Mutagenetix > Incidental Mutation

Incidental Mutation 'R8826:Shank3'

673492

Institutional Source

Beutler Lab

Gene Symbol

Shank3

Ensembl Gene

ENSMUSG00000022623

Gene Name

SH3 and multiple ankyrin repeat domains 3

Synonyms

ProSAP2

MMRRC Submission

068729-MU

Accession Numbers

Essential gene?

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

Stock #

R8826 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

89383826-89444464 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 89433598 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Serine at position 1448 (T1448S)

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: T1373S

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

probably damaging
Transcript: ENSMUST00000109309
AA Change: T1448S

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000104932
Gene: ENSMUSG00000022623
AA Change: T1448S

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.9%

Validation Efficiency

100% (91/91)

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: 90 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acta1	T	C	8: 124,619,978 (GRCm39)	M121V	probably damaging	Het
AI987944	A	T	7: 41,024,627 (GRCm39)	H120Q	possibly damaging	Het
Aldh9a1	C	G	1: 167,184,119 (GRCm39)	P205A	probably damaging	Het
Ank2	A	T	3: 126,740,951 (GRCm39)	N1644K	unknown	Het
Arfgef2	A	T	2: 166,677,386 (GRCm39)		probably benign	Het
Bpifb4	G	T	2: 153,783,817 (GRCm39)	V54L	probably benign	Het
Cacna1c	T	A	6: 118,711,836 (GRCm39)	M456L		Het
Cbln1	T	C	8: 88,198,420 (GRCm39)	N95S	probably benign	Het
Ccl11	G	T	11: 81,953,044 (GRCm39)	R67S	possibly damaging	Het
Cd200	G	A	16: 45,215,157 (GRCm39)	R165C	probably benign	Het
Cd2bp2	A	T	7: 126,793,257 (GRCm39)	M283K	probably damaging	Het
Cd86	G	T	16: 36,435,650 (GRCm39)	L256I	possibly damaging	Het
Ces2f	T	A	8: 105,679,734 (GRCm39)	F409Y	probably benign	Het
Cisd3	A	T	11: 97,579,158 (GRCm39)	Q100L	probably damaging	Het
Cntnap1	C	T	11: 101,077,655 (GRCm39)	R1106C	probably damaging	Het
Col6a2	A	T	10: 76,439,433 (GRCm39)	M777K	probably damaging	Het
Cp	A	G	3: 20,039,739 (GRCm39)	Y852C	probably damaging	Het
Ddx1	T	C	12: 13,277,332 (GRCm39)	E523G	probably damaging	Het
Ddx60	T	A	8: 62,398,990 (GRCm39)	D236E	probably benign	Het
Dnah9	A	T	11: 65,740,742 (GRCm39)	F4148Y	probably benign	Het
Dusp6	G	T	10: 99,099,469 (GRCm39)		probably benign	Het
Eif2a	C	A	3: 58,456,049 (GRCm39)	Y349*	probably null	Het
Enpep	G	A	3: 129,065,067 (GRCm39)	T874I	probably damaging	Het
Eps15	A	G	4: 109,169,505 (GRCm39)	D105G	possibly damaging	Het
Ess2	A	T	16: 17,722,954 (GRCm39)	M320K	probably damaging	Het
Exosc10	G	A	4: 148,653,159 (GRCm39)		probably null	Het
Fam13b	A	T	18: 34,631,070 (GRCm39)	N36K	probably damaging	Het
Fanca	T	C	8: 123,995,209 (GRCm39)	D1431G	probably benign	Het
Fgg	A	G	3: 82,921,625 (GRCm39)	D436G	probably benign	Het
Fip1l1	C	T	5: 74,725,188 (GRCm39)	T251I	probably benign	Het
Galnt2	A	G	8: 125,032,347 (GRCm39)	N104S	probably damaging	Het
Gmip	T	C	8: 70,268,748 (GRCm39)	S458P	possibly damaging	Het
Herc2	A	G	7: 55,756,144 (GRCm39)	D728G	probably benign	Het
Hif3a	A	G	7: 16,788,671 (GRCm39)	L100P	probably damaging	Het
Hmox2	C	G	16: 4,583,866 (GRCm39)	P282R	possibly damaging	Het
Hook1	A	T	4: 95,880,432 (GRCm39)	H90L	probably benign	Het
Igf2bp2	C	A	16: 21,883,866 (GRCm39)	G473C	probably damaging	Het
Ip6k2	T	C	9: 108,675,379 (GRCm39)		probably null	Het
Ipo5	G	T	14: 121,157,366 (GRCm39)	R68L	probably damaging	Het
Kif19b	A	G	5: 140,455,434 (GRCm39)	M347V	probably damaging	Het
Klhdc1	G	T	12: 69,305,392 (GRCm39)	W234L	probably damaging	Het
Krt8	A	G	15: 101,909,870 (GRCm39)	V178A	possibly damaging	Het
Lgi3	T	A	14: 70,768,712 (GRCm39)		probably null	Het
Litaf	T	G	16: 10,784,421 (GRCm39)	N30H	probably benign	Het
Lman2	C	A	13: 55,510,368 (GRCm39)	W12L	unknown	Het
Macf1	A	G	4: 123,276,022 (GRCm39)	L6182P	probably damaging	Het
Magi3	A	T	3: 103,992,662 (GRCm39)	M270K	probably benign	Het
Mapre2	A	T	18: 23,886,888 (GRCm39)		probably benign	Het
Minar1	T	A	9: 89,483,234 (GRCm39)	E721V	probably damaging	Het
Mllt10	T	A	2: 18,167,353 (GRCm39)	V426D	probably benign	Het
Mrgprf	A	G	7: 144,862,046 (GRCm39)	I203V	probably benign	Het
Mrnip	G	A	11: 50,067,688 (GRCm39)	C27Y	probably damaging	Het
Mrpl24	C	T	3: 87,829,701 (GRCm39)	R96*	probably null	Het
Nbas	T	A	12: 13,402,875 (GRCm39)		probably benign	Het
Nipal4	G	A	11: 46,045,470 (GRCm39)	T131M	possibly damaging	Het
Nlrp12	T	C	7: 3,289,621 (GRCm39)	D297G	possibly damaging	Het
Nol6	A	C	4: 41,121,823 (GRCm39)	M237R	probably benign	Het
Olig1	A	G	16: 91,067,027 (GRCm39)	E88G	probably benign	Het
Or1j19	T	A	2: 36,676,855 (GRCm39)	L106*	probably null	Het
Parg	A	G	14: 31,931,175 (GRCm39)	D265G	possibly damaging	Het
Pcdhgb8	A	T	18: 37,895,301 (GRCm39)	I124L	probably damaging	Het
Pign	A	G	1: 105,481,827 (GRCm39)	F822L	probably damaging	Het
Plch2	T	C	4: 155,071,140 (GRCm39)	T1080A	probably benign	Het
Pld4	A	T	12: 112,733,210 (GRCm39)	Y262F	possibly damaging	Het
Ppp1r12b	A	G	1: 134,693,730 (GRCm39)	V977A	probably benign	Het
Ppp6r3	C	T	19: 3,521,984 (GRCm39)	E565K		Het
Psmg2	A	G	18: 67,787,158 (GRCm39)		probably benign	Het
Ptcd3	C	T	6: 71,885,645 (GRCm39)	G27D	probably benign	Het
Retreg2	G	T	1: 75,119,525 (GRCm39)	G7C	unknown	Het
Rlbp1	A	T	7: 79,027,114 (GRCm39)	F182Y	probably benign	Het
Rnf148	G	C	6: 23,654,378 (GRCm39)	S206C	probably benign	Het
Sash1	A	G	10: 8,637,869 (GRCm39)	M1T	probably null	Het
Sipa1l1	A	G	12: 82,389,207 (GRCm39)	K478E	probably damaging	Het
Slitrk6	A	G	14: 110,988,801 (GRCm39)	I302T	probably benign	Het
Smc1b	A	G	15: 84,950,529 (GRCm39)	V1165A	probably damaging	Het
Sncaip	A	T	18: 53,048,381 (GRCm39)	H939L	probably benign	Het
Stn1	T	C	19: 47,524,709 (GRCm39)	D27G	probably damaging	Het
Sugct	T	G	13: 17,427,180 (GRCm39)		probably null	Het
Tmem259	A	G	10: 79,814,983 (GRCm39)	S214P	probably damaging	Het
Trdv4	G	A	14: 54,312,946 (GRCm39)	G107S	probably damaging	Het
Ttc3	C	T	16: 94,232,829 (GRCm39)	L957F	possibly damaging	Het
Ttn	A	G	2: 76,711,471 (GRCm39)	Y8357H	unknown	Het
Twnk	T	C	19: 44,996,434 (GRCm39)	V289A	probably benign	Het
Umodl1	A	G	17: 31,202,958 (GRCm39)	D437G	possibly damaging	Het
Upf1	T	C	8: 70,790,930 (GRCm39)	T590A	probably benign	Het
Vmn2r63	A	T	7: 42,576,441 (GRCm39)	D457E	probably benign	Het
Wdr82	A	T	9: 106,061,975 (GRCm39)	T213S	probably benign	Het
Zfp267	T	C	3: 36,218,255 (GRCm39)	Y93H	possibly damaging	Het
Zfp672	A	T	11: 58,220,590 (GRCm39)	M3K	unknown	Het
Zfyve26	A	G	12: 79,285,742 (GRCm39)	V2345A	probably benign	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
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
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'- TTGCCAATGGGATCCTGCTG -3'
(R):5'- AACCCAGTAGAGGCAGCATG -3'

Sequencing Primer
(F):5'- AATGGGATCCTGCTGACCAC -3'
(R):5'- CACTGTCCGAGGATTGCTTCAG -3'

Posted On

2021-07-15