Incidental Mutation 'R0164:Sh2b3'
ID 60665
Institutional Source Beutler Lab
Gene Symbol Sh2b3
Ensembl Gene ENSMUSG00000042594
Gene Name SH2B adaptor protein 3
Synonyms Lnk
MMRRC Submission 038440-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.532) question?
Stock # R0164 (G1)
Quality Score 117
Status Validated
Chromosome 5
Chromosomal Location 121953551-121975709 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to G at 121967100 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Threonine to Proline at position 5 (T5P)
Ref Sequence ENSEMBL: ENSMUSP00000142666 (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: T5P

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000041611
Gene: ENSMUSG00000042594
AA Change: T5P

DomainStartEndE-ValueType
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: T5P

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000083490
Gene: ENSMUSG00000042594
AA Change: T5P

DomainStartEndE-ValueType
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: T5P

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000113808
Gene: ENSMUSG00000042594
AA Change: T5P

DomainStartEndE-ValueType
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: T5P

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000113926
Gene: ENSMUSG00000042594
AA Change: T5P

DomainStartEndE-ValueType
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: T5P

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000119086
Gene: ENSMUSG00000042594
AA Change: T5P

DomainStartEndE-ValueType
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: T5P

PolyPhen 2 Score 0.861 (Sensitivity: 0.83; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000118523
Gene: ENSMUSG00000042594
AA Change: T5P

DomainStartEndE-ValueType
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 damaging
Transcript: ENSMUST00000197892
AA Change: T5P

PolyPhen 2 Score 0.966 (Sensitivity: 0.77; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000142666
Gene: ENSMUSG00000042594
AA Change: T5P

DomainStartEndE-ValueType
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 0.6467 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.4%
  • 10x: 96.7%
  • 20x: 94.0%
Validation Efficiency 98% (85/87)
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: 89 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
2010315B03Rik T C 9: 124,057,789 (GRCm39) probably benign Het
4732465J04Rik GATCTATCTATCTATCTATCTATCTATCTATCTATCTATC GATCTATCTATCTATCTATCTATCTATCTATCTATCTATCTATC 10: 95,630,440 (GRCm39) probably null Het
4930522L14Rik T C 5: 109,884,713 (GRCm39) K382E probably damaging Het
Adck1 A G 12: 88,422,280 (GRCm39) E297G probably damaging Het
Ahrr G A 13: 74,431,143 (GRCm39) probably benign Het
Aldh3a2 C T 11: 61,139,714 (GRCm39) V473I probably benign Het
Arfgef3 A T 10: 18,523,663 (GRCm39) I369K possibly damaging Het
Atl2 A G 17: 80,161,260 (GRCm39) probably benign Het
Atp1b3 T C 9: 96,220,762 (GRCm39) I178V possibly damaging Het
Axdnd1 T C 1: 156,205,956 (GRCm39) E520G possibly damaging Het
Bahcc1 A T 11: 120,175,900 (GRCm39) probably benign Het
BB019430 A T 10: 58,540,093 (GRCm39) noncoding transcript Het
BC028528 A T 3: 95,794,646 (GRCm39) probably benign Het
Btbd1 T A 7: 81,450,751 (GRCm39) Q343L probably benign Het
Catsper1 A G 19: 5,389,503 (GRCm39) T473A possibly damaging Het
Ccn4 T C 15: 66,791,059 (GRCm39) L287P probably damaging Het
Chmp6 G A 11: 119,806,349 (GRCm39) probably null Het
Cstdc7 T A 18: 42,306,608 (GRCm39) D58E probably damaging Het
D130040H23Rik T C 8: 69,755,195 (GRCm39) V200A possibly damaging Het
D830013O20Rik C T 12: 73,411,105 (GRCm39) noncoding transcript Het
Dcaf1 T A 9: 106,721,344 (GRCm39) S379T possibly damaging Het
Dcaf4 G A 12: 83,582,762 (GRCm39) probably benign Het
Dhx58 T C 11: 100,586,150 (GRCm39) I624V probably benign Het
Disp3 T C 4: 148,338,708 (GRCm39) E821G probably damaging Het
Dlc1 T A 8: 37,066,594 (GRCm39) E464V probably damaging Het
Dnah10 G A 5: 124,860,898 (GRCm39) V2151I probably damaging Het
Dnah6 C T 6: 73,165,518 (GRCm39) probably benign Het
Dnah8 G A 17: 30,967,639 (GRCm39) G2617D probably benign Het
Dnah9 C A 11: 65,809,630 (GRCm39) E872* probably null Het
Dock9 T C 14: 121,835,077 (GRCm39) Y99C probably damaging Het
Dpy19l3 T A 7: 35,416,071 (GRCm39) I310F probably damaging Het
Fggy A T 4: 95,725,891 (GRCm39) I137F probably damaging Het
Gli2 A G 1: 118,818,013 (GRCm39) probably benign Het
Gm14421 A T 2: 176,748,515 (GRCm39) noncoding transcript Het
Grin2a A G 16: 9,812,685 (GRCm39) probably null Het
Grin2b A G 6: 135,755,646 (GRCm39) probably benign Het
Incenp A G 19: 9,872,243 (GRCm39) S72P probably benign Het
Ipo11 A G 13: 107,046,702 (GRCm39) probably benign Het
Klc3 T A 7: 19,128,851 (GRCm39) N469Y possibly damaging Het
Lrrc42 A G 4: 107,104,702 (GRCm39) S88P probably benign Het
Lrrc49 G A 9: 60,587,883 (GRCm39) T93I probably benign Het
Ltn1 G A 16: 87,202,407 (GRCm39) probably benign Het
Mlycd A T 8: 120,134,380 (GRCm39) Q294L probably damaging Het
Mmrn1 T A 6: 60,952,799 (GRCm39) probably benign Het
Mrpl22 T A 11: 58,062,647 (GRCm39) I19N probably benign Het
Msh3 T A 13: 92,485,717 (GRCm39) K202N probably damaging Het
N4bp2 T C 5: 65,960,916 (GRCm39) probably benign Het
Ncam1 C T 9: 49,479,709 (GRCm39) D90N probably damaging Het
Nckap5 A T 1: 125,952,144 (GRCm39) D1405E possibly damaging Het
Ncoa2 A G 1: 13,256,955 (GRCm39) probably null Het
Ncoa6 TGC TGCGC 2: 155,250,211 (GRCm39) probably null Het
Nlrp1b A T 11: 71,054,925 (GRCm39) W844R probably damaging Het
Nmnat1 G T 4: 149,553,607 (GRCm39) N168K possibly damaging Het
Or5b96 A G 19: 12,867,809 (GRCm39) L44P probably damaging Het
Ost4 T C 5: 31,064,803 (GRCm39) H26R probably damaging Het
Otog G A 7: 45,953,655 (GRCm39) V2638M probably damaging Het
Otogl A T 10: 107,710,391 (GRCm39) I566N probably damaging Het
Pcyt1a T C 16: 32,289,004 (GRCm39) S282P probably damaging Het
Prkcg G A 7: 3,377,635 (GRCm39) E581K probably damaging Het
Ralgps2 A G 1: 156,714,659 (GRCm39) probably null Het
Rnf157 A G 11: 116,245,636 (GRCm39) probably benign Het
Scmh1 T C 4: 120,387,062 (GRCm39) probably benign Het
Sgo2b T C 8: 64,391,417 (GRCm39) H150R possibly damaging Het
Skint6 A T 4: 112,848,433 (GRCm39) probably benign Het
Slfn10-ps T C 11: 82,926,128 (GRCm39) noncoding transcript Het
Sspo T A 6: 48,471,128 (GRCm39) probably benign Het
Tcp1 T A 17: 13,141,634 (GRCm39) probably benign Het
Tdp2 A G 13: 25,022,222 (GRCm39) M214V probably damaging Het
Tenm4 T G 7: 96,378,547 (GRCm39) probably benign Het
Tmem144 G A 3: 79,746,580 (GRCm39) probably benign Het
Tmem204 A G 17: 25,277,324 (GRCm39) I187T probably damaging Het
Tmem208 T G 8: 106,061,326 (GRCm39) D117E probably benign Het
Tnks1bp1 C T 2: 84,889,565 (GRCm39) P631S possibly damaging Het
Tomm70a T C 16: 56,968,184 (GRCm39) V517A probably damaging Het
Ttc7 T C 17: 87,687,323 (GRCm39) V801A probably damaging Het
Txndc5 A T 13: 38,691,929 (GRCm39) C146S probably damaging Het
Ubac2 A G 14: 122,246,329 (GRCm39) probably benign Het
Ube4b G T 4: 149,444,781 (GRCm39) T493K probably damaging Het
Ufl1 A T 4: 25,256,008 (GRCm39) Y504N probably benign Het
Ugt1a6a T C 1: 88,066,992 (GRCm39) V266A possibly damaging Het
Ugt1a6b T A 1: 88,035,189 (GRCm39) C176S probably damaging Het
Ulk3 T A 9: 57,497,969 (GRCm39) I90N probably damaging Het
Unc13c T C 9: 73,602,174 (GRCm39) I1357M probably benign Het
Vmn1r28 G A 6: 58,242,702 (GRCm39) A182T probably benign Het
Vmn2r114 A G 17: 23,528,800 (GRCm39) probably null Het
Vmn2r91 A C 17: 18,326,399 (GRCm39) N228T probably benign Het
Wdr43 T G 17: 71,938,992 (GRCm39) probably benign Het
Zbtb6 G T 2: 37,319,600 (GRCm39) Y109* probably null Het
Zfp980 A G 4: 145,428,567 (GRCm39) D432G probably benign Het
Other mutations in Sh2b3
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
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'- TAGCGCAATACGACCTCCTTGAGC -3'
(R):5'- TCATCTAGCCACTGTATCCACCACG -3'

Sequencing Primer
(F):5'- ATTGGTGTCACTGGTAGCCC -3'
(R):5'- TGGGCTCATTGCTTTCTGAC -3'
Posted On 2013-07-24