Incidental Mutation 'R0605:Shank3'
ID 55682
Institutional Source Beutler Lab
Gene Symbol Shank3
Ensembl Gene ENSMUSG00000022623
Gene Name SH3 and multiple ankyrin repeat domains 3
Synonyms ProSAP2
MMRRC Submission 038794-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.176) question?
Stock # R0605 (G1)
Quality Score 98
Status Validated
Chromosome 15
Chromosomal Location 89383826-89444464 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 89408350 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Phenylalanine to Leucine at position 67 (F67L)
Ref Sequence ENSEMBL: ENSMUSP00000154842 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000039074] [ENSMUST00000066545] [ENSMUST00000109309] [ENSMUST00000229559] [ENSMUST00000230807]
AlphaFold Q4ACU6
Predicted Effect probably benign
Transcript: ENSMUST00000039074
AA Change: F475L

PolyPhen 2 Score 0.053 (Sensitivity: 0.94; Specificity: 0.84)
SMART Domains Protein: ENSMUSP00000048062
Gene: ENSMUSG00000022623
AA Change: F475L

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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 benign
Transcript: ENSMUST00000109309
AA Change: F550L

PolyPhen 2 Score 0.034 (Sensitivity: 0.95; Specificity: 0.82)
SMART Domains Protein: ENSMUSP00000104932
Gene: ENSMUSG00000022623
AA Change: F550L

DomainStartEndE-ValueType
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: ENSMUST00000154240
Predicted Effect noncoding transcript
Transcript: ENSMUST00000155610
Predicted Effect possibly damaging
Transcript: ENSMUST00000229559
AA Change: F67L

PolyPhen 2 Score 0.494 (Sensitivity: 0.88; Specificity: 0.90)
Predicted Effect probably benign
Transcript: ENSMUST00000230807
AA Change: F67L

PolyPhen 2 Score 0.439 (Sensitivity: 0.89; Specificity: 0.90)
Meta Mutation Damage Score 0.0763 question?
Coding Region Coverage
  • 1x: 99.4%
  • 3x: 98.9%
  • 10x: 97.6%
  • 20x: 95.4%
Validation Efficiency 100% (85/85)
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: 84 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4933406P04Rik G A 10: 20,186,973 (GRCm39) probably benign Het
Adam28 A T 14: 68,844,049 (GRCm39) probably benign Het
Adamts3 A G 5: 90,009,334 (GRCm39) W110R possibly damaging Het
Add1 T C 5: 34,771,568 (GRCm39) V342A possibly damaging Het
Aff3 A G 1: 38,249,068 (GRCm39) S680P probably damaging Het
Ak9 T C 10: 41,221,135 (GRCm39) Y322H probably damaging Het
Als2 A G 1: 59,207,573 (GRCm39) L1528S probably benign Het
Ass1 A T 2: 31,404,831 (GRCm39) N371Y probably damaging Het
Atp6v1a A C 16: 43,931,859 (GRCm39) probably null Het
Bpi T C 2: 158,103,314 (GRCm39) L103P probably damaging Het
Cd80 G A 16: 38,303,056 (GRCm39) V168I probably benign Het
Cfh T C 1: 140,030,096 (GRCm39) S926G probably damaging Het
Chrd A T 16: 20,554,189 (GRCm39) T304S probably damaging Het
Chsy3 A G 18: 59,542,125 (GRCm39) Y421C probably damaging Het
Cmbl T G 15: 31,585,455 (GRCm39) V101G probably damaging Het
Colgalt2 T A 1: 152,371,543 (GRCm39) probably benign Het
Coq4 C T 2: 29,680,010 (GRCm39) Q101* probably null Het
Cr2 T C 1: 194,845,904 (GRCm39) probably benign Het
Cry1 T C 10: 85,020,223 (GRCm39) D38G probably damaging Het
Dmxl2 T C 9: 54,327,229 (GRCm39) D758G probably benign Het
Epsti1 C T 14: 78,164,677 (GRCm39) probably benign Het
Fam24b T C 7: 130,928,915 (GRCm39) probably benign Het
Fem1c G A 18: 46,638,227 (GRCm39) R592C probably benign Het
Foxred1 T C 9: 35,116,178 (GRCm39) Y490C possibly damaging Het
Gm9875 A G 2: 13,562,699 (GRCm39) K9R unknown Het
Grid2ip T C 5: 143,365,117 (GRCm39) S322P probably damaging Het
Gucy1b2 A G 14: 62,640,608 (GRCm39) probably benign Het
Hmcn1 A T 1: 150,533,127 (GRCm39) probably null Het
Hpdl C T 4: 116,677,984 (GRCm39) S159N possibly damaging Het
Hsd17b12 A T 2: 93,863,987 (GRCm39) M285K probably benign Het
Icam5 T C 9: 20,943,493 (GRCm39) I23T probably benign Het
Kat5 A G 19: 5,658,364 (GRCm39) probably benign Het
Lama3 A G 18: 12,640,006 (GRCm39) N67S probably benign Het
Lamb2 T C 9: 108,363,304 (GRCm39) probably benign Het
Lgals3bp A G 11: 118,284,220 (GRCm39) F453S probably damaging Het
Lypd4 A G 7: 24,564,800 (GRCm39) Y113H probably damaging Het
Mdm1 C T 10: 117,982,506 (GRCm39) T47M probably damaging Het
Mei1 C A 15: 81,954,351 (GRCm39) T52K probably benign Het
Meiob G A 17: 25,037,236 (GRCm39) probably benign Het
Ndufaf6 A G 4: 11,051,224 (GRCm39) V292A probably damaging Het
Neb T A 2: 52,154,038 (GRCm39) M2358L possibly damaging Het
Nlrp1b A G 11: 71,047,005 (GRCm39) S1119P possibly damaging Het
Nsmaf A G 4: 6,418,470 (GRCm39) probably null Het
Ogfod1 T C 8: 94,773,895 (GRCm39) probably benign Het
Or5ae2 T C 7: 84,506,345 (GRCm39) I256T probably damaging Het
Or8h7 T C 2: 86,720,763 (GRCm39) Y252C possibly damaging Het
Or9s14 G T 1: 92,535,618 (GRCm39) V20L probably benign Het
Osbpl1a T A 18: 13,015,336 (GRCm39) probably null Het
Otud7b T A 3: 96,052,270 (GRCm39) probably benign Het
P3h3 T A 6: 124,832,998 (GRCm39) H185L probably damaging Het
P4htm G A 9: 108,460,923 (GRCm39) A183V probably null Het
Peak1 C T 9: 56,134,382 (GRCm39) probably benign Het
Phf20l1 A G 15: 66,466,971 (GRCm39) K88R probably damaging Het
Phlpp2 A G 8: 110,659,843 (GRCm39) N721S probably benign Het
Plagl2 T C 2: 153,077,864 (GRCm39) K39R probably benign Het
Plppr1 A T 4: 49,323,466 (GRCm39) N252I probably damaging Het
Pom121l2 C T 13: 22,166,206 (GRCm39) A159V probably damaging Het
Prom2 C A 2: 127,381,915 (GRCm39) probably null Het
Prrc2c T C 1: 162,509,995 (GRCm39) T1017A probably damaging Het
Rimbp3 G T 16: 17,029,563 (GRCm39) A996S probably damaging Het
Rnf213 A G 11: 119,322,543 (GRCm39) T1387A probably benign Het
Scaper A T 9: 55,722,802 (GRCm39) probably benign Het
Scara5 A G 14: 65,997,097 (GRCm39) E403G possibly damaging Het
Scrib T C 15: 75,939,402 (GRCm39) I94V possibly damaging Het
Shprh T C 10: 11,082,856 (GRCm39) F1562L probably damaging Het
Src C T 2: 157,311,841 (GRCm39) T529M probably damaging Het
Sycp2l T A 13: 41,296,942 (GRCm39) M341K probably benign Het
Syde1 T C 10: 78,424,929 (GRCm39) probably benign Het
Tars3 A T 7: 65,327,819 (GRCm39) R509S probably damaging Het
Tle6 T A 10: 81,430,180 (GRCm39) H324L probably damaging Het
Tnfaip8 ACTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC ACTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC 18: 50,179,912 (GRCm39) probably benign Het
Tnfrsf14 T A 4: 155,009,837 (GRCm39) K115* probably null Het
Trappc10 T C 10: 78,037,331 (GRCm39) N824S possibly damaging Het
Tsc1 C T 2: 28,561,790 (GRCm39) S309F probably damaging Het
Ttc21a A G 9: 119,790,908 (GRCm39) I885V possibly damaging Het
Ttn C T 2: 76,570,797 (GRCm39) A26699T probably damaging Het
Ttn T C 2: 76,778,715 (GRCm39) Y1262C unknown Het
Usp49 T C 17: 47,985,851 (GRCm39) probably null Het
Vmn1r226 A T 17: 20,908,133 (GRCm39) T122S probably benign Het
Vps8 A T 16: 21,378,087 (GRCm39) T1033S probably benign Het
Vwf C A 6: 125,662,800 (GRCm39) T2728K probably benign Het
Wdr5b T C 16: 35,862,366 (GRCm39) S162P probably benign Het
Xrn1 C T 9: 95,908,930 (GRCm39) Q1235* probably null Het
Zfp1005 A G 2: 150,110,523 (GRCm39) I404M unknown Het
Other mutations in Shank3
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
R4434:Shank3 UTSW 15 89,387,562 (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'- CCGTCACCTACGTGTTCGTCTACAG -3'
(R):5'- GCTTCATGCCAGGAGCCCATAAAAC -3'

Sequencing Primer
(F):5'- GTGTTCGTCTACAGCCCCAG -3'
(R):5'- CAGCAGCTTGCTGGAATGAC -3'
Posted On 2013-07-11