Incidental Mutation 'R0054:Abcc9'
ID |
17047 |
Institutional Source |
Beutler Lab
|
Gene Symbol |
Abcc9
|
Ensembl Gene |
ENSMUSG00000030249 |
Gene Name |
ATP-binding cassette, sub-family C member 9 |
Synonyms |
SUR2A, Sur2, SUR2B |
MMRRC Submission |
038348-MU
|
Accession Numbers |
|
Essential gene? |
Probably non essential
(E-score: 0.108)
|
Stock # |
R0054 (G1)
|
Quality Score |
|
Status
|
Validated
|
Chromosome |
6 |
Chromosomal Location |
142533588-142648041 bp(-) (GRCm39) |
Type of Mutation |
critical splice donor site (2 bp from exon) |
DNA Base Change (assembly) |
A to G
at 142547500 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
|
Ref Sequence |
ENSEMBL: ENSMUSP00000144779
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000073173]
[ENSMUST00000087527]
[ENSMUST00000100827]
[ENSMUST00000111771]
[ENSMUST00000205202]
|
AlphaFold |
P70170 |
Predicted Effect |
probably null
Transcript: ENSMUST00000073173
|
SMART Domains |
Protein: ENSMUSP00000072914 Gene: ENSMUSG00000030249
Domain | Start | End | E-Value | Type |
transmembrane domain
|
28 |
50 |
N/A |
INTRINSIC |
transmembrane domain
|
71 |
93 |
N/A |
INTRINSIC |
transmembrane domain
|
103 |
125 |
N/A |
INTRINSIC |
transmembrane domain
|
137 |
159 |
N/A |
INTRINSIC |
transmembrane domain
|
169 |
188 |
N/A |
INTRINSIC |
low complexity region
|
265 |
276 |
N/A |
INTRINSIC |
Pfam:ABC_membrane
|
297 |
583 |
7.7e-33 |
PFAM |
AAA
|
659 |
867 |
3.11e-13 |
SMART |
coiled coil region
|
881 |
935 |
N/A |
INTRINSIC |
Pfam:ABC_membrane
|
956 |
1228 |
6.6e-35 |
PFAM |
AAA
|
1300 |
1502 |
9.94e-12 |
SMART |
|
Predicted Effect |
probably null
Transcript: ENSMUST00000087527
|
SMART Domains |
Protein: ENSMUSP00000084805 Gene: ENSMUSG00000030249
Domain | Start | End | E-Value | Type |
transmembrane domain
|
28 |
50 |
N/A |
INTRINSIC |
transmembrane domain
|
71 |
93 |
N/A |
INTRINSIC |
transmembrane domain
|
103 |
125 |
N/A |
INTRINSIC |
transmembrane domain
|
137 |
159 |
N/A |
INTRINSIC |
transmembrane domain
|
169 |
188 |
N/A |
INTRINSIC |
low complexity region
|
265 |
276 |
N/A |
INTRINSIC |
Pfam:ABC_membrane
|
297 |
583 |
8e-33 |
PFAM |
AAA
|
694 |
902 |
3.11e-13 |
SMART |
coiled coil region
|
916 |
970 |
N/A |
INTRINSIC |
Pfam:ABC_membrane
|
991 |
1263 |
6.8e-35 |
PFAM |
AAA
|
1335 |
1537 |
9.94e-12 |
SMART |
|
Predicted Effect |
probably null
Transcript: ENSMUST00000100827
|
SMART Domains |
Protein: ENSMUSP00000098390 Gene: ENSMUSG00000030249
Domain | Start | End | E-Value | Type |
transmembrane domain
|
28 |
50 |
N/A |
INTRINSIC |
transmembrane domain
|
71 |
93 |
N/A |
INTRINSIC |
transmembrane domain
|
103 |
125 |
N/A |
INTRINSIC |
transmembrane domain
|
137 |
159 |
N/A |
INTRINSIC |
transmembrane domain
|
169 |
188 |
N/A |
INTRINSIC |
low complexity region
|
265 |
276 |
N/A |
INTRINSIC |
Pfam:ABC_membrane
|
297 |
583 |
7.1e-35 |
PFAM |
AAA
|
694 |
902 |
3.11e-13 |
SMART |
coiled coil region
|
916 |
970 |
N/A |
INTRINSIC |
Pfam:ABC_membrane
|
991 |
1263 |
5.2e-38 |
PFAM |
AAA
|
1335 |
1520 |
5.13e-14 |
SMART |
|
Predicted Effect |
probably null
Transcript: ENSMUST00000111771
|
SMART Domains |
Protein: ENSMUSP00000107401 Gene: ENSMUSG00000030249
Domain | Start | End | E-Value | Type |
transmembrane domain
|
28 |
50 |
N/A |
INTRINSIC |
transmembrane domain
|
71 |
93 |
N/A |
INTRINSIC |
transmembrane domain
|
103 |
125 |
N/A |
INTRINSIC |
transmembrane domain
|
137 |
159 |
N/A |
INTRINSIC |
transmembrane domain
|
169 |
188 |
N/A |
INTRINSIC |
low complexity region
|
265 |
276 |
N/A |
INTRINSIC |
Pfam:ABC_membrane
|
297 |
583 |
1.4e-32 |
PFAM |
AAA
|
694 |
889 |
3.77e-12 |
SMART |
coiled coil region
|
903 |
957 |
N/A |
INTRINSIC |
Pfam:ABC_membrane
|
978 |
1250 |
1.2e-34 |
PFAM |
AAA
|
1322 |
1524 |
9.94e-12 |
SMART |
|
Predicted Effect |
probably null
Transcript: ENSMUST00000205202
|
SMART Domains |
Protein: ENSMUSP00000144779 Gene: ENSMUSG00000030249
Domain | Start | End | E-Value | Type |
transmembrane domain
|
28 |
50 |
N/A |
INTRINSIC |
transmembrane domain
|
71 |
93 |
N/A |
INTRINSIC |
transmembrane domain
|
103 |
125 |
N/A |
INTRINSIC |
transmembrane domain
|
137 |
159 |
N/A |
INTRINSIC |
transmembrane domain
|
169 |
188 |
N/A |
INTRINSIC |
low complexity region
|
265 |
276 |
N/A |
INTRINSIC |
Pfam:ABC_membrane
|
297 |
583 |
6.9e-35 |
PFAM |
AAA
|
659 |
867 |
3.11e-13 |
SMART |
coiled coil region
|
881 |
935 |
N/A |
INTRINSIC |
Pfam:ABC_membrane
|
956 |
1228 |
5e-38 |
PFAM |
AAA
|
1300 |
1502 |
9.94e-12 |
SMART |
|
Meta Mutation Damage Score |
0.9491 |
Coding Region Coverage |
- 1x: 88.8%
- 3x: 85.6%
- 10x: 76.3%
- 20x: 59.9%
|
Validation Efficiency |
96% (91/95) |
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 is thought to form ATP-sensitive potassium channels in cardiac, skeletal, and vascular and non-vascular smooth muscle. Protein structure suggests a role as the drug-binding channel-modulating subunit of the extrapancreatic ATP-sensitive potassium channels. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2015] PHENOTYPE: Mice homozygous for a null allele display lower serum glucose, enhanced insulin action, growth retardation, hypertension and spontaneous death due to episodic coronary artery vasospasm. Homozygous exon 5 deletion leads to cardiac mitochondrial defects, cardiomyopathy, and early postnatal death. [provided by MGI curators]
|
Allele List at MGI |
All alleles(4) : Targeted(4)
|
Other mutations in this stock |
Total: 57 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
Apoa4 |
A |
G |
9: 46,153,822 (GRCm39) |
D141G |
probably benign |
Het |
Atg9a |
T |
C |
1: 75,161,143 (GRCm39) |
Y701C |
probably damaging |
Het |
Baz2b |
C |
T |
2: 59,762,510 (GRCm39) |
R922Q |
probably damaging |
Het |
Bmal2 |
T |
G |
6: 146,731,216 (GRCm39) |
V507G |
probably benign |
Het |
Brms1 |
T |
A |
19: 5,096,727 (GRCm39) |
C136* |
probably null |
Het |
Ccdc180 |
T |
A |
4: 45,890,900 (GRCm39) |
V24E |
probably benign |
Het |
Clec4f |
C |
T |
6: 83,629,911 (GRCm39) |
V216M |
probably benign |
Het |
Cpd |
C |
G |
11: 76,681,664 (GRCm39) |
G1160R |
probably damaging |
Het |
Creb5 |
A |
G |
6: 53,424,642 (GRCm39) |
M128V |
probably benign |
Het |
Ddb2 |
G |
T |
2: 91,065,165 (GRCm39) |
Q87K |
probably benign |
Het |
Defb41 |
A |
G |
1: 18,321,471 (GRCm39) |
Y48H |
probably damaging |
Het |
Dido1 |
T |
C |
2: 180,303,267 (GRCm39) |
N1546D |
probably benign |
Het |
Dmac1 |
A |
G |
4: 75,196,337 (GRCm39) |
V51A |
possibly damaging |
Het |
Dnajb11 |
C |
T |
16: 22,681,369 (GRCm39) |
A49V |
probably damaging |
Het |
Dnajc14 |
G |
A |
10: 128,643,448 (GRCm39) |
D457N |
probably damaging |
Het |
Eif3a |
C |
A |
19: 60,755,264 (GRCm39) |
D973Y |
unknown |
Het |
Farsb |
T |
A |
1: 78,439,011 (GRCm39) |
K395* |
probably null |
Het |
Fem1b |
A |
G |
9: 62,704,082 (GRCm39) |
S393P |
probably damaging |
Het |
Fsip2 |
A |
C |
2: 82,817,299 (GRCm39) |
N4344T |
possibly damaging |
Het |
Gphn |
A |
G |
12: 78,684,277 (GRCm39) |
S558G |
probably damaging |
Het |
Gpr142 |
C |
A |
11: 114,689,755 (GRCm39) |
H2Q |
probably benign |
Het |
Grhpr |
T |
C |
4: 44,988,915 (GRCm39) |
|
probably benign |
Het |
Grik3 |
C |
A |
4: 125,517,368 (GRCm39) |
N70K |
probably damaging |
Het |
Gsap |
T |
A |
5: 21,455,933 (GRCm39) |
|
probably benign |
Het |
Iars1 |
T |
A |
13: 49,846,611 (GRCm39) |
C237S |
probably damaging |
Het |
Ighv1-9 |
A |
T |
12: 114,547,602 (GRCm39) |
F7L |
probably benign |
Het |
Ints8 |
A |
G |
4: 11,204,595 (GRCm39) |
|
probably benign |
Het |
Kcnj16 |
G |
T |
11: 110,915,549 (GRCm39) |
W70C |
probably damaging |
Het |
Kpna6 |
T |
C |
4: 129,551,251 (GRCm39) |
M85V |
probably benign |
Het |
Kri1 |
G |
A |
9: 21,186,661 (GRCm39) |
S447L |
probably damaging |
Het |
Lrp1b |
A |
G |
2: 40,632,829 (GRCm39) |
V3528A |
probably benign |
Het |
Lrrc46 |
A |
T |
11: 96,929,605 (GRCm39) |
L77Q |
probably damaging |
Het |
Mrpl44 |
T |
C |
1: 79,757,212 (GRCm39) |
L219S |
probably damaging |
Het |
Ms4a14 |
T |
C |
19: 11,281,303 (GRCm39) |
I418M |
probably benign |
Het |
Myo7a |
T |
C |
7: 97,714,905 (GRCm39) |
D112G |
probably damaging |
Het |
Ncoa3 |
A |
G |
2: 165,897,098 (GRCm39) |
T630A |
possibly damaging |
Het |
Nsl1 |
T |
C |
1: 190,814,381 (GRCm39) |
L194P |
probably damaging |
Het |
Or5ac23 |
T |
C |
16: 59,149,428 (GRCm39) |
Y148C |
possibly damaging |
Het |
Or8u10 |
T |
C |
2: 85,915,705 (GRCm39) |
K139E |
probably benign |
Het |
Pde4d |
A |
G |
13: 109,876,955 (GRCm39) |
S159G |
probably benign |
Het |
Pi4ka |
T |
C |
16: 17,142,978 (GRCm39) |
R845G |
probably null |
Het |
Pld1 |
A |
G |
3: 28,150,033 (GRCm39) |
|
probably benign |
Het |
Psd |
T |
A |
19: 46,311,781 (GRCm39) |
I300F |
probably damaging |
Het |
Ptprz1 |
T |
A |
6: 22,986,195 (GRCm39) |
W332R |
probably damaging |
Het |
Rnf212 |
T |
A |
5: 108,893,530 (GRCm39) |
M70L |
possibly damaging |
Het |
Sema4f |
A |
G |
6: 82,896,674 (GRCm39) |
|
probably benign |
Het |
Sez6 |
C |
A |
11: 77,844,699 (GRCm39) |
T7K |
possibly damaging |
Het |
Skint2 |
T |
C |
4: 112,502,660 (GRCm39) |
I290T |
probably benign |
Het |
Slc5a3 |
T |
A |
16: 91,874,522 (GRCm39) |
I193N |
probably damaging |
Het |
Snip1 |
T |
A |
4: 124,966,633 (GRCm39) |
Y354* |
probably null |
Het |
Tmco5 |
A |
G |
2: 116,717,768 (GRCm39) |
Y200C |
probably damaging |
Het |
Tmem87b |
T |
A |
2: 128,673,361 (GRCm39) |
|
probably benign |
Het |
Trim60 |
T |
C |
8: 65,453,973 (GRCm39) |
E92G |
probably benign |
Het |
Ttn |
A |
T |
2: 76,626,804 (GRCm39) |
D13067E |
possibly damaging |
Het |
Ufl1 |
A |
T |
4: 25,269,087 (GRCm39) |
I168N |
probably damaging |
Het |
Zfp385c |
G |
A |
11: 100,520,782 (GRCm39) |
P293S |
probably benign |
Het |
Zfp473 |
T |
A |
7: 44,383,899 (GRCm39) |
S144C |
probably damaging |
Het |
|
Other mutations in Abcc9 |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
IGL00090:Abcc9
|
APN |
6 |
142,578,916 (GRCm39) |
splice site |
probably benign |
|
IGL00670:Abcc9
|
APN |
6 |
142,633,007 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL00675:Abcc9
|
APN |
6 |
142,610,347 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL00741:Abcc9
|
APN |
6 |
142,632,956 (GRCm39) |
missense |
probably benign |
|
IGL01371:Abcc9
|
APN |
6 |
142,602,340 (GRCm39) |
missense |
probably benign |
0.04 |
IGL01686:Abcc9
|
APN |
6 |
142,548,801 (GRCm39) |
missense |
possibly damaging |
0.71 |
IGL01724:Abcc9
|
APN |
6 |
142,610,259 (GRCm39) |
missense |
probably benign |
0.00 |
IGL01807:Abcc9
|
APN |
6 |
142,551,640 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL01941:Abcc9
|
APN |
6 |
142,551,630 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL01946:Abcc9
|
APN |
6 |
142,571,763 (GRCm39) |
missense |
probably benign |
0.16 |
IGL02210:Abcc9
|
APN |
6 |
142,633,097 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL02498:Abcc9
|
APN |
6 |
142,617,265 (GRCm39) |
critical splice donor site |
probably null |
|
IGL02535:Abcc9
|
APN |
6 |
142,574,152 (GRCm39) |
missense |
probably benign |
0.00 |
IGL02552:Abcc9
|
APN |
6 |
142,551,645 (GRCm39) |
missense |
possibly damaging |
0.94 |
IGL02812:Abcc9
|
APN |
6 |
142,643,516 (GRCm39) |
missense |
possibly damaging |
0.77 |
IGL02954:Abcc9
|
APN |
6 |
142,592,007 (GRCm39) |
missense |
probably damaging |
0.97 |
IGL03035:Abcc9
|
APN |
6 |
142,573,319 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL03040:Abcc9
|
APN |
6 |
142,598,323 (GRCm39) |
nonsense |
probably null |
|
IGL03100:Abcc9
|
APN |
6 |
142,640,270 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL03157:Abcc9
|
APN |
6 |
142,551,649 (GRCm39) |
splice site |
probably benign |
|
R0054:Abcc9
|
UTSW |
6 |
142,547,500 (GRCm39) |
critical splice donor site |
probably null |
|
R0084:Abcc9
|
UTSW |
6 |
142,604,277 (GRCm39) |
missense |
probably damaging |
0.97 |
R0211:Abcc9
|
UTSW |
6 |
142,634,710 (GRCm39) |
missense |
probably benign |
0.01 |
R0349:Abcc9
|
UTSW |
6 |
142,610,351 (GRCm39) |
missense |
probably benign |
0.00 |
R0387:Abcc9
|
UTSW |
6 |
142,585,230 (GRCm39) |
nonsense |
probably null |
|
R0393:Abcc9
|
UTSW |
6 |
142,591,604 (GRCm39) |
splice site |
probably benign |
|
R0528:Abcc9
|
UTSW |
6 |
142,638,606 (GRCm39) |
missense |
probably damaging |
1.00 |
R0588:Abcc9
|
UTSW |
6 |
142,548,787 (GRCm39) |
nonsense |
probably null |
|
R0646:Abcc9
|
UTSW |
6 |
142,627,830 (GRCm39) |
missense |
probably benign |
0.05 |
R0691:Abcc9
|
UTSW |
6 |
142,584,979 (GRCm39) |
missense |
possibly damaging |
0.94 |
R0881:Abcc9
|
UTSW |
6 |
142,592,029 (GRCm39) |
missense |
probably damaging |
1.00 |
R1264:Abcc9
|
UTSW |
6 |
142,592,103 (GRCm39) |
splice site |
probably benign |
|
R1340:Abcc9
|
UTSW |
6 |
142,628,581 (GRCm39) |
splice site |
probably benign |
|
R1413:Abcc9
|
UTSW |
6 |
142,573,245 (GRCm39) |
missense |
possibly damaging |
0.65 |
R1413:Abcc9
|
UTSW |
6 |
142,536,222 (GRCm39) |
missense |
probably damaging |
1.00 |
R1535:Abcc9
|
UTSW |
6 |
142,610,361 (GRCm39) |
missense |
probably damaging |
1.00 |
R1595:Abcc9
|
UTSW |
6 |
142,578,821 (GRCm39) |
missense |
probably benign |
0.02 |
R1670:Abcc9
|
UTSW |
6 |
142,540,448 (GRCm39) |
missense |
possibly damaging |
0.89 |
R1769:Abcc9
|
UTSW |
6 |
142,573,194 (GRCm39) |
splice site |
probably benign |
|
R1888:Abcc9
|
UTSW |
6 |
142,625,040 (GRCm39) |
missense |
probably benign |
|
R1888:Abcc9
|
UTSW |
6 |
142,625,040 (GRCm39) |
missense |
probably benign |
|
R1918:Abcc9
|
UTSW |
6 |
142,643,408 (GRCm39) |
missense |
probably damaging |
1.00 |
R1925:Abcc9
|
UTSW |
6 |
142,617,333 (GRCm39) |
missense |
probably damaging |
0.98 |
R2019:Abcc9
|
UTSW |
6 |
142,621,160 (GRCm39) |
missense |
probably damaging |
1.00 |
R2698:Abcc9
|
UTSW |
6 |
142,578,862 (GRCm39) |
missense |
possibly damaging |
0.93 |
R2860:Abcc9
|
UTSW |
6 |
142,571,736 (GRCm39) |
missense |
probably benign |
0.01 |
R2861:Abcc9
|
UTSW |
6 |
142,571,736 (GRCm39) |
missense |
probably benign |
0.01 |
R2980:Abcc9
|
UTSW |
6 |
142,633,034 (GRCm39) |
missense |
probably benign |
0.00 |
R3115:Abcc9
|
UTSW |
6 |
142,634,755 (GRCm39) |
missense |
probably benign |
0.08 |
R3617:Abcc9
|
UTSW |
6 |
142,625,015 (GRCm39) |
missense |
probably damaging |
0.97 |
R3880:Abcc9
|
UTSW |
6 |
142,584,959 (GRCm39) |
missense |
probably damaging |
1.00 |
R4063:Abcc9
|
UTSW |
6 |
142,551,645 (GRCm39) |
missense |
possibly damaging |
0.94 |
R4065:Abcc9
|
UTSW |
6 |
142,591,616 (GRCm39) |
missense |
probably damaging |
1.00 |
R4290:Abcc9
|
UTSW |
6 |
142,539,738 (GRCm39) |
missense |
probably benign |
0.08 |
R4538:Abcc9
|
UTSW |
6 |
142,560,138 (GRCm39) |
critical splice donor site |
probably null |
|
R4615:Abcc9
|
UTSW |
6 |
142,634,833 (GRCm39) |
missense |
possibly damaging |
0.93 |
R4659:Abcc9
|
UTSW |
6 |
142,618,321 (GRCm39) |
splice site |
probably null |
|
R4774:Abcc9
|
UTSW |
6 |
142,585,043 (GRCm39) |
missense |
probably damaging |
1.00 |
R4788:Abcc9
|
UTSW |
6 |
142,566,456 (GRCm39) |
nonsense |
probably null |
|
R4832:Abcc9
|
UTSW |
6 |
142,617,282 (GRCm39) |
missense |
probably damaging |
1.00 |
R4844:Abcc9
|
UTSW |
6 |
142,634,824 (GRCm39) |
missense |
probably benign |
0.09 |
R4903:Abcc9
|
UTSW |
6 |
142,546,691 (GRCm39) |
missense |
probably damaging |
1.00 |
R4921:Abcc9
|
UTSW |
6 |
142,536,162 (GRCm39) |
missense |
probably benign |
|
R4960:Abcc9
|
UTSW |
6 |
142,566,509 (GRCm39) |
splice site |
probably null |
|
R4983:Abcc9
|
UTSW |
6 |
142,627,867 (GRCm39) |
missense |
probably benign |
0.44 |
R4986:Abcc9
|
UTSW |
6 |
142,573,317 (GRCm39) |
missense |
probably benign |
0.00 |
R5060:Abcc9
|
UTSW |
6 |
142,571,836 (GRCm39) |
intron |
probably benign |
|
R5120:Abcc9
|
UTSW |
6 |
142,602,344 (GRCm39) |
missense |
probably benign |
0.00 |
R5198:Abcc9
|
UTSW |
6 |
142,571,726 (GRCm39) |
missense |
probably benign |
0.00 |
R5301:Abcc9
|
UTSW |
6 |
142,536,207 (GRCm39) |
missense |
probably benign |
0.41 |
R5328:Abcc9
|
UTSW |
6 |
142,627,785 (GRCm39) |
missense |
probably benign |
0.25 |
R5568:Abcc9
|
UTSW |
6 |
142,634,742 (GRCm39) |
missense |
possibly damaging |
0.62 |
R5654:Abcc9
|
UTSW |
6 |
142,571,371 (GRCm39) |
intron |
probably benign |
|
R5694:Abcc9
|
UTSW |
6 |
142,546,673 (GRCm39) |
missense |
probably damaging |
1.00 |
R5734:Abcc9
|
UTSW |
6 |
142,571,457 (GRCm39) |
intron |
probably benign |
|
R5774:Abcc9
|
UTSW |
6 |
142,574,285 (GRCm39) |
missense |
probably damaging |
0.98 |
R5802:Abcc9
|
UTSW |
6 |
142,602,402 (GRCm39) |
critical splice acceptor site |
probably null |
|
R5890:Abcc9
|
UTSW |
6 |
142,550,554 (GRCm39) |
critical splice donor site |
probably null |
|
R5946:Abcc9
|
UTSW |
6 |
142,571,678 (GRCm39) |
missense |
probably damaging |
1.00 |
R5971:Abcc9
|
UTSW |
6 |
142,585,301 (GRCm39) |
missense |
probably damaging |
1.00 |
R6078:Abcc9
|
UTSW |
6 |
142,585,301 (GRCm39) |
missense |
probably damaging |
1.00 |
R6392:Abcc9
|
UTSW |
6 |
142,627,825 (GRCm39) |
missense |
probably damaging |
1.00 |
R6400:Abcc9
|
UTSW |
6 |
142,638,435 (GRCm39) |
makesense |
probably null |
|
R6478:Abcc9
|
UTSW |
6 |
142,625,034 (GRCm39) |
missense |
probably damaging |
1.00 |
R6481:Abcc9
|
UTSW |
6 |
142,550,621 (GRCm39) |
missense |
probably damaging |
0.99 |
R6564:Abcc9
|
UTSW |
6 |
142,548,834 (GRCm39) |
missense |
probably damaging |
1.00 |
R6700:Abcc9
|
UTSW |
6 |
142,633,013 (GRCm39) |
missense |
possibly damaging |
0.94 |
R6902:Abcc9
|
UTSW |
6 |
142,624,953 (GRCm39) |
missense |
probably damaging |
1.00 |
R6946:Abcc9
|
UTSW |
6 |
142,624,953 (GRCm39) |
missense |
probably damaging |
1.00 |
R6989:Abcc9
|
UTSW |
6 |
142,634,707 (GRCm39) |
missense |
probably damaging |
0.97 |
R7052:Abcc9
|
UTSW |
6 |
142,604,261 (GRCm39) |
missense |
probably benign |
0.00 |
R7062:Abcc9
|
UTSW |
6 |
142,544,872 (GRCm39) |
missense |
probably damaging |
1.00 |
R7121:Abcc9
|
UTSW |
6 |
142,634,853 (GRCm39) |
nonsense |
probably null |
|
R7284:Abcc9
|
UTSW |
6 |
142,628,643 (GRCm39) |
missense |
probably damaging |
1.00 |
R7296:Abcc9
|
UTSW |
6 |
142,617,319 (GRCm39) |
missense |
probably damaging |
1.00 |
R7353:Abcc9
|
UTSW |
6 |
142,546,731 (GRCm39) |
missense |
probably damaging |
1.00 |
R7359:Abcc9
|
UTSW |
6 |
142,617,408 (GRCm39) |
missense |
probably damaging |
1.00 |
R7815:Abcc9
|
UTSW |
6 |
142,598,331 (GRCm39) |
missense |
probably damaging |
1.00 |
R7894:Abcc9
|
UTSW |
6 |
142,539,733 (GRCm39) |
makesense |
probably null |
|
R8095:Abcc9
|
UTSW |
6 |
142,590,048 (GRCm39) |
missense |
probably benign |
0.22 |
R8099:Abcc9
|
UTSW |
6 |
142,621,257 (GRCm39) |
missense |
probably damaging |
1.00 |
R8245:Abcc9
|
UTSW |
6 |
142,539,870 (GRCm39) |
critical splice acceptor site |
probably null |
|
R8355:Abcc9
|
UTSW |
6 |
142,638,478 (GRCm39) |
missense |
probably benign |
0.00 |
R8356:Abcc9
|
UTSW |
6 |
142,536,096 (GRCm39) |
missense |
probably benign |
0.06 |
R8365:Abcc9
|
UTSW |
6 |
142,544,798 (GRCm39) |
missense |
probably benign |
0.03 |
R8846:Abcc9
|
UTSW |
6 |
142,551,610 (GRCm39) |
missense |
possibly damaging |
0.56 |
R8886:Abcc9
|
UTSW |
6 |
142,546,420 (GRCm39) |
intron |
probably benign |
|
R8939:Abcc9
|
UTSW |
6 |
142,624,977 (GRCm39) |
missense |
probably damaging |
0.99 |
R9049:Abcc9
|
UTSW |
6 |
142,628,658 (GRCm39) |
missense |
probably damaging |
0.99 |
R9113:Abcc9
|
UTSW |
6 |
142,591,656 (GRCm39) |
missense |
probably damaging |
1.00 |
R9368:Abcc9
|
UTSW |
6 |
142,640,251 (GRCm39) |
missense |
probably damaging |
1.00 |
R9401:Abcc9
|
UTSW |
6 |
142,543,836 (GRCm39) |
missense |
possibly damaging |
0.90 |
R9407:Abcc9
|
UTSW |
6 |
142,574,229 (GRCm39) |
missense |
possibly damaging |
0.88 |
R9597:Abcc9
|
UTSW |
6 |
142,578,813 (GRCm39) |
missense |
possibly damaging |
0.81 |
R9600:Abcc9
|
UTSW |
6 |
142,536,102 (GRCm39) |
missense |
possibly damaging |
0.54 |
R9687:Abcc9
|
UTSW |
6 |
142,578,889 (GRCm39) |
missense |
probably benign |
0.00 |
R9698:Abcc9
|
UTSW |
6 |
142,571,757 (GRCm39) |
missense |
probably benign |
|
R9761:Abcc9
|
UTSW |
6 |
142,544,854 (GRCm39) |
missense |
possibly damaging |
0.78 |
U15987:Abcc9
|
UTSW |
6 |
142,585,301 (GRCm39) |
missense |
probably damaging |
1.00 |
Z1177:Abcc9
|
UTSW |
6 |
142,591,664 (GRCm39) |
missense |
probably null |
0.96 |
Z1177:Abcc9
|
UTSW |
6 |
142,571,708 (GRCm39) |
missense |
probably benign |
0.07 |
Z1177:Abcc9
|
UTSW |
6 |
142,540,484 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Protein Function and Prediction |
Abcc9 encodes SUR2, a member of the C-branch of the transport adenosine triphosphatase superfamily and regulatory subunit of ATP-sensitive potassium channels (KATP channels) (1;2). KATP channels function in responses to cardiac stress, vascular smooth muscle tone, skeletal muscle glucose uptake, neuronal excitability, transmitter release, ischemic preconditioning, and insulin secretion from pancreatic β-cells (3). The pore are octameric complexes comprised of four pore-forming Kir6.2 subunits and four regulatory SUR subunits (1). Mouse Sur2 has 13 transmembrane domains and intracellular Walker A and B ATP-binding domains (4). SUR2 can be alternatively spliced to generate SUR2A and SUR2B, which differ in their C-terminal 42 amino acids (1).
|
Expression/Localization |
Northern blot analysis detected three human SUR2 transcripts (9.4, 7.6, and 5.6 kb); the highest level of the longer transcript is in the heart and skeletal muscle; little to no SUR2 was detected in other tissues (4). In mouse tissues, Sur2 a 9.4 kb transcript was ubiquitously expressed; a 8.6 kb transcript was expressed at high levels in the skeletal muscle and heart (4). Western blot analysis determined that SUR2A is expressed in cardiac and skeletal muscle, while SUR2B is in smooth muscle and some neurons (5).
|
Background |
Mutations in ABCC9 are linked to familial atrial fibrillation 12 [OMIM: 614050; (6)], dilated cardiomyopathy 10 [OMIM: 608569; (7)], and hypertrichotic osteochondrodysplasia [alternatively, Cantu syndrome; OMIM: 239850; (8;9)]. Cantu syndrome is a rare disorder characterized by congenital hypertrichosis, neonatal macrosomia, a distinct osteochondrodysplasia, and cardiomegaly. The hypertrichosis leads to thick scalp hair which extends onto the forehead and to a general increase in body hair.
Abcc9tm1Cfb/tm1Cfb; MGI:2155916
involves: CD-1
Mice homozygous for disruptions in this gene display lower serum glucose, enhanced insulin action, growth retardation and slow postnatal weight gain, hypertension and spontaneous death starting at 6 weeks of age due to episodic coronary artery vasospasm (10).
Abcc9tm1Cfb/tm1Cfb; MGI:2155916
Not specified
In this genetic background, homozygotes also exhibit premature death (by 30 weeks), abnormal vasoconstriction, abnormal ST segment, hypertension, and absent glibenclamide-sensitive KATP current in aortic smooth muscle cells (11).
|
References |
1. de Wet, H., Fotinou, C., Amad, N., Dreger, M., and Ashcroft, F. M. (2010) The ATPase Activities of Sulfonylurea Receptor 2A and Sulfonylurea Receptor 2B are Influenced by the C-Terminal 42 Amino Acids. FEBS J. 277, 2654-2662.
2. Bryan, J., Munoz, A., Zhang, X., Dufer, M., Drews, G., Krippeit-Drews, P., and Aguilar-Bryan, L. (2007) ABCC8 and ABCC9: ABC Transporters that Regulate K+ Channels. Pflugers Arch. 453, 703-718.
4. Chutkow, W. A., Simon, M. C., Le Beau, M. M., and Burant, C. F. (1996) Cloning, Tissue Expression, and Chromosomal Localization of SUR2, the Putative Drug-Binding Subunit of Cardiac, Skeletal Muscle, and Vascular KATP Channels. Diabetes. 45, 1439-1445.
6. Olson, T. M., Alekseev, A. E., Liu, X. K., Park, S., Zingman, L. V., Bienengraeber, M., Sattiraju, S., Ballew, J. D., Jahangir, A., and Terzic, A. (2006) Kv1.5 Channelopathy due to KCNA5 Loss-of-Function Mutation Causes Human Atrial Fibrillation. Hum Mol Genet. 15, 2185-2191.
7. Bienengraeber, M., Olson, T. M., Selivanov, V. A., Kathmann, E. C., O'Cochlain, F., Gao, F., Karger, A. B., Ballew, J. D., Hodgson, D. M., Zingman, L. V., Pang, Y. P., Alekseev, A. E., and Terzic, A. (2004) ABCC9 Mutations Identified in Human Dilated Cardiomyopathy Disrupt Catalytic KATP Channel Gating. Nat Genet. 36, 382-387.
8. Harakalova, M., van Harssel, J. J., Terhal, P. A., van Lieshout, S., Duran, K., Renkens, I., Amor, D. J., Wilson, L. C., Kirk, E. P., Turner, C. L., Shears, D., Garcia-Minaur, S., Lees, M. M., Ross, A., Venselaar, H., Vriend, G., Takanari, H., Rook, M. B., van der Heyden, M. A., Asselbergs, F. W., Breur, H. M., Swinkels, M. E., Scurr, I. J., Smithson, S. F., Knoers, N. V., van der Smagt, J. J., Nijman, I. J., Kloosterman, W. P., van Haelst, M. M., van Haaften, G., and Cuppen, E. (2012) Dominant Missense Mutations in ABCC9 Cause Cantu Syndrome. Nat Genet. 44, 793-796.
9. van Bon, B. W., Gilissen, C., Grange, D. K., Hennekam, R. C., Kayserili, H., Engels, H., Reutter, H., Ostergaard, J. R., Morava, E., Tsiakas, K., Isidor, B., Le Merrer, M., Eser, M., Wieskamp, N., de Vries, P., Steehouwer, M., Veltman, J. A., Robertson, S. P., Brunner, H. G., de Vries, B. B., and Hoischen, A. (2012) Cantu Syndrome is Caused by Mutations in ABCC9. Am J Hum Genet. 90, 1094-1101.
10. Chutkow, W. A., Samuel, V., Hansen, P. A., Pu, J., Valdivia, C. R., Makielski, J. C., and Burant, C. F. (2001) Disruption of Sur2-Containing K(ATP) Channels Enhances Insulin-Stimulated Glucose Uptake in Skeletal Muscle. Proc Natl Acad Sci U S A. 98, 11760-11764.
11. Chutkow, W. A., Pu, J., Wheeler, M. T., Wada, T., Makielski, J. C., Burant, C. F., and McNally, E. M. (2002) Episodic Coronary Artery Vasospasm and Hypertension Develop in the Absence of Sur2 K(ATP) Channels. J Clin Invest. 110, 203-208.
|
Posted On |
2013-01-20 |
Science Writer |
Anne Murray |