Incidental Mutation 'P0005:Atp13a1'
| ID |
7606 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Atp13a1
|
| Ensembl Gene |
ENSMUSG00000031862 |
| Gene Name |
ATPase type 13A1 |
| Synonyms |
Cgi152, catp, Atp13a |
| MMRRC Submission |
038262-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
P0005 (G1)
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
8 |
| Chromosomal Location |
70243813-70260399 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 70256397 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Valine to Alanine
at position 845
(V845A)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000034326
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000034326]
[ENSMUST00000036074]
[ENSMUST00000123453]
|
| AlphaFold |
Q9EPE9 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000034326
AA Change: V845A
PolyPhen 2
Score 0.883 (Sensitivity: 0.82; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000034326
Gene: ENSMUSG00000031862
AA Change: V845A
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
54 |
62 |
N/A |
INTRINSIC |
|
transmembrane domain
|
64 |
86 |
N/A |
INTRINSIC |
|
transmembrane domain
|
96 |
118 |
N/A |
INTRINSIC |
|
Pfam:E1-E2_ATPase
|
264 |
515 |
3.2e-24 |
PFAM |
|
Pfam:Hydrolase
|
524 |
781 |
2.2e-11 |
PFAM |
|
Pfam:HAD
|
527 |
870 |
2.7e-27 |
PFAM |
|
low complexity region
|
883 |
894 |
N/A |
INTRINSIC |
|
transmembrane domain
|
1045 |
1067 |
N/A |
INTRINSIC |
|
transmembrane domain
|
1093 |
1115 |
N/A |
INTRINSIC |
|
transmembrane domain
|
1130 |
1147 |
N/A |
INTRINSIC |
|
low complexity region
|
1173 |
1184 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000036074
|
| SMART Domains |
Protein: ENSMUSP00000045676
Gene: ENSMUSG00000036246
| Domain | Start | End | E-Value | Type |
|---|
|
PDB:3QWE|A
|
85 |
356 |
1e-149 |
PDB |
|
low complexity region
|
358 |
367 |
N/A |
INTRINSIC |
|
low complexity region
|
389 |
406 |
N/A |
INTRINSIC |
|
low complexity region
|
419 |
431 |
N/A |
INTRINSIC |
|
C1
|
491 |
536 |
1.75e-6 |
SMART |
|
RhoGAP
|
561 |
753 |
1.06e-61 |
SMART |
|
Blast:RhoGAP
|
824 |
971 |
1e-53 |
BLAST |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000123453
|
| SMART Domains |
Protein: ENSMUSP00000116542
Gene: ENSMUSG00000036246
| Domain | Start | End | E-Value | Type |
|---|
|
PDB:3QWE|A
|
85 |
356 |
1e-150 |
PDB |
|
low complexity region
|
358 |
367 |
N/A |
INTRINSIC |
|
low complexity region
|
389 |
406 |
N/A |
INTRINSIC |
|
low complexity region
|
419 |
431 |
N/A |
INTRINSIC |
|
C1
|
491 |
536 |
1.75e-6 |
SMART |
|
RhoGAP
|
561 |
753 |
1.06e-61 |
SMART |
|
| Meta Mutation Damage Score |
0.8080 |
| Coding Region Coverage |
- 1x: 85.5%
- 3x: 80.5%
- 10x: 66.1%
- 20x: 49.6%
|
| Validation Efficiency |
95% (104/109) |
| Allele List at MGI |
All alleles(3) : Targeted(2) Gene trapped(1)
|
| Other mutations in this stock |
Total: 20 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Casp6 |
T |
C |
3: 129,705,792 (GRCm39) |
V153A |
probably benign |
Het |
| Col6a1 |
A |
G |
10: 76,553,163 (GRCm39) |
|
probably benign |
Het |
| Dars2 |
A |
G |
1: 160,881,509 (GRCm39) |
|
probably null |
Het |
| Hmgcll1 |
T |
A |
9: 75,982,041 (GRCm39) |
M162K |
possibly damaging |
Het |
| Hydin |
A |
T |
8: 111,220,921 (GRCm39) |
|
probably null |
Het |
| Ift74 |
A |
G |
4: 94,550,813 (GRCm39) |
|
probably benign |
Het |
| Itpr1 |
A |
T |
6: 108,358,218 (GRCm39) |
I595F |
probably damaging |
Het |
| Mgat4f |
T |
A |
1: 134,315,646 (GRCm39) |
M15K |
probably benign |
Het |
| Mmp17 |
T |
C |
5: 129,673,695 (GRCm39) |
V258A |
probably benign |
Het |
| Nek6 |
T |
C |
2: 38,459,749 (GRCm39) |
|
probably null |
Het |
| Nomo1 |
A |
T |
7: 45,686,981 (GRCm39) |
|
probably null |
Het |
| Nudt3 |
A |
G |
17: 27,815,689 (GRCm39) |
|
probably benign |
Het |
| Pramel32 |
A |
G |
4: 88,546,187 (GRCm39) |
L385P |
probably damaging |
Het |
| Prkg2 |
A |
C |
5: 99,117,806 (GRCm39) |
F512V |
probably damaging |
Het |
| Ptp4a3 |
T |
A |
15: 73,627,160 (GRCm39) |
D72E |
possibly damaging |
Het |
| Rpgrip1l |
A |
T |
8: 92,025,853 (GRCm39) |
|
probably benign |
Het |
| Rrp9 |
G |
A |
9: 106,358,376 (GRCm39) |
R101H |
probably benign |
Het |
| Slc7a6os |
T |
C |
8: 106,931,154 (GRCm39) |
I161V |
probably benign |
Het |
| Tex15 |
T |
C |
8: 34,060,896 (GRCm39) |
F109L |
probably benign |
Het |
| Tns2 |
A |
G |
15: 102,022,491 (GRCm39) |
Q1188R |
probably damaging |
Het |
|
| Other mutations in Atp13a1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00476:Atp13a1
|
APN |
8 |
70,249,547 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL00949:Atp13a1
|
APN |
8 |
70,252,653 (GRCm39) |
splice site |
probably benign |
|
|
IGL01122:Atp13a1
|
APN |
8 |
70,251,555 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02399:Atp13a1
|
APN |
8 |
70,259,751 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02616:Atp13a1
|
APN |
8 |
70,257,963 (GRCm39) |
missense |
probably benign |
|
|
IGL03073:Atp13a1
|
APN |
8 |
70,251,152 (GRCm39) |
missense |
probably damaging |
1.00 |
|
yun_nan
|
UTSW |
8 |
70,251,329 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0086:Atp13a1
|
UTSW |
8 |
70,250,424 (GRCm39) |
missense |
possibly damaging |
0.86 |
|
R0384:Atp13a1
|
UTSW |
8 |
70,249,974 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
R0973:Atp13a1
|
UTSW |
8 |
70,254,794 (GRCm39) |
critical splice donor site |
probably null |
|
|
R0973:Atp13a1
|
UTSW |
8 |
70,254,794 (GRCm39) |
critical splice donor site |
probably null |
|
|
R0974:Atp13a1
|
UTSW |
8 |
70,254,794 (GRCm39) |
critical splice donor site |
probably null |
|
|
R2010:Atp13a1
|
UTSW |
8 |
70,244,010 (GRCm39) |
missense |
possibly damaging |
0.77 |
|
R2040:Atp13a1
|
UTSW |
8 |
70,259,702 (GRCm39) |
missense |
possibly damaging |
0.76 |
|
R2069:Atp13a1
|
UTSW |
8 |
70,252,423 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4274:Atp13a1
|
UTSW |
8 |
70,257,942 (GRCm39) |
missense |
probably benign |
|
|
R4288:Atp13a1
|
UTSW |
8 |
70,246,728 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
R4470:Atp13a1
|
UTSW |
8 |
70,251,329 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5408:Atp13a1
|
UTSW |
8 |
70,249,490 (GRCm39) |
missense |
probably benign |
0.41 |
|
R5916:Atp13a1
|
UTSW |
8 |
70,259,748 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5920:Atp13a1
|
UTSW |
8 |
70,252,746 (GRCm39) |
missense |
probably benign |
0.02 |
|
R5951:Atp13a1
|
UTSW |
8 |
70,249,935 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6143:Atp13a1
|
UTSW |
8 |
70,258,010 (GRCm39) |
missense |
probably benign |
|
|
R6467:Atp13a1
|
UTSW |
8 |
70,259,424 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6487:Atp13a1
|
UTSW |
8 |
70,252,528 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R7166:Atp13a1
|
UTSW |
8 |
70,251,966 (GRCm39) |
splice site |
probably null |
|
|
R7652:Atp13a1
|
UTSW |
8 |
70,258,209 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R7942:Atp13a1
|
UTSW |
8 |
70,259,870 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R8014:Atp13a1
|
UTSW |
8 |
70,252,429 (GRCm39) |
nonsense |
probably null |
|
|
R8228:Atp13a1
|
UTSW |
8 |
70,251,569 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8496:Atp13a1
|
UTSW |
8 |
70,250,618 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8951:Atp13a1
|
UTSW |
8 |
70,246,484 (GRCm39) |
missense |
probably benign |
0.01 |
|
R9000:Atp13a1
|
UTSW |
8 |
70,254,725 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9087:Atp13a1
|
UTSW |
8 |
70,256,457 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9721:Atp13a1
|
UTSW |
8 |
70,252,087 (GRCm39) |
missense |
probably damaging |
1.00 |
|
RF001:Atp13a1
|
UTSW |
8 |
70,252,720 (GRCm39) |
missense |
probably damaging |
0.97 |
|
| Protein Function and Prediction |
The P-type ATPases transport inorganic cations or other substrates (e.g., phospholipids) across cell membranes (1;2). There are five subfamilies which include Cu2+-ATPases, Na+,K+-ATPases, H+,K+-ATPases, and Ca2+-ATPases; the specificity of the type V family is unknown (1). The Type V subfamily is only expressed in eukaryotes (the others are expressed in both prokaryotes and eukaryotes) (1;2). Five Type V P-type ATPases have been identified in mouse; each has an orthologue in the human genome (1). Sequence alignment has determined that there are highly conserved amino acid sequences among the Type V subfamily members (1). The Type V-ATPases ten transmembrane domains and both the N- and C-termini are within the cytoplasm. Sequences homologous to an actuator domain are downstream of putative transmembrane 2 (1). A portion of the central cytoplasmic domain downstream of transmembrane domain 4 includes the catalytic phosphorylation site (1). A nucleotide binding domain is between transmembrane domain 4 and 5. A sequence required for binding ATP is near transmembrane domain 5. Type V ATPases may transport nonmetallic substrates or couple with proteins that transport (or regulate) Ca2+ levels (2). Type V ATPases have been shown to be essential for protein secretion and trafficking and the unfolded protein response [(3;4); reviewed in (2)].
|
| Expression/Localization |
Northern blot analysis determined that the 4.1 kb Atp13a1 transcript is expressed in all of the tissues tested, with the most abundant expression observed in the brain, colon, kidney, liver, small intestine, stomach, and skeletal muscle (1). Quantitative real-time PCR of mouse embryos at embryonic (E) days 7, 11, 15, and 17 showed that Atp13a1 expression increases during development (2). The highest expression was seen at E15. After E16, expression decreases and by E17 the levels are lower than the other time points examined (2). Examination of Atp13a1 in the mouse brain determined that the highest expression was in the cerebellum; lowest expression was seen in the hippocampus. The expression in the frontal cortex was significantly higher than in the total cerebral cortex (2).
|
| References |
1. Schultheis, P. J., Hagen, T. T., O'Toole, K. K., Tachibana, A., Burke, C. R., McGill, D. L., Okunade, G. W., and Shull, G. E. (2004) Characterization of the P5 Subfamily of P-Type Transport ATPases in Mice. Biochem Biophys Res Commun. 323, 731-738. |
| Posted On |
2012-10-05 |
| Science Writer |
Anne Murray |
Incidental Mutation