Incidental Mutation 'R0021:Abcc5'
ID |
8348 |
Institutional Source |
Beutler Lab
|
Gene Symbol |
Abcc5
|
Ensembl Gene |
ENSMUSG00000022822 |
Gene Name |
ATP-binding cassette, sub-family C member 5 |
Synonyms |
2900011L11Rik, Abcc5b, Abcc5a, Mrp5 |
MMRRC Submission |
038316-MU
|
Accession Numbers |
|
Essential gene? |
Non essential
(E-score: 0.000)
|
Stock # |
R0021 (G1)
|
Quality Score |
|
Status
|
Validated
|
Chromosome |
16 |
Chromosomal Location |
20150053-20245144 bp(-) (GRCm39) |
Type of Mutation |
nonsense |
DNA Base Change (assembly) |
T to A
at 20197411 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Lysine to Stop codon
at position 647
(K647*)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000111209
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000079158]
[ENSMUST00000115547]
[ENSMUST00000232044]
|
AlphaFold |
Q9R1X5 |
Predicted Effect |
probably null
Transcript: ENSMUST00000079158
AA Change: K647*
|
SMART Domains |
Protein: ENSMUSP00000078158 Gene: ENSMUSG00000022822 AA Change: K647*
Domain | Start | End | E-Value | Type |
Pfam:ABC_membrane
|
179 |
447 |
1.6e-18 |
PFAM |
low complexity region
|
552 |
563 |
N/A |
INTRINSIC |
AAA
|
587 |
760 |
1.16e-12 |
SMART |
low complexity region
|
815 |
826 |
N/A |
INTRINSIC |
Pfam:ABC_membrane
|
858 |
1142 |
9.3e-36 |
PFAM |
AAA
|
1218 |
1403 |
1.26e-13 |
SMART |
|
Predicted Effect |
probably null
Transcript: ENSMUST00000115547
AA Change: K647*
|
SMART Domains |
Protein: ENSMUSP00000111209 Gene: ENSMUSG00000022822 AA Change: K647*
Domain | Start | End | E-Value | Type |
Pfam:ABC_membrane
|
179 |
447 |
2e-17 |
PFAM |
low complexity region
|
552 |
563 |
N/A |
INTRINSIC |
AAA
|
587 |
760 |
1.16e-12 |
SMART |
low complexity region
|
815 |
826 |
N/A |
INTRINSIC |
Pfam:ABC_membrane
|
858 |
1146 |
6.5e-30 |
PFAM |
AAA
|
1218 |
1403 |
1.26e-13 |
SMART |
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000127582
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000134413
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000150340
|
Predicted Effect |
probably benign
Transcript: ENSMUST00000232044
|
Meta Mutation Damage Score |
0.9755 |
Coding Region Coverage |
- 1x: 84.2%
- 3x: 78.9%
- 10x: 65.7%
- 20x: 50.3%
|
Validation Efficiency |
96% (92/96) |
MGI Phenotype |
FUNCTION: The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. The human protein functions in the cellular export of its substrate, cyclic nucleotides. This export contributes to the degradation of phosphodiesterases and possibly an elimination pathway for cyclic nucleotides. Studies show that the human protein provides resistance to thiopurine anticancer drugs, 6-mercatopurine and thioguanine, and the anti-HIV drug 9-(2-phosphonylmethoxyethyl)adenine. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008] PHENOTYPE: Mice homozygous for a knock-out allele display normal cGMP transport into erythrocyte membrane vesicles. [provided by MGI curators]
|
Allele List at MGI |
All alleles(81) : Targeted(4) Gene trapped(77)
|
Other mutations in this stock |
Total: 42 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
2310016G11Rik |
A |
G |
7: 44,326,620 (GRCm39) |
|
noncoding transcript |
Het |
Aplp1 |
A |
G |
7: 30,135,241 (GRCm39) |
|
probably benign |
Het |
Baiap3 |
T |
C |
17: 25,462,643 (GRCm39) |
E1105G |
probably damaging |
Het |
Brinp3 |
T |
G |
1: 146,777,189 (GRCm39) |
S545R |
probably benign |
Het |
Btnl1 |
A |
G |
17: 34,598,468 (GRCm39) |
E28G |
probably benign |
Het |
Ccr6 |
G |
A |
17: 8,475,598 (GRCm39) |
V268M |
possibly damaging |
Het |
Clstn1 |
G |
A |
4: 149,719,253 (GRCm39) |
V361M |
probably damaging |
Het |
Col1a2 |
G |
A |
6: 4,518,822 (GRCm39) |
|
probably benign |
Het |
D630045J12Rik |
G |
A |
6: 38,160,902 (GRCm39) |
Q1081* |
probably null |
Het |
Dhx15 |
T |
C |
5: 52,314,830 (GRCm39) |
T626A |
probably damaging |
Het |
Dhx36 |
T |
C |
3: 62,385,016 (GRCm39) |
I699V |
possibly damaging |
Het |
Dnah9 |
A |
G |
11: 65,860,805 (GRCm39) |
I2855T |
probably benign |
Het |
Duxf4 |
C |
A |
10: 58,071,385 (GRCm39) |
E276D |
probably benign |
Het |
Fsip2 |
T |
A |
2: 82,830,201 (GRCm39) |
|
probably benign |
Het |
Galnt11 |
A |
T |
5: 25,453,855 (GRCm39) |
D27V |
probably damaging |
Het |
Gm5134 |
T |
A |
10: 75,829,718 (GRCm39) |
C335S |
probably damaging |
Het |
Hdhd2 |
A |
T |
18: 77,058,311 (GRCm39) |
K227N |
probably damaging |
Het |
Itgb4 |
A |
T |
11: 115,870,453 (GRCm39) |
D94V |
possibly damaging |
Het |
Krtcap3 |
A |
G |
5: 31,410,303 (GRCm39) |
H227R |
probably benign |
Het |
Macf1 |
T |
C |
4: 123,369,370 (GRCm39) |
H232R |
probably damaging |
Het |
Map2k4 |
A |
G |
11: 65,603,110 (GRCm39) |
I174T |
probably damaging |
Het |
Mcc |
C |
G |
18: 44,652,583 (GRCm39) |
|
probably benign |
Het |
Mcm9 |
G |
A |
10: 53,413,997 (GRCm39) |
T1099I |
possibly damaging |
Het |
Nkapd1 |
A |
C |
9: 50,521,725 (GRCm39) |
D65E |
probably damaging |
Het |
Nqo2 |
T |
C |
13: 34,165,490 (GRCm39) |
I129T |
probably benign |
Het |
Pdgfrb |
T |
A |
18: 61,197,998 (GRCm39) |
|
probably benign |
Het |
Phf7 |
C |
T |
14: 30,960,443 (GRCm39) |
|
probably benign |
Het |
Plac8 |
T |
A |
5: 100,704,434 (GRCm39) |
T88S |
probably benign |
Het |
Prss52 |
T |
G |
14: 64,341,857 (GRCm39) |
V16G |
probably benign |
Het |
Psmb9 |
G |
A |
17: 34,403,277 (GRCm39) |
A80V |
probably benign |
Het |
Ptprk |
T |
A |
10: 28,468,891 (GRCm39) |
V1425E |
probably damaging |
Het |
Scart2 |
G |
A |
7: 139,876,310 (GRCm39) |
R594H |
probably benign |
Het |
Scn2a |
T |
C |
2: 65,500,859 (GRCm39) |
V7A |
possibly damaging |
Het |
Serpini1 |
T |
C |
3: 75,526,620 (GRCm39) |
Y291H |
probably damaging |
Het |
Setd6 |
A |
G |
8: 96,443,293 (GRCm39) |
K19E |
probably damaging |
Het |
Siah2 |
T |
C |
3: 58,583,713 (GRCm39) |
H191R |
probably benign |
Het |
Slc27a2 |
T |
C |
2: 126,409,806 (GRCm39) |
|
probably benign |
Het |
Tbc1d10a |
T |
C |
11: 4,163,680 (GRCm39) |
C277R |
probably damaging |
Het |
Trim55 |
A |
C |
3: 19,698,866 (GRCm39) |
M32L |
probably benign |
Het |
Unc5b |
T |
C |
10: 60,614,698 (GRCm39) |
T200A |
probably benign |
Het |
Wrap53 |
A |
T |
11: 69,454,712 (GRCm39) |
M219K |
probably damaging |
Het |
Zfp790 |
G |
A |
7: 29,525,113 (GRCm39) |
|
probably benign |
Het |
|
Other mutations in Abcc5 |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
IGL00917:Abcc5
|
APN |
16 |
20,241,107 (GRCm39) |
missense |
probably benign |
0.01 |
IGL00928:Abcc5
|
APN |
16 |
20,217,720 (GRCm39) |
unclassified |
probably benign |
|
IGL01350:Abcc5
|
APN |
16 |
20,187,208 (GRCm39) |
missense |
probably benign |
0.00 |
IGL01774:Abcc5
|
APN |
16 |
20,197,207 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL01934:Abcc5
|
APN |
16 |
20,241,191 (GRCm39) |
utr 5 prime |
probably benign |
|
IGL02413:Abcc5
|
APN |
16 |
20,241,187 (GRCm39) |
utr 5 prime |
probably benign |
|
IGL02426:Abcc5
|
APN |
16 |
20,157,675 (GRCm39) |
missense |
probably damaging |
0.98 |
IGL02797:Abcc5
|
APN |
16 |
20,187,214 (GRCm39) |
missense |
probably benign |
0.06 |
IGL02938:Abcc5
|
APN |
16 |
20,180,979 (GRCm39) |
missense |
possibly damaging |
0.64 |
IGL03367:Abcc5
|
APN |
16 |
20,211,561 (GRCm39) |
utr 3 prime |
probably benign |
|
IGL03411:Abcc5
|
APN |
16 |
20,218,310 (GRCm39) |
missense |
probably damaging |
0.97 |
PIT4508001:Abcc5
|
UTSW |
16 |
20,176,128 (GRCm39) |
missense |
probably damaging |
0.97 |
R0021:Abcc5
|
UTSW |
16 |
20,197,411 (GRCm39) |
nonsense |
probably null |
|
R0220:Abcc5
|
UTSW |
16 |
20,187,852 (GRCm39) |
missense |
probably benign |
|
R0281:Abcc5
|
UTSW |
16 |
20,241,150 (GRCm39) |
missense |
probably damaging |
1.00 |
R0401:Abcc5
|
UTSW |
16 |
20,195,308 (GRCm39) |
missense |
probably benign |
0.09 |
R0448:Abcc5
|
UTSW |
16 |
20,218,687 (GRCm39) |
missense |
probably damaging |
1.00 |
R0477:Abcc5
|
UTSW |
16 |
20,217,635 (GRCm39) |
missense |
probably damaging |
0.96 |
R0477:Abcc5
|
UTSW |
16 |
20,187,319 (GRCm39) |
missense |
possibly damaging |
0.51 |
R0601:Abcc5
|
UTSW |
16 |
20,223,309 (GRCm39) |
splice site |
probably benign |
|
R0648:Abcc5
|
UTSW |
16 |
20,184,632 (GRCm39) |
missense |
possibly damaging |
0.90 |
R0709:Abcc5
|
UTSW |
16 |
20,195,342 (GRCm39) |
missense |
possibly damaging |
0.91 |
R1144:Abcc5
|
UTSW |
16 |
20,241,188 (GRCm39) |
utr 5 prime |
probably benign |
|
R1552:Abcc5
|
UTSW |
16 |
20,217,617 (GRCm39) |
missense |
probably damaging |
0.99 |
R1625:Abcc5
|
UTSW |
16 |
20,184,567 (GRCm39) |
missense |
probably damaging |
0.99 |
R1748:Abcc5
|
UTSW |
16 |
20,152,338 (GRCm39) |
missense |
probably benign |
0.01 |
R1789:Abcc5
|
UTSW |
16 |
20,184,701 (GRCm39) |
missense |
probably damaging |
1.00 |
R1801:Abcc5
|
UTSW |
16 |
20,157,637 (GRCm39) |
missense |
probably benign |
0.43 |
R1909:Abcc5
|
UTSW |
16 |
20,195,259 (GRCm39) |
critical splice donor site |
probably null |
|
R2046:Abcc5
|
UTSW |
16 |
20,218,567 (GRCm39) |
missense |
possibly damaging |
0.90 |
R2203:Abcc5
|
UTSW |
16 |
20,224,632 (GRCm39) |
missense |
possibly damaging |
0.91 |
R3031:Abcc5
|
UTSW |
16 |
20,193,863 (GRCm39) |
missense |
probably damaging |
0.99 |
R3417:Abcc5
|
UTSW |
16 |
20,224,302 (GRCm39) |
splice site |
probably benign |
|
R3708:Abcc5
|
UTSW |
16 |
20,190,930 (GRCm39) |
missense |
probably benign |
0.30 |
R3731:Abcc5
|
UTSW |
16 |
20,217,684 (GRCm39) |
nonsense |
probably null |
|
R3829:Abcc5
|
UTSW |
16 |
20,184,615 (GRCm39) |
missense |
probably benign |
0.00 |
R3847:Abcc5
|
UTSW |
16 |
20,190,906 (GRCm39) |
missense |
probably benign |
0.12 |
R3850:Abcc5
|
UTSW |
16 |
20,190,906 (GRCm39) |
missense |
probably benign |
0.12 |
R3955:Abcc5
|
UTSW |
16 |
20,224,293 (GRCm39) |
missense |
probably damaging |
0.97 |
R4072:Abcc5
|
UTSW |
16 |
20,152,445 (GRCm39) |
missense |
probably damaging |
1.00 |
R4432:Abcc5
|
UTSW |
16 |
20,186,937 (GRCm39) |
splice site |
probably null |
|
R4433:Abcc5
|
UTSW |
16 |
20,186,937 (GRCm39) |
splice site |
probably null |
|
R4505:Abcc5
|
UTSW |
16 |
20,152,445 (GRCm39) |
missense |
probably damaging |
1.00 |
R4506:Abcc5
|
UTSW |
16 |
20,152,445 (GRCm39) |
missense |
probably damaging |
1.00 |
R4715:Abcc5
|
UTSW |
16 |
20,217,626 (GRCm39) |
missense |
probably damaging |
1.00 |
R4739:Abcc5
|
UTSW |
16 |
20,218,376 (GRCm39) |
missense |
probably damaging |
1.00 |
R4866:Abcc5
|
UTSW |
16 |
20,241,182 (GRCm39) |
start codon destroyed |
probably null |
1.00 |
R4905:Abcc5
|
UTSW |
16 |
20,218,678 (GRCm39) |
missense |
probably damaging |
1.00 |
R4907:Abcc5
|
UTSW |
16 |
20,195,296 (GRCm39) |
missense |
possibly damaging |
0.86 |
R5088:Abcc5
|
UTSW |
16 |
20,195,412 (GRCm39) |
missense |
probably damaging |
1.00 |
R5232:Abcc5
|
UTSW |
16 |
20,157,672 (GRCm39) |
missense |
probably damaging |
0.96 |
R5559:Abcc5
|
UTSW |
16 |
20,157,636 (GRCm39) |
missense |
probably damaging |
1.00 |
R5647:Abcc5
|
UTSW |
16 |
20,218,597 (GRCm39) |
missense |
probably damaging |
1.00 |
R5861:Abcc5
|
UTSW |
16 |
20,218,644 (GRCm39) |
missense |
probably damaging |
1.00 |
R6190:Abcc5
|
UTSW |
16 |
20,211,529 (GRCm39) |
missense |
probably benign |
0.02 |
R6213:Abcc5
|
UTSW |
16 |
20,218,762 (GRCm39) |
missense |
probably damaging |
1.00 |
R6511:Abcc5
|
UTSW |
16 |
20,195,344 (GRCm39) |
missense |
probably damaging |
0.99 |
R6732:Abcc5
|
UTSW |
16 |
20,223,434 (GRCm39) |
missense |
probably benign |
0.01 |
R6815:Abcc5
|
UTSW |
16 |
20,152,380 (GRCm39) |
missense |
probably damaging |
1.00 |
R6913:Abcc5
|
UTSW |
16 |
20,197,494 (GRCm39) |
missense |
possibly damaging |
0.73 |
R6945:Abcc5
|
UTSW |
16 |
20,218,759 (GRCm39) |
missense |
probably benign |
|
R7167:Abcc5
|
UTSW |
16 |
20,224,251 (GRCm39) |
missense |
possibly damaging |
0.70 |
R7276:Abcc5
|
UTSW |
16 |
20,195,258 (GRCm39) |
splice site |
probably null |
|
R7318:Abcc5
|
UTSW |
16 |
20,211,293 (GRCm39) |
missense |
probably benign |
0.01 |
R7380:Abcc5
|
UTSW |
16 |
20,215,784 (GRCm39) |
missense |
possibly damaging |
0.84 |
R7419:Abcc5
|
UTSW |
16 |
20,241,173 (GRCm39) |
missense |
possibly damaging |
0.57 |
R7451:Abcc5
|
UTSW |
16 |
20,193,820 (GRCm39) |
missense |
probably damaging |
1.00 |
R7475:Abcc5
|
UTSW |
16 |
20,218,739 (GRCm39) |
missense |
probably benign |
0.04 |
R7567:Abcc5
|
UTSW |
16 |
20,224,260 (GRCm39) |
missense |
probably damaging |
1.00 |
R7601:Abcc5
|
UTSW |
16 |
20,193,882 (GRCm39) |
nonsense |
probably null |
|
R7623:Abcc5
|
UTSW |
16 |
20,163,446 (GRCm39) |
missense |
possibly damaging |
0.95 |
R7682:Abcc5
|
UTSW |
16 |
20,186,803 (GRCm39) |
missense |
probably damaging |
1.00 |
R8128:Abcc5
|
UTSW |
16 |
20,184,473 (GRCm39) |
missense |
probably damaging |
0.98 |
R8327:Abcc5
|
UTSW |
16 |
20,241,068 (GRCm39) |
missense |
probably benign |
0.00 |
R8518:Abcc5
|
UTSW |
16 |
20,223,398 (GRCm39) |
missense |
possibly damaging |
0.80 |
R8678:Abcc5
|
UTSW |
16 |
20,184,685 (GRCm39) |
missense |
probably benign |
0.31 |
R8679:Abcc5
|
UTSW |
16 |
20,152,479 (GRCm39) |
missense |
possibly damaging |
0.89 |
R9206:Abcc5
|
UTSW |
16 |
20,208,139 (GRCm39) |
missense |
probably benign |
0.00 |
R9254:Abcc5
|
UTSW |
16 |
20,152,437 (GRCm39) |
missense |
probably damaging |
1.00 |
R9379:Abcc5
|
UTSW |
16 |
20,152,437 (GRCm39) |
missense |
probably damaging |
1.00 |
R9501:Abcc5
|
UTSW |
16 |
20,214,853 (GRCm39) |
missense |
probably damaging |
1.00 |
R9647:Abcc5
|
UTSW |
16 |
20,195,310 (GRCm39) |
missense |
probably benign |
0.01 |
X0022:Abcc5
|
UTSW |
16 |
20,211,337 (GRCm39) |
missense |
probably damaging |
1.00 |
X0053:Abcc5
|
UTSW |
16 |
20,182,792 (GRCm39) |
missense |
probably damaging |
0.98 |
|
Protein Function and Prediction |
Abcc5 encodes multidrug resistance-associated protein 5 (MRP5), a basolateral membrane (1) organic anion pump that transports acidic organic dyes (1) (but not calcein), DNP–GS, GSH (2), nucleoside monophosphate analogs (2), the cyclic nucleotides 3′, 5′-cAMP and –cGMP (3).
|
Expression/Localization |
ABCC5 is ubiquitously expressed, with highest levels in skeletal muscle followed by brain, kidney, testis, and heart (4). MRP5 localizes to the smooth muscle cells of the human genito-urinary tract and in epithelial cells of ureter and urethra and in blood vessels (5). In placenta, MRP5 was found in the basal membrane of syncytiotrophoblasts and in and around fetal vessels (6). In heart, MRP5 localizes to cardiomyocytes, endothelial cells, and smooth muscle cell (7). In the brain, MRP5 was found in astrocytes and in pyramidal neurons. MRP5 was also found at the luminal (apical) side of brain capillary endothelial cells, even though it routes basolaterally in MDCK cells (2).
|
Background |
Abcc5tm1Bor/tm1Bor; MGI:3794119
involves: 129P2/OlaHsd * FVB
Mice homozygous for a knock-out allele display normal cGMP transport into erythrocyte membrane vesicles (8).
|
References |
1. McAleer, M. A., Breen, M. A., White, N. L., and Matthews, N. (1999) PABC11 (also Known as MOAT-C and MRP5), a Member of the ABC Family of Proteins, has Anion Transporter Activity but does Not Confer Multidrug Resistance when Overexpressed in Human Embryonic Kidney 293 Cells. J Biol Chem. 274, 23541-23548.
2. Wijnholds, J., Mol, C. A., van Deemter, L., de Haas, M., Scheffer, G. L., Baas, F., Beijnen, J. H., Scheper, R. J., Hatse, S., De Clercq, E., Balzarini, J., and Borst, P. (2000) Multidrug-Resistance Protein 5 is a Multispecific Organic Anion Transporter Able to Transport Nucleotide Analogs. Proc Natl Acad Sci U S A. 97, 7476-7481.
4. Belinsky, M. G., Bain, L. J., Balsara, B. B., Testa, J. R., and Kruh, G. D. (1998) Characterization of MOAT-C and MOAT-D, New Members of the MRP/cMOAT Subfamily of Transporter Proteins. J Natl Cancer Inst. 90, 1735-1741.
5. Nies, A. T., Spring, H., Thon, W. F., Keppler, D., and Jedlitschky, G. (2002) Immunolocalization of Multidrug Resistance Protein 5 in the Human Genitourinary System. J Urol. 167, 2271-2275.
6. Meyer Zu Schwabedissen, H. E., Grube, M., Heydrich, B., Linnemann, K., Fusch, C., Kroemer, H. K., and Jedlitschky, G. (2005) Expression, Localization, and Function of MRP5 (ABCC5), a Transporter for Cyclic Nucleotides, in Human Placenta and Cultured Human Trophoblasts: Effects of Gestational Age and Cellular Differentiation. Am J Pathol. 166, 39-48.
7. Dazert, P., Meissner, K., Vogelgesang, S., Heydrich, B., Eckel, L., Bohm, M., Warzok, R., Kerb, R., Brinkmann, U., Schaeffeler, E., Schwab, M., Cascorbi, I., Jedlitschky, G., and Kroemer, H. K. (2003) Expression and Localization of the Multidrug Resistance Protein 5 (MRP5/ABCC5), a Cellular Export Pump for Cyclic Nucleotides, in Human Heart. Am J Pathol. 163, 1567-1577.
8. de Wolf, C. J., Yamaguchi, H., van der Heijden, I., Wielinga, P. R., Hundscheid, S. L., Ono, N., Scheffer, G. L., de Haas, M., Schuetz, J. D., Wijnholds, J., and Borst, P. (2007) CGMP Transport by Vesicles from Human and Mouse Erythrocytes. FEBS J. 274, 439-450.
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Posted On |
2012-11-27 |
Science Writer |
Anne Murray |