Incidental Mutation 'R1455:Npc1l1'
ID |
161739 |
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 |
039510-MU
|
Accession Numbers |
|
Essential gene? |
Probably non essential
(E-score: 0.098)
|
Stock # |
R1455 (G1)
|
Quality Score |
225 |
Status
|
Not validated
|
Chromosome |
11 |
Chromosomal Location |
6161013-6180143 bp(-) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
A to T
at 6178174 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Valine to Glutamic Acid
at position 412
(V412E)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000004505
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000004505]
|
AlphaFold |
no structure available at present |
Predicted Effect |
possibly damaging
Transcript: ENSMUST00000004505
AA Change: V412E
PolyPhen 2
Score 0.656 (Sensitivity: 0.87; Specificity: 0.91)
|
SMART Domains |
Protein: ENSMUSP00000004505 Gene: ENSMUSG00000020447 AA Change: V412E
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: 98.9%
- 3x: 97.9%
- 10x: 94.8%
- 20x: 87.9%
|
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: 41 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
4921509C19Rik |
T |
C |
2: 151,314,824 (GRCm39) |
N285D |
possibly damaging |
Het |
Adam9 |
T |
G |
8: 25,483,125 (GRCm39) |
M227L |
probably benign |
Het |
Ankrd35 |
A |
G |
3: 96,585,471 (GRCm39) |
D21G |
probably damaging |
Het |
Arhgap32 |
C |
T |
9: 32,171,381 (GRCm39) |
A1387V |
probably benign |
Het |
Atg4d |
T |
A |
9: 21,182,097 (GRCm39) |
V306E |
probably damaging |
Het |
Brsk1 |
G |
A |
7: 4,707,250 (GRCm39) |
V268M |
probably damaging |
Het |
Cfap300 |
T |
G |
9: 8,022,457 (GRCm39) |
N255T |
probably benign |
Het |
Clec4a4 |
A |
G |
6: 122,989,758 (GRCm39) |
E133G |
possibly damaging |
Het |
Col24a1 |
T |
A |
3: 145,166,593 (GRCm39) |
L1076H |
probably damaging |
Het |
Ddah1 |
G |
T |
3: 145,594,864 (GRCm39) |
R208L |
probably benign |
Het |
Dysf |
A |
G |
6: 84,090,368 (GRCm39) |
N960S |
probably benign |
Het |
Egln2 |
A |
G |
7: 26,859,796 (GRCm39) |
Y306H |
probably damaging |
Het |
Fgfr1 |
T |
C |
8: 26,052,292 (GRCm39) |
V293A |
possibly damaging |
Het |
Gja3 |
A |
G |
14: 57,273,842 (GRCm39) |
Y177H |
probably damaging |
Het |
Glul |
T |
A |
1: 153,782,845 (GRCm39) |
|
probably null |
Het |
Gprc5a |
G |
A |
6: 135,056,245 (GRCm39) |
V231I |
probably benign |
Het |
Kdm4d |
C |
A |
9: 14,375,691 (GRCm39) |
A56S |
probably damaging |
Het |
Lingo4 |
G |
A |
3: 94,306,699 (GRCm39) |
|
probably benign |
Het |
Map6 |
A |
G |
7: 98,917,421 (GRCm39) |
T65A |
probably damaging |
Het |
Mmrn2 |
T |
C |
14: 34,121,089 (GRCm39) |
I653T |
probably benign |
Het |
Ndufa12 |
A |
G |
10: 94,039,176 (GRCm39) |
T70A |
probably benign |
Het |
Nfe2l3 |
C |
A |
6: 51,434,744 (GRCm39) |
P435T |
possibly damaging |
Het |
Or51a39 |
A |
T |
7: 102,363,205 (GRCm39) |
Y138* |
probably null |
Het |
Or6aa1 |
A |
T |
7: 86,043,803 (GRCm39) |
F301Y |
probably damaging |
Het |
Pcnx1 |
T |
C |
12: 82,020,008 (GRCm39) |
F1344L |
probably damaging |
Het |
Pi4ka |
A |
G |
16: 17,181,818 (GRCm39) |
V297A |
probably benign |
Het |
Pole2 |
G |
A |
12: 69,254,703 (GRCm39) |
L381F |
probably benign |
Het |
Pramel7 |
T |
C |
2: 87,320,067 (GRCm39) |
T409A |
probably benign |
Het |
Proc |
C |
G |
18: 32,256,451 (GRCm39) |
M405I |
probably damaging |
Het |
Serinc2 |
C |
A |
4: 130,158,133 (GRCm39) |
A105S |
probably damaging |
Het |
Slc4a10 |
G |
T |
2: 62,117,274 (GRCm39) |
K744N |
probably damaging |
Het |
Spdye4c |
A |
T |
2: 128,438,478 (GRCm39) |
I279F |
probably damaging |
Het |
Srcap |
G |
T |
7: 127,129,822 (GRCm39) |
R568L |
probably damaging |
Het |
Stag3 |
T |
A |
5: 138,309,997 (GRCm39) |
M1215K |
probably benign |
Het |
Tenm3 |
C |
T |
8: 48,732,083 (GRCm39) |
A1274T |
possibly damaging |
Het |
Tet2 |
A |
G |
3: 133,179,406 (GRCm39) |
V1253A |
possibly damaging |
Het |
Tns2 |
C |
T |
15: 102,017,369 (GRCm39) |
R281C |
probably damaging |
Het |
Trip12 |
T |
C |
1: 84,736,821 (GRCm39) |
I800V |
probably benign |
Het |
Zfc3h1 |
T |
C |
10: 115,248,013 (GRCm39) |
I1072T |
probably benign |
Het |
Zfp148 |
T |
A |
16: 33,315,835 (GRCm39) |
|
probably null |
Het |
Zfp941 |
A |
G |
7: 140,392,687 (GRCm39) |
V224A |
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 |
R1300:Npc1l1
|
UTSW |
11 |
6,177,859 (GRCm39) |
missense |
probably damaging |
1.00 |
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'- GAAATGGTCCTTCCAGTCCACCAG -3'
(R):5'- CGTAAGCGCAGATTCTCACCTCAC -3'
Sequencing Primer
(F):5'- TTGACACAGCAGTCAGTGAG -3'
(R):5'- TCTTCGAGAGCTGGGGAAC -3'
|
Posted On |
2014-03-14 |