Incidental Mutation 'R1300:Npc1l1'
ID |
158313 |
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 |
039366-MU
|
Accession Numbers |
|
Essential gene? |
Probably non essential
(E-score: 0.098)
|
Stock # |
R1300 (G1)
|
Quality Score |
225 |
Status
|
Not validated
|
Chromosome |
11 |
Chromosomal Location |
6161013-6180143 bp(-) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
T to G
at 6177859 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Aspartic acid to Alanine
at position 517
(D517A)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000004505
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000004505]
|
AlphaFold |
no structure available at present |
Predicted Effect |
probably damaging
Transcript: ENSMUST00000004505
AA Change: D517A
PolyPhen 2
Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
|
SMART Domains |
Protein: ENSMUSP00000004505 Gene: ENSMUSG00000020447 AA Change: D517A
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: 99.1%
- 3x: 98.4%
- 10x: 96.5%
- 20x: 93.4%
|
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: 59 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
Abca12 |
A |
G |
1: 71,283,967 (GRCm39) |
I2535T |
probably damaging |
Het |
Adam34l |
A |
T |
8: 44,079,881 (GRCm39) |
Y114* |
probably null |
Het |
Ank3 |
A |
G |
10: 69,840,495 (GRCm39) |
I952V |
probably benign |
Het |
Ankar |
A |
C |
1: 72,682,323 (GRCm39) |
V1414G |
probably benign |
Het |
Arl2 |
A |
G |
19: 6,191,103 (GRCm39) |
M10T |
probably benign |
Het |
Arpp21 |
A |
G |
9: 111,972,442 (GRCm39) |
I352T |
probably damaging |
Het |
Cacna1e |
T |
A |
1: 154,274,419 (GRCm39) |
H2162L |
probably benign |
Het |
Cep170b |
A |
C |
12: 112,703,691 (GRCm39) |
M622L |
probably benign |
Het |
Cped1 |
T |
C |
6: 22,119,552 (GRCm39) |
V337A |
probably benign |
Het |
Cpn2 |
T |
A |
16: 30,078,481 (GRCm39) |
T407S |
probably benign |
Het |
Cpne4 |
T |
C |
9: 104,870,333 (GRCm39) |
W263R |
probably damaging |
Het |
Crtc1 |
A |
G |
8: 70,840,189 (GRCm39) |
|
probably null |
Het |
Cspg4b |
T |
C |
13: 113,502,694 (GRCm39) |
F133S |
probably damaging |
Het |
Dennd5a |
A |
T |
7: 109,518,614 (GRCm39) |
I485N |
probably benign |
Het |
Dnah6 |
T |
C |
6: 73,101,692 (GRCm39) |
Q1892R |
probably benign |
Het |
Dse |
G |
A |
10: 34,028,411 (GRCm39) |
A893V |
probably benign |
Het |
Dsg1a |
T |
G |
18: 20,465,206 (GRCm39) |
S466A |
probably benign |
Het |
Dstyk |
T |
C |
1: 132,377,651 (GRCm39) |
V419A |
probably benign |
Het |
Eif2ak4 |
T |
C |
2: 118,294,464 (GRCm39) |
V1125A |
possibly damaging |
Het |
Ep400 |
C |
A |
5: 110,821,426 (GRCm39) |
G2576C |
probably damaging |
Het |
Eps15l1 |
A |
T |
8: 73,145,746 (GRCm39) |
D162E |
probably damaging |
Het |
Fstl4 |
C |
A |
11: 52,959,454 (GRCm39) |
T165N |
probably benign |
Het |
Gm8674 |
T |
C |
13: 50,055,758 (GRCm39) |
|
noncoding transcript |
Het |
Gtsf2 |
T |
A |
15: 103,352,780 (GRCm39) |
L39F |
possibly damaging |
Het |
Hck |
A |
C |
2: 152,976,067 (GRCm39) |
D202A |
possibly damaging |
Het |
Il12b |
T |
A |
11: 44,298,903 (GRCm39) |
|
probably null |
Het |
Irf4 |
T |
C |
13: 30,941,568 (GRCm39) |
L307P |
probably damaging |
Het |
Keg1 |
G |
A |
19: 12,696,368 (GRCm39) |
R184Q |
probably damaging |
Het |
Kmt2c |
T |
C |
5: 25,610,452 (GRCm39) |
D218G |
probably damaging |
Het |
Map1b |
T |
C |
13: 99,569,029 (GRCm39) |
K1231E |
unknown |
Het |
Mapkbp1 |
T |
C |
2: 119,844,136 (GRCm39) |
Y293H |
probably benign |
Het |
Mfsd8 |
A |
T |
3: 40,778,333 (GRCm39) |
D310E |
probably benign |
Het |
Mmp9 |
A |
T |
2: 164,790,876 (GRCm39) |
D88V |
probably damaging |
Het |
Muc5ac |
G |
T |
7: 141,370,666 (GRCm39) |
C2522F |
possibly damaging |
Het |
Myo1e |
A |
T |
9: 70,209,065 (GRCm39) |
I110F |
probably damaging |
Het |
Neu1 |
A |
T |
17: 35,153,314 (GRCm39) |
Y279F |
possibly damaging |
Het |
Nhsl1 |
A |
G |
10: 18,284,209 (GRCm39) |
H50R |
probably benign |
Het |
Nlrp3 |
C |
T |
11: 59,446,594 (GRCm39) |
S780F |
possibly damaging |
Het |
Or14c43 |
T |
C |
7: 86,114,951 (GRCm39) |
F111L |
probably benign |
Het |
Or1e32 |
T |
C |
11: 73,705,072 (GRCm39) |
T279A |
probably benign |
Het |
Or2z2 |
T |
C |
11: 58,346,667 (GRCm39) |
Y36C |
probably damaging |
Het |
Or52e3 |
G |
A |
7: 102,869,324 (GRCm39) |
R133Q |
probably benign |
Het |
P3h2 |
C |
A |
16: 25,815,986 (GRCm39) |
E176* |
probably null |
Het |
Parp10 |
C |
A |
15: 76,126,190 (GRCm39) |
D333Y |
possibly damaging |
Het |
Pcdhb12 |
C |
T |
18: 37,570,450 (GRCm39) |
A532V |
possibly damaging |
Het |
Pde2a |
A |
T |
7: 101,159,611 (GRCm39) |
T818S |
possibly damaging |
Het |
Phf11 |
A |
T |
14: 59,488,563 (GRCm39) |
V78D |
probably damaging |
Het |
Phip |
A |
T |
9: 82,758,800 (GRCm39) |
L1450Q |
probably benign |
Het |
Pinx1 |
A |
G |
14: 64,156,859 (GRCm39) |
E262G |
probably benign |
Het |
Ppargc1a |
T |
C |
5: 51,706,014 (GRCm39) |
E19G |
probably damaging |
Het |
Pum1 |
T |
C |
4: 130,493,272 (GRCm39) |
I921T |
probably damaging |
Het |
Rgs22 |
T |
A |
15: 36,101,908 (GRCm39) |
H106L |
probably benign |
Het |
Slc10a6 |
T |
C |
5: 103,754,550 (GRCm39) |
D327G |
probably benign |
Het |
Syt1 |
A |
T |
10: 108,467,682 (GRCm39) |
V205D |
possibly damaging |
Het |
Tep1 |
C |
T |
14: 51,064,512 (GRCm39) |
|
probably null |
Het |
Thnsl2 |
T |
A |
6: 71,111,175 (GRCm39) |
Q231L |
probably damaging |
Het |
Ttc4 |
T |
A |
4: 106,524,763 (GRCm39) |
H304L |
probably damaging |
Het |
Unc5c |
G |
A |
3: 141,534,304 (GRCm39) |
V923M |
possibly damaging |
Het |
Zfp777 |
T |
C |
6: 48,002,704 (GRCm39) |
E506G |
probably benign |
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 |
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 |
R8081:Npc1l1
|
UTSW |
11 |
6,167,768 (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 |
PCR Primer
(F):5'- GTTGTGAGGCTACCAAAGTCCCTAC -3'
(R):5'- ATCTCCCTCCAGGACATCTGCTATG -3'
Sequencing Primer
(F):5'- ttcttcagcaccaggcac -3'
(R):5'- AGGACATCTGCTATGCTCCC -3'
|
Posted On |
2014-02-18 |