Mutagenetix > Incidental Mutation

Incidental Mutation 'R9130:Shank3'

693580

Institutional Source

Beutler Lab

Gene Symbol

Shank3

Ensembl Gene

ENSMUSG00000022623

Gene Name

SH3 and multiple ankyrin repeat domains 3

Synonyms

ProSAP2

MMRRC Submission

068928-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.176) question?

Stock #

R9130 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

89383826-89444464 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 89442419 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Alanine to Threonine at position 1771 (A1771T)

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: A1696T

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 benign
Transcript: ENSMUST00000109309
AA Change: A1771T

PolyPhen 2 Score 0.188 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000104932
Gene: ENSMUSG00000022623
AA Change: A1771T

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

0.0875

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.2%

Validation Efficiency

99% (87/88)

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
Abr	A	G	11: 76,342,753 (GRCm39)	C585R	possibly damaging	Het
Acaca	T	C	11: 84,202,145 (GRCm39)	L1380S	probably damaging	Het
Aifm2	A	C	10: 61,563,505 (GRCm39)	Q125P	probably null	Het
Ak5	A	T	3: 152,178,569 (GRCm39)	L482*	probably null	Het
Aldh3a2	T	C	11: 61,139,758 (GRCm39)	Q458R	probably benign	Het
Ank2	G	A	3: 126,810,565 (GRCm39)	T524I		Het
Apoc3	A	T	9: 46,146,481 (GRCm39)	S25T	unknown	Het
Ash1l	A	T	3: 88,965,848 (GRCm39)	R2417*	probably null	Het
Bbs12	A	G	3: 37,373,205 (GRCm39)		probably benign	Het
Birc6	T	A	17: 74,919,146 (GRCm39)	I1992N		Het
Brd9	G	A	13: 74,092,906 (GRCm39)	V299M	probably damaging	Het
Brwd1	A	T	16: 95,866,130 (GRCm39)	N217K	probably damaging	Het
C3	T	C	17: 57,518,678 (GRCm39)	Y1235C	probably damaging	Het
Cacna1c	T	C	6: 118,590,907 (GRCm39)	Y1538C		Het
Ccdc172	T	A	19: 58,525,779 (GRCm39)	H212Q	possibly damaging	Het
Cdc6	A	G	11: 98,802,999 (GRCm39)	D313G	probably damaging	Het
Cyp2e1	T	C	7: 140,353,022 (GRCm39)	V353A	probably damaging	Het
Dlg2	G	T	7: 92,080,258 (GRCm39)	V711F	probably damaging	Het
Dmac2	T	C	7: 25,320,448 (GRCm39)	F49S	probably damaging	Het
Dnah7b	A	G	1: 46,173,674 (GRCm39)	K660E	probably benign	Het
Dusp8	A	T	7: 141,642,155 (GRCm39)	S106T	probably benign	Het
Dynll1	T	A	5: 115,438,604 (GRCm39)	I34F	probably benign	Het
Epb41l4b	A	G	4: 57,103,447 (GRCm39)	F130L	possibly damaging	Het
Erc2	T	C	14: 27,751,418 (GRCm39)	Y705H	probably benign	Het
Exosc8	T	A	3: 54,638,503 (GRCm39)	L160F	probably damaging	Het
F5	A	G	1: 164,001,830 (GRCm39)	T178A	probably benign	Het
F7	C	A	8: 13,085,059 (GRCm39)	P362T	probably damaging	Het
Fkbp3	T	C	12: 65,112,567 (GRCm39)	K156E	possibly damaging	Het
Folh1	G	A	7: 86,368,913 (GRCm39)	T738I	probably benign	Het
Gatad2b	C	T	3: 90,255,936 (GRCm39)	A134V	probably benign	Het
Glud1	T	A	14: 34,057,349 (GRCm39)	W338R		Het
Gm21149	T	C	5: 15,680,261 (GRCm39)	K62E	possibly damaging	Het
Gm32742	A	G	9: 51,050,049 (GRCm39)	Y1517H	probably damaging	Het
Grik5	G	A	7: 24,767,429 (GRCm39)		probably benign	Het
Gse1	A	T	8: 121,295,052 (GRCm39)	E391V	unknown	Het
Gxylt2	C	T	6: 100,710,329 (GRCm39)	Q157*	probably null	Het
Hbq1b	C	T	11: 32,237,092 (GRCm39)	T27I	probably damaging	Het
Hoxd13	T	A	2: 74,499,382 (GRCm39)	D243E	probably benign	Het
Hsd3b3	T	A	3: 98,651,211 (GRCm39)	I80F	possibly damaging	Het
Hsf2bp	A	T	17: 32,230,082 (GRCm39)		probably benign	Het
Itch	G	A	2: 155,052,045 (GRCm39)		probably benign	Het
Kat14	T	C	2: 144,215,742 (GRCm39)	F76L	probably benign	Het
Kdm6b	T	C	11: 69,295,424 (GRCm39)	T948A	unknown	Het
Kmt2c	A	T	5: 25,516,102 (GRCm39)	H2580Q	probably benign	Het
Lrp1	T	C	10: 127,382,281 (GRCm39)	T3727A	probably benign	Het
Lrrc8a	A	G	2: 30,147,042 (GRCm39)	I619V	possibly damaging	Het
Mansc1	C	A	6: 134,586,951 (GRCm39)	G409W	probably damaging	Het
Map3k11	C	A	19: 5,746,038 (GRCm39)	L418I	possibly damaging	Het
Mettl4	T	A	17: 95,042,913 (GRCm39)	I308L	possibly damaging	Het
Myo9a	A	G	9: 59,739,514 (GRCm39)	D742G	probably damaging	Het
Mypn	T	C	10: 63,028,652 (GRCm39)	Q137R	probably benign	Het
Neurod4	A	T	10: 130,106,427 (GRCm39)	Y282*	probably null	Het
Nup210	A	G	6: 91,020,799 (GRCm39)	F965S	probably benign	Het
Oplah	T	C	15: 76,185,098 (GRCm39)	T872A	possibly damaging	Het
Or1ab2	G	T	8: 72,863,697 (GRCm39)	G96C	probably damaging	Het
Or4b12	A	G	2: 90,096,358 (GRCm39)	C139R	probably damaging	Het
Or5m8	T	G	2: 85,822,819 (GRCm39)	Y219*	probably null	Het
Or6c68	A	G	10: 129,157,897 (GRCm39)	N135S	probably benign	Het
Pkn2	A	T	3: 142,515,245 (GRCm39)	D696E	possibly damaging	Het
Pla2r1	A	T	2: 60,325,729 (GRCm39)		probably benign	Het
Plpp1	A	T	13: 112,988,038 (GRCm39)	I54L		Het
Ppp4r2	T	G	6: 100,842,113 (GRCm39)	N191K	probably damaging	Het
Ptpdc1	G	T	13: 48,739,655 (GRCm39)	P592Q	probably benign	Het
Qrich2	A	T	11: 116,347,692 (GRCm39)	L1044*	probably null	Het
Rb1cc1	A	G	1: 6,315,109 (GRCm39)	I421V	probably damaging	Het
Ripor3	A	T	2: 167,823,267 (GRCm39)	C881*	probably null	Het
Rreb1	T	C	13: 38,114,282 (GRCm39)	F547S	probably benign	Het
Scel	T	C	14: 103,770,746 (GRCm39)	V60A	probably benign	Het
Slc6a20a	A	G	9: 123,469,631 (GRCm39)		probably null	Het
Slfn5	C	T	11: 82,851,446 (GRCm39)	T581I	probably damaging	Het
Ssh3	A	C	19: 4,314,113 (GRCm39)	V412G	probably damaging	Het
Stx17	T	G	4: 48,159,071 (GRCm39)		probably benign	Het
Sun3	T	G	11: 8,968,170 (GRCm39)	T274P	probably benign	Het
Tm9sf1	T	C	14: 55,875,464 (GRCm39)	T427A	probably damaging	Het
Tmem114	T	A	16: 8,229,983 (GRCm39)	I140F		Het
Tmem40	T	C	6: 115,710,980 (GRCm39)	R167G	possibly damaging	Het
Top3a	C	A	11: 60,641,401 (GRCm39)		probably null	Het
Trafd1	A	G	5: 121,516,573 (GRCm39)	V210A	probably benign	Het
Trim66	T	C	7: 109,076,896 (GRCm39)	I348V	possibly damaging	Het
Ttn	G	A	2: 76,679,172 (GRCm39)	A10850V	unknown	Het
Unc80	G	A	1: 66,677,244 (GRCm39)	A2058T	possibly damaging	Het
Upp2	T	C	2: 58,668,020 (GRCm39)	Y238H	probably damaging	Het
Vmn1r224	T	A	17: 20,640,242 (GRCm39)	I273N	probably damaging	Het
Vps13c	T	C	9: 67,836,805 (GRCm39)	S1768P	probably damaging	Het
Zfp26	G	A	9: 20,348,723 (GRCm39)	H614Y	probably damaging	Het
Zfp263	C	T	16: 3,567,701 (GRCm39)	T672I	probably benign	Het
Zfp641	T	A	15: 98,186,732 (GRCm39)	Q297L	probably benign	Het
Zfp944	T	C	17: 22,560,031 (GRCm39)	E25G	probably damaging	Het
Zfp994	T	C	17: 22,418,981 (GRCm39)	E656G	unknown	Het
Zfyve19	A	G	2: 119,045,330 (GRCm39)	D206G	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
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
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'- ACCATCCTCAAGTCGTCCAG -3'
(R):5'- TTCATGCAACATTCCTGGCC -3'

Sequencing Primer
(F):5'- CGAACCCAAGGAAGTGCGC -3'
(R):5'- AACATTCCTGGCCCGGGC -3'

Posted On

2022-01-20