Incidental Mutation 'PIT4431001:Adcy1'
| ID |
555258 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Adcy1
|
| Ensembl Gene |
ENSMUSG00000020431 |
| Gene Name |
adenylate cyclase 1 |
| Synonyms |
AC1, I-AC, D11Bwg1392e |
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
PIT4431001 (G1)
|
| Quality Score |
185.009 |
|
Status
|
Not validated
|
| Chromosome |
11 |
| Chromosomal Location |
7013489-7128506 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
C to G
at 7014089 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Glutamine to Glutamic Acid
at position 164
(Q164E)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000020706
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000020706]
|
| AlphaFold |
O88444 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000020706
AA Change: Q164E
PolyPhen 2
Score 0.926 (Sensitivity: 0.81; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000020706
Gene: ENSMUSG00000020431
AA Change: Q164E
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
2 |
36 |
N/A |
INTRINSIC |
|
low complexity region
|
58 |
90 |
N/A |
INTRINSIC |
|
low complexity region
|
112 |
135 |
N/A |
INTRINSIC |
|
CYCc
|
257 |
455 |
2.05e-80 |
SMART |
|
transmembrane domain
|
608 |
630 |
N/A |
INTRINSIC |
|
transmembrane domain
|
634 |
656 |
N/A |
INTRINSIC |
|
transmembrane domain
|
676 |
698 |
N/A |
INTRINSIC |
|
CYCc
|
827 |
1038 |
1.71e-50 |
SMART |
|
low complexity region
|
1090 |
1104 |
N/A |
INTRINSIC |
|
| Coding Region Coverage |
- 1x: 93.2%
- 3x: 90.7%
- 10x: 84.7%
- 20x: 71.4%
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the of adenylate cyclase gene family that is primarily expressed in the brain. This protein is regulated by calcium/calmodulin concentration and may be involved in brain development. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
PHENOTYPE: Mice homozygous for an insertional or null mutation fail to develop normal patterned distribution of neurons in the brain and display behavioral and learning abnormalities. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 74 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4930449I24Rik |
A |
G |
5: 146,439,322 (GRCm39) |
I29V |
probably benign |
Het |
| 5730455P16Rik |
C |
A |
11: 80,254,750 (GRCm39) |
C357F |
probably damaging |
Het |
| Actr1a |
A |
T |
19: 46,370,731 (GRCm39) |
|
probably null |
Het |
| Arhgap35 |
A |
T |
7: 16,295,536 (GRCm39) |
S1176R |
possibly damaging |
Het |
| Atad2b |
A |
G |
12: 5,081,795 (GRCm39) |
T1235A |
possibly damaging |
Het |
| Atosb |
C |
A |
4: 43,036,024 (GRCm39) |
G236C |
probably damaging |
Het |
| Atp8a2 |
T |
C |
14: 59,892,075 (GRCm39) |
D1091G |
probably benign |
Het |
| Bmp6 |
T |
C |
13: 38,669,906 (GRCm39) |
S397P |
probably benign |
Het |
| C3 |
A |
T |
17: 57,513,242 (GRCm39) |
N1468K |
probably benign |
Het |
| Ccnjl |
CGCG |
CGCGGCG |
11: 43,470,534 (GRCm39) |
|
probably benign |
Het |
| Ccr1 |
T |
C |
9: 123,764,231 (GRCm39) |
I100V |
probably benign |
Het |
| Cep162 |
T |
A |
9: 87,126,398 (GRCm39) |
R171S |
probably benign |
Het |
| Chd8 |
T |
C |
14: 52,455,706 (GRCm39) |
H994R |
probably damaging |
Het |
| Cntn3 |
T |
A |
6: 102,441,527 (GRCm39) |
K6N |
probably benign |
Het |
| Cope |
A |
G |
8: 70,765,417 (GRCm39) |
E289G |
probably damaging |
Het |
| Cpne8 |
T |
G |
15: 90,436,178 (GRCm39) |
E279A |
probably damaging |
Het |
| Cyp11a1 |
A |
T |
9: 57,923,555 (GRCm39) |
|
probably null |
Het |
| Dcp2 |
A |
G |
18: 44,545,638 (GRCm39) |
K333R |
probably benign |
Het |
| Dpp6 |
G |
T |
5: 27,836,496 (GRCm39) |
V329F |
probably benign |
Het |
| Drc1 |
T |
A |
5: 30,504,417 (GRCm39) |
D186E |
probably damaging |
Het |
| Dsc2 |
G |
A |
18: 20,179,334 (GRCm39) |
Q245* |
probably null |
Het |
| Eef1e1 |
T |
C |
13: 38,842,938 (GRCm39) |
E11G |
probably damaging |
Het |
| Emilin2 |
G |
A |
17: 71,562,990 (GRCm39) |
P915S |
probably benign |
Het |
| Fpgt |
A |
G |
3: 154,792,422 (GRCm39) |
M535T |
possibly damaging |
Het |
| Fxyd3 |
G |
A |
7: 30,770,780 (GRCm39) |
L37F |
probably damaging |
Het |
| Gal3st2c |
T |
A |
1: 93,935,834 (GRCm39) |
I62N |
probably damaging |
Het |
| Gdpd3 |
T |
C |
7: 126,365,647 (GRCm39) |
I2T |
probably benign |
Het |
| Gm9611 |
T |
C |
14: 42,115,888 (GRCm39) |
M169V |
|
Het |
| Ints3 |
G |
A |
3: 90,303,767 (GRCm39) |
T720I |
probably damaging |
Het |
| Itpr2 |
T |
G |
6: 146,256,218 (GRCm39) |
M992L |
probably benign |
Het |
| L3mbtl2 |
T |
A |
15: 81,560,508 (GRCm39) |
H256Q |
probably benign |
Het |
| Lama2 |
T |
C |
10: 26,977,426 (GRCm39) |
T1918A |
probably damaging |
Het |
| Lpcat2b |
G |
A |
5: 107,581,997 (GRCm39) |
G442D |
probably damaging |
Het |
| Lrp1b |
C |
T |
2: 40,894,767 (GRCm39) |
V2268M |
|
Het |
| Macc1 |
T |
C |
12: 119,410,246 (GRCm39) |
L338P |
probably benign |
Het |
| Mtmr2 |
T |
C |
9: 13,704,475 (GRCm39) |
F201L |
probably benign |
Het |
| Mtr |
C |
T |
13: 12,227,329 (GRCm39) |
V772M |
probably damaging |
Het |
| Mtus2 |
A |
G |
5: 148,013,515 (GRCm39) |
T103A |
probably benign |
Het |
| Myo5c |
A |
G |
9: 75,159,853 (GRCm39) |
I294V |
possibly damaging |
Het |
| Ncam1 |
A |
T |
9: 49,709,993 (GRCm39) |
F13I |
probably benign |
Het |
| Or4a75 |
T |
C |
2: 89,448,201 (GRCm39) |
I112V |
probably benign |
Het |
| Paqr6 |
A |
T |
3: 88,273,084 (GRCm39) |
I52F |
possibly damaging |
Het |
| Pde2a |
T |
G |
7: 101,151,104 (GRCm39) |
V271G |
probably damaging |
Het |
| Pde7b |
T |
C |
10: 20,276,291 (GRCm39) |
H405R |
possibly damaging |
Het |
| Plxnb1 |
A |
G |
9: 108,929,786 (GRCm39) |
Y214C |
probably damaging |
Het |
| Pmp22 |
T |
C |
11: 63,042,067 (GRCm39) |
F101L |
probably benign |
Het |
| Pold1 |
A |
G |
7: 44,188,318 (GRCm39) |
L520P |
probably damaging |
Het |
| Pramel1 |
A |
G |
4: 143,124,960 (GRCm39) |
T295A |
possibly damaging |
Het |
| Psg20 |
A |
T |
7: 18,408,475 (GRCm39) |
I415N |
probably damaging |
Het |
| Ptcd2 |
T |
A |
13: 99,476,527 (GRCm39) |
R71* |
probably null |
Het |
| Ptgs1 |
A |
T |
2: 36,130,692 (GRCm39) |
N197I |
probably damaging |
Het |
| Rbfox3 |
T |
C |
11: 118,386,047 (GRCm39) |
D333G |
probably damaging |
Het |
| Rfx7 |
T |
A |
9: 72,525,253 (GRCm39) |
H814Q |
probably benign |
Het |
| Rptn |
TGGGTCAGAAAGGCAGGCATGACCAGAGTCCTCACCAGGGTCAGAAAGGCAGGCATGACCAGAGTCCTCACCAGGGTCAGAAAGGCAGACAAGACCTGAGTTCTCACCAGGGTCAGAAAGGCAGACAAGACCAGAGTCCTCACCTGGGTCAGAAAGGCAGGCATGACCAGAGTCCTCACCGGGGTCAGAAAGGCAGGCAAGACCAGAGTCCTCACCAGGGTCAGAAAGGCAG |
TGGGTCAGAAAGGCAGGCATGACCAGAGTCCTCACCAGGGTCAGAAAGGCAGACAAGACCTGAGTTCTCACCAGGGTCAGAAAGGCAGACAAGACCAGAGTCCTCACCTGGGTCAGAAAGGCAGGCATGACCAGAGTCCTCACCGGGGTCAGAAAGGCAGGCAAGACCAGAGTCCTCACCAGGGTCAGAAAGGCAG |
3: 93,304,704 (GRCm39) |
|
probably benign |
Het |
| Serpina3i |
A |
T |
12: 104,231,432 (GRCm39) |
H23L |
probably benign |
Het |
| Sipa1l1 |
T |
A |
12: 82,443,290 (GRCm39) |
V860E |
probably benign |
Het |
| Slc12a1 |
T |
A |
2: 125,032,124 (GRCm39) |
Y592N |
possibly damaging |
Het |
| Slco2a1 |
T |
C |
9: 102,927,467 (GRCm39) |
F120S |
probably damaging |
Het |
| Smyd4 |
T |
C |
11: 75,294,339 (GRCm39) |
F740S |
probably damaging |
Het |
| Sppl2a |
T |
C |
2: 126,765,396 (GRCm39) |
Y242C |
probably damaging |
Het |
| Sqle |
A |
G |
15: 59,195,509 (GRCm39) |
K288R |
probably benign |
Het |
| Tbc1d17 |
A |
G |
7: 44,494,498 (GRCm39) |
S246P |
probably benign |
Het |
| Tenm3 |
G |
A |
8: 48,688,642 (GRCm39) |
T2315M |
probably damaging |
Het |
| Tgfb1i1 |
C |
T |
7: 127,848,353 (GRCm39) |
R191C |
probably damaging |
Het |
| Thumpd3 |
T |
A |
6: 113,036,939 (GRCm39) |
N279K |
probably benign |
Het |
| Tmed5 |
T |
A |
5: 108,277,887 (GRCm39) |
H95L |
possibly damaging |
Het |
| Tmem161a |
T |
C |
8: 70,634,674 (GRCm39) |
L443P |
probably damaging |
Het |
| Ttc38 |
C |
A |
15: 85,720,328 (GRCm39) |
Q97K |
probably benign |
Het |
| Unc13c |
C |
A |
9: 73,656,829 (GRCm39) |
C1124F |
probably damaging |
Het |
| Vmn2r102 |
A |
G |
17: 19,896,958 (GRCm39) |
T102A |
possibly damaging |
Het |
| Vwce |
G |
A |
19: 10,641,946 (GRCm39) |
E891K |
possibly damaging |
Het |
| Xkr5 |
A |
T |
8: 18,984,361 (GRCm39) |
S394T |
possibly damaging |
Het |
| Zan |
C |
T |
5: 137,390,326 (GRCm39) |
C4747Y |
unknown |
Het |
| Zfp804a |
T |
C |
2: 82,089,536 (GRCm39) |
F1122L |
probably benign |
Het |
|
| Other mutations in Adcy1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01149:Adcy1
|
APN |
11 |
7,087,385 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL01325:Adcy1
|
APN |
11 |
7,014,102 (GRCm39) |
missense |
possibly damaging |
0.58 |
|
IGL01531:Adcy1
|
APN |
11 |
7,119,414 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
IGL01585:Adcy1
|
APN |
11 |
7,117,143 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01932:Adcy1
|
APN |
11 |
7,050,565 (GRCm39) |
splice site |
probably benign |
|
|
IGL01945:Adcy1
|
APN |
11 |
7,111,891 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02532:Adcy1
|
APN |
11 |
7,094,737 (GRCm39) |
missense |
probably benign |
0.26 |
|
IGL02649:Adcy1
|
APN |
11 |
7,117,156 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02658:Adcy1
|
APN |
11 |
7,088,279 (GRCm39) |
splice site |
probably benign |
|
|
IGL02813:Adcy1
|
APN |
11 |
7,096,591 (GRCm39) |
missense |
possibly damaging |
0.83 |
|
IGL02931:Adcy1
|
APN |
11 |
7,029,012 (GRCm39) |
missense |
probably benign |
0.19 |
|
IGL03116:Adcy1
|
APN |
11 |
7,100,071 (GRCm39) |
missense |
probably benign |
|
|
IGL03119:Adcy1
|
APN |
11 |
7,059,051 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03214:Adcy1
|
APN |
11 |
7,117,054 (GRCm39) |
splice site |
probably benign |
|
|
PIT4520001:Adcy1
|
UTSW |
11 |
7,117,133 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0032:Adcy1
|
UTSW |
11 |
7,094,729 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
R0032:Adcy1
|
UTSW |
11 |
7,094,729 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
R0080:Adcy1
|
UTSW |
11 |
7,099,497 (GRCm39) |
splice site |
probably benign |
|
|
R0082:Adcy1
|
UTSW |
11 |
7,099,497 (GRCm39) |
splice site |
probably benign |
|
|
R0238:Adcy1
|
UTSW |
11 |
7,089,162 (GRCm39) |
missense |
possibly damaging |
0.80 |
|
R0238:Adcy1
|
UTSW |
11 |
7,089,162 (GRCm39) |
missense |
possibly damaging |
0.80 |
|
R0312:Adcy1
|
UTSW |
11 |
7,099,538 (GRCm39) |
missense |
probably benign |
0.08 |
|
R0569:Adcy1
|
UTSW |
11 |
7,096,514 (GRCm39) |
missense |
probably benign |
0.34 |
|
R1055:Adcy1
|
UTSW |
11 |
7,059,075 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1144:Adcy1
|
UTSW |
11 |
7,087,400 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1179:Adcy1
|
UTSW |
11 |
7,117,054 (GRCm39) |
splice site |
probably null |
|
|
R1245:Adcy1
|
UTSW |
11 |
7,119,410 (GRCm39) |
splice site |
probably benign |
|
|
R1467:Adcy1
|
UTSW |
11 |
7,088,396 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R1467:Adcy1
|
UTSW |
11 |
7,088,396 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R1823:Adcy1
|
UTSW |
11 |
7,111,312 (GRCm39) |
missense |
probably benign |
0.23 |
|
R1953:Adcy1
|
UTSW |
11 |
7,028,991 (GRCm39) |
missense |
probably benign |
0.01 |
|
R1957:Adcy1
|
UTSW |
11 |
7,111,945 (GRCm39) |
missense |
probably benign |
0.00 |
|
R2029:Adcy1
|
UTSW |
11 |
7,089,142 (GRCm39) |
missense |
probably benign |
0.10 |
|
R2051:Adcy1
|
UTSW |
11 |
7,111,885 (GRCm39) |
nonsense |
probably null |
|
|
R2483:Adcy1
|
UTSW |
11 |
7,080,348 (GRCm39) |
missense |
probably benign |
0.01 |
|
R3108:Adcy1
|
UTSW |
11 |
7,119,453 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3623:Adcy1
|
UTSW |
11 |
7,080,348 (GRCm39) |
missense |
probably benign |
0.01 |
|
R3624:Adcy1
|
UTSW |
11 |
7,080,348 (GRCm39) |
missense |
probably benign |
0.01 |
|
R4082:Adcy1
|
UTSW |
11 |
7,014,117 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4159:Adcy1
|
UTSW |
11 |
7,013,889 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4470:Adcy1
|
UTSW |
11 |
7,094,804 (GRCm39) |
missense |
probably benign |
0.17 |
|
R4472:Adcy1
|
UTSW |
11 |
7,080,369 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4951:Adcy1
|
UTSW |
11 |
7,088,336 (GRCm39) |
missense |
possibly damaging |
0.83 |
|
R4997:Adcy1
|
UTSW |
11 |
7,111,298 (GRCm39) |
missense |
probably benign |
0.25 |
|
R5237:Adcy1
|
UTSW |
11 |
7,099,553 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5288:Adcy1
|
UTSW |
11 |
7,111,351 (GRCm39) |
missense |
probably benign |
0.01 |
|
R5304:Adcy1
|
UTSW |
11 |
7,014,198 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5341:Adcy1
|
UTSW |
11 |
7,080,375 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R5379:Adcy1
|
UTSW |
11 |
7,096,532 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5592:Adcy1
|
UTSW |
11 |
7,089,088 (GRCm39) |
nonsense |
probably null |
|
|
R5677:Adcy1
|
UTSW |
11 |
7,111,914 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5680:Adcy1
|
UTSW |
11 |
7,059,020 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5753:Adcy1
|
UTSW |
11 |
7,080,300 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5888:Adcy1
|
UTSW |
11 |
7,089,095 (GRCm39) |
missense |
possibly damaging |
0.66 |
|
R5943:Adcy1
|
UTSW |
11 |
7,111,337 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6435:Adcy1
|
UTSW |
11 |
7,111,367 (GRCm39) |
missense |
possibly damaging |
0.60 |
|
R6931:Adcy1
|
UTSW |
11 |
7,100,884 (GRCm39) |
missense |
possibly damaging |
0.81 |
|
R6998:Adcy1
|
UTSW |
11 |
7,029,026 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7368:Adcy1
|
UTSW |
11 |
7,094,765 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7378:Adcy1
|
UTSW |
11 |
7,119,543 (GRCm39) |
missense |
possibly damaging |
0.56 |
|
R7393:Adcy1
|
UTSW |
11 |
7,087,381 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7500:Adcy1
|
UTSW |
11 |
7,094,762 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7529:Adcy1
|
UTSW |
11 |
7,089,157 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R8681:Adcy1
|
UTSW |
11 |
7,111,328 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8682:Adcy1
|
UTSW |
11 |
7,111,328 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8683:Adcy1
|
UTSW |
11 |
7,111,328 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8831:Adcy1
|
UTSW |
11 |
7,111,362 (GRCm39) |
missense |
probably benign |
0.02 |
|
R8859:Adcy1
|
UTSW |
11 |
7,111,877 (GRCm39) |
missense |
probably benign |
0.06 |
|
R8894:Adcy1
|
UTSW |
11 |
7,087,375 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R8904:Adcy1
|
UTSW |
11 |
7,059,075 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8970:Adcy1
|
UTSW |
11 |
7,099,983 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9037:Adcy1
|
UTSW |
11 |
7,087,325 (GRCm39) |
missense |
possibly damaging |
0.78 |
|
R9172:Adcy1
|
UTSW |
11 |
7,110,317 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R9303:Adcy1
|
UTSW |
11 |
7,094,766 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9448:Adcy1
|
UTSW |
11 |
7,099,575 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R9694:Adcy1
|
UTSW |
11 |
7,094,774 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9763:Adcy1
|
UTSW |
11 |
7,014,126 (GRCm39) |
missense |
probably damaging |
1.00 |
|
X0027:Adcy1
|
UTSW |
11 |
7,111,930 (GRCm39) |
missense |
possibly damaging |
0.47 |
|
Z1088:Adcy1
|
UTSW |
11 |
7,100,019 (GRCm39) |
missense |
probably benign |
0.19 |
|
Z1176:Adcy1
|
UTSW |
11 |
7,100,857 (GRCm39) |
missense |
probably damaging |
0.96 |
|
Z1176:Adcy1
|
UTSW |
11 |
7,099,536 (GRCm39) |
missense |
probably damaging |
0.99 |
|
Z1176:Adcy1
|
UTSW |
11 |
7,059,098 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Z1176:Adcy1
|
UTSW |
11 |
7,100,858 (GRCm39) |
missense |
possibly damaging |
0.62 |
|
Z1177:Adcy1
|
UTSW |
11 |
7,094,802 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Z1177:Adcy1
|
UTSW |
11 |
7,050,642 (GRCm39) |
nonsense |
probably null |
|
|
| Predicted Primers |
PCR Primer
(F):5'- TGTTCGTGGTCACCAATGTCC -3'
(R):5'- GTTAAACTCCTGCCACCTCCAG -3'
Sequencing Primer
(F):5'- GTGGTCACCAATGTCCGATCC -3'
(R):5'- GATGTGTCTCCAACCCAATGG -3'
|
| Posted On |
2019-06-07 |
Incidental Mutation