Mutagenetix > Incidental Mutations

Incidental Mutation 'R2420:Shank3'

249239

Institutional Source

Beutler Lab

Gene Symbol

Shank3

Ensembl Gene

ENSMUSG00000022623

Gene Name

SH3 and multiple ankyrin repeat domains 3

Synonyms

MMRRC Submission

040382-MU

Accession Numbers

Is this an essential gene?

Possibly non essential (E-score: 0.276) question?

Stock #

R2420 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

89499623-89560261 bp(+) (GRCm38)

Type of Mutation

nonsense

DNA Base Change (assembly)

A to T at 89521210 bp

Zygosity

Heterozygous

Amino Acid Change

Lysine to Stop codon at position 455 (K455*)

Ref Sequence

ENSEMBL: ENSMUSP00000104932 (fasta)

Gene Model

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

Predicted Effect

probably null
Transcript: ENSMUST00000039074
AA Change: K380*

SMART Domains

Protein: ENSMUSP00000048062
Gene: ENSMUSG00000022623
AA Change: K380*

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 null
Transcript: ENSMUST00000109309
AA Change: K455*

SMART Domains

Protein: ENSMUSP00000104932
Gene: ENSMUSG00000022623
AA Change: K455*

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: ENSMUST00000154240

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000155610

Predicted Effect

probably benign
Transcript: ENSMUST00000229559

Predicted Effect

probably benign
Transcript: ENSMUST00000230807

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.9%
20x: 93.6%

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: 71 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700015F17Rik	T	C	5: 5,455,912	Y123C	probably benign	Het
6820408C15Rik	A	G	2: 152,429,001	K48R	probably damaging	Het
Acsm2	T	C	7: 119,563,634	F44L	probably damaging	Het
Actr5	T	C	2: 158,636,081	F457S	probably damaging	Het
Adamts3	A	G	5: 89,683,175	S1007P	probably damaging	Het
Ahnak	C	T	19: 9,009,256	P2635S	possibly damaging	Het
Ankrd17	A	T	5: 90,289,320	D555E	possibly damaging	Het
Arhgap29	A	G	3: 121,973,980	I24V	probably benign	Het
Atxn2	A	T	5: 121,802,079		probably null	Het
Birc6	T	A	17: 74,660,614	L301Q	probably damaging	Het
Ccdc137	G	A	11: 120,462,264		probably null	Het
Ccdc18	A	C	5: 108,228,588	E1298D	probably damaging	Het
Chst9	A	T	18: 15,452,284	N407K	probably damaging	Het
Cwf19l2	A	G	9: 3,411,341	K73E	possibly damaging	Het
Dhcr24	G	T	4: 106,561,094		probably benign	Het
Dnajc21	A	G	15: 10,461,935	S127P	probably benign	Het
Egln1	T	C	8: 124,948,246	N270S	probably benign	Het
Eme1	A	G	11: 94,645,814		probably null	Het
Emilin2	A	G	17: 71,274,279	I484T	possibly damaging	Het
Entpd2	T	C	2: 25,399,283	I259T	probably benign	Het
Fbp1	T	C	13: 62,871,306	K24E	probably benign	Het
Fga	A	T	3: 83,033,154	N705I	possibly damaging	Het
Gas1	G	T	13: 60,176,930		probably benign	Het
Glrb	A	G	3: 80,860,235	I226T	probably damaging	Het
Gm17421	T	A	12: 113,369,487		noncoding transcript	Het
Gm44501	A	T	17: 40,578,709	H38L	possibly damaging	Het
H2-M10.5	A	G	17: 36,774,999	I308V	probably benign	Het
Hjurp	GT	GTT	1: 88,266,524		probably null	Het
Jcad	T	C	18: 4,675,952	M1238T	probably damaging	Het
Kank1	T	C	19: 25,410,457	L498S	probably damaging	Het
Krt10	G	A	11: 99,387,107	T338I	possibly damaging	Het
Krt13	A	T	11: 100,120,051	L159Q	probably benign	Het
Lama1	A	T	17: 67,750,553	M541L	probably benign	Het
Lilra6	A	G	7: 3,914,858	Y96H	probably damaging	Het
Ltc4s	A	G	11: 50,237,339		probably null	Het
Ly6g6e	G	A	17: 35,078,146	R121Q	probably benign	Het
Mfn1	A	G	3: 32,569,515	I263V	probably benign	Het
Mmaa	T	A	8: 79,281,432	R59W	probably damaging	Het
Mug2	C	A	6: 122,083,460	T1385K	probably damaging	Het
Mypn	G	T	10: 63,192,869	Y138*	probably null	Het
Nav3	A	C	10: 109,863,813	S273R	probably damaging	Het
Ndufaf1	T	C	2: 119,655,737	E298G	probably damaging	Het
Olfr1219	T	C	2: 89,074,992	Y33C	possibly damaging	Het
Olfr1290	T	C	2: 111,489,257		probably null	Het
Olfr178	T	C	16: 58,889,965	E85G	probably benign	Het
Olfr470	T	C	7: 107,844,818	K305R	probably benign	Het
Olfr975	A	G	9: 39,950,528	L81P	possibly damaging	Het
Pak1	A	T	7: 97,854,479	D7V	probably benign	Het
Pax3	A	T	1: 78,196,864		probably null	Het
Plekhg1	G	A	10: 3,958,048	M988I	probably benign	Het
Prickle1	A	G	15: 93,503,637	F322S	probably damaging	Het
Prl8a2	A	G	13: 27,348,913	E36G	possibly damaging	Het
Prss45	A	G	9: 110,839,092	I118V	possibly damaging	Het
Psd4	T	G	2: 24,401,241	V597G	probably damaging	Het
Psmb10	A	G	8: 105,937,302	S108P	probably benign	Het
Spag17	T	A	3: 100,027,619	W714R	probably benign	Het
Synrg	A	G	11: 84,009,224	E674G	probably damaging	Het
Tep1	T	A	14: 50,834,023	H2055L	probably benign	Het
Terb1	T	C	8: 104,498,595	T14A	probably damaging	Het
Tmub2	T	A	11: 102,287,755	D161E	probably benign	Het
Ttc23l	CT	CTTGGATT	15: 10,537,562		probably benign	Het
Ttc23l	G	A	15: 10,537,566	S206L	probably benign	Het
Tyr	T	A	7: 87,429,189	I488F	probably benign	Het
Uba6	A	G	5: 86,132,616		probably null	Het
Unc13c	T	C	9: 73,931,547	Y674C	probably damaging	Het
Vmn2r105	T	A	17: 20,227,835	R242S	probably benign	Het
Vmn2r12	A	G	5: 109,086,532	Y605H	probably benign	Het
Wnk1	A	G	6: 119,936,367		probably null	Het
Zfhx4	C	A	3: 5,390,405	A1153E	probably benign	Het
Zfp13	A	C	17: 23,576,212	Y462D	probably damaging	Het
Zfp644	A	G	5: 106,637,244	M479T	possibly damaging	Het

Other mutations in Shank3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01070:Shank3	APN	15	89549416	missense	probably damaging	1.00
IGL01469:Shank3	APN	15	89521274	missense	probably damaging	1.00
IGL01886:Shank3	APN	15	89531663	missense	probably damaging	1.00
IGL01934:Shank3	APN	15	89549846	missense	probably damaging	1.00
IGL01989:Shank3	APN	15	89503299	splice site	probably benign
IGL02004:Shank3	APN	15	89503299	splice site	probably benign
IGL02085:Shank3	APN	15	89503915	critical splice donor site	probably null
IGL02195:Shank3	APN	15	89548118	missense	probably damaging	1.00
IGL02354:Shank3	APN	15	89504333	missense	probably damaging	1.00
IGL02361:Shank3	APN	15	89504333	missense	probably damaging	1.00
IGL02541:Shank3	APN	15	89501410	missense	probably damaging	1.00
R0294:Shank3	UTSW	15	89532098	missense	probably damaging	1.00
R0468:Shank3	UTSW	15	89549275	missense	probably benign	0.28
R0483:Shank3	UTSW	15	89543239	splice site	probably benign
R0605:Shank3	UTSW	15	89524147	missense	possibly damaging	0.49
R0675:Shank3	UTSW	15	89531388	missense	possibly damaging	0.92
R1082:Shank3	UTSW	15	89549371	missense	probably damaging	1.00
R1576:Shank3	UTSW	15	89503663	missense	probably benign	0.11
R1702:Shank3	UTSW	15	89499896	missense	probably damaging	0.99
R1726:Shank3	UTSW	15	89557986	missense	probably damaging	1.00
R1958:Shank3	UTSW	15	89503148	missense	probably damaging	0.99
R1961:Shank3	UTSW	15	89557964	missense	possibly damaging	0.60
R2513:Shank3	UTSW	15	89548686	missense	probably benign	0.05
R3917:Shank3	UTSW	15	89503384	missense	possibly damaging	0.77
R4163:Shank3	UTSW	15	89549594	missense	probably damaging	1.00
R4205:Shank3	UTSW	15	89503318	missense	probably damaging	1.00
R4434:Shank3	UTSW	15	89503359	missense	probably damaging	1.00
R4791:Shank3	UTSW	15	89500354	missense	probably damaging	1.00
R4816:Shank3	UTSW	15	89543115	missense	probably damaging	1.00
R4828:Shank3	UTSW	15	89500199	intron	probably benign
R4911:Shank3	UTSW	15	89504344	missense	probably damaging	1.00
R4997:Shank3	UTSW	15	89549698	missense	probably damaging	1.00
R5213:Shank3	UTSW	15	89533278	missense	possibly damaging	0.82
R5338:Shank3	UTSW	15	89531711	splice site	probably null
R5494:Shank3	UTSW	15	89548238	missense	probably damaging	0.99
R5543:Shank3	UTSW	15	89532354	missense	probably damaging	1.00
R5654:Shank3	UTSW	15	89521326	missense	probably benign	0.07
R5900:Shank3	UTSW	15	89503390	missense	probably damaging	1.00
R5906:Shank3	UTSW	15	89548916	missense	probably damaging	1.00
R6385:Shank3	UTSW	15	89521375	critical splice donor site	probably null
R6432:Shank3	UTSW	15	89503413	missense	possibly damaging	0.75
R6724:Shank3	UTSW	15	89532453	missense	probably damaging	1.00
R6822:Shank3	UTSW	15	89531627	missense	probably damaging	1.00
R6845:Shank3	UTSW	15	89548325	missense	probably benign	0.00
R7088:Shank3	UTSW	15	89503525	splice site	probably null
R7390:Shank3	UTSW	15	89549312	missense	probably benign	0.05
R7808:Shank3	UTSW	15	89548880	missense	probably damaging	1.00
R7862:Shank3	UTSW	15	89505445	missense	possibly damaging	0.73
R8039:Shank3	UTSW	15	89505439	missense	probably damaging	1.00
R8090:Shank3	UTSW	15	89505458	critical splice donor site	probably null
R8170:Shank3	UTSW	15	89548840	missense	possibly damaging	0.69
R8189:Shank3	UTSW	15	89549236	missense	probably benign
R8246:Shank3	UTSW	15	89533346	missense	possibly damaging	0.90
R8515:Shank3	UTSW	15	89503572	nonsense	probably null
R8525:Shank3	UTSW	15	89547770	missense	probably damaging	0.99
R8537:Shank3	UTSW	15	89532215	missense	probably damaging	1.00
RF020:Shank3	UTSW	15	89500390	missense	probably benign	0.20
Z1177:Shank3	UTSW	15	89558322	makesense	probably null

Predicted Primers

PCR Primer
(F):5'- GTGTGTACATTTATAGATATGCAGGT -3'
(R):5'- AGCTCTCGACCCATCCTGAC -3'

Sequencing Primer
(F):5'- AGCAGCTTATGTCCAGGTAC -3'
(R):5'- ATCCTGACCCTTCCTTCCAGG -3'

Posted On

2014-11-12