Incidental Mutation 'R3917:Shank3'
ID 307381
Institutional Source Beutler Lab
Gene Symbol Shank3
Ensembl Gene ENSMUSG00000022623
Gene Name SH3 and multiple ankyrin repeat domains 3
Synonyms ProSAP2
MMRRC Submission 040914-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.176) question?
Stock # R3917 (G1)
Quality Score 225
Status Validated
Chromosome 15
Chromosomal Location 89383826-89444464 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 89387587 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Aspartic acid to Glycine at position 252 (D252G)
Ref Sequence ENSEMBL: ENSMUSP00000104932 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000039074] [ENSMUST00000066545] [ENSMUST00000109309]
AlphaFold Q4ACU6
Predicted Effect probably benign
Transcript: ENSMUST00000039074
AA Change: D177G

PolyPhen 2 Score 0.139 (Sensitivity: 0.92; Specificity: 0.86)
SMART Domains Protein: ENSMUSP00000048062
Gene: ENSMUSG00000022623
AA Change: D177G

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 possibly damaging
Transcript: ENSMUST00000109309
AA Change: D252G

PolyPhen 2 Score 0.768 (Sensitivity: 0.85; Specificity: 0.92)
SMART Domains Protein: ENSMUSP00000104932
Gene: ENSMUSG00000022623
AA Change: D252G

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: ENSMUST00000135214
Meta Mutation Damage Score 0.2456 question?
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.7%
  • 10x: 97.3%
  • 20x: 95.0%
Validation Efficiency 97% (74/76)
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: 74 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Acad12 A G 5: 121,737,277 (GRCm39) V498A probably damaging Het
Adam19 A G 11: 45,951,762 (GRCm39) E37G probably benign Het
Apol11b A G 15: 77,519,504 (GRCm39) I192T probably benign Het
Appl1 A T 14: 26,650,561 (GRCm39) F537Y probably damaging Het
Atad5 A C 11: 79,994,120 (GRCm39) K785N probably null Het
Atp1b2 A G 11: 69,493,901 (GRCm39) V93A probably damaging Het
Bcam T C 7: 19,499,375 (GRCm39) Y216C probably damaging Het
Brca2 A G 5: 150,464,292 (GRCm39) E1352G probably damaging Het
C030005K15Rik A C 10: 97,561,453 (GRCm39) S93A unknown Het
Cadps C T 14: 12,457,702 (GRCm38) A1060T probably benign Het
Ccdc88c A G 12: 100,907,366 (GRCm39) probably null Het
Ccdc89 A G 7: 90,076,033 (GRCm39) D81G probably damaging Het
Ccnt1 A G 15: 98,441,940 (GRCm39) S443P probably benign Het
Cd109 CATTTATTTATTTATTTATTTATTTATTTATTTAT CATTTATTTATTTATTTATTTATTTATTTATTTATTTAT 9: 78,619,782 (GRCm39) probably benign Het
Cdc42bpa T C 1: 179,933,719 (GRCm39) probably null Het
Cdk11b T C 4: 155,711,258 (GRCm39) S47P probably damaging Het
Cfap43 T C 19: 47,886,189 (GRCm39) D142G probably benign Het
Cntnap4 C G 8: 113,602,165 (GRCm39) P1190A probably benign Het
Colgalt2 T A 1: 152,384,362 (GRCm39) Y567* probably null Het
Dner CGCTGCTGCTGCTGCTGCTGCTGCTGC CGCTGCTGCTGCTGCTGCTGCTGC 1: 84,563,270 (GRCm39) probably benign Het
Dock7 T C 4: 98,904,922 (GRCm39) Y651C probably damaging Het
Fzd3 A T 14: 65,473,379 (GRCm39) F130I probably damaging Het
Gabarapl2 T A 8: 112,679,028 (GRCm39) F115L probably benign Het
Gm1043 G A 5: 37,350,285 (GRCm39) probably benign Het
Gm12185 A G 11: 48,806,760 (GRCm39) F144L probably benign Het
Gm21961 A T 15: 64,886,733 (GRCm39) D7E unknown Het
Gtf3a A G 5: 146,892,244 (GRCm39) K332E probably benign Het
Haao A G 17: 84,146,228 (GRCm39) probably null Het
Habp2 T A 19: 56,299,611 (GRCm39) C170S probably damaging Het
Heatr3 T G 8: 88,876,999 (GRCm39) probably null Het
Herc1 T G 9: 66,341,748 (GRCm39) C1846G possibly damaging Het
Hivep3 T C 4: 119,956,624 (GRCm39) S1647P probably benign Het
Hnrnpul1 C T 7: 25,426,300 (GRCm39) R517Q probably damaging Het
Hspg2 A G 4: 137,286,625 (GRCm39) E3648G probably damaging Het
Jaml T C 9: 45,012,449 (GRCm39) probably benign Het
Jund C T 8: 71,151,673 (GRCm39) probably benign Het
Klra14-ps T C 6: 130,134,595 (GRCm39) noncoding transcript Het
Krt88 G A 15: 101,350,809 (GRCm39) probably null Het
Lrp5 G A 19: 3,662,330 (GRCm39) R173C probably damaging Het
Lyzl4 T A 9: 121,412,101 (GRCm39) D105V probably damaging Het
Mst1 A G 9: 107,961,494 (GRCm39) I575V probably benign Het
Myd88 T C 9: 119,170,464 (GRCm39) probably benign Het
Myo1d A T 11: 80,557,404 (GRCm39) V512E probably damaging Het
Ndufv1 A G 19: 4,060,002 (GRCm39) Y33H probably damaging Het
Nwd1 T A 8: 73,394,439 (GRCm39) C608* probably null Het
Or10al2 T A 17: 37,983,684 (GRCm39) F257I probably damaging Het
Or8b37 A T 9: 37,958,841 (GRCm39) I108F probably damaging Het
Patj A T 4: 98,480,245 (GRCm39) K1317* probably null Het
Pld5 A G 1: 175,791,504 (GRCm39) S501P probably benign Het
Pnpo A G 11: 96,830,583 (GRCm39) V146A probably damaging Het
Ppdpf A G 2: 180,829,521 (GRCm39) Y16C probably benign Het
Ppp1r27 A G 11: 120,441,785 (GRCm39) V32A possibly damaging Het
Rbm28 T C 6: 29,154,788 (GRCm39) D294G probably benign Het
Sdk1 T A 5: 142,036,999 (GRCm39) D817E probably damaging Het
Slc29a1 A T 17: 45,899,899 (GRCm39) probably null Het
Slc35a5 G C 16: 44,978,521 (GRCm39) probably benign Het
Slc6a5 T C 7: 49,561,617 (GRCm39) S50P probably damaging Het
Slfn8 A T 11: 82,907,819 (GRCm39) Y241* probably null Het
Slu7 G T 11: 43,331,511 (GRCm39) probably null Het
Smad2 T A 18: 76,421,008 (GRCm39) D82E probably benign Het
Spx A C 6: 142,359,757 (GRCm39) E33A probably damaging Het
Tdp1 A G 12: 99,860,976 (GRCm39) Y205C probably damaging Het
Tekt1 A G 11: 72,236,574 (GRCm39) I296T possibly damaging Het
Tgm1 G A 14: 55,950,214 (GRCm39) probably benign Het
Tnks A G 8: 35,320,515 (GRCm39) S719P probably damaging Het
Trip6 A G 5: 137,311,941 (GRCm39) C47R probably benign Het
Trpv3 A G 11: 73,174,560 (GRCm39) D309G possibly damaging Het
Tti2 A G 8: 31,643,547 (GRCm39) K221E possibly damaging Het
Ugcg C T 4: 59,207,798 (GRCm39) P46S probably benign Het
Vmn1r57 A T 7: 5,223,630 (GRCm39) N52Y probably damaging Het
Vmn2r94 A G 17: 18,464,620 (GRCm39) F557L probably benign Het
Zbed5 T C 5: 129,931,118 (GRCm39) Y356H possibly damaging Het
Zfp1005 T A 2: 150,108,039 (GRCm39) probably benign Het
Zic4 C A 9: 91,266,394 (GRCm39) probably benign 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
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
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'- TACACAGCACAGATAAGGTGGC -3'
(R):5'- GTCCTTGTAGTCAGGCGAAG -3'

Sequencing Primer
(F):5'- GGCTGGACCCCAATTTCCATG -3'
(R):5'- GAAGCCCCCAGGTCCAG -3'
Posted On 2015-04-17