Incidental Mutation 'R9645:Shank3'
ID 726241
Institutional Source Beutler Lab
Gene Symbol Shank3
Ensembl Gene ENSMUSG00000022623
Gene Name SH3 and multiple ankyrin repeat domains 3
Synonyms ProSAP2
MMRRC Submission
Accession Numbers
Essential gene? Probably non essential (E-score: 0.176) question?
Stock # R9645 (G1)
Quality Score 225.009
Status Not validated
Chromosome 15
Chromosomal Location 89383826-89444464 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to G at 89409453 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Methionine to Arginine at position 604 (M604R)
Ref Sequence ENSEMBL: ENSMUSP00000104932 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000039074] [ENSMUST00000109309] [ENSMUST00000229559] [ENSMUST00000230807]
AlphaFold Q4ACU6
Predicted Effect
SMART Domains Protein: ENSMUSP00000048062
Gene: ENSMUSG00000022623
AA Change: M529R

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 possibly damaging
Transcript: ENSMUST00000109309
AA Change: M604R

PolyPhen 2 Score 0.956 (Sensitivity: 0.79; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000104932
Gene: ENSMUSG00000022623
AA Change: M604R

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 possibly damaging
Transcript: ENSMUST00000229559
AA Change: M121R

PolyPhen 2 Score 0.794 (Sensitivity: 0.85; Specificity: 0.93)
Predicted Effect possibly damaging
Transcript: ENSMUST00000230807
AA Change: M121R

PolyPhen 2 Score 0.708 (Sensitivity: 0.86; Specificity: 0.92)
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.7%
  • 20x: 99.0%
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: 72 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
A430033K04Rik T C 5: 138,644,793 (GRCm39) V226A probably benign Het
Acan G T 7: 78,749,653 (GRCm39) V1475F probably benign Het
Acin1 T A 14: 54,901,913 (GRCm39) R626S probably benign Het
Aff3 T C 1: 38,249,121 (GRCm39) K662R probably damaging Het
Ankrd11 C T 8: 123,617,682 (GRCm39) A2057T probably benign Het
Ano9 T G 7: 140,687,388 (GRCm39) N309T probably benign Het
Ap3d1 G A 10: 80,545,062 (GRCm39) S1092L probably benign Het
B4galt7 C T 13: 55,756,556 (GRCm39) H257Y probably damaging Het
BC051665 G T 13: 60,932,545 (GRCm39) Q47K possibly damaging Het
Brip1 A G 11: 85,952,512 (GRCm39) F1090L probably benign Het
Cabin1 A G 10: 75,494,543 (GRCm39) V1612A probably benign Het
Ccar1 A T 10: 62,602,369 (GRCm39) D434E probably benign Het
Ccdc15 T C 9: 37,227,083 (GRCm39) D297G probably benign Het
Celsr3 C A 9: 108,704,691 (GRCm39) Y391* probably null Het
Cfap52 A G 11: 67,837,179 (GRCm39) I194T possibly damaging Het
Ctif T C 18: 75,757,352 (GRCm39) E67G probably benign Het
Cxcr6 T C 9: 123,639,151 (GRCm39) F58L possibly damaging Het
Cyp2c69 T C 19: 39,869,593 (GRCm39) E142G probably damaging Het
Dnah6 T A 6: 73,115,750 (GRCm39) R1549S possibly damaging Het
Duxf3 A T 10: 58,066,803 (GRCm39) H75Q probably benign Het
Ehbp1 A T 11: 22,051,052 (GRCm39) I500N probably damaging Het
F13a1 A T 13: 37,082,154 (GRCm39) S517T probably benign Het
Fbln7 C T 2: 128,719,316 (GRCm39) R38C probably damaging Het
Fn1 T C 1: 71,667,629 (GRCm39) N788S probably benign Het
Foxc1 A T 13: 31,991,882 (GRCm39) E231V probably damaging Het
Gal3st2b T C 1: 93,866,328 (GRCm39) S10P probably damaging Het
Gm6899 G A 11: 26,543,592 (GRCm39) C53Y unknown Het
Hps3 T C 3: 20,084,831 (GRCm39) E119G probably benign Het
Impg2 A G 16: 56,038,767 (GRCm39) E135G probably damaging Het
Kalrn G A 16: 34,032,583 (GRCm39) T1155M probably benign Het
Kcna6 G A 6: 126,716,022 (GRCm39) A289V probably benign Het
Kcnh5 T C 12: 75,134,191 (GRCm39) M453V probably benign Het
Krt222 A G 11: 99,131,320 (GRCm39) V75A possibly damaging Het
Lmtk3 A T 7: 45,450,431 (GRCm39) T1432S unknown Het
Ltbp2 G A 12: 84,837,864 (GRCm39) P1192L probably benign Het
Ltbp3 C G 19: 5,802,099 (GRCm39) N758K probably damaging Het
Map6d1 T A 16: 20,055,377 (GRCm39) H153L possibly damaging Het
Mefv A G 16: 3,528,782 (GRCm39) L583P probably damaging Het
Mrps28 T C 3: 8,867,389 (GRCm39) T160A probably damaging Het
Mtcl2 T C 2: 156,869,390 (GRCm39) K1082E probably damaging Het
Muc6 T C 7: 141,217,783 (GRCm39) T2297A possibly damaging Het
Mx1 G T 16: 97,253,409 (GRCm39) D338E probably benign Het
Myom1 G A 17: 71,399,204 (GRCm39) R1120H probably benign Het
Nif3l1 T C 1: 58,487,074 (GRCm39) F87L probably benign Het
Or1e35 T A 11: 73,797,713 (GRCm39) M202L probably benign Het
Or4p22 T C 2: 88,317,373 (GRCm39) V99A possibly damaging Het
Pex10 T A 4: 155,153,264 (GRCm39) L111Q probably damaging Het
Phf1 T C 17: 27,154,130 (GRCm39) probably null Het
Pigp A T 16: 94,166,278 (GRCm39) Y143* probably null Het
Pou2af2 A G 9: 51,229,579 (GRCm39) probably null Het
Prrc2a A G 17: 35,381,176 (GRCm39) probably null Het
Psd GCC GC 19: 46,301,841 (GRCm39) probably null Het
Pum3 A G 19: 27,403,412 (GRCm39) S30P probably benign Het
Rab12 A G 17: 66,826,421 (GRCm39) S97P probably damaging Het
Rigi T C 4: 40,220,437 (GRCm39) E482G possibly damaging Het
Ros1 A G 10: 51,948,148 (GRCm39) probably null Het
Scp2 A T 4: 107,948,519 (GRCm39) Y197N probably benign Het
Serpinb10 T C 1: 107,474,488 (GRCm39) F217L possibly damaging Het
Slc22a29 A G 19: 8,184,488 (GRCm39) S238P probably benign Het
Smarcc1 A G 9: 109,986,410 (GRCm39) D237G probably damaging Het
Stag3 T C 5: 138,299,701 (GRCm39) S871P possibly damaging Het
Tmem132d A G 5: 128,346,075 (GRCm39) F149S probably damaging Het
Tmem25 C T 9: 44,706,515 (GRCm39) E333K Het
Togaram1 T A 12: 65,066,082 (GRCm39) Y1695* probably null Het
Tox3 G A 8: 90,984,574 (GRCm39) P202S probably damaging Het
Trim34b T A 7: 103,980,474 (GRCm39) N187K probably benign Het
Vcan A G 13: 89,841,081 (GRCm39) S1488P probably benign Het
Vps26a A C 10: 62,305,791 (GRCm39) V124G probably benign Het
Vps50 T G 6: 3,516,706 (GRCm39) S63A possibly damaging Het
Wbp4 T A 14: 79,707,553 (GRCm39) E186V possibly damaging Het
Zfp52 A G 17: 21,781,937 (GRCm39) D595G possibly damaging Het
Zfr2 C A 10: 81,084,252 (GRCm39) S1* probably null 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
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
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'- TGCTGGCTTGAAAAGAGAGC -3'
(R):5'- TTGCCCACCATGGATATGTG -3'

Sequencing Primer
(F):5'- TCGTGGGCAAAACCTGAGC -3'
(R):5'- CCACCATGGATATGTGCAAATCTG -3'
Posted On 2022-09-12