.99 |
|
X0019:Nbr1
|
UTSW |
11 |
101,457,950 (GRCm39) |
missense |
possibly damaging |
0.50 |
|
Z1176:Nbr1
|
UTSW |
11 |
101,463,380 (GRCm39) |
missense |
probably benign |
0.04 |
|
| Predicted Primers |
PCR Primer
(F):5'- CTCTACCTCAGCAAATCGATGTCCC -3'
(R):5'- TGCAGAATCCAGGCAGCACAAG -3'
Sequencing Primer
(F):5'- CATGGCATCCCTCGCTC -3'
(R):5'- CTGTAATTCCCCTGAGAGAGGAC -3'
|
| Posted On |
2014-03-28 |
Incidental Mutation