Incidental Mutation 'R7499:Sh2b3'
| ID |
581367 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Sh2b3
|
| Ensembl Gene |
ENSMUSG00000042594 |
| Gene Name |
SH2B adaptor protein 3 |
| Synonyms |
Lnk |
| MMRRC Submission |
045572-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly essential
(E-score: 0.532)
|
| Stock # |
R7499 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Not validated
|
| Chromosome |
5 |
| Chromosomal Location |
121953551-121975709 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 121956536 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Arginine to Glycine
at position 382
(R382G)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000041611
(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 damaging
Transcript: ENSMUST00000040308
AA Change: R382G
PolyPhen 2
Score 0.967 (Sensitivity: 0.77; Specificity: 0.95)
|
| SMART Domains |
Protein: ENSMUSP00000041611
Gene: ENSMUSG00000042594
AA Change: R382G
| 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 damaging
Transcript: ENSMUST00000086310
AA Change: R382G
PolyPhen 2
Score 0.967 (Sensitivity: 0.77; Specificity: 0.95)
|
| SMART Domains |
Protein: ENSMUSP00000083490
Gene: ENSMUSG00000042594
AA Change: R382G
| 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: R372G
PolyPhen 2
Score 0.225 (Sensitivity: 0.91; Specificity: 0.88)
|
| SMART Domains |
Protein: ENSMUSP00000113808
Gene: ENSMUSG00000042594
AA Change: R372G
| 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 damaging
Transcript: ENSMUST00000122426
AA Change: R382G
PolyPhen 2
Score 0.967 (Sensitivity: 0.77; Specificity: 0.95)
|
| SMART Domains |
Protein: ENSMUSP00000113926
Gene: ENSMUSG00000042594
AA Change: R382G
| 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
|
| SMART Domains |
Protein: ENSMUSP00000119086
Gene: ENSMUSG00000042594
| 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: 100.0%
- 10x: 99.8%
- 20x: 99.2%
|
| 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: 57 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4930563M21Rik |
T |
A |
9: 55,907,186 (GRCm39) |
D180V |
possibly damaging |
Het |
| Abat |
T |
C |
16: 8,421,618 (GRCm39) |
|
probably null |
Het |
| Ankfn1 |
G |
A |
11: 89,282,576 (GRCm39) |
T357I |
probably benign |
Het |
| Armc3 |
C |
T |
2: 19,290,790 (GRCm39) |
T423I |
probably benign |
Het |
| Asb6 |
T |
C |
2: 30,714,472 (GRCm39) |
T213A |
possibly damaging |
Het |
| Atp11a |
T |
C |
8: 12,882,575 (GRCm39) |
C488R |
probably benign |
Het |
| Bag6 |
G |
A |
17: 35,363,368 (GRCm39) |
R736H |
probably benign |
Het |
| Bche |
G |
A |
3: 73,609,231 (GRCm39) |
P65L |
probably damaging |
Het |
| Cela3a |
T |
A |
4: 137,132,950 (GRCm39) |
I101F |
probably damaging |
Het |
| Cep170 |
A |
T |
1: 176,602,028 (GRCm39) |
D359E |
probably damaging |
Het |
| Chfr |
T |
C |
5: 110,299,549 (GRCm39) |
V314A |
probably benign |
Het |
| Clpb |
T |
C |
7: 101,371,935 (GRCm39) |
F224L |
possibly damaging |
Het |
| Coro2a |
T |
C |
4: 46,539,188 (GRCm39) |
K527R |
probably benign |
Het |
| Cpa5 |
A |
G |
6: 30,630,856 (GRCm39) |
T373A |
possibly damaging |
Het |
| Ctsd |
A |
T |
7: 141,937,149 (GRCm39) |
|
probably null |
Het |
| Dlx5 |
G |
A |
6: 6,878,340 (GRCm39) |
S230F |
possibly damaging |
Het |
| Dlx5 |
A |
C |
6: 6,878,341 (GRCm39) |
S230A |
probably benign |
Het |
| Dmc1 |
G |
T |
15: 79,486,621 (GRCm39) |
S11* |
probably null |
Het |
| Dnah1 |
G |
A |
14: 31,037,079 (GRCm39) |
Q256* |
probably null |
Het |
| Dnah3 |
A |
G |
7: 119,660,135 (GRCm39) |
F846L |
probably damaging |
Het |
| Dnah5 |
A |
T |
15: 28,302,596 (GRCm39) |
I1618F |
probably damaging |
Het |
| Emsy |
A |
G |
7: 98,279,538 (GRCm39) |
V267A |
possibly damaging |
Het |
| Fgfr3 |
GGACCTCTCCGTG |
GG |
5: 33,892,766 (GRCm39) |
|
probably null |
Het |
| Frem1 |
T |
C |
4: 82,924,007 (GRCm39) |
I317M |
probably damaging |
Het |
| G6pc1 |
C |
A |
11: 101,267,520 (GRCm39) |
Y323* |
probably null |
Het |
| Gm5114 |
A |
G |
7: 39,058,489 (GRCm39) |
C377R |
possibly damaging |
Het |
| Gm7361 |
C |
A |
5: 26,466,188 (GRCm39) |
H183Q |
probably benign |
Het |
| Hmbox1 |
A |
G |
14: 65,134,126 (GRCm39) |
V158A |
possibly damaging |
Het |
| Hmg20a |
A |
G |
9: 56,396,227 (GRCm39) |
R340G |
unknown |
Het |
| Ifi206 |
T |
A |
1: 173,309,607 (GRCm39) |
I130F |
|
Het |
| Ifnb1 |
T |
C |
4: 88,440,911 (GRCm39) |
N34S |
probably benign |
Het |
| Il16 |
T |
C |
7: 83,323,702 (GRCm39) |
K283E |
probably damaging |
Het |
| Maf |
T |
C |
8: 116,419,920 (GRCm39) |
D374G |
probably benign |
Het |
| Mettl14 |
A |
G |
3: 123,168,503 (GRCm39) |
I179T |
probably benign |
Het |
| Mpped1 |
G |
A |
15: 83,684,251 (GRCm39) |
R91H |
probably damaging |
Het |
| Nop2 |
C |
A |
6: 125,121,171 (GRCm39) |
P651Q |
possibly damaging |
Het |
| Or5p62 |
A |
G |
7: 107,771,007 (GRCm39) |
*315Q |
probably null |
Het |
| Phkg1 |
G |
A |
5: 129,902,109 (GRCm39) |
Q89* |
probably null |
Het |
| Phykpl |
T |
A |
11: 51,482,285 (GRCm39) |
V133E |
probably damaging |
Het |
| Polr3gl |
A |
T |
3: 96,487,137 (GRCm39) |
Y183N |
probably benign |
Het |
| Rab13 |
A |
G |
3: 90,132,840 (GRCm39) |
T187A |
probably benign |
Het |
| Ripor2 |
A |
G |
13: 24,877,755 (GRCm39) |
M252V |
probably damaging |
Het |
| Sec61a2 |
T |
C |
2: 5,882,725 (GRCm39) |
N186S |
probably benign |
Het |
| Serpinb5 |
T |
C |
1: 106,800,119 (GRCm39) |
|
probably null |
Het |
| Serpine3 |
G |
A |
14: 62,902,476 (GRCm39) |
W29* |
probably null |
Het |
| Slc66a1 |
T |
A |
4: 139,033,823 (GRCm39) |
D32V |
probably damaging |
Het |
| Slc7a5 |
A |
G |
8: 122,610,461 (GRCm39) |
L451P |
probably damaging |
Het |
| Slco1a5 |
T |
C |
6: 142,208,257 (GRCm39) |
|
probably null |
Het |
| Tep1 |
G |
A |
14: 51,091,047 (GRCm39) |
A695V |
probably damaging |
Het |
| Tnik |
T |
C |
3: 28,684,743 (GRCm39) |
V857A |
possibly damaging |
Het |
| Trdn |
A |
T |
10: 33,072,097 (GRCm39) |
M255L |
probably benign |
Het |
| Tsc22d4 |
G |
A |
5: 137,745,985 (GRCm39) |
S203N |
probably benign |
Het |
| Tsfm |
T |
C |
10: 126,858,417 (GRCm39) |
E316G |
possibly damaging |
Het |
| Tvp23b |
T |
C |
11: 62,770,289 (GRCm39) |
|
probably benign |
Het |
| Vgf |
C |
A |
5: 137,061,099 (GRCm39) |
D420E |
probably damaging |
Het |
| Zan |
G |
A |
5: 137,462,618 (GRCm39) |
P854S |
probably benign |
Het |
| Zfp831 |
T |
C |
2: 174,485,816 (GRCm39) |
S164P |
possibly damaging |
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 |
|
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 |
|
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'- AGCTGCTCCACATTCCAGTG -3'
(R):5'- TATGTGCCAGGTCCTTGGTC -3'
Sequencing Primer
(F):5'- CACATTCCAGTGGGATAGGAG -3'
(R):5'- TGTCCTTGGACATGTGGCCC -3'
|
| Posted On |
2019-10-17 |
Incidental Mutation