Mutagenetix > Incidental Mutation

Incidental Mutation 'R1961:Shank3'

317972

Institutional Source

Beutler Lab

Gene Symbol

Shank3

Ensembl Gene

ENSMUSG00000022623

Gene Name

SH3 and multiple ankyrin repeat domains 3

Synonyms

ProSAP2

MMRRC Submission

039975-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.179) question?

Stock #

R1961 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

89383826-89444464 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 89442167 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 1612 (S1612P)

Ref Sequence

ENSEMBL: ENSMUSP00000048062 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000039074] [ENSMUST00000066545] [ENSMUST00000109309] [ENSMUST00000229559] [ENSMUST00000230807]

AlphaFold

Q4ACU6

PDB Structure

Tetrahydroquinoline carboxylates are potent inhibitors of the Shank PDZ domain, a putative target in autism disorders [X-RAY DIFFRACTION]

Predicted Effect

possibly damaging
Transcript: ENSMUST00000039074
AA Change: S1612P

PolyPhen 2 Score 0.601 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000048062
Gene: ENSMUSG00000022623
AA Change: S1612P

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 benign
Transcript: ENSMUST00000109309
AA Change: S1687P

PolyPhen 2 Score 0.452 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000104932
Gene: ENSMUSG00000022623
AA Change: S1687P

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

probably benign
Transcript: ENSMUST00000229559

Predicted Effect

probably benign
Transcript: ENSMUST00000230807

Meta Mutation Damage Score

0.0768

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.9%
20x: 94.4%

Validation Efficiency

99% (93/94)

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: 92 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcc1	T	C	16: 14,214,257 (GRCm39)	Y191H	probably damaging	Het
Abcc4	C	A	14: 118,848,871 (GRCm39)	V494L	possibly damaging	Het
Abcc4	C	A	14: 118,848,868 (GRCm39)	G495C	probably damaging	Het
Acsm4	T	C	7: 119,307,963 (GRCm39)	Y367H	probably benign	Het
Adam21	A	T	12: 81,606,282 (GRCm39)	Y493*	probably null	Het
Add2	T	C	6: 86,073,738 (GRCm39)	F209S	probably damaging	Het
Adgre4	T	C	17: 56,098,497 (GRCm39)	S136P	probably benign	Het
Aff4	T	G	11: 53,263,826 (GRCm39)	L282R	probably damaging	Het
Akt3	A	G	1: 176,924,561 (GRCm39)	I178T	probably damaging	Het
Ap3m1	T	C	14: 21,091,083 (GRCm39)	Y174C	probably damaging	Het
Arb2a	C	A	13: 78,050,839 (GRCm39)	H50N	probably benign	Het
Atl1	A	G	12: 70,000,274 (GRCm39)	E308G	probably benign	Het
Atp8b5	T	G	4: 43,369,688 (GRCm39)	V942G	probably damaging	Het
B3gntl1	A	G	11: 121,535,351 (GRCm39)		probably null	Het
Btrc	T	G	19: 45,515,782 (GRCm39)	I480S	probably damaging	Het
Cacna1c	A	T	6: 118,607,283 (GRCm39)	I1366N	probably benign	Het
Ccdc113	T	A	8: 96,267,459 (GRCm39)	N141K	probably benign	Het
Ccdc167	T	C	17: 29,923,405 (GRCm39)	N77D	possibly damaging	Het
Ccser1	T	C	6: 61,290,630 (GRCm39)		probably benign	Het
Cenpe	A	G	3: 134,948,254 (GRCm39)	E1230G	probably damaging	Het
Clec12a	A	C	6: 129,327,444 (GRCm39)	T21P	possibly damaging	Het
Cyp26c1	T	A	19: 37,675,825 (GRCm39)	F230I	probably damaging	Het
Exog	A	G	9: 119,281,332 (GRCm39)	E190G	possibly damaging	Het
Fam162b	A	G	10: 51,466,430 (GRCm39)	W30R	probably benign	Het
Fndc3b	G	A	3: 27,510,600 (GRCm39)	Q841*	probably null	Het
Frzb	T	A	2: 80,254,945 (GRCm39)	Y197F	probably benign	Het
G530012D18Rik	CAGAGAGA	CAGAGAGAGA	1: 85,504,945 (GRCm39)		probably null	Het
Gabrb1	G	A	5: 71,857,679 (GRCm39)	R43Q	probably benign	Het
Gm21060	A	T	19: 61,285,445 (GRCm39)	H21Q	possibly damaging	Het
Gm4825	A	G	15: 85,395,245 (GRCm39)		noncoding transcript	Het
Gm5581	A	C	6: 131,145,125 (GRCm39)		noncoding transcript	Het
Gm9894	T	C	13: 67,912,034 (GRCm39)		noncoding transcript	Het
Gpr15	T	A	16: 58,538,370 (GRCm39)	I240L	probably benign	Het
Gria4	A	T	9: 4,519,546 (GRCm39)		probably benign	Het
Grid2	T	C	6: 63,885,877 (GRCm39)	L91S	probably damaging	Het
Igsf5	A	C	16: 96,179,551 (GRCm39)	T215P	probably damaging	Het
Kif13a	G	A	13: 47,018,314 (GRCm39)		probably benign	Het
Kif21a	G	A	15: 90,855,051 (GRCm39)	A703V	probably damaging	Het
Kif27	T	G	13: 58,440,937 (GRCm39)	R1159S	probably benign	Het
Kifc2	T	A	15: 76,547,025 (GRCm39)	L226H	probably damaging	Het
Klf10	T	C	15: 38,296,240 (GRCm39)	H435R	probably damaging	Het
Masp1	T	C	16: 23,271,682 (GRCm39)	Y623C	probably damaging	Het
Megf10	T	A	18: 57,345,426 (GRCm39)	C118S	probably damaging	Het
Mical3	A	G	6: 120,959,568 (GRCm39)	V909A	possibly damaging	Het
Mmrn2	A	G	14: 34,120,432 (GRCm39)		probably null	Het
Mpeg1	G	A	19: 12,440,275 (GRCm39)	V578M	probably damaging	Het
Nlrp2	T	C	7: 5,330,737 (GRCm39)	E553G	probably damaging	Het
Nmi	A	T	2: 51,838,632 (GRCm39)	S301T	probably benign	Het
Nr2f2	G	T	7: 70,007,903 (GRCm39)	T193K	possibly damaging	Het
Ntng2	T	C	2: 29,087,110 (GRCm39)	N404S	probably damaging	Het
Nup50l	A	G	6: 96,142,250 (GRCm39)	S265P	possibly damaging	Het
Oplah	G	A	15: 76,181,664 (GRCm39)	T1119I	probably damaging	Het
Or1x2	T	G	11: 50,918,302 (GRCm39)	S158A	probably benign	Het
Or52e3	T	C	7: 102,869,204 (GRCm39)	V93A	probably benign	Het
Otoa	T	A	7: 120,717,792 (GRCm39)	D336E	probably benign	Het
Pde4b	A	G	4: 102,454,657 (GRCm39)	E108G	probably damaging	Het
Pdgfrb	G	A	18: 61,194,577 (GRCm39)	R118H	possibly damaging	Het
Phactr4	G	A	4: 132,104,559 (GRCm39)	T256I	probably benign	Het
Pla2g3	C	T	11: 3,440,983 (GRCm39)	T316I	probably benign	Het
Plekhg4	A	G	8: 106,108,096 (GRCm39)	E982G	probably damaging	Het
Pmfbp1	T	G	8: 110,256,776 (GRCm39)		probably benign	Het
Pot1b	A	T	17: 55,969,531 (GRCm39)	Y546N	probably damaging	Het
Pphln1-ps1	T	A	16: 13,495,592 (GRCm39)	H230Q	probably benign	Het
Rab11fip5	C	A	6: 85,325,973 (GRCm39)	Q144H	possibly damaging	Het
Reep3	A	T	10: 66,875,278 (GRCm39)		probably null	Het
Rgl2	T	C	17: 34,152,589 (GRCm39)	L400P	probably damaging	Het
Rnf122	A	G	8: 31,614,874 (GRCm39)		probably benign	Het
Scgb1b21	G	T	7: 33,226,803 (GRCm39)		noncoding transcript	Het
Sec63	A	T	10: 42,699,882 (GRCm39)	K647N	probably damaging	Het
Sema4a	C	T	3: 88,345,483 (GRCm39)		probably benign	Het
Serpinf1	C	T	11: 75,307,245 (GRCm39)	V31I	probably benign	Het
Sez6l	C	T	5: 112,572,481 (GRCm39)		probably benign	Het
Slc19a3	G	A	1: 83,000,519 (GRCm39)	T166M	probably benign	Het
Slc22a29	C	A	19: 8,146,557 (GRCm39)	R415M	probably benign	Het
Slc38a11	A	T	2: 65,160,683 (GRCm39)	F304I	possibly damaging	Het
Slitrk1	T	A	14: 109,149,622 (GRCm39)	N363I	probably damaging	Het
Slx4ip	A	G	2: 136,909,601 (GRCm39)	T129A	probably benign	Het
Spop	T	C	11: 95,382,537 (GRCm39)	V332A	possibly damaging	Het
Sptlc1	A	C	13: 53,512,916 (GRCm39)	D147E	probably benign	Het
Tnpo1	T	C	13: 98,989,440 (GRCm39)	Y754C	probably damaging	Het
Tox	C	A	4: 6,688,886 (GRCm39)	V493L	probably damaging	Het
Ttbk1	A	C	17: 46,791,150 (GRCm39)	F45V	probably damaging	Het
Ttc27	T	A	17: 75,087,851 (GRCm39)	M472K	probably damaging	Het
Ttll7	A	G	3: 146,621,550 (GRCm39)		probably benign	Het
Ttn	A	T	2: 76,552,104 (GRCm39)	C22851S	probably benign	Het
Ttn	T	A	2: 76,628,556 (GRCm39)	M14535L	possibly damaging	Het
Txlna	T	C	4: 129,534,055 (GRCm39)	T54A	probably benign	Het
Usp33	T	C	3: 152,086,265 (GRCm39)	V668A	probably damaging	Het
Vmn2r28	C	A	7: 5,484,070 (GRCm39)	C710F	possibly damaging	Het
Vmn2r8	T	A	5: 108,945,961 (GRCm39)	M549L	probably benign	Het
Vwa5b2	T	C	16: 20,420,941 (GRCm39)		probably null	Het
Wnk1	T	C	6: 119,946,208 (GRCm39)	I648M	probably damaging	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
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'- GATATTCCTCCAGCCCTAGACC -3'
(R):5'- CCACATCGAACTTGCTCCAG -3'

Sequencing Primer
(F):5'- GTGAGCTGAGCACCATCTC -3'
(R):5'- AGAGCTGCAGGGGCTTCTG -3'

Posted On

2015-05-19