Incidental Mutation 'R8081:Npc1l1'
ID |
629360 |
Institutional Source |
Beutler Lab
|
Gene Symbol |
Npc1l1
|
Ensembl Gene |
ENSMUSG00000020447 |
Gene Name |
NPC1 like intracellular cholesterol transporter 1 |
Synonyms |
Niemann-Pick disease, type C1, 9130221N23Rik |
MMRRC Submission |
067514-MU
|
Accession Numbers |
|
Essential gene? |
Probably non essential
(E-score: 0.098)
|
Stock # |
R8081 (G1)
|
Quality Score |
225.009 |
Status
|
Not validated
|
Chromosome |
11 |
Chromosomal Location |
6161013-6180143 bp(-) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
G to C
at 6167768 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Glutamine to Glutamic Acid
at position 1008
(Q1008E)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000004505
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000004505]
|
AlphaFold |
no structure available at present |
Predicted Effect |
probably benign
Transcript: ENSMUST00000004505
AA Change: Q1008E
PolyPhen 2
Score 0.014 (Sensitivity: 0.96; Specificity: 0.79)
|
SMART Domains |
Protein: ENSMUSP00000004505 Gene: ENSMUSG00000020447 AA Change: Q1008E
Domain | Start | End | E-Value | Type |
signal peptide
|
1 |
20 |
N/A |
INTRINSIC |
Pfam:NPC1_N
|
28 |
283 |
8.7e-74 |
PFAM |
low complexity region
|
294 |
307 |
N/A |
INTRINSIC |
transmembrane domain
|
348 |
370 |
N/A |
INTRINSIC |
Pfam:Patched
|
385 |
897 |
4.7e-52 |
PFAM |
Pfam:Sterol-sensing
|
661 |
815 |
5.7e-55 |
PFAM |
Pfam:MMPL
|
665 |
830 |
2.3e-11 |
PFAM |
Pfam:Patched
|
1063 |
1268 |
6.2e-34 |
PFAM |
|
Coding Region Coverage |
- 1x: 99.9%
- 3x: 99.7%
- 10x: 98.9%
- 20x: 95.7%
|
Validation Efficiency |
|
MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a multi-pass membrane protein. It contains a conserved N-terminal Niemann-Pick C1 (NPC1) domain and a putative sterol-sensing domain (SSD) which includes a YQRL motif functioning as a plasma membrane to trans-Golgi network transport signal in other proteins. This protein takes up free cholesterol into cells through vesicular endocytosis and plays a critical role in the absorption of intestinal cholesterol. It also has the ability to transport alpha-tocopherol (vitamin E). The drug ezetimibe targets this protein and inhibits the absorption of intestinal cholesterol and alpha-tocopherol. In addition, this protein may play a critical role in regulating lipid metabolism. Polymorphic variations in this gene are associated with plasma total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels and coronary heart disease (CHD) risk. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009] PHENOTYPE: Mice homozygous for a targeted null mutation exhibit normal intestinal development, fertility and plasma cholesterol and triglyceride levels; however, intestinal cholesterol absorption was substantially reduced. [provided by MGI curators]
|
Allele List at MGI |
|
Other mutations in this stock |
Total: 67 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
1700003E16Rik |
A |
T |
6: 83,138,313 (GRCm39) |
E119V |
probably damaging |
Het |
Adamts2 |
A |
T |
11: 50,668,004 (GRCm39) |
D522V |
probably damaging |
Het |
Agtpbp1 |
A |
T |
13: 59,676,221 (GRCm39) |
L183* |
probably null |
Het |
Arhgap10 |
T |
C |
8: 78,109,375 (GRCm39) |
I403V |
possibly damaging |
Het |
Arhgef11 |
T |
C |
3: 87,632,949 (GRCm39) |
S687P |
probably damaging |
Het |
Cdhr1 |
C |
T |
14: 36,815,967 (GRCm39) |
V144I |
probably benign |
Het |
Cdk20 |
A |
G |
13: 64,586,766 (GRCm39) |
I339V |
probably benign |
Het |
Ceacam13 |
A |
G |
7: 17,747,113 (GRCm39) |
K189E |
probably damaging |
Het |
Cep290 |
C |
T |
10: 100,394,038 (GRCm39) |
Q2082* |
probably null |
Het |
Cgrrf1 |
A |
G |
14: 47,091,468 (GRCm39) |
T331A |
probably benign |
Het |
Cntn4 |
G |
A |
6: 106,651,568 (GRCm39) |
V706I |
possibly damaging |
Het |
Csrnp2 |
T |
C |
15: 100,387,462 (GRCm39) |
D2G |
probably damaging |
Het |
Cux2 |
A |
G |
5: 122,007,519 (GRCm39) |
I714T |
probably benign |
Het |
Cx3cr1 |
C |
T |
9: 119,880,878 (GRCm39) |
E175K |
possibly damaging |
Het |
Dennd1c |
G |
A |
17: 57,381,139 (GRCm39) |
P163L |
possibly damaging |
Het |
Dhtkd1 |
C |
T |
2: 5,928,919 (GRCm39) |
E251K |
probably damaging |
Het |
Epas1 |
C |
T |
17: 87,136,797 (GRCm39) |
P787S |
probably benign |
Het |
Epha2 |
T |
C |
4: 141,049,605 (GRCm39) |
V737A |
probably damaging |
Het |
Fam50b |
G |
A |
13: 34,931,084 (GRCm39) |
E187K |
possibly damaging |
Het |
Fcsk |
T |
A |
8: 111,615,783 (GRCm39) |
R515S |
probably benign |
Het |
Fscb |
A |
T |
12: 64,518,802 (GRCm39) |
M888K |
unknown |
Het |
Gldc |
ACGACC |
AC |
19: 30,135,987 (GRCm39) |
|
probably null |
Het |
Gm14443 |
A |
T |
2: 175,012,238 (GRCm39) |
C69* |
probably null |
Het |
Gm19668 |
G |
A |
10: 77,634,420 (GRCm39) |
A183V |
unknown |
Het |
Gm49368 |
A |
G |
7: 127,726,280 (GRCm39) |
R1231G |
unknown |
Het |
Grin2c |
T |
C |
11: 115,140,719 (GRCm39) |
Y1133C |
probably damaging |
Het |
H3c13 |
C |
A |
3: 96,176,309 (GRCm39) |
Y100* |
probably null |
Het |
Hydin |
T |
C |
8: 111,092,101 (GRCm39) |
S425P |
possibly damaging |
Het |
Ifnl3 |
T |
C |
7: 28,223,682 (GRCm39) |
S173P |
probably damaging |
Het |
Igkv4-63 |
A |
T |
6: 69,355,018 (GRCm39) |
S88T |
possibly damaging |
Het |
Klhl5 |
C |
A |
5: 65,320,268 (GRCm39) |
N607K |
possibly damaging |
Het |
Lag3 |
A |
T |
6: 124,882,410 (GRCm39) |
L362* |
probably null |
Het |
Lats2 |
C |
A |
14: 57,937,968 (GRCm39) |
G174C |
probably damaging |
Het |
Mcm6 |
T |
C |
1: 128,265,905 (GRCm39) |
E622G |
probably damaging |
Het |
Med13l |
C |
A |
5: 118,866,333 (GRCm39) |
H462Q |
probably damaging |
Het |
Mrpl53 |
T |
A |
6: 83,086,159 (GRCm39) |
F23I |
probably damaging |
Het |
Muc5b |
T |
G |
7: 141,417,743 (GRCm39) |
I3563S |
possibly damaging |
Het |
Myo16 |
A |
C |
8: 10,372,743 (GRCm39) |
L147F |
unknown |
Het |
Npy4r |
A |
G |
14: 33,868,524 (GRCm39) |
S255P |
probably damaging |
Het |
Nup210 |
T |
C |
6: 91,053,657 (GRCm39) |
N287D |
probably benign |
Het |
Opn3 |
T |
A |
1: 175,493,135 (GRCm39) |
H143L |
probably damaging |
Het |
Or12e7 |
G |
T |
2: 87,287,513 (GRCm39) |
M1I |
probably null |
Het |
Or12j3 |
A |
T |
7: 139,952,972 (GRCm39) |
L184M |
probably damaging |
Het |
Or12j5 |
A |
T |
7: 140,084,369 (GRCm39) |
M1K |
probably null |
Het |
Or4k2 |
T |
A |
14: 50,423,825 (GRCm39) |
N284I |
probably damaging |
Het |
Or5ap2b-ps1 |
C |
T |
2: 85,693,839 (GRCm39) |
P28L |
probably damaging |
Het |
Pdcd7 |
C |
T |
9: 65,253,967 (GRCm39) |
R182C |
probably damaging |
Het |
Peg10 |
GC |
GCTCC |
6: 4,756,452 (GRCm39) |
|
probably benign |
Het |
Picalm |
T |
A |
7: 89,840,451 (GRCm39) |
L540* |
probably null |
Het |
Ppp1r21 |
T |
A |
17: 88,866,272 (GRCm39) |
I356N |
probably damaging |
Het |
Rgs6 |
C |
T |
12: 83,094,347 (GRCm39) |
Q67* |
probably null |
Het |
Ripor2 |
C |
A |
13: 24,897,683 (GRCm39) |
Q794K |
probably benign |
Het |
Rnf216 |
A |
T |
5: 143,013,719 (GRCm39) |
I702N |
probably damaging |
Het |
Robo4 |
T |
C |
9: 37,316,936 (GRCm39) |
L417P |
probably damaging |
Het |
Samhd1 |
A |
T |
2: 156,943,358 (GRCm39) |
C605* |
probably null |
Het |
Scaper |
C |
T |
9: 55,823,330 (GRCm39) |
G22D |
unknown |
Het |
Senp5 |
T |
C |
16: 31,784,577 (GRCm39) |
T692A |
probably damaging |
Het |
Six6 |
G |
T |
12: 72,986,875 (GRCm39) |
G16W |
probably damaging |
Het |
Slc38a8 |
A |
T |
8: 120,212,269 (GRCm39) |
M358K |
possibly damaging |
Het |
Snx2 |
T |
C |
18: 53,349,459 (GRCm39) |
F407L |
probably benign |
Het |
Srrm2 |
T |
A |
17: 24,039,219 (GRCm39) |
N1954K |
probably damaging |
Het |
Syk |
A |
T |
13: 52,792,195 (GRCm39) |
M429L |
probably benign |
Het |
Tln2 |
T |
A |
9: 67,264,029 (GRCm39) |
N537Y |
probably damaging |
Het |
Usp29 |
T |
A |
7: 6,966,629 (GRCm39) |
M824K |
probably benign |
Het |
Utrn |
A |
G |
10: 12,423,803 (GRCm39) |
|
probably benign |
Het |
Wdr37 |
C |
T |
13: 8,885,406 (GRCm39) |
D346N |
probably damaging |
Het |
Zfpm2 |
T |
A |
15: 40,965,644 (GRCm39) |
C710S |
probably damaging |
Het |
|
Other mutations in Npc1l1 |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
IGL00163:Npc1l1
|
APN |
11 |
6,174,199 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL01348:Npc1l1
|
APN |
11 |
6,177,974 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL01891:Npc1l1
|
APN |
11 |
6,164,280 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL01897:Npc1l1
|
APN |
11 |
6,177,879 (GRCm39) |
missense |
probably benign |
|
IGL02098:Npc1l1
|
APN |
11 |
6,164,581 (GRCm39) |
missense |
probably damaging |
0.99 |
IGL02121:Npc1l1
|
APN |
11 |
6,178,157 (GRCm39) |
missense |
probably benign |
|
IGL02724:Npc1l1
|
APN |
11 |
6,164,684 (GRCm39) |
missense |
possibly damaging |
0.88 |
IGL02947:Npc1l1
|
APN |
11 |
6,179,246 (GRCm39) |
missense |
probably benign |
0.01 |
IGL03328:Npc1l1
|
APN |
11 |
6,168,643 (GRCm39) |
nonsense |
probably null |
|
R0137:Npc1l1
|
UTSW |
11 |
6,178,148 (GRCm39) |
nonsense |
probably null |
|
R0322:Npc1l1
|
UTSW |
11 |
6,179,042 (GRCm39) |
missense |
probably benign |
|
R0352:Npc1l1
|
UTSW |
11 |
6,173,076 (GRCm39) |
missense |
probably benign |
0.00 |
R0492:Npc1l1
|
UTSW |
11 |
6,173,040 (GRCm39) |
missense |
possibly damaging |
0.82 |
R0918:Npc1l1
|
UTSW |
11 |
6,168,239 (GRCm39) |
missense |
probably damaging |
1.00 |
R1300:Npc1l1
|
UTSW |
11 |
6,177,859 (GRCm39) |
missense |
probably damaging |
1.00 |
R1455:Npc1l1
|
UTSW |
11 |
6,178,174 (GRCm39) |
missense |
possibly damaging |
0.66 |
R1588:Npc1l1
|
UTSW |
11 |
6,167,785 (GRCm39) |
missense |
probably benign |
0.01 |
R1803:Npc1l1
|
UTSW |
11 |
6,178,846 (GRCm39) |
missense |
probably damaging |
1.00 |
R1882:Npc1l1
|
UTSW |
11 |
6,167,473 (GRCm39) |
splice site |
probably null |
|
R1944:Npc1l1
|
UTSW |
11 |
6,164,588 (GRCm39) |
missense |
possibly damaging |
0.67 |
R1945:Npc1l1
|
UTSW |
11 |
6,175,199 (GRCm39) |
nonsense |
probably null |
|
R1945:Npc1l1
|
UTSW |
11 |
6,164,588 (GRCm39) |
missense |
possibly damaging |
0.67 |
R3155:Npc1l1
|
UTSW |
11 |
6,171,840 (GRCm39) |
missense |
probably benign |
|
R4343:Npc1l1
|
UTSW |
11 |
6,167,773 (GRCm39) |
missense |
probably benign |
|
R4504:Npc1l1
|
UTSW |
11 |
6,178,741 (GRCm39) |
missense |
possibly damaging |
0.61 |
R4610:Npc1l1
|
UTSW |
11 |
6,178,215 (GRCm39) |
missense |
probably damaging |
1.00 |
R4807:Npc1l1
|
UTSW |
11 |
6,168,723 (GRCm39) |
missense |
probably damaging |
1.00 |
R4829:Npc1l1
|
UTSW |
11 |
6,164,010 (GRCm39) |
critical splice donor site |
probably null |
|
R5135:Npc1l1
|
UTSW |
11 |
6,174,245 (GRCm39) |
missense |
possibly damaging |
0.94 |
R5290:Npc1l1
|
UTSW |
11 |
6,172,221 (GRCm39) |
missense |
probably benign |
0.00 |
R5369:Npc1l1
|
UTSW |
11 |
6,167,705 (GRCm39) |
critical splice donor site |
probably null |
|
R5388:Npc1l1
|
UTSW |
11 |
6,164,733 (GRCm39) |
missense |
probably damaging |
1.00 |
R5532:Npc1l1
|
UTSW |
11 |
6,174,245 (GRCm39) |
missense |
probably damaging |
0.98 |
R5540:Npc1l1
|
UTSW |
11 |
6,164,546 (GRCm39) |
missense |
probably damaging |
1.00 |
R5754:Npc1l1
|
UTSW |
11 |
6,177,839 (GRCm39) |
missense |
probably damaging |
1.00 |
R5760:Npc1l1
|
UTSW |
11 |
6,179,031 (GRCm39) |
missense |
probably benign |
0.02 |
R6057:Npc1l1
|
UTSW |
11 |
6,167,806 (GRCm39) |
missense |
possibly damaging |
0.66 |
R6388:Npc1l1
|
UTSW |
11 |
6,174,145 (GRCm39) |
missense |
probably damaging |
1.00 |
R6644:Npc1l1
|
UTSW |
11 |
6,164,014 (GRCm39) |
missense |
probably damaging |
0.98 |
R6644:Npc1l1
|
UTSW |
11 |
6,164,013 (GRCm39) |
missense |
probably damaging |
1.00 |
R6756:Npc1l1
|
UTSW |
11 |
6,165,153 (GRCm39) |
missense |
probably damaging |
1.00 |
R6790:Npc1l1
|
UTSW |
11 |
6,164,260 (GRCm39) |
splice site |
probably null |
|
R7006:Npc1l1
|
UTSW |
11 |
6,167,731 (GRCm39) |
missense |
probably benign |
|
R7062:Npc1l1
|
UTSW |
11 |
6,167,807 (GRCm39) |
missense |
probably benign |
|
R7273:Npc1l1
|
UTSW |
11 |
6,168,320 (GRCm39) |
missense |
probably damaging |
1.00 |
R7383:Npc1l1
|
UTSW |
11 |
6,167,777 (GRCm39) |
missense |
probably benign |
0.30 |
R8003:Npc1l1
|
UTSW |
11 |
6,165,129 (GRCm39) |
missense |
probably benign |
0.01 |
R8272:Npc1l1
|
UTSW |
11 |
6,179,327 (GRCm39) |
nonsense |
probably null |
|
R8549:Npc1l1
|
UTSW |
11 |
6,168,675 (GRCm39) |
missense |
probably damaging |
1.00 |
R8849:Npc1l1
|
UTSW |
11 |
6,179,038 (GRCm39) |
missense |
probably damaging |
0.97 |
R8887:Npc1l1
|
UTSW |
11 |
6,175,665 (GRCm39) |
missense |
probably damaging |
1.00 |
R8907:Npc1l1
|
UTSW |
11 |
6,178,157 (GRCm39) |
missense |
probably benign |
0.28 |
R9102:Npc1l1
|
UTSW |
11 |
6,164,684 (GRCm39) |
missense |
possibly damaging |
0.88 |
R9289:Npc1l1
|
UTSW |
11 |
6,168,355 (GRCm39) |
nonsense |
probably null |
|
R9626:Npc1l1
|
UTSW |
11 |
6,177,854 (GRCm39) |
missense |
probably benign |
0.05 |
R9785:Npc1l1
|
UTSW |
11 |
6,180,090 (GRCm39) |
missense |
unknown |
|
X0022:Npc1l1
|
UTSW |
11 |
6,178,058 (GRCm39) |
missense |
probably damaging |
1.00 |
Z1177:Npc1l1
|
UTSW |
11 |
6,175,209 (GRCm39) |
missense |
possibly damaging |
0.92 |
Z1177:Npc1l1
|
UTSW |
11 |
6,168,681 (GRCm39) |
missense |
probably damaging |
0.99 |
Z1177:Npc1l1
|
UTSW |
11 |
6,164,343 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Predicted Primers |
|
Posted On |
2020-06-30 |