Mutagenetix > Incidental Mutation

Incidental Mutation 'R5888:Sh2b3'

457783

Institutional Source

Beutler Lab

Gene Symbol

Sh2b3

Ensembl Gene

ENSMUSG00000042594

Gene Name

SH2B adaptor protein 3

Synonyms

Lnk

MMRRC Submission

044089-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.532) question?

Stock #

R5888 (G1)

Quality Score

103

Status

Validated

Chromosome

Chromosomal Location

121953551-121975709 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to G at 121967084 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Proline at position 10 (R10P)

Ref Sequence

ENSEMBL: ENSMUSP00000118523 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000040308] [ENSMUST00000086310] [ENSMUST00000118580] [ENSMUST00000122426] [ENSMUST00000136960] [ENSMUST00000137682] [ENSMUST00000197892]

AlphaFold

O09039

Predicted Effect

probably benign
Transcript: ENSMUST00000040308
AA Change: R10P

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000041611
Gene: ENSMUSG00000042594
AA Change: R10P

Domain	Start	End	E-Value	Type
low complexity region	12	21	N/A	INTRINSIC
Pfam:Phe_ZIP	23	76	1.1e-20	PFAM
low complexity region	114	128	N/A	INTRINSIC
PH	168	281	1.2e-2	SMART
SH2	334	419	3.53e-19	SMART
low complexity region	512	525	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000086310
AA Change: R10P

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000083490
Gene: ENSMUSG00000042594
AA Change: R10P

Domain	Start	End	E-Value	Type
low complexity region	12	21	N/A	INTRINSIC
Pfam:Phe_ZIP	22	77	2e-22	PFAM
low complexity region	114	128	N/A	INTRINSIC
PH	168	281	1.2e-2	SMART
SH2	334	419	3.53e-19	SMART
low complexity region	512	525	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000118580
AA Change: R10P

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000113808
Gene: ENSMUSG00000042594
AA Change: R10P

Domain	Start	End	E-Value	Type
low complexity region	12	21	N/A	INTRINSIC
Pfam:Phe_ZIP	22	77	4.1e-23	PFAM
low complexity region	114	128	N/A	INTRINSIC
PH	168	281	1.2e-2	SMART
SH2	324	409	3.53e-19	SMART
low complexity region	502	515	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000122426
AA Change: R10P

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000113926
Gene: ENSMUSG00000042594
AA Change: R10P

Domain	Start	End	E-Value	Type
low complexity region	12	21	N/A	INTRINSIC
Pfam:Phe_ZIP	22	77	2e-22	PFAM
low complexity region	114	128	N/A	INTRINSIC
PH	168	281	1.2e-2	SMART
SH2	334	419	3.53e-19	SMART
low complexity region	512	525	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000136960
AA Change: R10P

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000119086
Gene: ENSMUSG00000042594
AA Change: R10P

Domain	Start	End	E-Value	Type
low complexity region	12	21	N/A	INTRINSIC
Pfam:Phe_ZIP	22	77	2.4e-23	PFAM
low complexity region	114	128	N/A	INTRINSIC
PH	168	281	1.2e-2	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000137682
AA Change: R10P

PolyPhen 2 Score 0.734 (Sensitivity: 0.85; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000118523
Gene: ENSMUSG00000042594
AA Change: R10P

Domain	Start	End	E-Value	Type
low complexity region	12	21	N/A	INTRINSIC
Pfam:Phe_ZIP	22	77	2e-23	PFAM
low complexity region	114	128	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000197892
AA Change: R10P

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000142666
Gene: ENSMUSG00000042594
AA Change: R10P

Domain	Start	End	E-Value	Type
low complexity region	12	21	N/A	INTRINSIC
Pfam:Phe_ZIP	22	77	6.3e-20	PFAM
low complexity region	114	128	N/A	INTRINSIC
Blast:PH	168	250	3e-53	BLAST
PDB:1V5M\|A	171	250	1e-12	PDB

Predicted Effect

probably benign
Transcript: ENSMUST00000198161

Meta Mutation Damage Score

0.1795

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 98.2%
20x: 94.9%

Validation Efficiency

94% (96/102)

MGI Phenotype

FUNCTION: This gene encodes a member of the SH2B family of adapter proteins that play an important role in T cell receptor signaling. This gene is preferentially expressed in hematopoietic stem cells, hematopoietic progenitors, pre and immature B cells, as well as megakaryocytes and mastocytes. In hematopoietic stem cells, the encoded protein is a key regulator of self-renewal, proliferation and apoptosis. Mice lacking the encoded protein exhibit pre and immature B cell expansion in spleen and the bone marrow. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit severe perturbations in hematopoiesis, splenomegaly, and abnormal lymphoid and myeloid homeostasis. Mice homozygous for a different knock-out allele display altered mobility of hematopoietic stem/progenitor cells. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 92 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adcy1	T	A	11: 7,089,095 (GRCm39)	V503E	possibly damaging	Het
Alk	C	A	17: 72,181,938 (GRCm39)	V1362L	probably damaging	Het
Ankrd55	T	A	13: 112,492,453 (GRCm39)	I208N	possibly damaging	Het
Asap2	T	A	12: 21,268,191 (GRCm39)	I319N	probably damaging	Het
Atp11b	T	C	3: 35,891,696 (GRCm39)	I1036T	probably benign	Het
B4gat1	T	C	19: 5,089,560 (GRCm39)	F186L	probably benign	Het
C3	T	A	17: 57,521,831 (GRCm39)	T1079S	probably damaging	Het
Cacul1	G	T	19: 60,525,902 (GRCm39)	T287K	possibly damaging	Het
Cbr3	G	C	16: 93,487,614 (GRCm39)	G266R	probably damaging	Het
Cd63	T	A	10: 128,748,160 (GRCm39)		probably null	Het
Chd7	G	A	4: 8,866,382 (GRCm39)	M851I	probably damaging	Het
Chst13	T	A	6: 90,286,554 (GRCm39)	H136L	probably benign	Het
Cyp2d22	T	C	15: 82,258,014 (GRCm39)	T179A	probably benign	Het
Dclre1b	A	T	3: 103,711,053 (GRCm39)	V286E	probably damaging	Het
Defb45	G	A	2: 152,435,154 (GRCm39)		probably benign	Het
Dlg1	T	C	16: 31,610,704 (GRCm39)		probably null	Het
Dock3	A	G	9: 106,901,002 (GRCm39)	V321A	probably benign	Het
Dytn	A	T	1: 63,716,396 (GRCm39)	V59E	possibly damaging	Het
Efcab3	T	C	11: 104,612,227 (GRCm39)		probably benign	Het
Eif2ak1	A	G	5: 143,823,733 (GRCm39)	I393M	probably damaging	Het
Fam83g	A	T	11: 61,593,420 (GRCm39)	E318V	probably benign	Het
Fbxo34	T	A	14: 47,767,176 (GRCm39)	F179I	probably damaging	Het
Fmo5	T	A	3: 97,549,041 (GRCm39)	Y230N	probably benign	Het
Fzd9	T	G	5: 135,278,317 (GRCm39)		probably null	Het
Gata2	T	C	6: 88,177,722 (GRCm39)	S251P	probably benign	Het
Gigyf1	A	G	5: 137,523,959 (GRCm39)	D1043G	probably damaging	Het
Gm10322	T	A	10: 59,452,125 (GRCm39)	S81T	probably benign	Het
Gm15517	A	T	7: 43,910,066 (GRCm39)		probably benign	Het
Haus4	T	C	14: 54,781,676 (GRCm39)	T232A	probably benign	Het
Hgfac	A	T	5: 35,202,751 (GRCm39)	H417L	probably damaging	Het
Iqgap2	T	C	13: 95,772,118 (GRCm39)	K1354E	possibly damaging	Het
Kcnk12	C	A	17: 88,054,077 (GRCm39)	R195L	probably benign	Het
Kcnn2	A	T	18: 45,725,412 (GRCm39)	I303F	probably damaging	Het
Kcnt1	T	C	2: 25,798,122 (GRCm39)	F879S	probably damaging	Het
Kndc1	T	C	7: 139,475,133 (GRCm39)	F11L	probably benign	Het
Kpna7	A	G	5: 144,926,605 (GRCm39)	F449S	probably damaging	Het
Krt77	G	T	15: 101,773,888 (GRCm39)	N255K	probably benign	Het
Lair1	A	T	7: 4,013,844 (GRCm39)	D134E	probably damaging	Het
Loxhd1	T	C	18: 77,490,211 (GRCm39)	V1318A	probably damaging	Het
Marchf10	A	T	11: 105,292,972 (GRCm39)	V145D	possibly damaging	Het
Mcpt1	T	A	14: 56,256,969 (GRCm39)	M169K	probably benign	Het
Mdc1	T	A	17: 36,158,712 (GRCm39)	V364E	probably benign	Het
Mfsd11	T	C	11: 116,762,210 (GRCm39)	F270S	probably damaging	Het
Mfsd4b2	T	G	10: 39,798,031 (GRCm39)	D108A	probably benign	Het
Mink1	A	T	11: 70,500,885 (GRCm39)		probably benign	Het
Mmp25	T	C	17: 23,850,048 (GRCm39)	Y504C	probably damaging	Het
Ms4a13	C	T	19: 11,168,870 (GRCm39)	V52I	probably benign	Het
Msh4	C	T	3: 153,573,360 (GRCm39)		probably null	Het
Muc5b	T	G	7: 141,412,158 (GRCm39)	S1701R	unknown	Het
Naalad2	A	T	9: 18,241,937 (GRCm39)	S656T	probably benign	Het
Ncapd2	T	C	6: 125,164,052 (GRCm39)	Y64C	probably damaging	Het
Ncapg2	T	A	12: 116,389,420 (GRCm39)	S347T	possibly damaging	Het
Ndufb11b	T	C	15: 81,864,872 (GRCm39)	S38P	probably benign	Het
Nipal4	T	C	11: 46,042,166 (GRCm39)	T172A	probably damaging	Het
Nrros	T	C	16: 31,961,905 (GRCm39)	K652R	probably benign	Het
Nrxn3	G	T	12: 89,478,855 (GRCm39)	A983S	possibly damaging	Het
Or4a76	T	A	2: 89,461,143 (GRCm39)	Y33F	probably damaging	Het
Or4ac1-ps1	T	C	2: 88,370,588 (GRCm39)		noncoding transcript	Het
Or4c115	T	A	2: 88,928,269 (GRCm39)	M1L	probably damaging	Het
Or4k77	T	C	2: 111,199,088 (GRCm39)	M37T	probably benign	Het
Or51m1	A	G	7: 103,578,239 (GRCm39)	T70A	possibly damaging	Het
Or8g24	A	T	9: 38,989,263 (GRCm39)	Y259*	probably null	Het
Or8k37	A	C	2: 86,469,488 (GRCm39)	L188R	probably damaging	Het
P2rx4	T	A	5: 122,857,228 (GRCm39)	S155T	probably benign	Het
P2rx4	T	G	5: 122,865,271 (GRCm39)	Y299D	probably damaging	Het
Pcsk6	A	T	7: 65,693,372 (GRCm39)	L7F	probably null	Het
Pdss2	T	C	10: 43,097,793 (GRCm39)		silent	Het
Pfkl	A	G	10: 77,827,204 (GRCm39)	V494A	possibly damaging	Het
Prep	G	T	10: 44,943,460 (GRCm39)	D12Y	possibly damaging	Het
Prg4	A	G	1: 150,328,101 (GRCm39)	F188S	probably damaging	Het
Ripor3	T	C	2: 167,839,207 (GRCm39)	Y98C	probably damaging	Het
Rnf216	T	A	5: 143,054,069 (GRCm39)		probably null	Het
Rnf24	A	G	2: 131,164,165 (GRCm39)		probably benign	Het
Rps18-ps6	G	A	13: 97,896,901 (GRCm39)	R66*	probably null	Het
Scn3a	A	G	2: 65,327,742 (GRCm39)	M916T	probably benign	Het
Scnm1	T	C	3: 95,037,596 (GRCm39)	I157V	probably benign	Het
Slc25a27	T	C	17: 43,960,585 (GRCm39)	D211G	probably damaging	Het
Slc36a4	A	T	9: 15,638,324 (GRCm39)	Y250F	probably damaging	Het
Slc4a1	T	A	11: 102,247,351 (GRCm39)	E448V	probably damaging	Het
Slit1	C	A	19: 41,731,735 (GRCm39)	C38F	probably damaging	Het
Spock3	T	A	8: 63,808,334 (GRCm39)	N410K	unknown	Het
Supt20	G	T	3: 54,619,628 (GRCm39)	W370L	probably benign	Het
Tas2r139	T	A	6: 42,118,430 (GRCm39)	N187K	probably damaging	Het
Tbc1d9b	G	A	11: 50,031,311 (GRCm39)	V111I	probably benign	Het
Thsd7b	T	A	1: 130,138,057 (GRCm39)	Y1578*	probably null	Het
Tln2	T	A	9: 67,136,685 (GRCm39)	I1267F	probably damaging	Het
Tnk2	G	A	16: 32,490,185 (GRCm39)	V363I	probably damaging	Het
Ttc32	A	G	12: 9,085,870 (GRCm39)	K139R	possibly damaging	Het
Vmn1r30	G	C	6: 58,412,550 (GRCm39)	T94S	possibly damaging	Het
Vmn1r90	G	A	7: 14,295,780 (GRCm39)	T106I	probably damaging	Het
Zfp677	T	A	17: 21,618,520 (GRCm39)	C526S	probably damaging	Het
Zfp831	T	G	2: 174,485,420 (GRCm39)	S32A	probably benign	Het

Other mutations in Sh2b3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02283:Sh2b3	APN	5	121,956,718 (GRCm39)	missense	probably benign	0.09
IGL02328:Sh2b3	APN	5	121,955,922 (GRCm39)	missense	probably benign	0.00
PIT4449001:Sh2b3	UTSW	5	121,966,742 (GRCm39)	missense	possibly damaging	0.95
R0164:Sh2b3	UTSW	5	121,967,100 (GRCm39)	missense	probably damaging	0.97
R0164:Sh2b3	UTSW	5	121,967,100 (GRCm39)	missense	probably damaging	0.97
R2898:Sh2b3	UTSW	5	121,967,111 (GRCm39)	start codon destroyed	probably null	0.93
R4374:Sh2b3	UTSW	5	121,966,549 (GRCm39)	unclassified	probably benign
R4688:Sh2b3	UTSW	5	121,956,697 (GRCm39)	missense	probably benign	0.23
R4822:Sh2b3	UTSW	5	121,966,618 (GRCm39)	unclassified	probably benign
R5743:Sh2b3	UTSW	5	121,966,520 (GRCm39)	missense	probably damaging	1.00
R6130:Sh2b3	UTSW	5	121,953,626 (GRCm39)	splice site	probably null
R6167:Sh2b3	UTSW	5	121,966,418 (GRCm39)	splice site	probably null
R6413:Sh2b3	UTSW	5	121,966,986 (GRCm39)	missense	probably damaging	1.00
R7499:Sh2b3	UTSW	5	121,956,536 (GRCm39)	missense	probably damaging	0.97
R7615:Sh2b3	UTSW	5	121,956,763 (GRCm39)	missense	probably benign	0.00
R7672:Sh2b3	UTSW	5	121,956,822 (GRCm39)	critical splice donor site	probably null
R9748:Sh2b3	UTSW	5	121,955,874 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- ATTGGTGTCACTGGTAGCC -3'
(R):5'- TAGCCACTGTATCCACCACG -3'

Sequencing Primer
(F):5'- AGTGGCGCTGGAAGAGCTC -3'
(R):5'- ACCACGTGGGAGCTGCAG -3'

Posted On

2017-02-15