Incidental Mutation 'R0363:Cntnap4'
| ID |
30189 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Cntnap4
|
| Ensembl Gene |
ENSMUSG00000031772 |
| Gene Name |
contactin associated protein-like 4 |
| Synonyms |
Caspr4, E130114F09Rik |
| MMRRC Submission |
038569-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably non essential
(E-score: 0.082)
|
| Stock # |
R0363 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
8 |
| Chromosomal Location |
113296675-113609349 bp(+) (GRCm39) |
| Type of Mutation |
nonsense |
| DNA Base Change (assembly) |
A to T
at 113583143 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Lysine to Stop codon
at position 1074
(K1074*)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000112511
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000034225]
[ENSMUST00000118171]
|
| AlphaFold |
Q99P47 |
| Predicted Effect |
probably null
Transcript: ENSMUST00000034225
AA Change: K1074*
|
| SMART Domains |
Protein: ENSMUSP00000034225
Gene: ENSMUSG00000031772
AA Change: K1074*
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
27 |
N/A |
INTRINSIC |
|
FA58C
|
32 |
179 |
2.35e-19 |
SMART |
|
LamG
|
206 |
343 |
5.14e-25 |
SMART |
|
LamG
|
392 |
526 |
1.04e-25 |
SMART |
|
EGF
|
554 |
588 |
1.4e0 |
SMART |
|
Blast:FBG
|
591 |
775 |
1e-120 |
BLAST |
|
LamG
|
815 |
942 |
1.01e-32 |
SMART |
|
EGF
|
963 |
999 |
1.36e1 |
SMART |
|
LamG
|
1040 |
1178 |
7.8e-16 |
SMART |
|
transmembrane domain
|
1244 |
1266 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably null
Transcript: ENSMUST00000118171
AA Change: K1074*
|
| SMART Domains |
Protein: ENSMUSP00000112511
Gene: ENSMUSG00000031772
AA Change: K1074*
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
27 |
N/A |
INTRINSIC |
|
FA58C
|
32 |
179 |
2.35e-19 |
SMART |
|
LamG
|
206 |
343 |
5.14e-25 |
SMART |
|
LamG
|
392 |
526 |
1.04e-25 |
SMART |
|
EGF
|
554 |
588 |
1.4e0 |
SMART |
|
Blast:FBG
|
591 |
775 |
1e-120 |
BLAST |
|
LamG
|
815 |
942 |
1.01e-32 |
SMART |
|
EGF
|
963 |
999 |
1.36e1 |
SMART |
|
LamG
|
1040 |
1178 |
2.06e-15 |
SMART |
|
transmembrane domain
|
1244 |
1266 |
N/A |
INTRINSIC |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000125976
|
| Meta Mutation Damage Score |
0.9755 |
| Coding Region Coverage |
- 1x: 98.9%
- 3x: 97.8%
- 10x: 94.7%
- 20x: 86.5%
|
| Validation Efficiency |
98% (78/80) |
| 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 neurexin protein family. Members of this family function in the vertebrate nervous system as cell adhesion molecules and receptors. This protein contains epidermal growth factor repeats and laminin G domains. In addition, it includes an F5/8 type C domain, discoidin/neuropilin- and fibrinogen-like domains, and thrombospondin N-terminal-like domains. This protein may also play a role in proper neurotransmission in the dopaminergic and GABAergic systems and mutations in this gene may be associated with certain psychiatric illnesses. A polymorphism in an intron of this gene may be associated with longevity. [provided by RefSeq, Apr 2016]
PHENOTYPE: Homozygous knock-out mice show increased midbrain dopaminergic release in the nucleus accumbens, synaptic defects, impaired sensory-motor gating, and increased grooming behavior. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 75 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4930522H14Rik |
T |
A |
4: 109,381,520 (GRCm39) |
Q86L |
probably null |
Het |
| Abhd2 |
A |
G |
7: 79,000,561 (GRCm39) |
D262G |
possibly damaging |
Het |
| Abhd5 |
T |
C |
9: 122,197,211 (GRCm39) |
F133L |
possibly damaging |
Het |
| Agap2 |
T |
A |
10: 126,926,834 (GRCm39) |
V957E |
probably damaging |
Het |
| Ankrd12 |
T |
C |
17: 66,292,676 (GRCm39) |
K919R |
probably damaging |
Het |
| Ap1m1 |
T |
C |
8: 73,006,738 (GRCm39) |
S245P |
probably benign |
Het |
| Ap1m1 |
T |
C |
8: 73,010,568 (GRCm39) |
|
probably benign |
Het |
| Apcdd1 |
A |
G |
18: 63,070,168 (GRCm39) |
Y145C |
possibly damaging |
Het |
| Apob |
A |
T |
12: 8,060,136 (GRCm39) |
N2840Y |
probably damaging |
Het |
| Arel1 |
A |
G |
12: 84,981,027 (GRCm39) |
S327P |
probably damaging |
Het |
| Arhgap21 |
C |
A |
2: 20,885,944 (GRCm39) |
R421L |
probably damaging |
Het |
| Ccdc85a |
A |
T |
11: 28,533,400 (GRCm39) |
I48N |
probably damaging |
Het |
| Chd6 |
A |
G |
2: 160,856,244 (GRCm39) |
S672P |
probably damaging |
Het |
| Ciz1 |
G |
C |
2: 32,267,375 (GRCm39) |
|
probably null |
Het |
| Cmbl |
G |
A |
15: 31,585,588 (GRCm39) |
|
probably null |
Het |
| Cmya5 |
A |
G |
13: 93,231,377 (GRCm39) |
V1237A |
possibly damaging |
Het |
| Cntnap5b |
A |
G |
1: 100,202,193 (GRCm39) |
M347V |
probably benign |
Het |
| Col1a2 |
G |
A |
6: 4,518,822 (GRCm39) |
|
probably benign |
Het |
| Cuzd1 |
A |
T |
7: 130,917,991 (GRCm39) |
M203K |
probably benign |
Het |
| Cyp3a16 |
T |
C |
5: 145,392,689 (GRCm39) |
|
probably benign |
Het |
| Dlgap3 |
A |
G |
4: 127,129,314 (GRCm39) |
E892G |
probably damaging |
Het |
| Dnah7b |
T |
C |
1: 46,275,948 (GRCm39) |
S2612P |
probably damaging |
Het |
| Epas1 |
T |
G |
17: 87,113,276 (GRCm39) |
|
probably benign |
Het |
| Etv5 |
G |
A |
16: 22,230,458 (GRCm39) |
A192V |
probably benign |
Het |
| Fa2h |
T |
A |
8: 112,075,921 (GRCm39) |
H234L |
probably damaging |
Het |
| Fcho1 |
T |
C |
8: 72,170,134 (GRCm39) |
Y47C |
probably damaging |
Het |
| Flvcr1 |
T |
A |
1: 190,744,451 (GRCm39) |
|
probably benign |
Het |
| Il1rl1 |
CTTGTTGTTGTTGTTGTTG |
CTTGTTGTTGTTGTTGTTGTTG |
1: 40,481,734 (GRCm39) |
|
probably benign |
Het |
| Ino80 |
G |
A |
2: 119,213,441 (GRCm39) |
R1249C |
probably damaging |
Het |
| Inpp4b |
T |
C |
8: 82,610,886 (GRCm39) |
|
probably benign |
Het |
| Isy1 |
G |
A |
6: 87,796,167 (GRCm39) |
R257W |
probably damaging |
Het |
| Kmt2a |
A |
G |
9: 44,721,010 (GRCm39) |
|
probably null |
Het |
| Krt4 |
G |
A |
15: 101,833,081 (GRCm39) |
R9C |
possibly damaging |
Het |
| Map1a |
T |
C |
2: 121,132,525 (GRCm39) |
S876P |
probably damaging |
Het |
| Mettl21e |
A |
G |
1: 44,250,190 (GRCm39) |
|
probably null |
Het |
| Msh2 |
C |
T |
17: 88,024,904 (GRCm39) |
T594M |
probably benign |
Het |
| Mtmr3 |
A |
G |
11: 4,437,536 (GRCm39) |
S973P |
probably damaging |
Het |
| Muc5ac |
A |
T |
7: 141,354,697 (GRCm39) |
M889L |
probably benign |
Het |
| Ntn1 |
A |
G |
11: 68,276,369 (GRCm39) |
I193T |
probably benign |
Het |
| Nudt13 |
A |
T |
14: 20,359,851 (GRCm39) |
I193F |
probably damaging |
Het |
| Or2n1 |
A |
G |
17: 38,486,338 (GRCm39) |
D121G |
probably damaging |
Het |
| Or3a1 |
C |
T |
11: 74,225,925 (GRCm39) |
G44D |
probably damaging |
Het |
| Or4b1b |
A |
T |
2: 90,112,200 (GRCm39) |
S240T |
probably damaging |
Het |
| Or5p73 |
A |
T |
7: 108,064,941 (GRCm39) |
T137S |
possibly damaging |
Het |
| Otulin |
A |
G |
15: 27,606,381 (GRCm39) |
V344A |
probably damaging |
Het |
| P2rx7 |
C |
T |
5: 122,795,093 (GRCm39) |
Q128* |
probably null |
Het |
| Pcdhb22 |
G |
A |
18: 37,652,213 (GRCm39) |
R227H |
probably benign |
Het |
| Plekha5 |
G |
A |
6: 140,537,473 (GRCm39) |
R646K |
possibly damaging |
Het |
| Pltp |
C |
T |
2: 164,682,056 (GRCm39) |
R394H |
probably benign |
Het |
| Ppip5k1 |
C |
G |
2: 121,177,836 (GRCm39) |
A324P |
probably damaging |
Het |
| Pramel14 |
C |
T |
4: 143,718,221 (GRCm39) |
M407I |
probably benign |
Het |
| Prdm13 |
A |
C |
4: 21,679,737 (GRCm39) |
V251G |
unknown |
Het |
| Prkg1 |
T |
C |
19: 31,641,596 (GRCm39) |
E29G |
probably damaging |
Het |
| Prrc2c |
A |
G |
1: 162,525,380 (GRCm39) |
S409P |
unknown |
Het |
| Rp1 |
T |
A |
1: 4,417,941 (GRCm39) |
D1057V |
probably damaging |
Het |
| Rttn |
G |
A |
18: 89,029,079 (GRCm39) |
C599Y |
probably damaging |
Het |
| Shisa6 |
C |
T |
11: 66,416,153 (GRCm39) |
R213Q |
probably benign |
Het |
| Slc3a1 |
T |
C |
17: 85,340,273 (GRCm39) |
Y232H |
probably damaging |
Het |
| Slx4 |
G |
A |
16: 3,797,953 (GRCm39) |
A1477V |
probably damaging |
Het |
| Ssrp1 |
T |
G |
2: 84,871,018 (GRCm39) |
I218S |
probably damaging |
Het |
| St6galnac1 |
A |
C |
11: 116,659,756 (GRCm39) |
S186A |
probably benign |
Het |
| Stab1 |
A |
G |
14: 30,880,965 (GRCm39) |
|
probably benign |
Het |
| Sycp2 |
T |
C |
2: 177,988,204 (GRCm39) |
|
probably benign |
Het |
| Syne2 |
T |
A |
12: 76,118,981 (GRCm39) |
I5867N |
probably damaging |
Het |
| Taar7f |
T |
A |
10: 23,925,839 (GRCm39) |
D144E |
probably damaging |
Het |
| Tlcd5 |
A |
T |
9: 43,023,048 (GRCm39) |
M84K |
probably damaging |
Het |
| Tmem87b |
T |
A |
2: 128,673,153 (GRCm39) |
S196T |
probably damaging |
Het |
| Tnfrsf21 |
A |
G |
17: 43,348,768 (GRCm39) |
T127A |
probably benign |
Het |
| Trp73 |
A |
G |
4: 154,148,406 (GRCm39) |
I336T |
probably benign |
Het |
| Ttl |
A |
G |
2: 128,917,981 (GRCm39) |
I148V |
probably damaging |
Het |
| Ttll7 |
T |
C |
3: 146,649,970 (GRCm39) |
Y667H |
probably benign |
Het |
| Ubr4 |
A |
G |
4: 139,119,171 (GRCm39) |
T152A |
probably damaging |
Het |
| Vmn1r58 |
A |
T |
7: 5,413,636 (GRCm39) |
V198E |
probably damaging |
Het |
| Vps52 |
T |
A |
17: 34,181,091 (GRCm39) |
F376L |
probably benign |
Het |
| Zfp1007 |
T |
C |
5: 109,824,754 (GRCm39) |
E232G |
probably benign |
Het |
|
| Other mutations in Cntnap4 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00847:Cntnap4
|
APN |
8 |
113,494,251 (GRCm39) |
splice site |
probably benign |
|
|
IGL01898:Cntnap4
|
APN |
8 |
113,582,939 (GRCm39) |
missense |
possibly damaging |
0.46 |
|
IGL01918:Cntnap4
|
APN |
8 |
113,478,866 (GRCm39) |
missense |
possibly damaging |
0.67 |
|
IGL02257:Cntnap4
|
APN |
8 |
113,343,126 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02302:Cntnap4
|
APN |
8 |
113,512,535 (GRCm39) |
splice site |
probably benign |
|
|
IGL02621:Cntnap4
|
APN |
8 |
113,537,355 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03008:Cntnap4
|
APN |
8 |
113,500,222 (GRCm39) |
missense |
probably benign |
0.06 |
|
IGL03327:Cntnap4
|
APN |
8 |
113,500,208 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL03346:Cntnap4
|
APN |
8 |
113,500,208 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0025:Cntnap4
|
UTSW |
8 |
113,529,796 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0025:Cntnap4
|
UTSW |
8 |
113,529,796 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0058:Cntnap4
|
UTSW |
8 |
113,512,416 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R0310:Cntnap4
|
UTSW |
8 |
113,569,148 (GRCm39) |
critical splice acceptor site |
probably null |
|
|
R0497:Cntnap4
|
UTSW |
8 |
113,296,783 (GRCm39) |
missense |
probably benign |
0.00 |
|
R1495:Cntnap4
|
UTSW |
8 |
113,608,395 (GRCm39) |
missense |
possibly damaging |
0.81 |
|
R1579:Cntnap4
|
UTSW |
8 |
113,608,462 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
R1704:Cntnap4
|
UTSW |
8 |
113,484,155 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1943:Cntnap4
|
UTSW |
8 |
113,542,128 (GRCm39) |
missense |
probably benign |
0.10 |
|
R2160:Cntnap4
|
UTSW |
8 |
113,484,203 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2226:Cntnap4
|
UTSW |
8 |
113,542,120 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R3148:Cntnap4
|
UTSW |
8 |
113,484,071 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3916:Cntnap4
|
UTSW |
8 |
113,602,165 (GRCm39) |
missense |
probably benign |
0.02 |
|
R3917:Cntnap4
|
UTSW |
8 |
113,602,165 (GRCm39) |
missense |
probably benign |
0.02 |
|
R4097:Cntnap4
|
UTSW |
8 |
113,478,939 (GRCm39) |
missense |
probably benign |
0.03 |
|
R4348:Cntnap4
|
UTSW |
8 |
113,480,554 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4469:Cntnap4
|
UTSW |
8 |
113,391,898 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4530:Cntnap4
|
UTSW |
8 |
113,584,842 (GRCm39) |
missense |
probably benign |
0.32 |
|
R4531:Cntnap4
|
UTSW |
8 |
113,537,240 (GRCm39) |
missense |
possibly damaging |
0.90 |
|
R4586:Cntnap4
|
UTSW |
8 |
113,537,342 (GRCm39) |
missense |
probably benign |
|
|
R4611:Cntnap4
|
UTSW |
8 |
113,500,371 (GRCm39) |
critical splice donor site |
probably null |
|
|
R4675:Cntnap4
|
UTSW |
8 |
113,512,468 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4801:Cntnap4
|
UTSW |
8 |
113,500,222 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R4802:Cntnap4
|
UTSW |
8 |
113,500,222 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R5273:Cntnap4
|
UTSW |
8 |
113,460,070 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6114:Cntnap4
|
UTSW |
8 |
113,568,385 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6194:Cntnap4
|
UTSW |
8 |
113,602,061 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6222:Cntnap4
|
UTSW |
8 |
113,569,353 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6262:Cntnap4
|
UTSW |
8 |
113,529,843 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R6276:Cntnap4
|
UTSW |
8 |
113,478,921 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R6483:Cntnap4
|
UTSW |
8 |
113,484,105 (GRCm39) |
missense |
possibly damaging |
0.82 |
|
R6819:Cntnap4
|
UTSW |
8 |
113,529,858 (GRCm39) |
missense |
probably benign |
0.03 |
|
R7031:Cntnap4
|
UTSW |
8 |
113,584,874 (GRCm39) |
missense |
probably benign |
0.01 |
|
R7107:Cntnap4
|
UTSW |
8 |
113,542,120 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R7146:Cntnap4
|
UTSW |
8 |
113,537,268 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7192:Cntnap4
|
UTSW |
8 |
113,608,432 (GRCm39) |
missense |
probably benign |
0.05 |
|
R7232:Cntnap4
|
UTSW |
8 |
113,391,731 (GRCm39) |
splice site |
probably null |
|
|
R7348:Cntnap4
|
UTSW |
8 |
113,391,909 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7482:Cntnap4
|
UTSW |
8 |
113,460,194 (GRCm39) |
critical splice donor site |
probably null |
|
|
R7832:Cntnap4
|
UTSW |
8 |
113,484,113 (GRCm39) |
missense |
probably benign |
|
|
R7895:Cntnap4
|
UTSW |
8 |
113,478,829 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R8014:Cntnap4
|
UTSW |
8 |
113,480,577 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R8185:Cntnap4
|
UTSW |
8 |
113,391,897 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8197:Cntnap4
|
UTSW |
8 |
113,296,857 (GRCm39) |
missense |
probably benign |
0.00 |
|
R8287:Cntnap4
|
UTSW |
8 |
113,585,775 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8299:Cntnap4
|
UTSW |
8 |
113,500,324 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8498:Cntnap4
|
UTSW |
8 |
113,602,211 (GRCm39) |
missense |
possibly damaging |
0.52 |
|
R8699:Cntnap4
|
UTSW |
8 |
113,484,228 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8774:Cntnap4
|
UTSW |
8 |
113,529,820 (GRCm39) |
missense |
probably benign |
0.01 |
|
R8774-TAIL:Cntnap4
|
UTSW |
8 |
113,529,820 (GRCm39) |
missense |
probably benign |
0.01 |
|
R8872:Cntnap4
|
UTSW |
8 |
113,585,759 (GRCm39) |
missense |
possibly damaging |
0.79 |
|
R8895:Cntnap4
|
UTSW |
8 |
113,479,598 (GRCm39) |
missense |
probably benign |
0.40 |
|
R8965:Cntnap4
|
UTSW |
8 |
113,479,646 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9189:Cntnap4
|
UTSW |
8 |
113,602,600 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
R9260:Cntnap4
|
UTSW |
8 |
113,500,276 (GRCm39) |
missense |
probably benign |
0.08 |
|
R9474:Cntnap4
|
UTSW |
8 |
113,460,103 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R9565:Cntnap4
|
UTSW |
8 |
113,582,982 (GRCm39) |
missense |
probably benign |
0.43 |
|
R9625:Cntnap4
|
UTSW |
8 |
113,602,181 (GRCm39) |
missense |
possibly damaging |
0.82 |
|
R9629:Cntnap4
|
UTSW |
8 |
113,568,349 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9745:Cntnap4
|
UTSW |
8 |
113,391,808 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
R9765:Cntnap4
|
UTSW |
8 |
113,568,496 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R9765:Cntnap4
|
UTSW |
8 |
113,484,110 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9793:Cntnap4
|
UTSW |
8 |
113,608,357 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9795:Cntnap4
|
UTSW |
8 |
113,608,357 (GRCm39) |
missense |
probably benign |
0.00 |
|
X0025:Cntnap4
|
UTSW |
8 |
113,585,775 (GRCm39) |
missense |
probably damaging |
1.00 |
|
X0063:Cntnap4
|
UTSW |
8 |
113,602,211 (GRCm39) |
missense |
probably benign |
0.05 |
|
Z1088:Cntnap4
|
UTSW |
8 |
113,542,152 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Z1176:Cntnap4
|
UTSW |
8 |
113,584,821 (GRCm39) |
missense |
possibly damaging |
0.70 |
|
Z1186:Cntnap4
|
UTSW |
8 |
113,479,002 (GRCm39) |
missense |
probably damaging |
0.99 |
|
| Predicted Primers |
PCR Primer
(F):5'- AGAACTCCAGCTTTCACGCTGCTTCAT -3'
(R):5'- GGACCAACAGGTCATCTCCTGGACATT -3'
Sequencing Primer
(F):5'- ACCAAGCTTGCTGCTTCA -3'
(R):5'- aatgcctctaaccaccacc -3'
|
| Posted On |
2013-04-24 |
Incidental Mutation