Mutagenetix > Incidental Mutation

Incidental Mutation 'R7615:Sh2b3'

628266

Institutional Source

Beutler Lab

Gene Symbol

Sh2b3

Ensembl Gene

ENSMUSG00000042594

Gene Name

SH2B adaptor protein 3

Synonyms

Lnk

MMRRC Submission

045683-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.628) question?

Stock #

R7615 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

121815488-121837646 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 121818700 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Proline to Serine at position 333 (P333S)

Ref Sequence

ENSEMBL: ENSMUSP00000119086 (fasta)

Gene Model

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

AlphaFold

O09039

Predicted Effect

probably benign
Transcript: ENSMUST00000040308

SMART Domains

Protein: ENSMUSP00000041611
Gene: ENSMUSG00000042594

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

SMART Domains

Protein: ENSMUSP00000083490
Gene: ENSMUSG00000042594

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

SMART Domains

Protein: ENSMUSP00000113808
Gene: ENSMUSG00000042594

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

SMART Domains

Protein: ENSMUSP00000113926
Gene: ENSMUSG00000042594

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: P333S

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)

SMART Domains

Protein: ENSMUSP00000119086
Gene: ENSMUSG00000042594
AA Change: P333S

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

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: 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

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: 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: 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: ENSMUST00000198161

Predicted Effect

probably benign
Transcript: ENSMUST00000199864

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.0%

Validation Efficiency

100% (101/101)

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: 100 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4931406B18Rik	T	C	7: 43,497,849	I320V	possibly damaging	Het
Adat2	A	G	10: 13,553,276	K4R	probably benign	Het
Adgb	G	A	10: 10,436,010	L226F	probably damaging	Het
Adgrb3	C	T	1: 25,098,897	V1192I	probably damaging	Het
Ahsa2	T	A	11: 23,496,750	N71I	possibly damaging	Het
Amigo2	T	G	15: 97,245,342	T400P	probably damaging	Het
Ankhd1	A	T	18: 36,656,773	Q466L		Het
Auh	T	C	13: 52,919,013	I111V	probably benign	Het
Brwd1	A	G	16: 96,033,839	F942L	probably damaging	Het
C1qtnf7	A	G	5: 43,616,144	N262D	probably damaging	Het
Cdh9	T	A	15: 16,856,230	S785R	probably damaging	Het
Celsr3	A	G	9: 108,837,652	T2046A	possibly damaging	Het
Cep170b	T	C	12: 112,744,665	V1493A	probably damaging	Het
Cep290	C	T	10: 100,492,681	R111W	probably benign	Het
Chd2	T	A	7: 73,441,642	H1617L	probably damaging	Het
Clnk	T	C	5: 38,706,698	D404G	probably damaging	Het
Col18a1	C	T	10: 77,067,005	G795D	probably damaging	Het
Csf3r	T	A	4: 126,037,656	Y477*	probably null	Het
Ddx58	T	A	4: 40,229,653	I89F	possibly damaging	Het
Dnah17	T	A	11: 118,110,547	K857*	probably null	Het
Dnah2	T	G	11: 69,435,304	I3674L	probably damaging	Het
Dnah6	A	C	6: 73,095,206	I2431S	possibly damaging	Het
Eml6	T	A	11: 29,802,501	I971F	possibly damaging	Het
Fam135b	A	T	15: 71,463,323	I674N	probably damaging	Het
Fancc	T	A	13: 63,317,558		probably null	Het
Gabrb2	A	C	11: 42,626,742	K464Q	probably benign	Het
Gbp4	T	A	5: 105,122,982	D261V	possibly damaging	Het
Gdf3	A	G	6: 122,606,916	V164A	probably benign	Het
Gm19410	A	G	8: 35,796,359	D978G	probably damaging	Het
Gm20730	C	T	6: 43,081,774	G35R	probably null	Het
Gm9733	A	G	3: 15,320,485	V119A	probably damaging	Het
Grin2b	G	A	6: 135,923,364	T173I	probably damaging	Het
Gtf3c3	A	T	1: 54,423,572	V344E	possibly damaging	Het
Hsd3b5	A	G	3: 98,630,104	I32T	probably damaging	Het
Ido1	G	C	8: 24,593,188	L74V	probably damaging	Het
Igkv1-88	T	A	6: 68,862,373	D85V	probably damaging	Het
Il22ra1	A	G	4: 135,737,459	I159V	probably benign	Het
Iqgap1	A	T	7: 80,730,100	F1175Y	probably damaging	Het
Iqgap1	A	G	7: 80,751,346	V531A	probably benign	Het
Itga1	T	A	13: 114,996,922	Q484L	probably null	Het
Itga11	A	T	9: 62,744,018	E281V	probably benign	Het
Kpna3	T	C	14: 61,372,962	N343S	possibly damaging	Het
Larp1b	A	G	3: 41,033,534	K64E	possibly damaging	Het
Larp1b	A	G	3: 41,035,816	N133S	probably benign	Het
Lctl	T	A	9: 64,122,110	L161H	probably damaging	Het
Mlip	A	G	9: 77,230,483	S381P	probably damaging	Het
Mroh9	A	G	1: 163,046,032	I518T	probably benign	Het
Mst1r	A	G	9: 107,920,012	Q1360R	probably benign	Het
Muc5b	T	A	7: 141,864,892	C3858*	probably null	Het
Naip1	A	T	13: 100,425,776	H960Q	probably benign	Het
Narfl	C	T	17: 25,782,129	P452S	probably benign	Het
Neo1	A	T	9: 58,884,503	S1321T	probably benign	Het
Nid2	C	A	14: 19,802,530	T1102K	probably damaging	Het
Nsmaf	C	T	4: 6,408,563	V739M	probably damaging	Het
Olfr1019	T	A	2: 85,841,657	M45L	probably benign	Het
Olfr1167	T	C	2: 88,149,518	Q167R	probably benign	Het
Olfr1464-ps1	A	G	19: 13,282,590	I156T	probably damaging	Het
Olfr727	T	G	14: 50,126,989	S137R	probably benign	Het
Olfr97	T	G	17: 37,231,450	K307Q	probably benign	Het
Osbpl9	G	A	4: 109,086,339	P159S	probably damaging	Het
Parpbp	A	G	10: 88,093,637	S450P	probably damaging	Het
Pdgfrb	A	G	18: 61,064,046	T185A	probably benign	Het
Pkd1	T	C	17: 24,593,502	V3803A	probably damaging	Het
Plau	A	T	14: 20,839,466	K200*	probably null	Het
Plce1	A	T	19: 38,524,665	Q136L	probably benign	Het
Plekhd1	C	T	12: 80,722,445	T493I	probably benign	Het
Pofut1	T	C	2: 153,259,418	S31P	unknown	Het
Prlr	T	A	15: 10,325,924	I243N	probably damaging	Het
Ptgis	A	G	2: 167,223,988	L174P	probably damaging	Het
Ralgapb	T	A	2: 158,450,270	I792K	probably damaging	Het
Retreg3	C	T	11: 101,102,980	S136N	probably damaging	Het
Rnf213	C	T	11: 119,467,297	T4291M		Het
Rtn1	A	G	12: 72,304,143	Y431H	probably damaging	Het
Rwdd3	A	G	3: 121,171,604		probably benign	Het
Scyl3	A	T	1: 163,950,338		probably null	Het
Sh2b2	G	T	5: 136,219,657	Q510K	probably damaging	Het
Slc27a6	A	T	18: 58,609,183	N490Y	probably damaging	Het
Slc45a1	C	T	4: 150,638,545	R294Q	probably benign	Het
Sorl1	A	C	9: 41,977,582	I1974S	possibly damaging	Het
Specc1l	C	A	10: 75,263,286	N857K	probably benign	Het
Speg	T	C	1: 75,429,242	L3030P	probably damaging	Het
Spsb1	A	C	4: 149,906,900	D70E	probably benign	Het
Srsf11	A	G	3: 158,016,425	S270P	unknown	Het
Ssr3	A	C	3: 65,387,792	V100G	probably damaging	Het
Synpo	G	A	18: 60,604,475	T133I	probably damaging	Het
Tas2r120	T	G	6: 132,657,810	V285G	probably benign	Het
Tenm4	T	A	7: 96,845,926	V1187D	probably damaging	Het
Tmed8	C	A	12: 87,181,388		probably null	Het
Tmem51	G	A	4: 142,037,564	T61M	probably damaging	Het
Tonsl	A	T	15: 76,630,607	D1132E	probably benign	Het
Tor1aip1	C	T	1: 156,007,584	V358I	possibly damaging	Het
Txlna	A	T	4: 129,630,319	M415K	probably damaging	Het
Tyms	T	A	5: 30,073,560		probably benign	Het
Uggt2	G	T	14: 119,089,269	L177I	probably benign	Het
Uqcrh	T	C	4: 116,069,879	H74R	probably benign	Het
Wnk1	A	T	6: 119,932,738	S33T	probably benign	Het
Zfp553	T	A	7: 127,236,016	C248S	probably damaging	Het
Zfp574	G	A	7: 25,080,576	C341Y	possibly damaging	Het
Zfp729b	T	C	13: 67,591,498	T883A	possibly damaging	Het
Zfp738	T	A	13: 67,670,203	K556N	probably damaging	Het

Other mutations in Sh2b3

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02283:Sh2b3	APN	5	121818655	missense	probably benign	0.09
IGL02328:Sh2b3	APN	5	121817859	missense	probably benign	0.00
PIT4449001:Sh2b3	UTSW	5	121828679	missense	possibly damaging	0.95
R0164:Sh2b3	UTSW	5	121829037	missense	probably damaging	0.97
R0164:Sh2b3	UTSW	5	121829037	missense	probably damaging	0.97
R2898:Sh2b3	UTSW	5	121829048	start codon destroyed	probably null	0.93
R4374:Sh2b3	UTSW	5	121828486	unclassified	probably benign
R4688:Sh2b3	UTSW	5	121818634	missense	probably benign	0.23
R4822:Sh2b3	UTSW	5	121828555	unclassified	probably benign
R5743:Sh2b3	UTSW	5	121828457	missense	probably damaging	1.00
R5888:Sh2b3	UTSW	5	121829021	missense	possibly damaging	0.73
R6130:Sh2b3	UTSW	5	121815563	splice site	probably null
R6167:Sh2b3	UTSW	5	121828355	splice site	probably null
R6413:Sh2b3	UTSW	5	121828923	missense	probably damaging	1.00
R7499:Sh2b3	UTSW	5	121818473	missense	probably damaging	0.97
R7672:Sh2b3	UTSW	5	121818759	critical splice donor site	probably null
R9748:Sh2b3	UTSW	5	121817811	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TGCCCTGTAAGTTGAATGTGAG -3'
(R):5'- GATAATCCCTGCTGGTTCCC -3'

Sequencing Primer
(F):5'- GAGTACATACTCTCCTCTCCGGGAC -3'
(R):5'- GCTGGTTCCCTTCTTACCCAG -3'

Posted On

2020-02-20