Mutagenetix > Incidental Mutation

Incidental Mutation 'R8786:Sh2b2'

670625

Institutional Source

Beutler Lab

Gene Symbol

Sh2b2

Ensembl Gene

ENSMUSG00000005057

Gene Name

SH2B adaptor protein 2

Synonyms

Aps

MMRRC Submission

068632-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.925) question?

Stock #

R8786 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

136247001-136275410 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 136260658 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 186 (D186G)

Ref Sequence

ENSEMBL: ENSMUSP00000005188 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000005188] [ENSMUST00000196245] [ENSMUST00000196397] [ENSMUST00000196447]

AlphaFold

Q9JID9

PDB Structure

Solution Structure of the Pleckstrin Homology Domain of Mouse APS [SOLUTION NMR]

Predicted Effect

probably benign
Transcript: ENSMUST00000005188
AA Change: D186G

PolyPhen 2 Score 0.293 (Sensitivity: 0.91; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000005188
Gene: ENSMUSG00000005057
AA Change: D186G

Domain	Start	End	E-Value	Type
low complexity region	6	16	N/A	INTRINSIC
Pfam:Phe_ZIP	17	73	9.3e-22	PFAM
Blast:PH	95	168	2e-21	BLAST
low complexity region	169	180	N/A	INTRINSIC
PH	187	301	4.97e-9	SMART
low complexity region	340	350	N/A	INTRINSIC
low complexity region	388	404	N/A	INTRINSIC
SH2	407	492	1.38e-21	SMART
low complexity region	509	525	N/A	INTRINSIC
low complexity region	548	576	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000196245

Predicted Effect

probably benign
Transcript: ENSMUST00000196397
AA Change: D186G

PolyPhen 2 Score 0.293 (Sensitivity: 0.91; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000142398
Gene: ENSMUSG00000005057
AA Change: D186G

Domain	Start	End	E-Value	Type
Pfam:Phe_ZIP	16	74	1.5e-30	PFAM
Blast:PH	95	168	2e-21	BLAST
low complexity region	169	180	N/A	INTRINSIC
PH	187	301	4.97e-9	SMART
low complexity region	340	350	N/A	INTRINSIC
low complexity region	388	404	N/A	INTRINSIC
SH2	407	492	1.38e-21	SMART
low complexity region	509	525	N/A	INTRINSIC
low complexity region	548	576	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000196447
AA Change: D186G

PolyPhen 2 Score 0.984 (Sensitivity: 0.74; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000142728
Gene: ENSMUSG00000005057
AA Change: D186G

Domain	Start	End	E-Value	Type
Pfam:Phe_ZIP	16	74	9.1e-28	PFAM
Blast:PH	95	168	9e-22	BLAST
low complexity region	169	180	N/A	INTRINSIC
PH	187	301	2.2e-11	SMART
low complexity region	340	350	N/A	INTRINSIC
low complexity region	406	417	N/A	INTRINSIC

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.1%

Validation Efficiency

100% (72/72)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is expressed in B lymphocytes and contains pleckstrin homology and src homology 2 (SH2) domains. In Burkitt's lymphoma cell lines, it is tyrosine-phosphorylated in response to B cell receptor stimulation. Because it binds Shc independent of stimulation and Grb2 after stimulation, it appears to play a role in signal transduction from the receptor to the Shc/Grb2 pathway. [provided by RefSeq, Jun 2009]
PHENOTYPE: Inactivation of this gene results in increased insulin sensitivity accompanied by hypoinsulinemia. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 72 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adamtsl4	A	T	3: 95,592,784 (GRCm39)	M1K	probably null	Het
Atg2a	G	T	19: 6,294,460 (GRCm39)	V59L	probably damaging	Het
Atxn7	C	A	14: 14,103,316 (GRCm38)	T888K	possibly damaging	Het
Btbd9	T	C	17: 30,749,144 (GRCm39)	R57G	probably damaging	Het
Catspere2	T	A	1: 177,843,362 (GRCm39)		probably benign	Het
Catspere2	G	A	1: 177,843,555 (GRCm39)		probably benign	Het
Ccdc9b	C	A	2: 118,587,732 (GRCm39)	S534I	unknown	Het
Crp	T	C	1: 172,526,293 (GRCm39)	V126A	probably benign	Het
Csf1r	A	T	18: 61,247,942 (GRCm39)	T337S	probably damaging	Het
Dcaf12	T	C	4: 41,296,439 (GRCm39)	N299S	probably damaging	Het
Dcaf17	T	C	2: 70,917,744 (GRCm39)		probably null	Het
Dip2c	A	G	13: 9,665,830 (GRCm39)	D985G	probably damaging	Het
Dtna	A	G	18: 23,716,190 (GRCm39)	T138A	probably benign	Het
Emid1	T	C	11: 5,081,517 (GRCm39)	D212G	probably benign	Het
Epyc	G	A	10: 97,511,525 (GRCm39)	D173N	probably damaging	Het
Fanci	A	G	7: 79,052,298 (GRCm39)	D162G	probably benign	Het
Firrm	A	T	1: 163,792,040 (GRCm39)	L626Q	probably damaging	Het
Fry	T	C	5: 150,317,501 (GRCm39)	V827A	probably benign	Het
Ggps1	T	C	13: 14,228,505 (GRCm39)	E226G	probably benign	Het
Gopc	G	A	10: 52,230,750 (GRCm39)	R183*	probably null	Het
Grik4	C	T	9: 42,453,130 (GRCm39)	G752S	probably damaging	Het
H2-D1	T	A	17: 35,482,844 (GRCm39)	C125S	probably damaging	Het
H2-Q1	T	A	17: 35,539,869 (GRCm39)	V46D	probably damaging	Het
Hsd17b3	T	C	13: 64,219,862 (GRCm39)	N126S	probably damaging	Het
Igsf10	G	A	3: 59,238,063 (GRCm39)	T706I	probably benign	Het
Kmt2e	A	G	5: 23,669,864 (GRCm39)	D117G	probably damaging	Het
Kmt5a	C	T	5: 124,584,074 (GRCm39)	A18V	probably benign	Het
Krtap29-1	C	T	11: 99,869,465 (GRCm39)	G139R	probably damaging	Het
Lama5	T	C	2: 179,838,100 (GRCm39)	Y872C	probably damaging	Het
Lrriq4	T	A	3: 30,704,752 (GRCm39)	M260K	probably benign	Het
Map2	G	A	1: 66,472,755 (GRCm39)		probably benign	Het
Mrpl51	C	T	6: 125,169,340 (GRCm39)	A8V	probably benign	Het
Ndufs3	T	C	2: 90,732,778 (GRCm39)	T103A	probably benign	Het
Numa1	T	G	7: 101,647,616 (GRCm39)	L449R	probably benign	Het
Or10g3b	C	T	14: 52,587,021 (GRCm39)	A161T	possibly damaging	Het
Pan3	C	T	5: 147,424,951 (GRCm39)	P295S	possibly damaging	Het
Pds5b	T	C	5: 150,704,134 (GRCm39)	S846P	probably damaging	Het
Phf2	A	T	13: 48,967,219 (GRCm39)	M712K	unknown	Het
Phlda2	A	T	7: 143,056,211 (GRCm39)	V6E	probably benign	Het
Pkdrej	C	A	15: 85,704,044 (GRCm39)	A631S	probably benign	Het
Plcd3	G	T	11: 102,962,569 (GRCm39)	N627K	probably damaging	Het
Prpf6	T	C	2: 181,262,415 (GRCm39)	I138T	possibly damaging	Het
Psd4	G	A	2: 24,295,444 (GRCm39)	S866N	probably benign	Het
Ptprb	A	C	10: 116,155,306 (GRCm39)	T400P	probably benign	Het
Rxfp1	T	C	3: 79,570,677 (GRCm39)		probably null	Het
Sbf2	A	G	7: 110,063,793 (GRCm39)		probably null	Het
Serpinb9h	G	A	13: 33,588,204 (GRCm39)	R263H	probably benign	Het
Setd4	C	T	16: 93,390,162 (GRCm39)	R89Q	probably benign	Het
Sgpp1	A	G	12: 75,763,152 (GRCm39)	I343T	probably benign	Het
Slc12a4	A	T	8: 106,680,549 (GRCm39)	I191N	probably damaging	Het
Slc4a4	A	T	5: 89,232,549 (GRCm39)	D251V	probably benign	Het
Slc6a5	A	T	7: 49,561,843 (GRCm39)	D125V	possibly damaging	Het
Slf1	T	A	13: 77,274,806 (GRCm39)	I16F	possibly damaging	Het
Sncaip	T	C	18: 53,031,334 (GRCm39)	V521A	probably damaging	Het
Spmip10	T	C	18: 56,727,568 (GRCm39)	F89L	probably damaging	Het
Stx19	T	C	16: 62,642,775 (GRCm39)	L197P	probably damaging	Het
Sucla2	A	G	14: 73,797,905 (GRCm39)	N39D	probably benign	Het
Sult1d1	T	A	5: 87,712,575 (GRCm39)	T90S	probably benign	Het
Syna	C	T	5: 134,588,723 (GRCm39)	M75I	probably benign	Het
Tas2r138	A	G	6: 40,589,611 (GRCm39)	S212P	probably damaging	Het
Tdrd3	T	A	14: 87,709,637 (GRCm39)	C106*	probably null	Het
Tlk2	C	T	11: 105,172,059 (GRCm39)	A743V	unknown	Het
Tlr3	T	C	8: 45,851,286 (GRCm39)	D537G	possibly damaging	Het
Tmc1	A	G	19: 20,803,953 (GRCm39)	Y375H	probably damaging	Het
Tsen54	T	A	11: 115,711,498 (GRCm39)	M305K	probably damaging	Het
Umod	C	T	7: 119,076,581 (GRCm39)	V62M	possibly damaging	Het
Vmn1r10	A	G	6: 57,091,010 (GRCm39)	T201A	probably benign	Het
Vmn1r103	T	C	7: 20,243,676 (GRCm39)	T262A	probably benign	Het
Vmn2r100	T	C	17: 19,742,838 (GRCm39)	V404A	probably damaging	Het
Vmn2r56	A	G	7: 12,449,393 (GRCm39)	F282L	probably damaging	Het
Wdr64	A	T	1: 175,636,327 (GRCm39)	K982*	probably null	Het
Xpo6	A	T	7: 125,712,127 (GRCm39)		probably benign	Het

Other mutations in Sh2b2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00332:Sh2b2	APN	5	136,253,273 (GRCm39)	missense	probably damaging	1.00
IGL01456:Sh2b2	APN	5	136,253,321 (GRCm39)	missense	probably damaging	0.98
IGL01612:Sh2b2	APN	5	136,260,656 (GRCm39)	missense	probably benign	0.02
IGL02798:Sh2b2	APN	5	136,250,817 (GRCm39)	missense	probably damaging	1.00
BB002:Sh2b2	UTSW	5	136,253,115 (GRCm39)	missense	probably benign	0.04
BB012:Sh2b2	UTSW	5	136,253,115 (GRCm39)	missense	probably benign	0.04
R0492:Sh2b2	UTSW	5	136,261,117 (GRCm39)	missense	probably damaging	1.00
R0539:Sh2b2	UTSW	5	136,254,155 (GRCm39)	splice site	probably benign
R0707:Sh2b2	UTSW	5	136,261,117 (GRCm39)	missense	probably damaging	1.00
R1569:Sh2b2	UTSW	5	136,260,589 (GRCm39)	missense	possibly damaging	0.89
R1777:Sh2b2	UTSW	5	136,256,276 (GRCm39)	missense	probably damaging	1.00
R2088:Sh2b2	UTSW	5	136,260,968 (GRCm39)	missense	possibly damaging	0.87
R3702:Sh2b2	UTSW	5	136,253,087 (GRCm39)	missense	probably damaging	0.99
R4223:Sh2b2	UTSW	5	136,247,907 (GRCm39)	missense	possibly damaging	0.91
R4597:Sh2b2	UTSW	5	136,260,616 (GRCm39)	missense	probably damaging	0.99
R4683:Sh2b2	UTSW	5	136,260,574 (GRCm39)	missense	probably damaging	1.00
R4766:Sh2b2	UTSW	5	136,260,811 (GRCm39)	missense	probably damaging	0.99
R5486:Sh2b2	UTSW	5	136,260,944 (GRCm39)	missense	probably benign	0.10
R6060:Sh2b2	UTSW	5	136,261,209 (GRCm39)	missense	possibly damaging	0.72
R6322:Sh2b2	UTSW	5	136,253,042 (GRCm39)	missense	probably damaging	0.99
R7020:Sh2b2	UTSW	5	136,253,153 (GRCm39)	missense	possibly damaging	0.69
R7034:Sh2b2	UTSW	5	136,247,739 (GRCm39)	missense	probably benign	0.18
R7036:Sh2b2	UTSW	5	136,247,739 (GRCm39)	missense	probably benign	0.18
R7615:Sh2b2	UTSW	5	136,248,511 (GRCm39)	missense	probably damaging	1.00
R7715:Sh2b2	UTSW	5	136,247,889 (GRCm39)	missense	probably benign	0.09
R7925:Sh2b2	UTSW	5	136,253,115 (GRCm39)	missense	probably benign	0.04
R8244:Sh2b2	UTSW	5	136,256,291 (GRCm39)	nonsense	probably null
R8291:Sh2b2	UTSW	5	136,261,209 (GRCm39)	missense	possibly damaging	0.72
R9293:Sh2b2	UTSW	5	136,260,893 (GRCm39)	missense	possibly damaging	0.90
R9364:Sh2b2	UTSW	5	136,253,006 (GRCm39)	missense	probably benign	0.03
R9554:Sh2b2	UTSW	5	136,253,006 (GRCm39)	missense	probably benign	0.03

Predicted Primers

PCR Primer
(F):5'- GACTGTGCAGGTAAATGGGTC -3'
(R):5'- CTGCGTAACATGAGCCTGTG -3'

Sequencing Primer
(F):5'- GGAAGATTGTTGGTGACATACATCC -3'
(R):5'- AACATGAGCCTGTGTGTGG -3'

Posted On

2021-04-30