Incidental Mutation 'R6015:Atxn2'
| ID |
478554 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Atxn2
|
| Ensembl Gene |
ENSMUSG00000042605 |
| Gene Name |
ataxin 2 |
| Synonyms |
9630045M23Rik, ATX2, Sca2 |
| MMRRC Submission |
043254-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.783)
|
| Stock # |
R6015 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Not validated
|
| Chromosome |
5 |
| Chromosomal Location |
121849672-121954372 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to A
at 121949055 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Valine to Aspartic acid
at position 817
(V817D)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000124070
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000051950]
[ENSMUST00000086310]
[ENSMUST00000136960]
[ENSMUST00000160220]
[ENSMUST00000160462]
[ENSMUST00000161064]
[ENSMUST00000162327]
[ENSMUST00000161159]
|
| AlphaFold |
no structure available at present |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000051950
AA Change: V1144D
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000056715
Gene: ENSMUSG00000042605
AA Change: V1144D
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
32 |
42 |
N/A |
INTRINSIC |
|
low complexity region
|
46 |
69 |
N/A |
INTRINSIC |
|
low complexity region
|
93 |
116 |
N/A |
INTRINSIC |
|
low complexity region
|
128 |
144 |
N/A |
INTRINSIC |
|
low complexity region
|
168 |
219 |
N/A |
INTRINSIC |
|
Pfam:SM-ATX
|
236 |
307 |
6.4e-23 |
PFAM |
|
LsmAD
|
378 |
446 |
8.57e-25 |
SMART |
|
low complexity region
|
520 |
540 |
N/A |
INTRINSIC |
|
low complexity region
|
544 |
576 |
N/A |
INTRINSIC |
|
low complexity region
|
685 |
705 |
N/A |
INTRINSIC |
|
low complexity region
|
807 |
838 |
N/A |
INTRINSIC |
|
low complexity region
|
864 |
879 |
N/A |
INTRINSIC |
|
Pfam:PAM2
|
880 |
897 |
5.7e-9 |
PFAM |
|
low complexity region
|
1128 |
1165 |
N/A |
INTRINSIC |
|
low complexity region
|
1185 |
1196 |
N/A |
INTRINSIC |
|
low complexity region
|
1245 |
1261 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000086310
|
| SMART Domains |
Protein: ENSMUSP00000083490
Gene: ENSMUSG00000042594
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
12 |
21 |
N/A |
INTRINSIC |
|
Pfam:Phe_ZIP
|
22 |
77 |
2e-22 |
PFAM |
|
low complexity region
|
114 |
128 |
N/A |
INTRINSIC |
|
PH
|
168 |
281 |
1.2e-2 |
SMART |
|
SH2
|
334 |
419 |
3.53e-19 |
SMART |
|
low complexity region
|
512 |
525 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000136960
|
| SMART Domains |
Protein: ENSMUSP00000119086
Gene: ENSMUSG00000042594
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
12 |
21 |
N/A |
INTRINSIC |
|
Pfam:Phe_ZIP
|
22 |
77 |
2.4e-23 |
PFAM |
|
low complexity region
|
114 |
128 |
N/A |
INTRINSIC |
|
PH
|
168 |
281 |
1.2e-2 |
SMART |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000159928
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000160220
|
| SMART Domains |
Protein: ENSMUSP00000124059
Gene: ENSMUSG00000042605
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
15 |
26 |
N/A |
INTRINSIC |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000160462
AA Change: V58D
PolyPhen 2
Score 0.915 (Sensitivity: 0.81; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000124092
Gene: ENSMUSG00000042605
AA Change: V58D
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
42 |
52 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000161064
AA Change: V817D
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000124070
Gene: ENSMUSG00000042605
AA Change: V817D
| Domain | Start | End | E-Value | Type |
|---|
|
LsmAD
|
69 |
137 |
8.57e-25 |
SMART |
|
low complexity region
|
211 |
231 |
N/A |
INTRINSIC |
|
low complexity region
|
235 |
267 |
N/A |
INTRINSIC |
|
low complexity region
|
376 |
396 |
N/A |
INTRINSIC |
|
low complexity region
|
498 |
529 |
N/A |
INTRINSIC |
|
low complexity region
|
555 |
570 |
N/A |
INTRINSIC |
|
Pfam:PAM2
|
571 |
588 |
3.5e-9 |
PFAM |
|
low complexity region
|
801 |
838 |
N/A |
INTRINSIC |
|
low complexity region
|
858 |
869 |
N/A |
INTRINSIC |
|
low complexity region
|
915 |
923 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000162327
AA Change: V520D
PolyPhen 2
Score 0.972 (Sensitivity: 0.77; Specificity: 0.96)
|
| SMART Domains |
Protein: ENSMUSP00000123784
Gene: ENSMUSG00000042605
AA Change: V520D
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
1 |
32 |
N/A |
INTRINSIC |
|
low complexity region
|
58 |
73 |
N/A |
INTRINSIC |
|
Pfam:PAM2
|
74 |
91 |
1.3e-9 |
PFAM |
|
low complexity region
|
302 |
339 |
N/A |
INTRINSIC |
|
low complexity region
|
359 |
370 |
N/A |
INTRINSIC |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000161159
AA Change: V122D
PolyPhen 2
Score 0.893 (Sensitivity: 0.82; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000123833
Gene: ENSMUSG00000042605
AA Change: V122D
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
74 |
111 |
N/A |
INTRINSIC |
|
low complexity region
|
131 |
142 |
N/A |
INTRINSIC |
|
low complexity region
|
188 |
196 |
N/A |
INTRINSIC |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000199451
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000162459
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000161836
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000161433
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000199864
|
| Coding Region Coverage |
- 1x: 99.9%
- 3x: 99.7%
- 10x: 98.3%
- 20x: 95.1%
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene belongs to a group of genes that is associated with microsatellite-expansion diseases, a class of neurological and neuromuscular disorders caused by expansion of short stretches of repetitive DNA. The protein encoded by this gene has two globular domains near the N-terminus, one of which contains a clathrin-mediated trans-Golgi signal and an endoplasmic reticulum exit signal. The encoded cytoplasmic protein localizes to the endoplasmic reticulum and plasma membrane, is involved in endocytosis, and modulates mTOR signals, modifying ribosomal translation and mitochondrial function. The N-terminal region of the protein contains a polyglutamine tract of 14-31 residues that can be expanded in the pathogenic state to 32-200 residues. Intermediate length expansions of this tract increase susceptibility to amyotrophic lateral sclerosis, while long expansions of this tract result in spinocerebellar ataxia-2, an autosomal-dominantly inherited, neurodegenerative disorder. Genome-wide association studies indicate that loss-of-function mutations in this gene may be associated with susceptibility to type I diabetes, obesity and hypertension. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]
PHENOTYPE: Homozygous mice exhibit an enlarged fat pad, hepatic steatosis and enlarged seminal vesicles. A mild defect in motor learning is seen, but no other notable behavioral or neurological defects are detectable. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 44 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Ano5 |
A |
C |
7: 51,224,525 (GRCm39) |
S480R |
probably benign |
Het |
| Aqr |
A |
G |
2: 114,005,646 (GRCm39) |
M1T |
probably null |
Het |
| Arhgef28 |
A |
G |
13: 98,211,530 (GRCm39) |
V151A |
possibly damaging |
Het |
| Atp6v1b2 |
T |
A |
8: 69,555,148 (GRCm39) |
I170N |
probably damaging |
Het |
| Cdh23 |
A |
C |
10: 60,143,761 (GRCm39) |
I2950S |
probably damaging |
Het |
| Ces1h |
A |
G |
8: 94,083,691 (GRCm39) |
L417P |
unknown |
Het |
| Cimap3 |
T |
C |
3: 105,906,937 (GRCm39) |
D154G |
possibly damaging |
Het |
| Csf1r |
A |
G |
18: 61,242,784 (GRCm39) |
E49G |
possibly damaging |
Het |
| Eml2 |
G |
A |
7: 18,935,088 (GRCm39) |
V432I |
probably damaging |
Het |
| Fat3 |
A |
G |
9: 16,287,346 (GRCm39) |
S726P |
possibly damaging |
Het |
| Grik2 |
A |
T |
10: 49,399,959 (GRCm39) |
|
probably null |
Het |
| Il9r |
A |
G |
11: 32,142,674 (GRCm39) |
V287A |
probably benign |
Het |
| Inpp5b |
T |
C |
4: 124,692,143 (GRCm39) |
C909R |
possibly damaging |
Het |
| Kat7 |
G |
A |
11: 95,174,860 (GRCm39) |
H384Y |
probably damaging |
Het |
| Lama5 |
A |
G |
2: 179,827,185 (GRCm39) |
S2272P |
probably benign |
Het |
| Megf10 |
A |
G |
18: 57,386,100 (GRCm39) |
H371R |
probably benign |
Het |
| Moxd2 |
A |
T |
6: 40,860,688 (GRCm39) |
Y310N |
probably damaging |
Het |
| Ntrk2 |
A |
T |
13: 59,208,209 (GRCm39) |
E685V |
probably damaging |
Het |
| Ogfr |
G |
T |
2: 180,236,467 (GRCm39) |
G351W |
probably damaging |
Het |
| Or52ac1 |
G |
T |
7: 104,245,915 (GRCm39) |
P158T |
probably damaging |
Het |
| Parp3 |
C |
T |
9: 106,351,481 (GRCm39) |
V207M |
possibly damaging |
Het |
| Pfkfb3 |
T |
C |
2: 11,486,146 (GRCm39) |
|
probably null |
Het |
| Pigr |
T |
C |
1: 130,774,998 (GRCm39) |
V475A |
probably benign |
Het |
| Pik3ap1 |
T |
A |
19: 41,316,640 (GRCm39) |
Y250F |
probably benign |
Het |
| Ppp1r3c |
A |
T |
19: 36,711,206 (GRCm39) |
I188N |
probably damaging |
Het |
| Prmt7 |
T |
G |
8: 106,961,640 (GRCm39) |
|
probably benign |
Het |
| Psapl1 |
T |
C |
5: 36,361,594 (GRCm39) |
V62A |
probably benign |
Het |
| Relch |
T |
C |
1: 105,619,683 (GRCm39) |
L280S |
probably damaging |
Het |
| Rpp14 |
G |
A |
14: 8,090,462 (GRCm38) |
V129I |
probably benign |
Het |
| Sema4f |
A |
G |
6: 82,916,553 (GRCm39) |
|
probably benign |
Het |
| Serpinb13 |
C |
A |
1: 106,928,337 (GRCm39) |
A319E |
probably benign |
Het |
| Sez6l2 |
A |
T |
7: 126,552,625 (GRCm39) |
S134C |
probably damaging |
Het |
| Slc4a10 |
T |
A |
2: 62,059,046 (GRCm39) |
H184Q |
probably benign |
Het |
| Slc9a9 |
G |
T |
9: 94,821,602 (GRCm39) |
A330S |
probably benign |
Het |
| Sord |
T |
C |
2: 122,087,424 (GRCm39) |
V176A |
probably damaging |
Het |
| Ssbp2 |
G |
T |
13: 91,817,862 (GRCm39) |
|
probably null |
Het |
| Stab2 |
G |
T |
10: 86,773,906 (GRCm39) |
N808K |
probably damaging |
Het |
| Syne1 |
A |
G |
10: 5,296,819 (GRCm39) |
|
probably null |
Het |
| Tpcn2 |
A |
G |
7: 144,820,588 (GRCm39) |
V341A |
probably damaging |
Het |
| Unc13b |
C |
A |
4: 43,177,995 (GRCm39) |
S2941* |
probably null |
Het |
| Utrn |
T |
A |
10: 12,354,168 (GRCm39) |
H2806L |
possibly damaging |
Het |
| Vmn1r40 |
C |
A |
6: 89,691,588 (GRCm39) |
A135D |
probably damaging |
Het |
| Vmn1r68 |
C |
T |
7: 10,261,616 (GRCm39) |
V161M |
probably benign |
Het |
| Wiz |
T |
A |
17: 32,606,574 (GRCm39) |
I54F |
probably damaging |
Het |
|
| Other mutations in Atxn2 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00656:Atxn2
|
APN |
5 |
121,933,118 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL00798:Atxn2
|
APN |
5 |
121,933,298 (GRCm39) |
missense |
possibly damaging |
0.58 |
|
IGL01518:Atxn2
|
APN |
5 |
121,949,042 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01737:Atxn2
|
APN |
5 |
121,935,407 (GRCm39) |
missense |
probably damaging |
0.98 |
|
IGL01832:Atxn2
|
APN |
5 |
121,944,331 (GRCm39) |
nonsense |
probably null |
|
|
IGL02122:Atxn2
|
APN |
5 |
121,916,093 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02333:Atxn2
|
APN |
5 |
121,919,450 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02742:Atxn2
|
APN |
5 |
121,919,399 (GRCm39) |
missense |
possibly damaging |
0.75 |
|
IGL03028:Atxn2
|
APN |
5 |
121,948,972 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03282:Atxn2
|
APN |
5 |
121,923,298 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0387:Atxn2
|
UTSW |
5 |
121,940,206 (GRCm39) |
missense |
possibly damaging |
0.83 |
|
R0653:Atxn2
|
UTSW |
5 |
121,910,841 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R0849:Atxn2
|
UTSW |
5 |
121,885,484 (GRCm39) |
splice site |
probably null |
|
|
R1305:Atxn2
|
UTSW |
5 |
121,887,247 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1440:Atxn2
|
UTSW |
5 |
121,941,145 (GRCm39) |
critical splice donor site |
probably null |
|
|
R1471:Atxn2
|
UTSW |
5 |
121,924,437 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1521:Atxn2
|
UTSW |
5 |
121,917,654 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1528:Atxn2
|
UTSW |
5 |
121,951,593 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1528:Atxn2
|
UTSW |
5 |
121,940,171 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R2083:Atxn2
|
UTSW |
5 |
121,922,069 (GRCm39) |
missense |
probably benign |
0.00 |
|
R2197:Atxn2
|
UTSW |
5 |
121,944,280 (GRCm39) |
splice site |
probably null |
|
|
R2217:Atxn2
|
UTSW |
5 |
121,941,140 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2218:Atxn2
|
UTSW |
5 |
121,941,140 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2420:Atxn2
|
UTSW |
5 |
121,940,142 (GRCm39) |
critical splice acceptor site |
probably null |
|
|
R2421:Atxn2
|
UTSW |
5 |
121,940,142 (GRCm39) |
critical splice acceptor site |
probably null |
|
|
R2510:Atxn2
|
UTSW |
5 |
121,919,456 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3706:Atxn2
|
UTSW |
5 |
121,923,931 (GRCm39) |
critical splice donor site |
probably null |
|
|
R4604:Atxn2
|
UTSW |
5 |
121,919,406 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4852:Atxn2
|
UTSW |
5 |
121,952,474 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R4914:Atxn2
|
UTSW |
5 |
121,887,159 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4982:Atxn2
|
UTSW |
5 |
121,952,406 (GRCm39) |
missense |
possibly damaging |
0.66 |
|
R5172:Atxn2
|
UTSW |
5 |
121,933,098 (GRCm39) |
splice site |
probably null |
|
|
R5213:Atxn2
|
UTSW |
5 |
121,952,543 (GRCm39) |
splice site |
probably null |
|
|
R5655:Atxn2
|
UTSW |
5 |
121,885,489 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R5775:Atxn2
|
UTSW |
5 |
121,951,512 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5782:Atxn2
|
UTSW |
5 |
121,935,373 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6438:Atxn2
|
UTSW |
5 |
121,917,495 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6529:Atxn2
|
UTSW |
5 |
121,949,677 (GRCm39) |
critical splice donor site |
probably null |
|
|
R6659:Atxn2
|
UTSW |
5 |
121,916,027 (GRCm39) |
missense |
probably benign |
0.10 |
|
R6864:Atxn2
|
UTSW |
5 |
121,917,557 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7035:Atxn2
|
UTSW |
5 |
121,949,530 (GRCm39) |
nonsense |
probably null |
|
|
R7166:Atxn2
|
UTSW |
5 |
121,934,460 (GRCm39) |
missense |
possibly damaging |
0.90 |
|
R7253:Atxn2
|
UTSW |
5 |
121,916,084 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7257:Atxn2
|
UTSW |
5 |
121,923,880 (GRCm39) |
missense |
possibly damaging |
0.62 |
|
R7467:Atxn2
|
UTSW |
5 |
121,940,330 (GRCm39) |
critical splice donor site |
probably null |
|
|
R7544:Atxn2
|
UTSW |
5 |
121,919,431 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7648:Atxn2
|
UTSW |
5 |
121,934,440 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R7883:Atxn2
|
UTSW |
5 |
121,940,180 (GRCm39) |
missense |
possibly damaging |
0.79 |
|
R8097:Atxn2
|
UTSW |
5 |
121,887,286 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8784:Atxn2
|
UTSW |
5 |
121,933,091 (GRCm39) |
missense |
probably benign |
0.00 |
|
R8835:Atxn2
|
UTSW |
5 |
121,940,248 (GRCm39) |
missense |
possibly damaging |
0.63 |
|
R8880:Atxn2
|
UTSW |
5 |
121,948,973 (GRCm39) |
missense |
probably benign |
0.24 |
|
R8983:Atxn2
|
UTSW |
5 |
121,916,063 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9254:Atxn2
|
UTSW |
5 |
121,885,509 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9332:Atxn2
|
UTSW |
5 |
121,923,425 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9379:Atxn2
|
UTSW |
5 |
121,885,509 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9412:Atxn2
|
UTSW |
5 |
121,940,201 (GRCm39) |
missense |
possibly damaging |
0.84 |
|
R9649:Atxn2
|
UTSW |
5 |
121,949,055 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R9656:Atxn2
|
UTSW |
5 |
121,922,061 (GRCm39) |
missense |
possibly damaging |
0.78 |
|
X0028:Atxn2
|
UTSW |
5 |
121,940,146 (GRCm39) |
missense |
probably benign |
0.01 |
|
Z1176:Atxn2
|
UTSW |
5 |
121,916,053 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- CAGTGAATTAGGCATAGTGGGC -3'
(R):5'- CCAACAGGAAGGCAGCATTG -3'
Sequencing Primer
(F):5'- CAGTGGTCGTCAGAATTGTACAC -3'
(R):5'- GCGGCTTGCCTTCAGGAATG -3'
|
| Posted On |
2017-06-26 |
Incidental Mutation