Mutagenetix > Incidental Mutation

Incidental Mutation 'R4688:Sh2b3'

353845

Institutional Source

Beutler Lab

Gene Symbol

Sh2b3

Ensembl Gene

ENSMUSG00000042594

Gene Name

SH2B adaptor protein 3

Synonyms

Lnk

MMRRC Submission

041939-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.406) question?

Stock #

R4688 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

121953551-121975709 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 121956697 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Valine at position 318 (D318V)

Ref Sequence

ENSEMBL: ENSMUSP00000113808 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000040308] [ENSMUST00000051950] [ENSMUST00000086310] [ENSMUST00000118580] [ENSMUST00000122426] [ENSMUST00000136960] [ENSMUST00000162327] [ENSMUST00000160220] [ENSMUST00000197892] [ENSMUST00000161159] [ENSMUST00000161064]

AlphaFold

O09039

Predicted Effect

probably benign
Transcript: ENSMUST00000040308
AA Change: D328V

PolyPhen 2 Score 0.116 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000041611
Gene: ENSMUSG00000042594
AA Change: D328V

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: ENSMUST00000051950

SMART Domains

Protein: ENSMUSP00000056715
Gene: ENSMUSG00000042605

Domain	Start	End	E-Value	Type
low complexity region	32	42	N/A	INTRINSIC
low complexity region	46	69	N/A	INTRINSIC
low complexity region	93	116	N/A	INTRINSIC
low complexity region	128	144	N/A	INTRINSIC
low complexity region	168	219	N/A	INTRINSIC
Pfam:SM-ATX	236	307	6.4e-23	PFAM
LsmAD	378	446	8.57e-25	SMART
low complexity region	520	540	N/A	INTRINSIC
low complexity region	544	576	N/A	INTRINSIC
low complexity region	685	705	N/A	INTRINSIC
low complexity region	807	838	N/A	INTRINSIC
low complexity region	864	879	N/A	INTRINSIC
Pfam:PAM2	880	897	5.7e-9	PFAM
low complexity region	1128	1165	N/A	INTRINSIC
low complexity region	1185	1196	N/A	INTRINSIC
low complexity region	1245	1261	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000086310
AA Change: D328V

PolyPhen 2 Score 0.116 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000083490
Gene: ENSMUSG00000042594
AA Change: D328V

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: D318V

PolyPhen 2 Score 0.228 (Sensitivity: 0.91; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000113808
Gene: ENSMUSG00000042594
AA Change: D318V

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: D328V

PolyPhen 2 Score 0.116 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000113926
Gene: ENSMUSG00000042594
AA Change: D328V

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

unknown
Transcript: ENSMUST00000136960
AA Change: I355F

SMART Domains

Protein: ENSMUSP00000119086
Gene: ENSMUSG00000042594
AA Change: I355F

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

noncoding transcript
Transcript: ENSMUST00000159928

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000183860

Predicted Effect

probably benign
Transcript: ENSMUST00000162327

SMART Domains

Protein: ENSMUSP00000123784
Gene: ENSMUSG00000042605

Domain	Start	End	E-Value	Type
low complexity region	1	32	N/A	INTRINSIC
low complexity region	58	73	N/A	INTRINSIC
Pfam:PAM2	74	91	1.3e-9	PFAM
low complexity region	302	339	N/A	INTRINSIC
low complexity region	359	370	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000198161

Predicted Effect

probably benign
Transcript: ENSMUST00000160220

SMART Domains

Protein: ENSMUSP00000124059
Gene: ENSMUSG00000042605

Domain	Start	End	E-Value	Type
low complexity region	15	26	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000199864

Predicted Effect

probably benign
Transcript: ENSMUST00000197892

SMART Domains

Protein: ENSMUSP00000142666
Gene: ENSMUSG00000042594

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: ENSMUST00000161159

SMART Domains

Protein: ENSMUSP00000123833
Gene: ENSMUSG00000042605

Domain	Start	End	E-Value	Type
low complexity region	74	111	N/A	INTRINSIC
low complexity region	131	142	N/A	INTRINSIC
low complexity region	188	196	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000161064

SMART Domains

Protein: ENSMUSP00000124070
Gene: ENSMUSG00000042605

Domain	Start	End	E-Value	Type
LsmAD	69	137	8.57e-25	SMART
low complexity region	211	231	N/A	INTRINSIC
low complexity region	235	267	N/A	INTRINSIC
low complexity region	376	396	N/A	INTRINSIC
low complexity region	498	529	N/A	INTRINSIC
low complexity region	555	570	N/A	INTRINSIC
Pfam:PAM2	571	588	3.5e-9	PFAM
low complexity region	801	838	N/A	INTRINSIC
low complexity region	858	869	N/A	INTRINSIC
low complexity region	915	923	N/A	INTRINSIC

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 96.9%
20x: 94.3%

Validation Efficiency

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: 96 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700003E16Rik	A	G	6: 83,139,680 (GRCm39)	N535S	probably damaging	Het
Abcc12	T	C	8: 87,275,323 (GRCm39)	S452G	possibly damaging	Het
Acacb	C	A	5: 114,342,824 (GRCm39)	Q897K	probably benign	Het
Acot3	C	A	12: 84,100,691 (GRCm39)	R145S	probably damaging	Het
Ankrd54	A	T	15: 78,938,782 (GRCm39)	Y247N	probably damaging	Het
Arl11	G	A	14: 61,548,546 (GRCm39)	V119I	probably benign	Het
Atosb	A	G	4: 43,034,663 (GRCm39)	F352S	probably damaging	Het
Atxn7	T	A	14: 14,089,288 (GRCm38)	M268K	probably benign	Het
Bms1	G	A	6: 118,369,667 (GRCm39)	R934C	probably damaging	Het
Brd10	A	G	19: 29,694,501 (GRCm39)	I1664T	probably benign	Het
Chrnb3	T	C	8: 27,884,147 (GRCm39)	S295P	probably damaging	Het
Cic	TCCCCC	TCCCCCCC	7: 24,991,095 (GRCm39)		probably null	Het
Cnr1	A	T	4: 33,944,571 (GRCm39)	I320F	probably benign	Het
Cntn4	C	T	6: 106,414,910 (GRCm39)	P147L	probably damaging	Het
Col24a1	G	A	3: 145,020,144 (GRCm39)	V172I	probably benign	Het
Col9a3	A	G	2: 180,249,424 (GRCm39)	D262G	probably damaging	Het
Csrnp2	A	G	15: 100,380,241 (GRCm39)	V350A	probably damaging	Het
D630045J12Rik	A	G	6: 38,173,592 (GRCm39)	V192A	possibly damaging	Het
Deptor	A	G	15: 55,072,177 (GRCm39)	M219V	probably benign	Het
Dmrtb1	A	T	4: 107,541,247 (GRCm39)	L38Q	probably damaging	Het
Dvl2	G	A	11: 69,898,344 (GRCm39)	R367Q	possibly damaging	Het
Dync1h1	T	G	12: 110,621,962 (GRCm39)	I3435S	probably damaging	Het
Ecpas	A	G	4: 58,840,757 (GRCm39)	V667A	probably damaging	Het
Eif2b3	A	G	4: 116,916,046 (GRCm39)	N218D	probably benign	Het
Epha2	A	G	4: 141,046,292 (GRCm39)	D497G	probably benign	Het
Epha7	G	T	4: 28,821,367 (GRCm39)	L177F	probably damaging	Het
Fam98c	C	T	7: 28,854,666 (GRCm39)	E147K	probably damaging	Het
Fbxo17	A	G	7: 28,431,979 (GRCm39)	T19A	probably benign	Het
Fbxo47	A	G	11: 97,747,049 (GRCm39)	F339S	probably damaging	Het
Frmd4a	G	T	2: 4,542,122 (GRCm39)	V234L	possibly damaging	Het
Gal3st2	A	G	1: 93,800,245 (GRCm39)	D32G	probably damaging	Het
Gpr135	T	C	12: 72,117,720 (GRCm39)	T16A	probably benign	Het
Gpr160	A	T	3: 30,950,835 (GRCm39)	R302S	probably benign	Het
Hrh2	C	A	13: 54,368,820 (GRCm39)	N265K	probably benign	Het
Htatip2	C	A	7: 49,423,171 (GRCm39)	A242E	probably damaging	Het
Igfbp7	T	C	5: 77,555,482 (GRCm39)	Y127C	probably damaging	Het
Igkv16-104	A	G	6: 68,402,878 (GRCm39)	Q57R	possibly damaging	Het
Ino80c	A	G	18: 24,241,903 (GRCm39)	S161P	probably damaging	Het
Itprid1	G	A	6: 55,944,132 (GRCm39)		probably null	Het
Kcnc1	A	G	7: 46,047,259 (GRCm39)	D53G	probably benign	Het
Khdc4	T	A	3: 88,593,824 (GRCm39)	M71K	probably damaging	Het
Lce1h	G	T	3: 92,670,874 (GRCm39)	R93S	unknown	Het
Lce1k	T	C	3: 92,713,951 (GRCm39)	S78G	unknown	Het
Lhcgr	T	A	17: 89,072,580 (GRCm39)	I156F	probably damaging	Het
Lpl	T	C	8: 69,352,077 (GRCm39)	Y343H	probably damaging	Het
Lrp6	G	T	6: 134,456,706 (GRCm39)	R853S	probably damaging	Het
Lrrc7	A	G	3: 157,854,242 (GRCm39)	V1322A	probably damaging	Het
Lrrc74a	C	T	12: 86,784,472 (GRCm39)	Q67*	probably null	Het
Megf6	A	T	4: 154,338,271 (GRCm39)	D447V	probably damaging	Het
Mep1a	T	C	17: 43,793,139 (GRCm39)	D355G	possibly damaging	Het
Ncoa1	T	C	12: 4,365,781 (GRCm39)	D95G	probably benign	Het
Npepl1	A	T	2: 173,956,235 (GRCm39)	I139F	possibly damaging	Het
Nrcam	T	C	12: 44,594,020 (GRCm39)	S262P	probably benign	Het
Nrp1	A	G	8: 129,229,047 (GRCm39)	N842D	probably benign	Het
Olfml3	A	G	3: 103,639,497 (GRCm39)		probably benign	Het
Or1x6	A	G	11: 50,939,815 (GRCm39)	R294G	probably damaging	Het
Or4b1d	T	A	2: 89,969,343 (GRCm39)	N47Y	possibly damaging	Het
Or6b6	T	A	7: 106,571,068 (GRCm39)	Y161F	probably benign	Het
Or6c204	G	A	10: 129,022,514 (GRCm39)	P259S	probably damaging	Het
Or6k8-ps1	T	C	1: 173,979,162 (GRCm39)	Y27H	possibly damaging	Het
Or8b3b	A	G	9: 38,584,659 (GRCm39)	L27P	probably damaging	Het
Or9i1b	A	T	19: 13,896,605 (GRCm39)	T74S	probably benign	Het
Pde2a	A	G	7: 101,152,041 (GRCm39)	N316S	probably benign	Het
Pde4dip	T	A	3: 97,750,993 (GRCm39)	R74*	probably null	Het
Pex13	A	T	11: 23,605,472 (GRCm39)	W253R	possibly damaging	Het
Piezo1	A	T	8: 123,215,278 (GRCm39)	W1444R	probably damaging	Het
Pla2g4e	T	C	2: 119,998,414 (GRCm39)	K843R	possibly damaging	Het
Plxna2	C	T	1: 194,326,753 (GRCm39)	P229L	probably damaging	Het
Prelid3b	G	T	2: 174,308,592 (GRCm39)	T131K	probably benign	Het
Pros1	T	C	16: 62,709,370 (GRCm39)		probably null	Het
Prrc2c	G	T	1: 162,525,256 (GRCm39)	P450Q	unknown	Het
Ptbp1	G	T	10: 79,692,342 (GRCm39)	V5F	possibly damaging	Het
Ptk2	T	A	15: 73,078,074 (GRCm39)	L997F	probably damaging	Het
Rims1	G	T	1: 22,518,528 (GRCm39)	S525*	probably null	Het
Sanbr	A	G	11: 23,543,449 (GRCm39)	S530P	probably benign	Het
Slc16a13	A	T	11: 70,111,101 (GRCm39)	I88N	probably damaging	Het
Slit2	T	A	5: 48,414,345 (GRCm39)		probably null	Het
Snx10	A	G	6: 51,556,918 (GRCm39)	N67S	probably damaging	Het
Stil	A	G	4: 114,898,505 (GRCm39)	Y1045C	probably damaging	Het
Stra6	A	G	9: 58,042,359 (GRCm39)		probably null	Het
Sympk	A	G	7: 18,788,335 (GRCm39)	S1254G	probably benign	Het
Syt15	G	T	14: 33,950,011 (GRCm39)	G377V	probably damaging	Het
Taar4	A	T	10: 23,836,731 (GRCm39)	I114F	probably damaging	Het
Tcaf3	G	A	6: 42,570,300 (GRCm39)		probably null	Het
Tgm7	A	T	2: 120,924,502 (GRCm39)	N558K	probably benign	Het
Tln2	T	G	9: 67,304,935 (GRCm39)	M1L	probably benign	Het
Trim50	C	T	5: 135,395,994 (GRCm39)	T314I	probably damaging	Het
Trp53rka	A	T	2: 165,333,312 (GRCm39)	Y192*	probably null	Het
Ube3b	T	C	5: 114,531,139 (GRCm39)	V211A	probably benign	Het
Ush2a	A	G	1: 188,132,138 (GRCm39)	S787G	probably benign	Het
Vmn1r189	T	C	13: 22,286,289 (GRCm39)	M183V	probably damaging	Het
Vps13d	G	T	4: 144,904,782 (GRCm39)	Q115K	probably benign	Het
Zfp358	A	G	8: 3,545,493 (GRCm39)	D25G	probably damaging	Het
Zfp521	T	G	18: 13,977,647 (GRCm39)	K922T	probably damaging	Het
Zfp521	T	A	18: 13,977,648 (GRCm39)	K922*	probably null	Het
Zfp68	T	A	5: 138,614,743 (GRCm39)	K4*	probably null	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
R4822:Sh2b3	UTSW	5	121,966,618 (GRCm39)	unclassified	probably benign
R5743:Sh2b3	UTSW	5	121,966,520 (GRCm39)	missense	probably damaging	1.00
R5888:Sh2b3	UTSW	5	121,967,084 (GRCm39)	missense	possibly damaging	0.73
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'- TAAAGATCAGCCTGCTGCC -3'
(R):5'- CTCTTTCCTTAGCGGCAGAG -3'

Sequencing Primer
(F):5'- TGCCCAGGCTGCATTTG -3'
(R):5'- AGCCTGGCCCAGCTAGATC -3'

Posted On

2015-10-21