Mutagenetix > Incidental Mutation

Incidental Mutation 'R8039:Shank3'

618442

Institutional Source

Beutler Lab

Gene Symbol

Shank3

Ensembl Gene

ENSMUSG00000022623

Gene Name

SH3 and multiple ankyrin repeat domains 3

Synonyms

MMRRC Submission

067476-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.273) question?

Stock #

R8039 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

89499623-89560261 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 89505439 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Leucine at position 413 (H413L)

Ref Sequence

ENSEMBL: ENSMUSP00000104932 (fasta)

Gene Model

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

AlphaFold

Q4ACU6

Predicted Effect

SMART Domains

Protein: ENSMUSP00000048062
Gene: ENSMUSG00000022623
AA Change: H338L

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: H413L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000104932
Gene: ENSMUSG00000022623
AA Change: H413L

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.5%

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: 86 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4932438A13Rik	T	A	3: 36,943,214	V1140E	probably benign	Het
Abca17	T	C	17: 24,328,725	H225R	probably damaging	Het
Adgrb2	T	A	4: 130,022,268	L1451Q	probably damaging	Het
Afdn	T	C	17: 13,899,141	L1713P	probably damaging	Het
Agr2	A	T	12: 35,995,559	I15F	probably benign	Het
Agrn	T	C	4: 156,169,011	T1808A	probably benign	Het
Akap6	A	G	12: 53,141,676	I1958V	probably benign	Het
Ankrd60	C	A	2: 173,572,491		probably null	Het
Anpep	A	G	7: 79,839,400		probably null	Het
Apoa4	A	T	9: 46,242,293	D64V	possibly damaging	Het
Arhgef26	C	A	3: 62,339,930	T145N	probably benign	Het
Art1	A	T	7: 102,106,845	Q81L	probably benign	Het
Astl	A	T	2: 127,343,983	S71C	probably damaging	Het
Atp2a1	A	G	7: 126,448,805	I611T	probably damaging	Het
Cacna2d2	T	A	9: 107,527,433	V1139D	possibly damaging	Het
Chst10	T	A	1: 38,866,031	K198*	probably null	Het
Ckmt2	G	A	13: 91,863,312	H60Y	possibly damaging	Het
Coq7	G	C	7: 118,533,246	S2R	possibly damaging	Het
Cspp1	T	A	1: 10,113,013	D814E	probably benign	Het
Cyp2c54	CCTCTTTCATAGCTCT	CCTCT	19: 40,073,732		probably null	Het
Daam2	C	A	17: 49,464,538	G860V	probably damaging	Het
Ecm2	A	T	13: 49,514,850	I10F	probably benign	Het
Epb41l1	A	T	2: 156,506,412	D312V	probably damaging	Het
Epsti1	G	A	14: 77,931,301	R126H	probably damaging	Het
Erc1	A	T	6: 119,773,665	Y367*	probably null	Het
Erh	T	A	12: 80,637,578	R42W	probably damaging	Het
Fam124a	C	T	14: 62,605,876	Q278*	probably null	Het
Fam155a	T	C	8: 9,207,892	T419A	probably benign	Het
Fbxo3	T	A	2: 104,054,941	L385Q	probably damaging	Het
Fbxo31	T	A	8: 121,559,055	T219S	probably damaging	Het
Fstl5	T	G	3: 76,648,418	V534G	possibly damaging	Het
Gatsl3	G	T	11: 4,221,639	A288S	probably damaging	Het
Gbp2b	A	T	3: 142,618,164	I577F	probably benign	Het
Gbp8	A	T	5: 105,050,917	L44*	probably null	Het
Gck	C	T	11: 5,910,301	A114T	probably benign	Het
Gm16486	T	C	8: 70,710,906	V916A	probably benign	Het
Gtf2i	A	G	5: 134,255,834	V537A	possibly damaging	Het
Iqcm	C	A	8: 75,763,105	H400Q	probably damaging	Het
Itpr1	T	C	6: 108,386,628	L737P	probably damaging	Het
Jakmip1	A	G	5: 37,100,772	E254G	probably damaging	Het
Kif15	A	T	9: 123,007,425	R1095W	possibly damaging	Het
Klhdc8a	G	A	1: 132,303,108	R237Q	probably benign	Het
Klhl38	T	C	15: 58,322,862	E157G	probably benign	Het
Klrk1	T	A	6: 129,612,823	N221I	probably benign	Het
Lhx8	A	T	3: 154,306,939	H345Q	probably damaging	Het
Lims1	T	A	10: 58,409,672	N174K	probably benign	Het
Madd	T	A	2: 91,167,061	Q754L	probably benign	Het
Mau2	T	C	8: 70,019,790	D581G	probably damaging	Het
Miga1	A	T	3: 152,276,756	I561N	probably benign	Het
Mmp1a	TG	TGG	9: 7,465,083		probably null	Het
Mob3c	T	C	4: 115,831,687	V139A	probably benign	Het
Nadk	G	T	4: 155,577,067	D17Y	probably benign	Het
Ncapd2	C	T	6: 125,181,026	V380I	probably damaging	Het
Nes	G	A	3: 87,977,008	R858K	probably benign	Het
Nphp3	T	C	9: 104,031,963	S791P	probably benign	Het
Nup210	T	C	6: 91,070,233	T496A	probably benign	Het
Ogfr	GGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGGGCCAGAGGACCCCCAAAGCCAGGTGG	GGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGAGCCAGAGGACCCCAAAAGCCAGGTGGGGCCAGAGGACCCCCAAAGCCAGGTGG	2: 180,595,266		probably benign	Het
Olfr1186	C	T	2: 88,525,871	T96I	probably benign	Het
Olfr220	T	A	1: 174,449,596	S324R	unknown	Het
Olfr914	T	A	9: 38,607,389	M308K	probably benign	Het
Ovgp1	T	A	3: 105,976,023	S105T	probably benign	Het
Pbld2	T	A	10: 63,047,992	C79S	probably damaging	Het
Pik3cd	T	A	4: 149,659,866	M143L	possibly damaging	Het
Plat	G	T	8: 22,772,232	G91W	probably damaging	Het
Poln	A	G	5: 34,122,672	V282A	probably benign	Het
Ppp1r11	T	C	17: 36,951,446	T21A	probably damaging	Het
Prpf8	T	A	11: 75,502,542	I1664N	possibly damaging	Het
Prr29	C	T	11: 106,376,912	A161V	probably benign	Het
Rasa3	T	C	8: 13,588,931	D292G	probably damaging	Het
Rnf25	T	C	1: 74,593,964	T411A	probably damaging	Het
Rraga	C	T	4: 86,575,980	T21I	probably damaging	Het
Setdb2	T	A	14: 59,402,375	Y673F	probably damaging	Het
Sf3a1	C	T	11: 4,167,787	T183I	probably damaging	Het
Slc30a5	A	G	13: 100,813,681		probably null	Het
Slc6a18	T	C	13: 73,665,626	S523G	probably benign	Het
Spaca1	C	T	4: 34,044,207	V96I	probably damaging	Het
Sycp2	C	T	2: 178,374,585	A695T	probably benign	Het
Tnrc18	C	A	5: 142,732,052	G2216C	unknown	Het
Trak2	T	C	1: 58,946,288	N17S	probably benign	Het
Ttn	T	A	2: 76,878,432	N8792I	unknown	Het
Ttyh1	T	C	7: 4,122,541	V64A	probably benign	Het
Usb1	T	A	8: 95,333,413	S50R	probably damaging	Het
Ush2a	T	A	1: 188,957,373	I5044N	probably damaging	Het
Vmn1r84	A	T	7: 12,362,008	F253I	possibly damaging	Het
Vmn2r99	T	C	17: 19,380,040	I442T	probably benign	Het
Vsig1	C	T	X: 140,933,126	H232Y	probably benign	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
G1citation:Shank3	UTSW	15	89531627	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
R2420:Shank3	UTSW	15	89521210	nonsense	probably null
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
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
R8673:Shank3	UTSW	15	89549776	missense	probably damaging	1.00
R8826:Shank3	UTSW	15	89549395	missense	probably damaging	1.00
R8932:Shank3	UTSW	15	89548783	missense	possibly damaging	0.86
R8954:Shank3	UTSW	15	89549228	missense	possibly damaging	0.88
R8976:Shank3	UTSW	15	89558178	missense	probably damaging	1.00
R8992:Shank3	UTSW	15	89548685	missense	possibly damaging	0.95
R8994:Shank3	UTSW	15	89533213	missense	probably benign	0.27
R9130:Shank3	UTSW	15	89558216	missense	probably benign	0.19
R9258:Shank3	UTSW	15	89504318	missense	probably damaging	1.00
R9645:Shank3	UTSW	15	89525250	missense	possibly damaging	0.96
RF020:Shank3	UTSW	15	89500390	missense	probably benign	0.20
Z1177:Shank3	UTSW	15	89558322	makesense	probably null

Predicted Primers

PCR Primer
(F):5'- ACCCTAGTTACTGGCATCCTTG -3'
(R):5'- TGTTCAGTCCACACAGGCTC -3'

Sequencing Primer
(F):5'- AGGTCCCAGTAGACATTTTGGC -3'
(R):5'- AGTCCACACAGGCTCTTTTTC -3'

Posted On

2020-01-23