Incidental Mutation 'P0018:Pclo'
ID |
7775 |
Institutional Source |
Beutler Lab
|
Gene Symbol |
Pclo
|
Ensembl Gene |
ENSMUSG00000061601 |
Gene Name |
piccolo (presynaptic cytomatrix protein) |
Synonyms |
Acz, Pico |
MMRRC Submission |
038271-MU
|
Accession Numbers |
Ncbi RefSeq: NM_011995.4; NM_001110796.1; MGI:1349390
|
Is this an essential gene? |
Non essential
(E-score: 0.000)
|
Stock # |
P0018 (G1)
|
Quality Score |
|
Status
|
Validated
|
Chromosome |
5 |
Chromosomal Location |
14514918-14863459 bp(+) (GRCm38) |
Type of Mutation |
unclassified |
DNA Base Change (assembly) |
A to T
at 14677721 bp (GRCm38)
|
Zygosity |
Heterozygous |
Amino Acid Change |
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000030691]
[ENSMUST00000182407]
|
AlphaFold |
no structure available at present |
Predicted Effect |
unknown
Transcript: ENSMUST00000030691
AA Change: I2198F
|
SMART Domains |
Protein: ENSMUSP00000030691 Gene: ENSMUSG00000061601 AA Change: I2198F
Domain | Start | End | E-Value | Type |
low complexity region
|
4 |
30 |
N/A |
INTRINSIC |
low complexity region
|
90 |
106 |
N/A |
INTRINSIC |
internal_repeat_2
|
192 |
304 |
1.23e-13 |
PROSPERO |
internal_repeat_2
|
305 |
389 |
1.23e-13 |
PROSPERO |
low complexity region
|
393 |
489 |
N/A |
INTRINSIC |
low complexity region
|
513 |
525 |
N/A |
INTRINSIC |
Pfam:zf-piccolo
|
530 |
589 |
5.2e-30 |
PFAM |
low complexity region
|
636 |
647 |
N/A |
INTRINSIC |
low complexity region
|
657 |
686 |
N/A |
INTRINSIC |
low complexity region
|
709 |
720 |
N/A |
INTRINSIC |
low complexity region
|
722 |
738 |
N/A |
INTRINSIC |
low complexity region
|
798 |
824 |
N/A |
INTRINSIC |
low complexity region
|
825 |
839 |
N/A |
INTRINSIC |
low complexity region
|
898 |
910 |
N/A |
INTRINSIC |
low complexity region
|
961 |
978 |
N/A |
INTRINSIC |
Pfam:zf-piccolo
|
995 |
1053 |
6.7e-33 |
PFAM |
low complexity region
|
1070 |
1090 |
N/A |
INTRINSIC |
low complexity region
|
1092 |
1107 |
N/A |
INTRINSIC |
low complexity region
|
1150 |
1179 |
N/A |
INTRINSIC |
internal_repeat_4
|
1196 |
1249 |
1.65e-5 |
PROSPERO |
low complexity region
|
1275 |
1289 |
N/A |
INTRINSIC |
low complexity region
|
1320 |
1331 |
N/A |
INTRINSIC |
low complexity region
|
1332 |
1343 |
N/A |
INTRINSIC |
low complexity region
|
1397 |
1411 |
N/A |
INTRINSIC |
low complexity region
|
1444 |
1457 |
N/A |
INTRINSIC |
low complexity region
|
1497 |
1511 |
N/A |
INTRINSIC |
low complexity region
|
1668 |
1681 |
N/A |
INTRINSIC |
coiled coil region
|
1704 |
1748 |
N/A |
INTRINSIC |
low complexity region
|
1789 |
1800 |
N/A |
INTRINSIC |
low complexity region
|
2046 |
2061 |
N/A |
INTRINSIC |
low complexity region
|
2109 |
2137 |
N/A |
INTRINSIC |
low complexity region
|
2335 |
2366 |
N/A |
INTRINSIC |
low complexity region
|
2374 |
2389 |
N/A |
INTRINSIC |
low complexity region
|
2413 |
2423 |
N/A |
INTRINSIC |
low complexity region
|
2487 |
2498 |
N/A |
INTRINSIC |
low complexity region
|
2605 |
2633 |
N/A |
INTRINSIC |
low complexity region
|
2727 |
2738 |
N/A |
INTRINSIC |
low complexity region
|
2792 |
2808 |
N/A |
INTRINSIC |
low complexity region
|
3117 |
3128 |
N/A |
INTRINSIC |
coiled coil region
|
3136 |
3189 |
N/A |
INTRINSIC |
coiled coil region
|
3210 |
3243 |
N/A |
INTRINSIC |
internal_repeat_4
|
3473 |
3521 |
1.65e-5 |
PROSPERO |
coiled coil region
|
3688 |
3731 |
N/A |
INTRINSIC |
low complexity region
|
3735 |
3750 |
N/A |
INTRINSIC |
low complexity region
|
3863 |
3883 |
N/A |
INTRINSIC |
low complexity region
|
3947 |
3961 |
N/A |
INTRINSIC |
low complexity region
|
4004 |
4015 |
N/A |
INTRINSIC |
low complexity region
|
4149 |
4160 |
N/A |
INTRINSIC |
low complexity region
|
4185 |
4196 |
N/A |
INTRINSIC |
low complexity region
|
4210 |
4225 |
N/A |
INTRINSIC |
low complexity region
|
4229 |
4245 |
N/A |
INTRINSIC |
PDZ
|
4439 |
4518 |
3.74e-14 |
SMART |
low complexity region
|
4575 |
4602 |
N/A |
INTRINSIC |
C2
|
4636 |
4750 |
1.44e-21 |
SMART |
low complexity region
|
4764 |
4778 |
N/A |
INTRINSIC |
low complexity region
|
4801 |
4817 |
N/A |
INTRINSIC |
low complexity region
|
4840 |
4850 |
N/A |
INTRINSIC |
low complexity region
|
4870 |
4892 |
N/A |
INTRINSIC |
C2
|
4951 |
5057 |
8.56e-15 |
SMART |
|
Predicted Effect |
unknown
Transcript: ENSMUST00000182407
AA Change: I2198F
|
SMART Domains |
Protein: ENSMUSP00000138419 Gene: ENSMUSG00000061601 AA Change: I2198F
Domain | Start | End | E-Value | Type |
low complexity region
|
4 |
30 |
N/A |
INTRINSIC |
low complexity region
|
90 |
106 |
N/A |
INTRINSIC |
internal_repeat_2
|
192 |
304 |
1.06e-13 |
PROSPERO |
internal_repeat_2
|
305 |
389 |
1.06e-13 |
PROSPERO |
low complexity region
|
393 |
489 |
N/A |
INTRINSIC |
low complexity region
|
513 |
525 |
N/A |
INTRINSIC |
Pfam:zf-piccolo
|
528 |
589 |
3e-36 |
PFAM |
low complexity region
|
636 |
647 |
N/A |
INTRINSIC |
low complexity region
|
657 |
686 |
N/A |
INTRINSIC |
low complexity region
|
709 |
720 |
N/A |
INTRINSIC |
low complexity region
|
722 |
738 |
N/A |
INTRINSIC |
low complexity region
|
798 |
824 |
N/A |
INTRINSIC |
low complexity region
|
825 |
839 |
N/A |
INTRINSIC |
low complexity region
|
898 |
910 |
N/A |
INTRINSIC |
low complexity region
|
961 |
978 |
N/A |
INTRINSIC |
Pfam:zf-piccolo
|
993 |
1053 |
4.3e-37 |
PFAM |
low complexity region
|
1070 |
1090 |
N/A |
INTRINSIC |
low complexity region
|
1092 |
1107 |
N/A |
INTRINSIC |
low complexity region
|
1150 |
1179 |
N/A |
INTRINSIC |
internal_repeat_3
|
1196 |
1249 |
1.46e-5 |
PROSPERO |
low complexity region
|
1275 |
1289 |
N/A |
INTRINSIC |
low complexity region
|
1320 |
1331 |
N/A |
INTRINSIC |
low complexity region
|
1332 |
1343 |
N/A |
INTRINSIC |
low complexity region
|
1397 |
1411 |
N/A |
INTRINSIC |
low complexity region
|
1444 |
1457 |
N/A |
INTRINSIC |
low complexity region
|
1497 |
1511 |
N/A |
INTRINSIC |
low complexity region
|
1668 |
1681 |
N/A |
INTRINSIC |
coiled coil region
|
1704 |
1748 |
N/A |
INTRINSIC |
low complexity region
|
1789 |
1800 |
N/A |
INTRINSIC |
low complexity region
|
2046 |
2061 |
N/A |
INTRINSIC |
low complexity region
|
2109 |
2137 |
N/A |
INTRINSIC |
low complexity region
|
2335 |
2366 |
N/A |
INTRINSIC |
low complexity region
|
2374 |
2389 |
N/A |
INTRINSIC |
low complexity region
|
2413 |
2423 |
N/A |
INTRINSIC |
low complexity region
|
2487 |
2498 |
N/A |
INTRINSIC |
low complexity region
|
2605 |
2633 |
N/A |
INTRINSIC |
low complexity region
|
2727 |
2738 |
N/A |
INTRINSIC |
low complexity region
|
2792 |
2808 |
N/A |
INTRINSIC |
low complexity region
|
3117 |
3128 |
N/A |
INTRINSIC |
coiled coil region
|
3136 |
3189 |
N/A |
INTRINSIC |
coiled coil region
|
3210 |
3243 |
N/A |
INTRINSIC |
internal_repeat_3
|
3473 |
3521 |
1.46e-5 |
PROSPERO |
coiled coil region
|
3688 |
3731 |
N/A |
INTRINSIC |
low complexity region
|
3735 |
3750 |
N/A |
INTRINSIC |
low complexity region
|
3863 |
3883 |
N/A |
INTRINSIC |
low complexity region
|
3947 |
3961 |
N/A |
INTRINSIC |
low complexity region
|
4004 |
4015 |
N/A |
INTRINSIC |
low complexity region
|
4149 |
4160 |
N/A |
INTRINSIC |
low complexity region
|
4185 |
4196 |
N/A |
INTRINSIC |
low complexity region
|
4210 |
4225 |
N/A |
INTRINSIC |
low complexity region
|
4229 |
4245 |
N/A |
INTRINSIC |
PDZ
|
4439 |
4518 |
3.74e-14 |
SMART |
low complexity region
|
4575 |
4602 |
N/A |
INTRINSIC |
C2
|
4636 |
4750 |
1.44e-21 |
SMART |
low complexity region
|
4764 |
4778 |
N/A |
INTRINSIC |
low complexity region
|
4801 |
4817 |
N/A |
INTRINSIC |
low complexity region
|
4840 |
4850 |
N/A |
INTRINSIC |
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000182426
|
Predicted Effect |
probably benign
Transcript: ENSMUST00000182915
|
Meta Mutation Damage Score |
0.0743  |
Coding Region Coverage |
- 1x: 83.8%
- 3x: 77.4%
- 10x: 57.9%
- 20x: 38.3%
|
Validation Efficiency |
72% (76/106) |
MGI Phenotype |
Strain: 3699630; 4442915; 4442914
Lethality: D60
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is part of the presynaptic cytoskeletal matrix, which is involved in establishing active synaptic zones and in synaptic vesicle trafficking. Variations in this gene have been associated with bipolar disorder and major depressive disorder. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011] PHENOTYPE: Mice homozygous for one deletion of Pclo are viable and fertile, and display no overt abnormal phenotype. Mice homozygous for another knock-out allele exhibit some premature lethality, decreased body size, and abnormal synaptic vesicle number. [provided by MGI curators]
|
Allele List at MGI |
All alleles(7) : Targeted(5) Gene trapped(2)
|
Other mutations in this stock |
Total: 14 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
BC067074 |
A |
G |
13: 113,367,506 |
D1723G |
possibly damaging |
Het |
Brip1 |
C |
T |
11: 86,108,868 |
V763I |
possibly damaging |
Het |
Cxxc1 |
C |
T |
18: 74,220,921 |
R593C |
probably damaging |
Het |
Erbb4 |
T |
A |
1: 68,071,676 |
M993L |
probably benign |
Het |
Ftsj3 |
C |
A |
11: 106,254,808 |
M66I |
possibly damaging |
Het |
Galnt2 |
T |
A |
8: 124,336,611 |
Y357N |
probably damaging |
Het |
Gm13178 |
A |
T |
4: 144,703,197 |
D407E |
probably benign |
Het |
Hgsnat |
C |
T |
8: 25,968,354 |
|
probably benign |
Het |
Katna1 |
A |
T |
10: 7,741,459 |
T72S |
probably damaging |
Het |
Nell1 |
A |
G |
7: 50,120,691 |
D166G |
probably damaging |
Het |
Nlgn1 |
G |
T |
3: 25,436,577 |
P329T |
probably damaging |
Het |
Robo2 |
T |
C |
16: 74,046,806 |
I174V |
possibly damaging |
Het |
Sufu |
A |
G |
19: 46,475,494 |
|
probably benign |
Het |
Tmub1 |
C |
A |
5: 24,446,757 |
A55S |
possibly damaging |
Het |
|
Other mutations in Pclo |
|
Protein Function and Prediction |
Piccolo is a member of the presynaptic cytoskeletal matrix between synaptic vesicles that maintains the neurotransmitter release site in register with the postsynaptic reception apparatus. Piccolo is proposed to be a scaffold in regulating active zone assembly (1), actin cytoskeleton, and synaptic vesicle trafficking (2-4). Other studies have determined that Piccolo is a negative presynaptic modulator for behavioral hypersensitivity (5). It also functions to blunt excessive dopaminergic synaptic plasticity (5).
|
Expression/Localization |
Northern blot analysis of mouse tissues revealed high levels of Pclo in cerebrum and cerebellum and moderate levels in pituitary gland, pancreatic islets, and a pheochromocytoma-derived mouse cell line. In situ hybridization of mouse brain revealed piccolo mRNA expressed in cerebral cortex, hippocampus, olfactory bulb, cerebellar cortex, and pituitary gland (6).
|
Background |
Pclotm1Sud/tm1Sud; MGI:3699630
involves: 129S6/SvEvTac
Mice homozygous for one deletion of Pclo are viable and fertile, and display no overt abnormal phenotype.
Pclotm3.2Sud/tm3.2Sud; MGI:4442914
involves: 129S1/Sv * 129X1/SvJ
Mice homozygous for another knock-out allele exhibit some premature lethality (20% die by P60), decreased body size, increased synaptic depression, and abnormal synaptic vesicle number (7).
Pclotm3.3Sud/tm3.3Sud; MGI:4442915
involves: 129S1/Sv * 129X1/SvJ
Mice homozygous for one deletion of Pclo are viable and fertile, and display no overt abnormal phenotype (7).
|
References |
1. Zhai, R. G., Vardinon-Friedman, H., Cases-Langhoff, C., Becker, B., Gundelfinger, E. D., Ziv, N. E., and Garner, C. C. (2001) Assembling the Presynaptic Active Zone: A Characterization of an Active One Precursor Vesicle. Neuron. 29, 131-143.
2. Fenster, S. D., Kessels, M. M., Qualmann, B., Chung, W. J., Nash, J., Gundelfinger, E. D., and Garner, C. C. (2003) Interactions between Piccolo and the actin/dynamin-Binding Protein Abp1 Link Vesicle Endocytosis to Presynaptic Active Zones. J Biol Chem. 278, 20268-20277.
3. Fenster, S. D., Chung, W. J., Zhai, R., Cases-Langhoff, C., Voss, B., Garner, A. M., Kaempf, U., Kindler, S., Gundelfinger, E. D., and Garner, C. C. (2000) Piccolo, a Presynaptic Zinc Finger Protein Structurally Related to Bassoon. Neuron. 25, 203-214.
4. Leal-Ortiz, S., Waites, C. L., Terry-Lorenzo, R., Zamorano, P., Gundelfinger, E. D., and Garner, C. C. (2008) Piccolo Modulation of Synapsin1a Dynamics Regulates Synaptic Vesicle Exocytosis. J Cell Biol. 181, 831-846.
5. Cen, X., Nitta, A., Ibi, D., Zhao, Y., Niwa, M., Taguchi, K., Hamada, M., Ito, Y., Ito, Y., Wang, L., and Nabeshima, T. (2008) Identification of Piccolo as a Regulator of Behavioral Plasticity and Dopamine Transporter Internalization. Mol Psychiatry. 13, 349, 451-63.
6. Fujimoto, K., Shibasaki, T., Yokoi, N., Kashima, Y., Matsumoto, M., Sasaki, T., Tajima, N., Iwanaga, T., and Seino, S. (2002) Piccolo, a Ca2+ Sensor in Pancreatic Beta-Cells. Involvement of cAMP-GEFII.Rim2. Piccolo Complex in cAMP-Dependent Exocytosis. J Biol Chem. 277, 50497-50502.
7. Mukherjee, K., Yang, X., Gerber, S. H., Kwon, H. B., Ho, A., Castillo, P. E., Liu, X., and Sudhof, T. C. (2010) Piccolo and Bassoon Maintain Synaptic Vesicle Clustering without Directly Participating in Vesicle Exocytosis. Proc Natl Acad Sci U S A. 107, 6504-6509.
|
Posted On |
2012-10-29 |
Science Writer |
Anne Murray |