Incidental Mutation 'R4434:Shank3'
| ID |
328774 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Shank3
|
| Ensembl Gene |
ENSMUSG00000022623 |
| Gene Name |
SH3 and multiple ankyrin repeat domains 3 |
| Synonyms |
ProSAP2 |
| MMRRC Submission |
041148-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably non essential
(E-score: 0.176)
|
| Stock # |
R4434 (G1)
|
| Quality Score |
225 |
|
Status
|
Not validated
|
| Chromosome |
15 |
| Chromosomal Location |
89383826-89444464 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
C to A
at 89387562 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Leucine to Isoleucine
at position 244
(L244I)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000104932
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000039074]
[ENSMUST00000066545]
[ENSMUST00000109309]
|
| AlphaFold |
Q4ACU6 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000039074
AA Change: L169I
PolyPhen 2
Score 0.879 (Sensitivity: 0.82; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000048062
Gene: ENSMUSG00000022623
AA Change: L169I
| Domain | Start | End | E-Value | Type |
|---|
|
ANK
|
182 |
211 |
1.54e-1 |
SMART |
|
ANK
|
215 |
245 |
3.36e2 |
SMART |
|
ANK
|
249 |
278 |
2.47e0 |
SMART |
|
ANK
|
282 |
311 |
3.71e-4 |
SMART |
|
ANK
|
315 |
345 |
5.03e2 |
SMART |
|
low complexity region
|
434 |
462 |
N/A |
INTRINSIC |
|
SH3
|
473 |
528 |
1.28e-14 |
SMART |
|
PDZ
|
579 |
664 |
3.95e-13 |
SMART |
|
low complexity region
|
672 |
684 |
N/A |
INTRINSIC |
|
low complexity region
|
813 |
843 |
N/A |
INTRINSIC |
|
low complexity region
|
857 |
869 |
N/A |
INTRINSIC |
|
low complexity region
|
905 |
923 |
N/A |
INTRINSIC |
|
low complexity region
|
1078 |
1092 |
N/A |
INTRINSIC |
|
low complexity region
|
1109 |
1121 |
N/A |
INTRINSIC |
|
low complexity region
|
1173 |
1194 |
N/A |
INTRINSIC |
|
low complexity region
|
1235 |
1252 |
N/A |
INTRINSIC |
|
low complexity region
|
1266 |
1278 |
N/A |
INTRINSIC |
|
low complexity region
|
1318 |
1332 |
N/A |
INTRINSIC |
|
low complexity region
|
1341 |
1355 |
N/A |
INTRINSIC |
|
low complexity region
|
1370 |
1395 |
N/A |
INTRINSIC |
|
low complexity region
|
1409 |
1427 |
N/A |
INTRINSIC |
|
low complexity region
|
1552 |
1558 |
N/A |
INTRINSIC |
|
low complexity region
|
1584 |
1599 |
N/A |
INTRINSIC |
|
low complexity region
|
1626 |
1658 |
N/A |
INTRINSIC |
|
SAM
|
1664 |
1730 |
3.08e-18 |
SMART |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000066545
|
| SMART Domains |
Protein: ENSMUSP00000064477
Gene: ENSMUSG00000022623
| Domain | Start | End | E-Value | Type |
|---|
|
ANK
|
109 |
138 |
1.54e-1 |
SMART |
|
ANK
|
142 |
172 |
3.36e2 |
SMART |
|
ANK
|
176 |
205 |
2.47e0 |
SMART |
|
ANK
|
209 |
238 |
3.71e-4 |
SMART |
|
ANK
|
242 |
272 |
5.03e2 |
SMART |
|
low complexity region
|
361 |
389 |
N/A |
INTRINSIC |
|
SH3
|
400 |
455 |
1.28e-14 |
SMART |
|
PDZ
|
506 |
591 |
3.95e-13 |
SMART |
|
low complexity region
|
599 |
611 |
N/A |
INTRINSIC |
|
low complexity region
|
625 |
636 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000109309
AA Change: L244I
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000104932
Gene: ENSMUSG00000022623
AA Change: L244I
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
5 |
55 |
N/A |
INTRINSIC |
|
Pfam:FERM_f0
|
84 |
167 |
2.5e-14 |
PFAM |
|
ANK
|
257 |
286 |
1.54e-1 |
SMART |
|
ANK
|
290 |
320 |
3.36e2 |
SMART |
|
ANK
|
324 |
353 |
2.47e0 |
SMART |
|
ANK
|
357 |
386 |
3.71e-4 |
SMART |
|
ANK
|
390 |
420 |
5.03e2 |
SMART |
|
low complexity region
|
509 |
537 |
N/A |
INTRINSIC |
|
SH3
|
548 |
603 |
1.28e-14 |
SMART |
|
PDZ
|
654 |
739 |
3.95e-13 |
SMART |
|
low complexity region
|
747 |
759 |
N/A |
INTRINSIC |
|
low complexity region
|
888 |
918 |
N/A |
INTRINSIC |
|
low complexity region
|
932 |
944 |
N/A |
INTRINSIC |
|
low complexity region
|
980 |
998 |
N/A |
INTRINSIC |
|
low complexity region
|
1153 |
1167 |
N/A |
INTRINSIC |
|
low complexity region
|
1184 |
1196 |
N/A |
INTRINSIC |
|
low complexity region
|
1248 |
1269 |
N/A |
INTRINSIC |
|
low complexity region
|
1310 |
1327 |
N/A |
INTRINSIC |
|
low complexity region
|
1341 |
1353 |
N/A |
INTRINSIC |
|
low complexity region
|
1393 |
1407 |
N/A |
INTRINSIC |
|
low complexity region
|
1416 |
1430 |
N/A |
INTRINSIC |
|
low complexity region
|
1445 |
1470 |
N/A |
INTRINSIC |
|
low complexity region
|
1484 |
1502 |
N/A |
INTRINSIC |
|
low complexity region
|
1627 |
1633 |
N/A |
INTRINSIC |
|
low complexity region
|
1659 |
1674 |
N/A |
INTRINSIC |
|
low complexity region
|
1701 |
1733 |
N/A |
INTRINSIC |
|
SAM
|
1739 |
1805 |
3.08e-18 |
SMART |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000135214
|
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.6%
- 10x: 97.3%
- 20x: 95.4%
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the Shank gene family. Shank proteins are multidomain scaffold proteins of the postsynaptic density that connect neurotransmitter receptors, ion channels, and other membrane proteins to the actin cytoskeleton and G-protein-coupled signaling pathways. Shank proteins also play a role in synapse formation and dendritic spine maturation. Mutations in this gene are a cause of autism spectrum disorder (ASD), which is characterized by impairments in social interaction and communication, and restricted behavioral patterns and interests. Mutations in this gene also cause schizophrenia type 15, and are a major causative factor in the neurological symptoms of 22q13.3 deletion syndrome, which is also known as Phelan-McDermid syndrome. Additional isoforms have been described for this gene but they have not yet been experimentally verified. [provided by RefSeq, Mar 2012]
PHENOTYPE: Mice carrying various deletions of exons encoding the ankyrin repeats (exons 4-9) exhibit a range of synaptic and autism-related impairments. Homozygotes lacking exon 9 show altered excitation/inhibition balance, increased rearing, and mildly impaired spatial memory. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 52 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Aars1 |
A |
T |
8: 111,781,253 (GRCm39) |
Q907L |
probably null |
Het |
| Adam6b |
A |
C |
12: 113,454,281 (GRCm39) |
Q366P |
probably damaging |
Het |
| AI597479 |
C |
T |
1: 43,139,959 (GRCm39) |
Q62* |
probably null |
Het |
| Akap9 |
T |
A |
5: 4,082,708 (GRCm39) |
M1944K |
probably damaging |
Het |
| Akr1c19 |
T |
C |
13: 4,292,615 (GRCm39) |
V212A |
probably benign |
Het |
| Ank3 |
C |
T |
10: 69,822,900 (GRCm39) |
S523L |
probably damaging |
Het |
| Antxrl |
G |
A |
14: 33,793,574 (GRCm39) |
|
probably benign |
Het |
| Arhgap21 |
A |
G |
2: 20,972,146 (GRCm39) |
C26R |
probably benign |
Het |
| Cdc37l1 |
T |
C |
19: 28,985,021 (GRCm39) |
F224L |
probably damaging |
Het |
| Csmd3 |
G |
A |
15: 47,763,191 (GRCm39) |
T1215I |
possibly damaging |
Het |
| Dnah7c |
G |
A |
1: 46,705,442 (GRCm39) |
R2485H |
probably damaging |
Het |
| Dnah9 |
T |
A |
11: 65,998,901 (GRCm39) |
N1049I |
possibly damaging |
Het |
| Dnaja3 |
T |
G |
16: 4,507,859 (GRCm39) |
Y120* |
probably null |
Het |
| Ehbp1l1 |
G |
T |
19: 5,766,276 (GRCm39) |
R412S |
possibly damaging |
Het |
| Fam169a |
A |
G |
13: 97,263,248 (GRCm39) |
D567G |
probably damaging |
Het |
| Gcnt4 |
T |
A |
13: 97,082,850 (GRCm39) |
Y49N |
probably benign |
Het |
| Gm5849 |
T |
A |
3: 90,685,182 (GRCm39) |
K1M |
probably null |
Het |
| Gngt1 |
A |
G |
6: 3,994,282 (GRCm39) |
D20G |
probably benign |
Het |
| Gnptab |
A |
G |
10: 88,248,484 (GRCm39) |
N104S |
probably damaging |
Het |
| Gpn3 |
A |
G |
5: 122,520,115 (GRCm39) |
D223G |
probably benign |
Het |
| Hectd1 |
A |
T |
12: 51,798,835 (GRCm39) |
I2095K |
probably damaging |
Het |
| Hephl1 |
C |
T |
9: 14,988,092 (GRCm39) |
R672H |
probably damaging |
Het |
| Hpse2 |
A |
G |
19: 43,282,708 (GRCm39) |
S182P |
probably benign |
Het |
| Itgb4 |
T |
A |
11: 115,890,640 (GRCm39) |
S1109R |
probably benign |
Het |
| Itgbl1 |
A |
T |
14: 124,209,611 (GRCm39) |
D330V |
probably damaging |
Het |
| Krt77 |
A |
T |
15: 101,773,904 (GRCm39) |
V250E |
probably damaging |
Het |
| Mycbp2 |
T |
A |
14: 103,371,225 (GRCm39) |
N4108Y |
probably damaging |
Het |
| Nampt |
T |
C |
12: 32,888,362 (GRCm39) |
I171T |
probably damaging |
Het |
| Nckap5l |
A |
C |
15: 99,320,744 (GRCm39) |
S1270A |
probably benign |
Het |
| Opa1 |
A |
G |
16: 29,430,801 (GRCm39) |
I500M |
probably damaging |
Het |
| Or10j5 |
C |
T |
1: 172,785,111 (GRCm39) |
H250Y |
probably damaging |
Het |
| Pax8 |
G |
A |
2: 24,319,621 (GRCm39) |
P350L |
possibly damaging |
Het |
| Plxnb2 |
A |
G |
15: 89,047,006 (GRCm39) |
C772R |
probably damaging |
Het |
| Prh1 |
A |
T |
6: 132,548,841 (GRCm39) |
H116L |
unknown |
Het |
| Rgsl1 |
C |
T |
1: 153,678,087 (GRCm39) |
A114T |
possibly damaging |
Het |
| Rln1 |
A |
T |
19: 29,311,962 (GRCm39) |
F12Y |
possibly damaging |
Het |
| Robo4 |
CGG |
CG |
9: 37,322,786 (GRCm39) |
|
probably null |
Het |
| Scube1 |
A |
T |
15: 83,606,125 (GRCm39) |
I49N |
probably damaging |
Het |
| Shc3 |
T |
C |
13: 51,603,302 (GRCm39) |
T268A |
probably benign |
Het |
| Sp7 |
A |
G |
15: 102,267,536 (GRCm39) |
L90P |
probably damaging |
Het |
| Tacc2 |
G |
A |
7: 130,225,271 (GRCm39) |
S652N |
probably damaging |
Het |
| Tacstd2 |
A |
G |
6: 67,512,128 (GRCm39) |
V188A |
possibly damaging |
Het |
| Tasor |
G |
A |
14: 27,171,818 (GRCm39) |
|
probably null |
Het |
| Tex26 |
T |
C |
5: 149,376,820 (GRCm39) |
S70P |
probably benign |
Het |
| Tmc4 |
C |
T |
7: 3,675,006 (GRCm39) |
V222M |
probably benign |
Het |
| Tnc |
T |
C |
4: 63,926,066 (GRCm39) |
T905A |
possibly damaging |
Het |
| Trim65 |
G |
A |
11: 116,018,435 (GRCm39) |
Q253* |
probably null |
Het |
| Tuba3a |
A |
T |
6: 125,258,506 (GRCm39) |
Y161* |
probably null |
Het |
| Zfand2b |
A |
G |
1: 75,147,330 (GRCm39) |
S197G |
possibly damaging |
Het |
| Zfp109 |
T |
A |
7: 23,928,771 (GRCm39) |
T213S |
probably benign |
Het |
| Zfp985 |
A |
C |
4: 147,668,368 (GRCm39) |
D412A |
probably benign |
Het |
| Zswim3 |
T |
A |
2: 164,662,563 (GRCm39) |
C348S |
probably benign |
Het |
|
| Other mutations in Shank3 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01070:Shank3
|
APN |
15 |
89,433,619 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01469:Shank3
|
APN |
15 |
89,405,477 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01886:Shank3
|
APN |
15 |
89,415,866 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01934:Shank3
|
APN |
15 |
89,434,049 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01989:Shank3
|
APN |
15 |
89,387,502 (GRCm39) |
splice site |
probably benign |
|
|
IGL02004:Shank3
|
APN |
15 |
89,387,502 (GRCm39) |
splice site |
probably benign |
|
|
IGL02085:Shank3
|
APN |
15 |
89,388,118 (GRCm39) |
critical splice donor site |
probably null |
|
|
IGL02195:Shank3
|
APN |
15 |
89,432,321 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02354:Shank3
|
APN |
15 |
89,388,536 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02361:Shank3
|
APN |
15 |
89,388,536 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02541:Shank3
|
APN |
15 |
89,385,613 (GRCm39) |
missense |
probably damaging |
1.00 |
|
G1citation:Shank3
|
UTSW |
15 |
89,415,830 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0294:Shank3
|
UTSW |
15 |
89,416,301 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0468:Shank3
|
UTSW |
15 |
89,433,478 (GRCm39) |
missense |
probably benign |
0.28 |
|
R0483:Shank3
|
UTSW |
15 |
89,427,442 (GRCm39) |
splice site |
probably benign |
|
|
R0605:Shank3
|
UTSW |
15 |
89,408,350 (GRCm39) |
missense |
possibly damaging |
0.49 |
|
R0675:Shank3
|
UTSW |
15 |
89,415,591 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
R1082:Shank3
|
UTSW |
15 |
89,433,574 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1576:Shank3
|
UTSW |
15 |
89,387,866 (GRCm39) |
missense |
probably benign |
0.11 |
|
R1702:Shank3
|
UTSW |
15 |
89,384,099 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1726:Shank3
|
UTSW |
15 |
89,442,189 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1958:Shank3
|
UTSW |
15 |
89,387,351 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1961:Shank3
|
UTSW |
15 |
89,442,167 (GRCm39) |
missense |
possibly damaging |
0.60 |
|
R2420:Shank3
|
UTSW |
15 |
89,405,413 (GRCm39) |
nonsense |
probably null |
|
|
R2513:Shank3
|
UTSW |
15 |
89,432,889 (GRCm39) |
missense |
probably benign |
0.05 |
|
R3917:Shank3
|
UTSW |
15 |
89,387,587 (GRCm39) |
missense |
possibly damaging |
0.77 |
|
R4163:Shank3
|
UTSW |
15 |
89,433,797 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4205:Shank3
|
UTSW |
15 |
89,387,521 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4791:Shank3
|
UTSW |
15 |
89,384,557 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4816:Shank3
|
UTSW |
15 |
89,427,318 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4828:Shank3
|
UTSW |
15 |
89,384,402 (GRCm39) |
intron |
probably benign |
|
|
R4911:Shank3
|
UTSW |
15 |
89,388,547 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4997:Shank3
|
UTSW |
15 |
89,433,901 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5213:Shank3
|
UTSW |
15 |
89,417,481 (GRCm39) |
missense |
possibly damaging |
0.82 |
|
R5338:Shank3
|
UTSW |
15 |
89,415,914 (GRCm39) |
splice site |
probably null |
|
|
R5494:Shank3
|
UTSW |
15 |
89,432,441 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R5543:Shank3
|
UTSW |
15 |
89,416,557 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5654:Shank3
|
UTSW |
15 |
89,405,529 (GRCm39) |
missense |
probably benign |
0.07 |
|
R5900:Shank3
|
UTSW |
15 |
89,387,593 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5906:Shank3
|
UTSW |
15 |
89,433,119 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6385:Shank3
|
UTSW |
15 |
89,405,578 (GRCm39) |
critical splice donor site |
probably null |
|
|
R6432:Shank3
|
UTSW |
15 |
89,387,616 (GRCm39) |
missense |
possibly damaging |
0.75 |
|
R6724:Shank3
|
UTSW |
15 |
89,416,656 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6822:Shank3
|
UTSW |
15 |
89,415,830 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6845:Shank3
|
UTSW |
15 |
89,432,528 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7088:Shank3
|
UTSW |
15 |
89,387,728 (GRCm39) |
splice site |
probably null |
|
|
R7390:Shank3
|
UTSW |
15 |
89,433,515 (GRCm39) |
missense |
probably benign |
0.05 |
|
R7808:Shank3
|
UTSW |
15 |
89,433,083 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7862:Shank3
|
UTSW |
15 |
89,389,648 (GRCm39) |
missense |
possibly damaging |
0.73 |
|
R8039:Shank3
|
UTSW |
15 |
89,389,642 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8090:Shank3
|
UTSW |
15 |
89,389,661 (GRCm39) |
critical splice donor site |
probably null |
|
|
R8170:Shank3
|
UTSW |
15 |
89,433,043 (GRCm39) |
missense |
possibly damaging |
0.69 |
|
R8189:Shank3
|
UTSW |
15 |
89,433,439 (GRCm39) |
missense |
probably benign |
|
|
R8246:Shank3
|
UTSW |
15 |
89,417,549 (GRCm39) |
missense |
possibly damaging |
0.90 |
|
R8515:Shank3
|
UTSW |
15 |
89,387,775 (GRCm39) |
nonsense |
probably null |
|
|
R8525:Shank3
|
UTSW |
15 |
89,431,973 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R8537:Shank3
|
UTSW |
15 |
89,416,418 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8673:Shank3
|
UTSW |
15 |
89,433,979 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8826:Shank3
|
UTSW |
15 |
89,433,598 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8932:Shank3
|
UTSW |
15 |
89,432,986 (GRCm39) |
missense |
possibly damaging |
0.86 |
|
R8954:Shank3
|
UTSW |
15 |
89,433,431 (GRCm39) |
missense |
possibly damaging |
0.88 |
|
R8976:Shank3
|
UTSW |
15 |
89,442,381 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8992:Shank3
|
UTSW |
15 |
89,432,888 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R8994:Shank3
|
UTSW |
15 |
89,417,416 (GRCm39) |
missense |
probably benign |
0.27 |
|
R9130:Shank3
|
UTSW |
15 |
89,442,419 (GRCm39) |
missense |
probably benign |
0.19 |
|
R9258:Shank3
|
UTSW |
15 |
89,388,521 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9645:Shank3
|
UTSW |
15 |
89,409,453 (GRCm39) |
missense |
possibly damaging |
0.96 |
|
RF020:Shank3
|
UTSW |
15 |
89,384,593 (GRCm39) |
missense |
probably benign |
0.20 |
|
Z1177:Shank3
|
UTSW |
15 |
89,442,525 (GRCm39) |
makesense |
probably null |
|
|
| Predicted Primers |
PCR Primer
(F):5'- CACAGCACAGATAAGGTGGC -3'
(R):5'- GTCCTTGTAGTCAGGCGAAG -3'
Sequencing Primer
(F):5'- AGATAAGGTGGCCCGCCTG -3'
(R):5'- TCTGAGGGTTAAGGCACCTC -3'
|
| Posted On |
2015-07-21 |
Incidental Mutation