Incidental Mutation 'R0166:Impa1'
| ID |
24149 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Impa1
|
| Ensembl Gene |
ENSMUSG00000027531 |
| Gene Name |
inositol (myo)-1(or 4)-monophosphatase 1 |
| Synonyms |
lithium-sensitive myo-inositol monophosphatase A1, 2900059K10Rik, 2610002K09Rik |
| MMRRC Submission |
038442-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R0166 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
(trace)
|
| Chromosome |
3 |
| Chromosomal Location |
10377016-10396499 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
C to T
at 10394020 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Alanine to Threonine
at position 16
(A16T)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000141345
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000065938]
[ENSMUST00000078748]
[ENSMUST00000118410]
[ENSMUST00000128912]
[ENSMUST00000191670]
[ENSMUST00000192603]
|
| AlphaFold |
no structure available at present |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000065938
AA Change: A16T
PolyPhen 2
Score 0.415 (Sensitivity: 0.89; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000068174
Gene: ENSMUSG00000027531
AA Change: A16T
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Inositol_P
|
5 |
271 |
1.5e-86 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000078748
|
| SMART Domains |
Protein: ENSMUSP00000077808
Gene: ENSMUSG00000058921
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
18 |
N/A |
INTRINSIC |
|
Pfam:SBF
|
144 |
328 |
1.1e-34 |
PFAM |
|
transmembrane domain
|
336 |
358 |
N/A |
INTRINSIC |
|
transmembrane domain
|
365 |
384 |
N/A |
INTRINSIC |
|
transmembrane domain
|
394 |
416 |
N/A |
INTRINSIC |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000118410
AA Change: A16T
PolyPhen 2
Score 0.855 (Sensitivity: 0.83; Specificity: 0.93)
|
| SMART Domains |
Protein: ENSMUSP00000113860
Gene: ENSMUSG00000027531
AA Change: A16T
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Inositol_P
|
5 |
271 |
7.7e-79 |
PFAM |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000128912
AA Change: A30T
PolyPhen 2
Score 0.888 (Sensitivity: 0.82; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000116088
Gene: ENSMUSG00000027531
AA Change: A30T
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Inositol_P
|
19 |
90 |
4.4e-16 |
PFAM |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000191670
AA Change: A16T
PolyPhen 2
Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)
|
| SMART Domains |
Protein: ENSMUSP00000141345
Gene: ENSMUSG00000027531
AA Change: A16T
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Inositol_P
|
5 |
180 |
4.7e-49 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000192603
|
| SMART Domains |
Protein: ENSMUSP00000141735
Gene: ENSMUSG00000103392
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
18 |
N/A |
INTRINSIC |
|
low complexity region
|
69 |
85 |
N/A |
INTRINSIC |
|
| Meta Mutation Damage Score |
0.5605 |
| Coding Region Coverage |
- 1x: 99.0%
- 3x: 98.1%
- 10x: 95.9%
- 20x: 91.4%
|
| Validation Efficiency |
91% (49/54) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes an enzyme that dephosphorylates myo-inositol monophosphate to generate free myo-inositol, a precursor of phosphatidylinositol, and is therefore an important modulator of intracellular signal transduction via the production of the second messengers myoinositol 1,4,5-trisphosphate and diacylglycerol. This enzyme can also use myo-inositol-1,3-diphosphate, myo-inositol-1,4-diphosphate, scyllo-inositol-phosphate, glucose-1-phosphate, glucose-6-phosphate, fructose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates. This enzyme shows magnesium-dependent phosphatase activity and is inhibited by therapeutic concentrations of lithium. Inhibition of inositol monophosphate hydroylosis and subsequent depletion of inositol for phosphatidylinositol synthesis may explain the anti-manic and anti-depressive effects of lithium administered to treat bipolar disorder. Alternative splicing results in multiple transcript variants encoding distinct isoforms. A pseudogene of this gene is also present on chromosome 8q21.13. [provided by RefSeq, Dec 2014]
PHENOTYPE: Most mice homozygous for a knock-out allele die between E9.5 and E10.5 with surviving mice exhibiting hyperactivity, increased rearing, and increased susceptibility to pilocarpine-induced seizures. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 51 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abcb1b |
T |
C |
5: 8,903,468 (GRCm39) |
F1040L |
probably damaging |
Het |
| Adamts7 |
A |
G |
9: 90,075,745 (GRCm39) |
N1201S |
probably benign |
Het |
| Ahnak |
C |
T |
19: 8,983,089 (GRCm39) |
P1458S |
probably damaging |
Het |
| Akap6 |
T |
C |
12: 53,187,707 (GRCm39) |
V1707A |
probably benign |
Het |
| Akr1c21 |
T |
A |
13: 4,631,263 (GRCm39) |
V266E |
probably damaging |
Het |
| Arap2 |
A |
C |
5: 62,833,361 (GRCm39) |
C894G |
probably damaging |
Het |
| Atp2a2 |
T |
C |
5: 122,604,901 (GRCm39) |
D426G |
possibly damaging |
Het |
| Azi2 |
A |
T |
9: 117,884,909 (GRCm39) |
Q132L |
possibly damaging |
Het |
| Carmil1 |
C |
T |
13: 24,283,032 (GRCm39) |
D91N |
probably damaging |
Het |
| Cnot7 |
A |
T |
8: 40,960,494 (GRCm39) |
|
probably null |
Het |
| Cntnap5b |
A |
G |
1: 100,202,086 (GRCm39) |
E311G |
probably benign |
Het |
| Csmd1 |
A |
G |
8: 16,283,036 (GRCm39) |
V640A |
probably benign |
Het |
| Cst7 |
T |
C |
2: 150,417,647 (GRCm39) |
S31P |
probably benign |
Het |
| Cyp7b1 |
T |
A |
3: 18,151,530 (GRCm39) |
I228L |
probably benign |
Het |
| Ddx28 |
G |
A |
8: 106,736,921 (GRCm39) |
T379I |
probably benign |
Het |
| Drd1 |
T |
A |
13: 54,207,600 (GRCm39) |
I205F |
probably damaging |
Het |
| Flnb |
T |
A |
14: 7,896,115 (GRCm38) |
V837D |
probably damaging |
Het |
| Fsd1l |
A |
G |
4: 53,647,664 (GRCm39) |
|
probably null |
Het |
| Fubp1 |
T |
A |
3: 151,925,841 (GRCm39) |
Y264* |
probably null |
Het |
| Gbp5 |
T |
A |
3: 142,212,680 (GRCm39) |
|
probably null |
Het |
| Gm7094 |
A |
G |
1: 21,342,958 (GRCm39) |
|
noncoding transcript |
Het |
| Gpr55 |
A |
G |
1: 85,868,858 (GRCm39) |
V241A |
probably benign |
Het |
| Llgl2 |
T |
C |
11: 115,735,680 (GRCm39) |
L92P |
probably damaging |
Het |
| Ltbp2 |
T |
A |
12: 84,833,132 (GRCm39) |
Q1472L |
probably benign |
Het |
| Lyplal1 |
A |
T |
1: 185,820,943 (GRCm39) |
M168K |
probably benign |
Het |
| Macc1 |
A |
T |
12: 119,410,815 (GRCm39) |
R528* |
probably null |
Het |
| Mdm1 |
T |
A |
10: 118,002,585 (GRCm39) |
D635E |
probably damaging |
Het |
| Miox |
C |
T |
15: 89,220,477 (GRCm39) |
L189F |
possibly damaging |
Het |
| Mrpl23 |
C |
T |
7: 142,088,851 (GRCm39) |
R69W |
probably damaging |
Het |
| Ncoa6 |
TGC |
TGCGC |
2: 155,250,211 (GRCm39) |
|
probably null |
Het |
| Nr0b2 |
A |
G |
4: 133,281,049 (GRCm39) |
Q105R |
probably damaging |
Het |
| Or8b53 |
T |
A |
9: 38,667,484 (GRCm39) |
S167T |
probably benign |
Het |
| Otog |
G |
A |
7: 45,953,655 (GRCm39) |
V2638M |
probably damaging |
Het |
| Pcdhb14 |
A |
T |
18: 37,581,542 (GRCm39) |
|
probably null |
Het |
| Plxna1 |
A |
G |
6: 89,310,001 (GRCm39) |
W1055R |
probably damaging |
Het |
| Pramel22 |
T |
A |
4: 143,381,081 (GRCm39) |
H314L |
probably benign |
Het |
| Prdm1 |
C |
T |
10: 44,316,087 (GRCm39) |
R716Q |
probably damaging |
Het |
| Proser1 |
C |
A |
3: 53,388,038 (GRCm39) |
Q909K |
possibly damaging |
Het |
| Pus10 |
T |
A |
11: 23,617,358 (GRCm39) |
C24S |
probably damaging |
Het |
| Rpl27 |
T |
A |
11: 101,336,146 (GRCm39) |
F69I |
possibly damaging |
Het |
| Sctr |
A |
T |
1: 119,983,124 (GRCm39) |
I325F |
probably damaging |
Het |
| Slc49a4 |
G |
A |
16: 35,539,684 (GRCm39) |
T379I |
possibly damaging |
Het |
| Slc5a3 |
G |
A |
16: 91,874,581 (GRCm39) |
V213I |
possibly damaging |
Het |
| Spib |
G |
T |
7: 44,179,324 (GRCm39) |
D28E |
probably damaging |
Het |
| Spic |
T |
C |
10: 88,511,579 (GRCm39) |
S226G |
possibly damaging |
Het |
| Tet1 |
T |
A |
10: 62,676,058 (GRCm39) |
T673S |
probably benign |
Het |
| Tph1 |
A |
G |
7: 46,297,020 (GRCm39) |
F392L |
probably damaging |
Het |
| Ttc28 |
T |
C |
5: 111,373,500 (GRCm39) |
S979P |
probably benign |
Het |
| Unc79 |
T |
C |
12: 103,122,812 (GRCm39) |
L2110P |
probably damaging |
Het |
| Vmn1r28 |
G |
A |
6: 58,242,702 (GRCm39) |
A182T |
probably benign |
Het |
| Zfp467 |
T |
C |
6: 48,415,615 (GRCm39) |
T346A |
probably benign |
Het |
|
| Other mutations in Impa1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01777:Impa1
|
APN |
3 |
10,388,008 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02411:Impa1
|
APN |
3 |
10,388,018 (GRCm39) |
missense |
possibly damaging |
0.90 |
|
IGL02733:Impa1
|
APN |
3 |
10,394,025 (GRCm39) |
missense |
probably benign |
|
|
IGL03183:Impa1
|
APN |
3 |
10,388,054 (GRCm39) |
missense |
probably damaging |
1.00 |
|
lofty
|
UTSW |
3 |
10,394,064 (GRCm39) |
start codon destroyed |
probably null |
1.00 |
|
olympian
|
UTSW |
3 |
10,380,340 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0782:Impa1
|
UTSW |
3 |
10,387,956 (GRCm39) |
splice site |
probably benign |
|
|
R1645:Impa1
|
UTSW |
3 |
10,393,501 (GRCm39) |
missense |
possibly damaging |
0.79 |
|
R3196:Impa1
|
UTSW |
3 |
10,394,075 (GRCm39) |
splice site |
probably null |
|
|
R3905:Impa1
|
UTSW |
3 |
10,381,094 (GRCm39) |
missense |
probably benign |
|
|
R4953:Impa1
|
UTSW |
3 |
10,380,340 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5495:Impa1
|
UTSW |
3 |
10,391,230 (GRCm39) |
missense |
probably benign |
0.08 |
|
R5884:Impa1
|
UTSW |
3 |
10,381,284 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5972:Impa1
|
UTSW |
3 |
10,394,064 (GRCm39) |
start codon destroyed |
probably null |
1.00 |
|
R6927:Impa1
|
UTSW |
3 |
10,380,348 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7605:Impa1
|
UTSW |
3 |
10,389,147 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R7801:Impa1
|
UTSW |
3 |
10,386,727 (GRCm39) |
missense |
probably benign |
|
|
R8086:Impa1
|
UTSW |
3 |
10,387,988 (GRCm39) |
missense |
probably benign |
0.02 |
|
R8190:Impa1
|
UTSW |
3 |
10,386,688 (GRCm39) |
missense |
possibly damaging |
0.48 |
|
R9685:Impa1
|
UTSW |
3 |
10,393,430 (GRCm39) |
missense |
probably benign |
0.00 |
|
X0054:Impa1
|
UTSW |
3 |
10,381,160 (GRCm39) |
splice site |
probably null |
|
|
Z1177:Impa1
|
UTSW |
3 |
10,381,134 (GRCm39) |
missense |
probably benign |
0.03 |
|
| Predicted Primers |
PCR Primer
(F):5'- CACACAGGAAATCAGCCATTTTCACTG -3'
(R):5'- GTCACTTGGGAGACAGCTTCATAGAAC -3'
Sequencing Primer
(F):5'- AAATCAGCCATTTTCACTGTATTTAC -3'
(R):5'- acagacggggtcaggag -3'
|
| Posted On |
2013-04-16 |
Incidental Mutation