Incidental Mutation 'R8537:Gnas'
| ID |
659275 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Gnas
|
| Ensembl Gene |
ENSMUSG00000027523 |
| Gene Name |
GNAS complex locus |
| Synonyms |
P2, Gnasxl, Gnas1, Nesp, neuroendocrine-specific Golgi protein p55 isoform 1, XLalphas, Gsa, Oedsml, Gs alpha, Nesp55, Galphas, Nespl, SCG6, Gs-alpha, P1, P3, G alpha s |
| MMRRC Submission |
067891-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R8537 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Not validated
|
| Chromosome |
2 |
| Chromosomal Location |
174126113-174188537 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 174140394 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Serine to Proline
at position 188
(S188P)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000139839
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000080493]
[ENSMUST00000087876]
[ENSMUST00000087877]
[ENSMUST00000109088]
[ENSMUST00000109095]
[ENSMUST00000109096]
[ENSMUST00000130761]
[ENSMUST00000130940]
[ENSMUST00000180362]
[ENSMUST00000185956]
[ENSMUST00000186907]
|
| AlphaFold |
Q6R0H7 |
| Predicted Effect |
unknown
Transcript: ENSMUST00000080493
AA Change: V247A
|
| SMART Domains |
Protein: ENSMUSP00000079341
Gene: ENSMUSG00000027523
AA Change: V247A
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
19 |
48 |
N/A |
INTRINSIC |
|
internal_repeat_1
|
89 |
166 |
3.02e-8 |
PROSPERO |
|
internal_repeat_1
|
209 |
276 |
3.02e-8 |
PROSPERO |
|
low complexity region
|
350 |
365 |
N/A |
INTRINSIC |
|
low complexity region
|
391 |
404 |
N/A |
INTRINSIC |
|
low complexity region
|
459 |
477 |
N/A |
INTRINSIC |
|
low complexity region
|
480 |
498 |
N/A |
INTRINSIC |
|
low complexity region
|
515 |
525 |
N/A |
INTRINSIC |
|
low complexity region
|
535 |
570 |
N/A |
INTRINSIC |
|
low complexity region
|
576 |
626 |
N/A |
INTRINSIC |
|
low complexity region
|
633 |
643 |
N/A |
INTRINSIC |
|
low complexity region
|
659 |
678 |
N/A |
INTRINSIC |
|
low complexity region
|
685 |
696 |
N/A |
INTRINSIC |
|
G_alpha
|
759 |
1132 |
5.01e-185 |
SMART |
|
| Predicted Effect |
unknown
Transcript: ENSMUST00000087876
AA Change: V247A
|
| SMART Domains |
Protein: ENSMUSP00000085184
Gene: ENSMUSG00000027523
AA Change: V247A
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
19 |
48 |
N/A |
INTRINSIC |
|
internal_repeat_1
|
89 |
166 |
2.42e-8 |
PROSPERO |
|
internal_repeat_1
|
209 |
276 |
2.42e-8 |
PROSPERO |
|
low complexity region
|
350 |
365 |
N/A |
INTRINSIC |
|
low complexity region
|
391 |
404 |
N/A |
INTRINSIC |
|
low complexity region
|
459 |
477 |
N/A |
INTRINSIC |
|
low complexity region
|
480 |
498 |
N/A |
INTRINSIC |
|
low complexity region
|
515 |
525 |
N/A |
INTRINSIC |
|
low complexity region
|
535 |
570 |
N/A |
INTRINSIC |
|
low complexity region
|
576 |
626 |
N/A |
INTRINSIC |
|
low complexity region
|
633 |
643 |
N/A |
INTRINSIC |
|
low complexity region
|
659 |
678 |
N/A |
INTRINSIC |
|
low complexity region
|
685 |
696 |
N/A |
INTRINSIC |
|
G_alpha
|
759 |
1118 |
8.32e-191 |
SMART |
|
| Predicted Effect |
unknown
Transcript: ENSMUST00000087877
AA Change: V247A
|
| SMART Domains |
Protein: ENSMUSP00000085185
Gene: ENSMUSG00000027523
AA Change: V247A
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
19 |
48 |
N/A |
INTRINSIC |
|
internal_repeat_1
|
89 |
166 |
1.1e-8 |
PROSPERO |
|
internal_repeat_1
|
209 |
276 |
1.1e-8 |
PROSPERO |
|
low complexity region
|
350 |
365 |
N/A |
INTRINSIC |
|
low complexity region
|
391 |
404 |
N/A |
INTRINSIC |
|
low complexity region
|
459 |
477 |
N/A |
INTRINSIC |
|
low complexity region
|
480 |
498 |
N/A |
INTRINSIC |
|
low complexity region
|
515 |
525 |
N/A |
INTRINSIC |
|
low complexity region
|
535 |
570 |
N/A |
INTRINSIC |
|
low complexity region
|
576 |
626 |
N/A |
INTRINSIC |
|
low complexity region
|
633 |
643 |
N/A |
INTRINSIC |
|
low complexity region
|
659 |
678 |
N/A |
INTRINSIC |
|
low complexity region
|
685 |
696 |
N/A |
INTRINSIC |
|
Blast:G_alpha
|
759 |
799 |
2e-14 |
BLAST |
|
low complexity region
|
802 |
816 |
N/A |
INTRINSIC |
|
low complexity region
|
847 |
859 |
N/A |
INTRINSIC |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000109088
AA Change: S188P
PolyPhen 2
Score 0.827 (Sensitivity: 0.84; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000104716
Gene: ENSMUSG00000027523
AA Change: S188P
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
192 |
209 |
N/A |
INTRINSIC |
|
low complexity region
|
336 |
352 |
N/A |
INTRINSIC |
|
low complexity region
|
402 |
415 |
N/A |
INTRINSIC |
|
low complexity region
|
421 |
446 |
N/A |
INTRINSIC |
|
low complexity region
|
459 |
481 |
N/A |
INTRINSIC |
|
low complexity region
|
493 |
510 |
N/A |
INTRINSIC |
|
low complexity region
|
529 |
599 |
N/A |
INTRINSIC |
|
low complexity region
|
643 |
658 |
N/A |
INTRINSIC |
|
low complexity region
|
700 |
716 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000109095
|
| SMART Domains |
Protein: ENSMUSP00000104723
Gene: ENSMUSG00000027523
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:NESP55
|
1 |
253 |
1.2e-157 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000109096
|
| SMART Domains |
Protein: ENSMUSP00000104724
Gene: ENSMUSG00000027523
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:NESP55
|
1 |
253 |
1.2e-157 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000130761
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000130940
|
| SMART Domains |
Protein: ENSMUSP00000118210
Gene: ENSMUSG00000027523
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:NESP55
|
1 |
59 |
1.6e-30 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000180362
|
| SMART Domains |
Protein: ENSMUSP00000136180
Gene: ENSMUSG00000027523
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:NESP55
|
1 |
253 |
1.2e-157 |
PFAM |
|
| Predicted Effect |
unknown
Transcript: ENSMUST00000185956
AA Change: V247A
|
| SMART Domains |
Protein: ENSMUSP00000140174
Gene: ENSMUSG00000027523
AA Change: V247A
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
19 |
48 |
N/A |
INTRINSIC |
|
internal_repeat_1
|
89 |
166 |
3.02e-8 |
PROSPERO |
|
internal_repeat_1
|
209 |
276 |
3.02e-8 |
PROSPERO |
|
low complexity region
|
350 |
365 |
N/A |
INTRINSIC |
|
low complexity region
|
391 |
404 |
N/A |
INTRINSIC |
|
low complexity region
|
459 |
477 |
N/A |
INTRINSIC |
|
low complexity region
|
480 |
498 |
N/A |
INTRINSIC |
|
low complexity region
|
515 |
525 |
N/A |
INTRINSIC |
|
low complexity region
|
535 |
570 |
N/A |
INTRINSIC |
|
low complexity region
|
576 |
626 |
N/A |
INTRINSIC |
|
low complexity region
|
633 |
643 |
N/A |
INTRINSIC |
|
low complexity region
|
659 |
678 |
N/A |
INTRINSIC |
|
low complexity region
|
685 |
696 |
N/A |
INTRINSIC |
|
G_alpha
|
759 |
1132 |
5.01e-185 |
SMART |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000186907
AA Change: S188P
PolyPhen 2
Score 0.827 (Sensitivity: 0.84; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000139839
Gene: ENSMUSG00000027523
AA Change: S188P
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
192 |
209 |
N/A |
INTRINSIC |
|
low complexity region
|
336 |
352 |
N/A |
INTRINSIC |
|
low complexity region
|
402 |
415 |
N/A |
INTRINSIC |
|
low complexity region
|
421 |
446 |
N/A |
INTRINSIC |
|
low complexity region
|
459 |
481 |
N/A |
INTRINSIC |
|
low complexity region
|
493 |
510 |
N/A |
INTRINSIC |
|
low complexity region
|
529 |
599 |
N/A |
INTRINSIC |
|
low complexity region
|
643 |
658 |
N/A |
INTRINSIC |
|
low complexity region
|
700 |
716 |
N/A |
INTRINSIC |
|
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 99.9%
- 10x: 99.7%
- 20x: 99.0%
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: This locus has a highly complex imprinted expression pattern. It gives rise to maternally, paternally, and biallelically expressed transcripts that are derived from four alternative promoters and 5' exons. Some transcripts contain a differentially methylated region (DMR) at their 5' exons, which is commonly found in imprinted genes and correlates with transcript expression. This gene has an antisense transcript. One of the transcripts produced from this locus, and the antisense transcript, are both paternally expressed noncoding RNAs, and may regulate imprinting in this region. In addition, one of the transcripts contains a second overlapping ORF, which encodes a structurally unrelated protein - Alex. Alternative splicing of downstream exons is also observed, which results in different forms of the stimulatory G-protein alpha subunit, a key element of the classical signal transduction pathway linking receptor-ligand interactions with the activation of adenylyl cyclase and a variety of cellular reponses. Additional transcript variants have been found for this gene, but the full-length nature and/or biological validity of some variants have not been determined. [provided by RefSeq, Jun 2015]
PHENOTYPE: Mutant homozygotes stop developing normally by embryonic day 10.5 and die prenatally. On some backgrounds heterozygotes show imprinted phenotypes, including differences in body shape/weight, locomotor activity, metabolism, and developmental anomalies. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 50 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Adgrv1 |
T |
A |
13: 81,684,491 (GRCm39) |
D1790V |
probably damaging |
Het |
| Aopep |
A |
T |
13: 63,338,364 (GRCm39) |
E579V |
probably damaging |
Het |
| Avl9 |
T |
A |
6: 56,705,644 (GRCm39) |
Y175* |
probably null |
Het |
| Bmp2 |
A |
T |
2: 133,403,202 (GRCm39) |
D251V |
probably damaging |
Het |
| Camsap2 |
T |
A |
1: 136,204,943 (GRCm39) |
K1191N |
probably damaging |
Het |
| Ccdc102a |
A |
C |
8: 95,632,684 (GRCm39) |
F431C |
probably benign |
Het |
| Ccdc186 |
T |
C |
19: 56,798,677 (GRCm39) |
I270M |
probably damaging |
Het |
| Copb2 |
A |
G |
9: 98,469,672 (GRCm39) |
Q851R |
probably null |
Het |
| Cyp11b2 |
C |
T |
15: 74,728,016 (GRCm39) |
R22K |
probably benign |
Het |
| Ddx50 |
A |
G |
10: 62,478,628 (GRCm39) |
F186S |
probably damaging |
Het |
| Dhx38 |
T |
C |
8: 110,280,012 (GRCm39) |
Y926C |
probably damaging |
Het |
| Dmrt2 |
T |
C |
19: 25,651,300 (GRCm39) |
M162T |
possibly damaging |
Het |
| Dnah10 |
G |
T |
5: 124,893,164 (GRCm39) |
G3309V |
probably damaging |
Het |
| Dnajb2 |
T |
C |
1: 75,216,242 (GRCm39) |
F107S |
probably damaging |
Het |
| Dock8 |
T |
A |
19: 25,107,870 (GRCm39) |
S867T |
probably benign |
Het |
| Eif2ak1 |
C |
A |
5: 143,835,887 (GRCm39) |
T526K |
probably damaging |
Het |
| Gpam |
T |
C |
19: 55,084,671 (GRCm39) |
D36G |
probably benign |
Het |
| Gucy2e |
C |
A |
11: 69,127,179 (GRCm39) |
R98L |
probably benign |
Het |
| Hmcn2 |
C |
A |
2: 31,281,088 (GRCm39) |
L1867I |
probably benign |
Het |
| Hnrnpu |
T |
C |
1: 178,161,199 (GRCm39) |
|
probably benign |
Het |
| Icos |
A |
G |
1: 61,033,101 (GRCm39) |
D100G |
probably damaging |
Het |
| Ifi203 |
A |
T |
1: 173,756,472 (GRCm39) |
|
probably benign |
Het |
| Ift46 |
T |
A |
9: 44,695,280 (GRCm39) |
L92Q |
probably damaging |
Het |
| Kcnip2 |
C |
T |
19: 45,804,169 (GRCm39) |
|
probably null |
Het |
| Lgr5 |
T |
C |
10: 115,288,307 (GRCm39) |
Y779C |
probably damaging |
Het |
| Ltk |
G |
T |
2: 119,588,588 (GRCm39) |
P287Q |
probably benign |
Het |
| Mapk8ip3 |
A |
T |
17: 25,120,652 (GRCm39) |
C852* |
probably null |
Het |
| Mmp27 |
A |
G |
9: 7,579,776 (GRCm39) |
M443V |
probably benign |
Het |
| Muc6 |
T |
C |
7: 141,234,184 (GRCm39) |
D769G |
probably benign |
Het |
| Myo7b |
T |
C |
18: 32,110,142 (GRCm39) |
I1107V |
probably benign |
Het |
| Nebl |
T |
A |
2: 17,355,520 (GRCm39) |
H211L |
probably benign |
Het |
| Oaz3 |
T |
A |
3: 94,343,742 (GRCm39) |
K40N |
probably damaging |
Het |
| Or5as1 |
T |
A |
2: 86,980,382 (GRCm39) |
T208S |
probably benign |
Het |
| Or7e169 |
T |
A |
9: 19,757,848 (GRCm39) |
E22D |
probably damaging |
Het |
| Osbpl10 |
G |
T |
9: 115,058,977 (GRCm39) |
A718S |
probably benign |
Het |
| Ppp3ca |
T |
A |
3: 136,503,619 (GRCm39) |
I64K |
possibly damaging |
Het |
| Prlr |
T |
C |
15: 10,314,266 (GRCm39) |
|
probably benign |
Het |
| Rab3ip |
A |
G |
10: 116,746,059 (GRCm39) |
I424T |
probably damaging |
Het |
| Rsf1 |
CGGCGGCGG |
CGGCGGCGGGGGCGGCGG |
7: 97,229,121 (GRCm39) |
|
probably benign |
Het |
| Sec62 |
G |
T |
3: 30,872,961 (GRCm39) |
R348L |
unknown |
Het |
| Sema5b |
C |
T |
16: 35,471,979 (GRCm39) |
A479V |
possibly damaging |
Het |
| Shank3 |
T |
C |
15: 89,416,418 (GRCm39) |
I222T |
probably damaging |
Het |
| Sp1 |
C |
T |
15: 102,316,964 (GRCm39) |
T154I |
possibly damaging |
Het |
| Spata31e1 |
A |
G |
13: 49,940,108 (GRCm39) |
V534A |
possibly damaging |
Het |
| Srek1 |
A |
G |
13: 103,888,957 (GRCm39) |
|
probably benign |
Het |
| Tmem129 |
A |
G |
5: 33,812,920 (GRCm39) |
S143P |
possibly damaging |
Het |
| Tmem202 |
A |
T |
9: 59,426,929 (GRCm39) |
C194S |
probably benign |
Het |
| Tmprss15 |
A |
T |
16: 78,884,403 (GRCm39) |
I93K |
probably damaging |
Het |
| Ttn |
A |
G |
2: 76,606,653 (GRCm39) |
Y16340H |
probably damaging |
Het |
| Uck1 |
C |
A |
2: 32,150,153 (GRCm39) |
|
probably benign |
Het |
|
| Other mutations in Gnas |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00565:Gnas
|
APN |
2 |
174,183,504 (GRCm39) |
splice site |
probably benign |
|
|
IGL00928:Gnas
|
APN |
2 |
174,139,746 (GRCm39) |
nonsense |
probably null |
|
|
IGL01014:Gnas
|
APN |
2 |
174,139,767 (GRCm39) |
utr 5 prime |
probably benign |
|
|
IGL01743:Gnas
|
APN |
2 |
174,140,125 (GRCm39) |
nonsense |
probably null |
|
|
IGL01808:Gnas
|
APN |
2 |
174,140,490 (GRCm39) |
missense |
probably damaging |
0.96 |
|
IGL02559:Gnas
|
APN |
2 |
174,183,729 (GRCm39) |
splice site |
probably benign |
|
|
R0555:Gnas
|
UTSW |
2 |
174,140,304 (GRCm39) |
missense |
possibly damaging |
0.78 |
|
R0627:Gnas
|
UTSW |
2 |
174,139,928 (GRCm39) |
intron |
probably benign |
|
|
R1418:Gnas
|
UTSW |
2 |
174,187,007 (GRCm39) |
splice site |
probably benign |
|
|
R1706:Gnas
|
UTSW |
2 |
174,141,768 (GRCm39) |
missense |
possibly damaging |
0.90 |
|
R1751:Gnas
|
UTSW |
2 |
174,139,687 (GRCm39) |
utr 5 prime |
probably benign |
|
|
R1968:Gnas
|
UTSW |
2 |
174,140,526 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R2290:Gnas
|
UTSW |
2 |
174,141,803 (GRCm39) |
missense |
probably benign |
0.09 |
|
R4125:Gnas
|
UTSW |
2 |
174,141,958 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R4128:Gnas
|
UTSW |
2 |
174,141,958 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R4697:Gnas
|
UTSW |
2 |
174,139,873 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4888:Gnas
|
UTSW |
2 |
174,139,882 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R5458:Gnas
|
UTSW |
2 |
174,140,124 (GRCm39) |
missense |
probably benign |
0.41 |
|
R5640:Gnas
|
UTSW |
2 |
174,126,764 (GRCm39) |
missense |
probably benign |
0.44 |
|
R5696:Gnas
|
UTSW |
2 |
174,141,468 (GRCm39) |
intron |
probably benign |
|
|
R5757:Gnas
|
UTSW |
2 |
174,187,040 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6053:Gnas
|
UTSW |
2 |
174,141,645 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
R6083:Gnas
|
UTSW |
2 |
174,139,655 (GRCm39) |
start codon destroyed |
probably null |
|
|
R6736:Gnas
|
UTSW |
2 |
174,176,044 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R7074:Gnas
|
UTSW |
2 |
174,126,842 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7239:Gnas
|
UTSW |
2 |
174,140,408 (GRCm39) |
missense |
unknown |
|
|
R7541:Gnas
|
UTSW |
2 |
174,139,892 (GRCm39) |
missense |
unknown |
|
|
R7679:Gnas
|
UTSW |
2 |
174,126,624 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R7694:Gnas
|
UTSW |
2 |
174,142,005 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7713:Gnas
|
UTSW |
2 |
174,140,820 (GRCm39) |
missense |
unknown |
|
|
R7834:Gnas
|
UTSW |
2 |
174,140,783 (GRCm39) |
nonsense |
probably null |
|
|
R8138:Gnas
|
UTSW |
2 |
174,140,179 (GRCm39) |
missense |
probably benign |
0.06 |
|
R8459:Gnas
|
UTSW |
2 |
174,126,732 (GRCm39) |
missense |
probably benign |
0.05 |
|
R8731:Gnas
|
UTSW |
2 |
174,126,699 (GRCm39) |
missense |
probably benign |
0.01 |
|
R8924:Gnas
|
UTSW |
2 |
174,141,277 (GRCm39) |
missense |
unknown |
|
|
R9431:Gnas
|
UTSW |
2 |
174,139,826 (GRCm39) |
missense |
unknown |
|
|
R9513:Gnas
|
UTSW |
2 |
174,185,089 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R9617:Gnas
|
UTSW |
2 |
174,141,988 (GRCm39) |
missense |
possibly damaging |
0.90 |
|
R9710:Gnas
|
UTSW |
2 |
174,141,132 (GRCm39) |
missense |
unknown |
|
|
R9711:Gnas
|
UTSW |
2 |
174,141,392 (GRCm39) |
missense |
unknown |
|
|
R9762:Gnas
|
UTSW |
2 |
174,140,639 (GRCm39) |
nonsense |
probably null |
|
|
X0022:Gnas
|
UTSW |
2 |
174,141,537 (GRCm39) |
missense |
probably benign |
0.33 |
|
Z1088:Gnas
|
UTSW |
2 |
174,140,166 (GRCm39) |
missense |
probably benign |
0.27 |
|
Z1176:Gnas
|
UTSW |
2 |
174,140,399 (GRCm39) |
missense |
unknown |
|
|
Z1177:Gnas
|
UTSW |
2 |
174,126,680 (GRCm39) |
missense |
unknown |
|
|
| Predicted Primers |
PCR Primer
(F):5'- CCATTTGAGTTCAACGAGCCTG -3'
(R):5'- AATCTCAAGCAGGGGTCTGG -3'
Sequencing Primer
(F):5'- TGCAAGTCCCAGACCTTGC -3'
(R):5'- CAGGGGTCTGGTGATCTCCATC -3'
|
| Posted On |
2021-01-18 |
Incidental Mutation