Incidental Mutation 'R6386:Inpp5d'
| ID |
515587 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Inpp5d
|
| Ensembl Gene |
ENSMUSG00000026288 |
| Gene Name |
inositol polyphosphate-5-phosphatase D |
| Synonyms |
SHIP1, Src homology 2 domain-containing inositol-5-phosphatase, s-SHIP, SHIP, SHIP-1 |
| MMRRC Submission |
044535-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.914)
|
| Stock # |
R6386 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Not validated
|
| Chromosome |
1 |
| Chromosomal Location |
87548034-87648229 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to A
at 87627397 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Leucine to Glutamine
at position 566
(L566Q)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000127941
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000042275]
[ENSMUST00000072999]
[ENSMUST00000167032]
[ENSMUST00000168783]
[ENSMUST00000169754]
[ENSMUST00000170300]
|
| AlphaFold |
Q9ES52 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000042275
AA Change: L565Q
PolyPhen 2
Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
|
| SMART Domains |
Protein: ENSMUSP00000044647
Gene: ENSMUSG00000026288
AA Change: L565Q
| Domain | Start | End | E-Value | Type |
|---|
|
SH2
|
6 |
95 |
7.15e-29 |
SMART |
|
low complexity region
|
107 |
120 |
N/A |
INTRINSIC |
|
IPPc
|
404 |
720 |
4.5e-104 |
SMART |
|
low complexity region
|
767 |
777 |
N/A |
INTRINSIC |
|
low complexity region
|
954 |
979 |
N/A |
INTRINSIC |
|
low complexity region
|
1045 |
1057 |
N/A |
INTRINSIC |
|
low complexity region
|
1119 |
1131 |
N/A |
INTRINSIC |
|
low complexity region
|
1139 |
1148 |
N/A |
INTRINSIC |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000072999
AA Change: L565Q
PolyPhen 2
Score 0.839 (Sensitivity: 0.84; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000072763
Gene: ENSMUSG00000026288
AA Change: L565Q
| Domain | Start | End | E-Value | Type |
|---|
|
SH2
|
6 |
95 |
7.15e-29 |
SMART |
|
low complexity region
|
107 |
120 |
N/A |
INTRINSIC |
|
IPPc
|
404 |
720 |
4.5e-104 |
SMART |
|
low complexity region
|
767 |
777 |
N/A |
INTRINSIC |
|
low complexity region
|
932 |
953 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000167032
AA Change: L303Q
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000126569
Gene: ENSMUSG00000026288
AA Change: L303Q
| Domain | Start | End | E-Value | Type |
|---|
|
IPPc
|
142 |
458 |
4.5e-104 |
SMART |
|
low complexity region
|
505 |
515 |
N/A |
INTRINSIC |
|
low complexity region
|
692 |
717 |
N/A |
INTRINSIC |
|
low complexity region
|
783 |
795 |
N/A |
INTRINSIC |
|
low complexity region
|
857 |
869 |
N/A |
INTRINSIC |
|
low complexity region
|
877 |
886 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000168783
AA Change: L566Q
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000131244
Gene: ENSMUSG00000026288
AA Change: L566Q
| Domain | Start | End | E-Value | Type |
|---|
|
SH2
|
6 |
95 |
7.15e-29 |
SMART |
|
low complexity region
|
107 |
118 |
N/A |
INTRINSIC |
|
IPPc
|
405 |
721 |
4.5e-104 |
SMART |
|
low complexity region
|
768 |
778 |
N/A |
INTRINSIC |
|
low complexity region
|
985 |
997 |
N/A |
INTRINSIC |
|
low complexity region
|
1059 |
1071 |
N/A |
INTRINSIC |
|
low complexity region
|
1079 |
1088 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000169754
AA Change: L566Q
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000127941
Gene: ENSMUSG00000026288
AA Change: L566Q
| Domain | Start | End | E-Value | Type |
|---|
|
SH2
|
6 |
95 |
4.6e-31 |
SMART |
|
low complexity region
|
107 |
118 |
N/A |
INTRINSIC |
|
IPPc
|
405 |
721 |
2.2e-106 |
SMART |
|
low complexity region
|
768 |
778 |
N/A |
INTRINSIC |
|
low complexity region
|
955 |
980 |
N/A |
INTRINSIC |
|
low complexity region
|
1046 |
1058 |
N/A |
INTRINSIC |
|
low complexity region
|
1120 |
1132 |
N/A |
INTRINSIC |
|
low complexity region
|
1140 |
1149 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000170300
AA Change: L303Q
PolyPhen 2
Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000132384
Gene: ENSMUSG00000026288
AA Change: L303Q
| Domain | Start | End | E-Value | Type |
|---|
|
IPPc
|
142 |
458 |
4.5e-104 |
SMART |
|
low complexity region
|
505 |
515 |
N/A |
INTRINSIC |
|
low complexity region
|
722 |
734 |
N/A |
INTRINSIC |
|
low complexity region
|
796 |
808 |
N/A |
INTRINSIC |
|
low complexity region
|
816 |
825 |
N/A |
INTRINSIC |
|
| Meta Mutation Damage Score |
0.9048 |
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 99.9%
- 10x: 99.1%
- 20x: 96.6%
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the inositol polyphosphate-5-phosphatase (INPP5) family and encodes a protein with an N-terminal SH2 domain, an inositol phosphatase domain, and two C-terminal protein interaction domains. Expression of this protein is restricted to hematopoietic cells where its movement from the cytosol to the plasma membrane is mediated by tyrosine phosphorylation. At the plasma membrane, the protein hydrolyzes the 5' phosphate from phosphatidylinositol (3,4,5)-trisphosphate and inositol-1,3,4,5-tetrakisphosphate, thereby affecting multiple signaling pathways. The protein is also partly localized to the nucleus, where it may be involved in nuclear inositol phosphate signaling processes. Overall, the protein functions as a negative regulator of myeloid cell proliferation and survival. Mutations in this gene are associated with defects and cancers of the immune system. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2014]
PHENOTYPE: Homozygous null mice fail to reject fully mismatched allogeneic marrow grafts, do not develop graft versus host disease, and show enhanced survival after such transplants. Homozygous splice site mutants exhibit wasting, granulocytic lung infiltration anddefective cytolysis by NK cells and CTLs. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 36 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Ak6 |
TGACGA |
TGA |
13: 100,792,311 (GRCm39) |
|
probably benign |
Het |
| Arap2 |
A |
T |
5: 62,761,865 (GRCm39) |
N1620K |
possibly damaging |
Het |
| Atf6b |
T |
C |
17: 34,870,825 (GRCm39) |
S396P |
probably damaging |
Het |
| Cc2d1a |
A |
G |
8: 84,865,166 (GRCm39) |
M469T |
probably damaging |
Het |
| Ceacam3 |
A |
G |
7: 16,892,144 (GRCm39) |
N296D |
probably benign |
Het |
| Cep57l1 |
A |
T |
10: 41,619,128 (GRCm39) |
S80T |
probably damaging |
Het |
| Clip4 |
C |
A |
17: 72,141,189 (GRCm39) |
Y514* |
probably null |
Het |
| Cop1 |
T |
C |
1: 159,116,601 (GRCm39) |
I125T |
probably damaging |
Het |
| Cstf1 |
T |
C |
2: 172,219,816 (GRCm39) |
V309A |
probably damaging |
Het |
| Cyp4a29 |
T |
G |
4: 115,104,272 (GRCm39) |
|
probably null |
Het |
| F830045P16Rik |
G |
A |
2: 129,314,738 (GRCm39) |
H180Y |
probably damaging |
Het |
| Foxp4 |
T |
C |
17: 48,189,387 (GRCm39) |
K237E |
unknown |
Het |
| Fstl5 |
A |
T |
3: 76,229,373 (GRCm39) |
H58L |
probably benign |
Het |
| Gje1 |
A |
G |
10: 14,592,365 (GRCm39) |
F139S |
probably damaging |
Het |
| Gpatch1 |
T |
C |
7: 34,991,265 (GRCm39) |
D593G |
probably damaging |
Het |
| Mtch2 |
A |
G |
2: 90,679,739 (GRCm39) |
T38A |
probably benign |
Het |
| Mvb12b |
A |
T |
2: 33,717,754 (GRCm39) |
I129N |
probably damaging |
Het |
| Npffr2 |
T |
C |
5: 89,730,556 (GRCm39) |
V162A |
probably benign |
Het |
| Or4d10b |
A |
T |
19: 12,036,920 (GRCm39) |
N65K |
probably damaging |
Het |
| Or5p61 |
A |
T |
7: 107,758,409 (GRCm39) |
Y224N |
probably damaging |
Het |
| Pkhd1 |
G |
A |
1: 20,621,244 (GRCm39) |
R805C |
probably damaging |
Het |
| Ppp4r4 |
T |
C |
12: 103,559,364 (GRCm39) |
L406P |
probably damaging |
Het |
| Prl3d2 |
A |
G |
13: 27,311,286 (GRCm39) |
D186G |
probably damaging |
Het |
| Rfc5 |
T |
C |
5: 117,523,463 (GRCm39) |
T112A |
probably benign |
Het |
| Rnf148 |
A |
G |
6: 23,654,483 (GRCm39) |
L171P |
probably damaging |
Het |
| Rps24 |
G |
A |
14: 24,542,116 (GRCm39) |
G71S |
possibly damaging |
Het |
| Slco2a1 |
G |
A |
9: 102,954,187 (GRCm39) |
V453I |
probably benign |
Het |
| Spidr |
T |
C |
16: 15,786,424 (GRCm39) |
K440E |
probably benign |
Het |
| Syndig1 |
C |
A |
2: 149,741,496 (GRCm39) |
N27K |
probably damaging |
Het |
| Tmem62 |
C |
T |
2: 120,829,595 (GRCm39) |
T316I |
probably benign |
Het |
| Tpgs2 |
A |
T |
18: 25,272,081 (GRCm39) |
I258N |
possibly damaging |
Het |
| Vmn2r78 |
A |
T |
7: 86,571,545 (GRCm39) |
R452* |
probably null |
Het |
| Wasf3 |
A |
T |
5: 146,390,227 (GRCm39) |
I124F |
possibly damaging |
Het |
| Wbp11 |
T |
C |
6: 136,797,523 (GRCm39) |
T299A |
probably benign |
Het |
| Wdr25 |
T |
C |
12: 108,990,991 (GRCm39) |
S41P |
probably damaging |
Het |
| Zfp874b |
T |
C |
13: 67,622,962 (GRCm39) |
D116G |
possibly damaging |
Het |
|
| Other mutations in Inpp5d |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00323:Inpp5d
|
APN |
1 |
87,611,537 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL00329:Inpp5d
|
APN |
1 |
87,595,725 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL00897:Inpp5d
|
APN |
1 |
87,639,836 (GRCm39) |
missense |
probably benign |
0.14 |
|
IGL01314:Inpp5d
|
APN |
1 |
87,611,472 (GRCm39) |
nonsense |
probably null |
|
|
IGL02145:Inpp5d
|
APN |
1 |
87,642,777 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02422:Inpp5d
|
APN |
1 |
87,635,854 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02538:Inpp5d
|
APN |
1 |
87,623,088 (GRCm39) |
missense |
probably null |
0.92 |
|
IGL02680:Inpp5d
|
APN |
1 |
87,629,205 (GRCm39) |
missense |
possibly damaging |
0.87 |
|
IGL03083:Inpp5d
|
APN |
1 |
87,638,863 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03308:Inpp5d
|
APN |
1 |
87,630,919 (GRCm39) |
missense |
probably damaging |
1.00 |
|
americas
|
UTSW |
1 |
87,642,864 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Apfelsine
|
UTSW |
1 |
87,611,567 (GRCm39) |
nonsense |
probably null |
|
|
Auburn
|
UTSW |
1 |
87,609,402 (GRCm39) |
splice site |
probably null |
|
|
Autumnal
|
UTSW |
1 |
87,619,433 (GRCm39) |
missense |
probably damaging |
0.97 |
|
Gourd
|
UTSW |
1 |
87,625,337 (GRCm39) |
intron |
probably benign |
|
|
lyda
|
UTSW |
1 |
87,611,484 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Mandarin
|
UTSW |
1 |
87,637,348 (GRCm39) |
missense |
probably damaging |
0.99 |
|
naranjo
|
UTSW |
1 |
87,635,933 (GRCm39) |
critical splice donor site |
probably null |
|
|
New_black
|
UTSW |
1 |
87,637,397 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Orange
|
UTSW |
1 |
87,625,268 (GRCm39) |
critical splice donor site |
probably null |
|
|
pantone
|
UTSW |
1 |
87,627,397 (GRCm39) |
missense |
probably damaging |
1.00 |
|
sailing
|
UTSW |
1 |
87,633,686 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Salamander
|
UTSW |
1 |
87,623,102 (GRCm39) |
missense |
probably damaging |
0.99 |
|
Sandstone
|
UTSW |
1 |
87,623,122 (GRCm39) |
missense |
probably damaging |
1.00 |
|
styx
|
UTSW |
1 |
87,597,506 (GRCm39) |
critical splice donor site |
probably benign |
|
|
tangerine
|
UTSW |
1 |
87,633,671 (GRCm39) |
missense |
probably damaging |
1.00 |
|
ulster
|
UTSW |
1 |
87,629,198 (GRCm39) |
nonsense |
probably null |
|
|
R0010:Inpp5d
|
UTSW |
1 |
87,625,268 (GRCm39) |
critical splice donor site |
probably null |
|
|
R0037:Inpp5d
|
UTSW |
1 |
87,635,851 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R0087:Inpp5d
|
UTSW |
1 |
87,642,860 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0492:Inpp5d
|
UTSW |
1 |
87,625,872 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R0520:Inpp5d
|
UTSW |
1 |
87,633,642 (GRCm39) |
splice site |
probably benign |
|
|
R0733:Inpp5d
|
UTSW |
1 |
87,595,799 (GRCm39) |
splice site |
probably benign |
|
|
R1464:Inpp5d
|
UTSW |
1 |
87,625,827 (GRCm39) |
splice site |
probably benign |
|
|
R1576:Inpp5d
|
UTSW |
1 |
87,609,280 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R1576:Inpp5d
|
UTSW |
1 |
87,597,407 (GRCm39) |
missense |
probably benign |
0.16 |
|
R1592:Inpp5d
|
UTSW |
1 |
87,593,254 (GRCm39) |
missense |
possibly damaging |
0.90 |
|
R1750:Inpp5d
|
UTSW |
1 |
87,626,803 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1774:Inpp5d
|
UTSW |
1 |
87,595,611 (GRCm39) |
missense |
probably benign |
0.30 |
|
R1972:Inpp5d
|
UTSW |
1 |
87,604,036 (GRCm39) |
missense |
probably benign |
0.00 |
|
R2024:Inpp5d
|
UTSW |
1 |
87,623,072 (GRCm39) |
nonsense |
probably null |
|
|
R2405:Inpp5d
|
UTSW |
1 |
87,627,451 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R3412:Inpp5d
|
UTSW |
1 |
87,595,779 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
R3414:Inpp5d
|
UTSW |
1 |
87,595,779 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
R3756:Inpp5d
|
UTSW |
1 |
87,629,130 (GRCm39) |
splice site |
probably benign |
|
|
R4652:Inpp5d
|
UTSW |
1 |
87,593,173 (GRCm39) |
missense |
probably benign |
0.03 |
|
R4676:Inpp5d
|
UTSW |
1 |
87,642,864 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4834:Inpp5d
|
UTSW |
1 |
87,625,245 (GRCm39) |
missense |
possibly damaging |
0.52 |
|
R5086:Inpp5d
|
UTSW |
1 |
87,633,686 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5159:Inpp5d
|
UTSW |
1 |
87,604,064 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5250:Inpp5d
|
UTSW |
1 |
87,637,397 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5442:Inpp5d
|
UTSW |
1 |
87,645,788 (GRCm39) |
missense |
probably benign |
0.02 |
|
R5875:Inpp5d
|
UTSW |
1 |
87,645,696 (GRCm39) |
missense |
possibly damaging |
0.47 |
|
R6135:Inpp5d
|
UTSW |
1 |
87,548,119 (GRCm39) |
splice site |
probably null |
|
|
R6371:Inpp5d
|
UTSW |
1 |
87,627,397 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6385:Inpp5d
|
UTSW |
1 |
87,627,397 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6526:Inpp5d
|
UTSW |
1 |
87,603,972 (GRCm39) |
start gained |
probably benign |
|
|
R6572:Inpp5d
|
UTSW |
1 |
87,623,118 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R6831:Inpp5d
|
UTSW |
1 |
87,629,198 (GRCm39) |
nonsense |
probably null |
|
|
R6853:Inpp5d
|
UTSW |
1 |
87,609,402 (GRCm39) |
splice site |
probably null |
|
|
R6883:Inpp5d
|
UTSW |
1 |
87,627,412 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R7082:Inpp5d
|
UTSW |
1 |
87,623,102 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R7215:Inpp5d
|
UTSW |
1 |
87,628,940 (GRCm39) |
missense |
probably benign |
0.30 |
|
R7418:Inpp5d
|
UTSW |
1 |
87,635,933 (GRCm39) |
critical splice donor site |
probably null |
|
|
R7471:Inpp5d
|
UTSW |
1 |
87,623,122 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7593:Inpp5d
|
UTSW |
1 |
87,645,500 (GRCm39) |
missense |
possibly damaging |
0.82 |
|
R7716:Inpp5d
|
UTSW |
1 |
87,593,121 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R7781:Inpp5d
|
UTSW |
1 |
87,627,394 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7808:Inpp5d
|
UTSW |
1 |
87,611,567 (GRCm39) |
nonsense |
probably null |
|
|
R7920:Inpp5d
|
UTSW |
1 |
87,633,671 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8788:Inpp5d
|
UTSW |
1 |
87,611,484 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8839:Inpp5d
|
UTSW |
1 |
87,619,433 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R8905:Inpp5d
|
UTSW |
1 |
87,637,348 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R8906:Inpp5d
|
UTSW |
1 |
87,625,337 (GRCm39) |
intron |
probably benign |
|
|
R9517:Inpp5d
|
UTSW |
1 |
87,638,853 (GRCm39) |
missense |
probably benign |
0.01 |
|
R9667:Inpp5d
|
UTSW |
1 |
87,623,128 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9716:Inpp5d
|
UTSW |
1 |
87,625,191 (GRCm39) |
missense |
possibly damaging |
0.90 |
|
Z1176:Inpp5d
|
UTSW |
1 |
87,630,853 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Z1176:Inpp5d
|
UTSW |
1 |
87,597,431 (GRCm39) |
missense |
probably benign |
0.16 |
|
Z1191:Inpp5d
|
UTSW |
1 |
87,611,492 (GRCm39) |
missense |
probably benign |
0.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- AGACTCTGTGTTCCCAGTTGG -3'
(R):5'- GTTCTGAGTGTTCACATGTCTC -3'
Sequencing Primer
(F):5'- GGTTTCCCAGACACACTCAGG -3'
(R):5'- CTTTGATTTTCTGTCCACAGCCGAC -3'
|
| Posted On |
2018-05-04 |
Incidental Mutation