Mutagenetix > Incidental Mutation

Incidental Mutation 'R1958:Shank3'

218070

Institutional Source

Beutler Lab

Gene Symbol

Shank3

Ensembl Gene

ENSMUSG00000022623

Gene Name

SH3 and multiple ankyrin repeat domains 3

Synonyms

ProSAP2

MMRRC Submission

039972-MU

Accession Numbers

Essential gene?

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

Stock #

R1958 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

89383826-89444464 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 89387351 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 198 (V198A)

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: V123A

PolyPhen 2 Score 0.439 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000048062
Gene: ENSMUSG00000022623
AA Change: V123A

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: V198A

PolyPhen 2 Score 0.987 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000104932
Gene: ENSMUSG00000022623
AA Change: V198A

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

Meta Mutation Damage Score

0.2885

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.7%
20x: 94.0%

Validation Efficiency

97% (99/102)

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: 100 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4933430I17Rik	A	T	4: 62,457,146 (GRCm39)	N155I	probably benign	Het
Abca14	A	G	7: 119,924,382 (GRCm39)	Y1678C	probably damaging	Het
Adamts19	A	T	18: 59,103,078 (GRCm39)	R706S	probably benign	Het
Adipor1	T	C	1: 134,350,771 (GRCm39)	S7P	probably benign	Het
Adss2	A	G	1: 177,597,544 (GRCm39)	I372T	probably damaging	Het
Arhgap15	T	A	2: 44,133,136 (GRCm39)	D347E	possibly damaging	Het
Arnt	C	T	3: 95,355,704 (GRCm39)	S16L	possibly damaging	Het
Asb8	T	C	15: 98,034,097 (GRCm39)	T153A	possibly damaging	Het
Aspscr1	G	T	11: 120,580,034 (GRCm39)	G191V	probably null	Het
Atm	T	C	9: 53,382,718 (GRCm39)	H1957R	probably damaging	Het
Atp13a5	A	G	16: 29,133,419 (GRCm39)	Y411H	probably damaging	Het
Cadm1	T	G	9: 47,761,633 (GRCm39)	I411S	probably damaging	Het
Cdh23	T	A	10: 60,246,652 (GRCm39)	M927L	probably benign	Het
Cdk15	A	T	1: 59,383,475 (GRCm39)	R423W	probably damaging	Het
Cep250	T	A	2: 155,818,301 (GRCm39)		probably null	Het
Cfap43	T	A	19: 47,885,649 (GRCm39)	Y322F	probably benign	Het
Cfap54	T	C	10: 92,833,204 (GRCm39)	S1141G	probably benign	Het
Clnk	T	C	5: 38,863,969 (GRCm39)	Y428C	possibly damaging	Het
Cnksr1	A	G	4: 133,955,727 (GRCm39)	S668P	probably benign	Het
Cpxm2	A	T	7: 131,663,876 (GRCm39)	I349N	probably damaging	Het
Csmd3	A	G	15: 47,868,035 (GRCm39)		probably null	Het
Cstdc3	T	C	16: 36,132,927 (GRCm39)	L68P	possibly damaging	Het
Dnmt1	C	T	9: 20,838,442 (GRCm39)	R207H	probably benign	Het
Dph2	A	T	4: 117,749,041 (GRCm39)	F5I	probably damaging	Het
Dst	T	A	1: 34,202,802 (GRCm39)	F325L	probably damaging	Het
Edem3	T	C	1: 151,680,076 (GRCm39)	L474S	probably damaging	Het
Emilin1	T	A	5: 31,075,160 (GRCm39)	L467Q	probably benign	Het
Fam170a	G	A	18: 50,415,181 (GRCm39)	E276K	probably benign	Het
Farp1	A	T	14: 121,456,787 (GRCm39)		probably null	Het
Fbrs	A	T	7: 127,085,163 (GRCm39)	T584S	possibly damaging	Het
Fbxo22	T	A	9: 55,116,626 (GRCm39)		probably null	Het
Fhod3	T	G	18: 25,223,522 (GRCm39)	L956R	probably damaging	Het
Fmo4	G	A	1: 162,631,259 (GRCm39)	T236I	probably benign	Het
Foxp4	C	T	17: 48,186,796 (GRCm39)	R378Q	unknown	Het
Gdf10	G	A	14: 33,654,710 (GRCm39)	A406T	probably benign	Het
Gm11444	A	T	11: 85,738,999 (GRCm39)		probably benign	Het
Gm14443	T	C	2: 175,011,497 (GRCm39)	I316M	probably benign	Het
Has3	A	T	8: 107,605,435 (GRCm39)	Y547F	probably benign	Het
Hdhd2	A	G	18: 77,052,841 (GRCm39)	T164A	probably benign	Het
Hoxb9	T	A	11: 96,162,880 (GRCm39)	D171E	possibly damaging	Het
Hpx	A	G	7: 105,245,603 (GRCm39)	Y118H	probably damaging	Het
Iqsec1	T	C	6: 90,647,441 (GRCm39)	K858E	probably damaging	Het
Kifc1	G	A	17: 34,103,685 (GRCm39)	R195C	probably benign	Het
Lama2	C	A	10: 26,857,594 (GRCm39)	R3085L	probably damaging	Het
Lyst	C	A	13: 13,791,203 (GRCm39)	A22E	probably damaging	Het
Man2a1	T	C	17: 65,057,830 (GRCm39)	F1079L	probably benign	Het
Marco	C	T	1: 120,412,593 (GRCm39)	G303R	probably damaging	Het
Marveld2	A	C	13: 100,733,858 (GRCm39)	I536R	probably damaging	Het
Mcm5	A	G	8: 75,848,257 (GRCm39)	D502G	probably benign	Het
Mdga1	A	T	17: 30,059,862 (GRCm39)	L653Q	probably damaging	Het
Mical2	A	G	7: 111,980,311 (GRCm39)	D161G	probably benign	Het
Mroh2a	C	T	1: 88,165,213 (GRCm39)	R445*	probably null	Het
Mrpl46	A	T	7: 78,431,146 (GRCm39)		probably null	Het
Nckipsd	C	A	9: 108,691,863 (GRCm39)		probably null	Het
Nek11	T	C	9: 105,170,916 (GRCm39)	D373G	probably benign	Het
Nle1	G	A	11: 82,795,068 (GRCm39)	S321F	probably benign	Het
Noxa1	A	G	2: 24,980,620 (GRCm39)	S130P	probably damaging	Het
Or10a5	A	G	7: 106,635,478 (GRCm39)	T39A	possibly damaging	Het
Or51v14	T	A	7: 103,260,618 (GRCm39)	*314L	probably null	Het
Or5l13	A	T	2: 87,779,809 (GRCm39)	L256H	probably damaging	Het
Or8b39	T	A	9: 37,996,419 (GRCm39)	C96S	probably damaging	Het
Parp3	T	G	9: 106,352,021 (GRCm39)		probably null	Het
Pask	A	T	1: 93,249,180 (GRCm39)	I740N	probably benign	Het
Pelp1	A	G	11: 70,289,347 (GRCm39)	F221S	probably damaging	Het
Pkd1l1	T	G	11: 8,824,161 (GRCm39)	K1135Q	probably benign	Het
Plcl2	A	T	17: 50,915,109 (GRCm39)	Q706L	probably damaging	Het
Psg26	T	C	7: 18,212,264 (GRCm39)	T364A	probably benign	Het
Ptprb	C	T	10: 116,177,441 (GRCm39)	T1047M	probably benign	Het
Ptpro	T	A	6: 137,420,592 (GRCm39)	V1007D	probably damaging	Het
Rab37	C	T	11: 115,051,177 (GRCm39)	A155V	probably damaging	Het
Rbbp6	A	C	7: 122,601,168 (GRCm39)		probably benign	Het
Rbmxl2	A	G	7: 106,809,405 (GRCm39)	D230G	probably benign	Het
Rsf1	CGGCGGCGGCGGCGGCGGCGGCGGCGGC	CGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC	7: 97,229,115 (GRCm39)		probably benign	Het
Sass6	G	T	3: 116,403,945 (GRCm39)	K194N	possibly damaging	Het
Sgpp1	T	G	12: 75,782,222 (GRCm39)	D39A	probably benign	Het
Sin3a	T	A	9: 57,012,893 (GRCm39)	S591T	probably damaging	Het
Slc12a6	C	T	2: 112,185,503 (GRCm39)	T924I	possibly damaging	Het
Sln	T	A	9: 53,760,785 (GRCm39)	I10N	probably benign	Het
St3gal3	A	T	4: 117,797,268 (GRCm39)	M309K	probably damaging	Het
Syne2	T	A	12: 76,016,319 (GRCm39)	D3301E	probably benign	Het
Tgtp2	A	G	11: 48,949,919 (GRCm39)	S218P	probably damaging	Het
Tha1	C	T	11: 117,760,179 (GRCm39)		probably benign	Het
Tmem102	A	G	11: 69,695,225 (GRCm39)	V249A	probably benign	Het
Top3b	G	A	16: 16,702,166 (GRCm39)	E268K	possibly damaging	Het
Trip4	T	C	9: 65,746,307 (GRCm39)	S530G	possibly damaging	Het
Tut1	T	A	19: 8,936,677 (GRCm39)	V167E	probably damaging	Het
Tut4	A	T	4: 108,412,903 (GRCm39)	S1535C	probably damaging	Het
Ube2u	A	T	4: 100,338,833 (GRCm39)	M33L	probably benign	Het
Unc79	T	C	12: 102,957,621 (GRCm39)	I12T	probably damaging	Het
Unc79	A	T	12: 103,041,178 (GRCm39)	D737V	probably benign	Het
Vmn1r26	A	G	6: 57,985,286 (GRCm39)	V301A	probably benign	Het
Vmn1r86	A	G	7: 12,836,621 (GRCm39)	V35A	possibly damaging	Het
Vmn2r98	A	C	17: 19,286,680 (GRCm39)	N393H	possibly damaging	Het
Vps13b	T	G	15: 35,878,835 (GRCm39)	S2945A	probably damaging	Het
Whrn	C	T	4: 63,353,666 (GRCm39)	R367H	possibly damaging	Het
Zfp235	A	T	7: 23,839,771 (GRCm39)	L133F	probably damaging	Het
Zfp74	T	C	7: 29,635,136 (GRCm39)	T191A	probably benign	Het
Zfp943	A	T	17: 22,211,979 (GRCm39)	K355I	probably damaging	Het
Zranb1	T	G	7: 132,584,458 (GRCm39)	S601R	probably damaging	Het
Zscan29	A	T	2: 121,000,289 (GRCm39)		probably null	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
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'- CCAAGCTGGAATGAGACCTG -3'
(R):5'- AGTGGCGTTGTCCAACTGTG -3'

Sequencing Primer
(F):5'- CCTGAGGTAAGAGTATAGGGTTG -3'
(R):5'- TTGTCCAACTGTGCCGCAAG -3'

Posted On

2014-08-01