Incidental Mutation 'R0322:Npc1l1'
ID |
25625 |
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 |
038532-MU
|
Accession Numbers |
|
Essential gene? |
Probably non essential
(E-score: 0.098)
|
Stock # |
R0322 (G1)
|
Quality Score |
225 |
Status
|
Validated
|
Chromosome |
11 |
Chromosomal Location |
6161013-6180143 bp(-) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
T to A
at 6179042 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Isoleucine to Leucine
at position 123
(I123L)
|
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: I123L
PolyPhen 2
Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
|
SMART Domains |
Protein: ENSMUSP00000004505 Gene: ENSMUSG00000020447 AA Change: I123L
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 |
|
Meta Mutation Damage Score |
0.0898 |
Coding Region Coverage |
- 1x: 98.7%
- 3x: 97.5%
- 10x: 93.8%
- 20x: 84.3%
|
Validation Efficiency |
98% (58/59) |
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: 55 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
9130401M01Rik |
A |
T |
15: 57,888,768 (GRCm39) |
S275T |
possibly damaging |
Het |
Adam34 |
G |
T |
8: 44,104,958 (GRCm39) |
T229N |
probably benign |
Het |
Adgrb3 |
C |
A |
1: 25,260,829 (GRCm39) |
|
probably benign |
Het |
Ankhd1 |
T |
A |
18: 36,791,061 (GRCm39) |
Y2478* |
probably null |
Het |
Arl9 |
A |
G |
5: 77,155,037 (GRCm39) |
|
probably benign |
Het |
Bub1b |
G |
A |
2: 118,470,099 (GRCm39) |
|
probably benign |
Het |
Chl1 |
A |
T |
6: 103,678,844 (GRCm39) |
|
probably benign |
Het |
Cobl |
T |
A |
11: 12,217,072 (GRCm39) |
E465V |
probably damaging |
Het |
Cobll1 |
A |
T |
2: 64,932,442 (GRCm39) |
M520K |
possibly damaging |
Het |
Dll3 |
A |
G |
7: 27,995,793 (GRCm39) |
V336A |
possibly damaging |
Het |
Dnmbp |
T |
C |
19: 43,843,285 (GRCm39) |
H1193R |
probably damaging |
Het |
Fbxo43 |
T |
C |
15: 36,152,338 (GRCm39) |
|
probably benign |
Het |
Gart |
G |
A |
16: 91,419,925 (GRCm39) |
|
probably benign |
Het |
Gjc3 |
A |
T |
5: 137,955,760 (GRCm39) |
M175K |
possibly damaging |
Het |
Gpc5 |
T |
A |
14: 115,636,563 (GRCm39) |
N415K |
probably benign |
Het |
Idh2 |
C |
T |
7: 79,748,005 (GRCm39) |
A232T |
probably damaging |
Het |
Il7r |
A |
T |
15: 9,510,301 (GRCm39) |
F251I |
probably benign |
Het |
Insc |
A |
G |
7: 114,391,500 (GRCm39) |
E141G |
probably damaging |
Het |
Itm2c |
C |
T |
1: 85,834,751 (GRCm39) |
T160M |
probably damaging |
Het |
Mboat1 |
T |
C |
13: 30,416,063 (GRCm39) |
|
probably benign |
Het |
Mdm2 |
G |
T |
10: 117,538,109 (GRCm39) |
H96Q |
possibly damaging |
Het |
Mettl13 |
A |
G |
1: 162,371,745 (GRCm39) |
|
probably benign |
Het |
Mfsd4b3-ps |
T |
C |
10: 39,823,526 (GRCm39) |
N245D |
probably damaging |
Het |
Mroh2a |
C |
T |
1: 88,158,402 (GRCm39) |
R150* |
probably null |
Het |
Mtmr3 |
T |
C |
11: 4,437,505 (GRCm39) |
Y982C |
possibly damaging |
Het |
Mymk |
A |
T |
2: 26,957,418 (GRCm39) |
L66Q |
probably damaging |
Het |
Myo18a |
T |
C |
11: 77,720,626 (GRCm39) |
S767P |
probably damaging |
Het |
Ndufa8 |
T |
C |
2: 35,926,634 (GRCm39) |
D134G |
probably benign |
Het |
Noxa1 |
A |
G |
2: 24,982,566 (GRCm39) |
F83S |
probably damaging |
Het |
Ogdhl |
A |
G |
14: 32,059,534 (GRCm39) |
T394A |
probably benign |
Het |
Or4s2b |
T |
C |
2: 88,509,011 (GRCm39) |
S264P |
probably damaging |
Het |
Or5ae1 |
A |
G |
7: 84,565,521 (GRCm39) |
Y178C |
probably damaging |
Het |
Pcdh20 |
T |
C |
14: 88,706,383 (GRCm39) |
T306A |
probably benign |
Het |
Pcid2 |
G |
A |
8: 13,140,775 (GRCm39) |
|
probably benign |
Het |
Phyhip |
G |
A |
14: 70,700,836 (GRCm39) |
V108M |
possibly damaging |
Het |
Pnpla5 |
G |
T |
15: 84,004,920 (GRCm39) |
L144M |
probably damaging |
Het |
Psmb4 |
A |
G |
3: 94,793,402 (GRCm39) |
Y160H |
probably benign |
Het |
Riox2 |
A |
T |
16: 59,309,752 (GRCm39) |
K369* |
probably null |
Het |
Rnf26rt |
T |
C |
6: 76,473,401 (GRCm39) |
Y405C |
probably benign |
Het |
Sh3tc1 |
G |
A |
5: 35,863,905 (GRCm39) |
P761S |
possibly damaging |
Het |
Slc6a3 |
T |
A |
13: 73,709,045 (GRCm39) |
V323D |
possibly damaging |
Het |
Smg7 |
A |
G |
1: 152,725,624 (GRCm39) |
|
probably null |
Het |
Srrt |
G |
A |
5: 137,294,870 (GRCm39) |
R370C |
probably damaging |
Het |
Stc1 |
T |
C |
14: 69,266,858 (GRCm39) |
V7A |
probably benign |
Het |
Svep1 |
G |
T |
4: 58,057,996 (GRCm39) |
|
probably benign |
Het |
Tbpl2 |
A |
G |
2: 23,984,991 (GRCm39) |
V51A |
probably benign |
Het |
Tecr |
A |
G |
8: 84,298,872 (GRCm39) |
Y248H |
probably damaging |
Het |
Tenm3 |
A |
G |
8: 48,689,947 (GRCm39) |
|
probably benign |
Het |
Tia1 |
C |
T |
6: 86,397,369 (GRCm39) |
A114V |
probably damaging |
Het |
Tmprss11f |
A |
T |
5: 86,739,275 (GRCm39) |
M2K |
probably benign |
Het |
Tnfsf8 |
T |
C |
4: 63,752,403 (GRCm39) |
T221A |
probably damaging |
Het |
Tubgcp5 |
G |
A |
7: 55,464,726 (GRCm39) |
G536S |
probably damaging |
Het |
Tyr |
A |
T |
7: 87,142,125 (GRCm39) |
I145N |
probably benign |
Het |
Ubr4 |
T |
A |
4: 139,149,729 (GRCm39) |
V1809E |
probably damaging |
Het |
Vmn2r65 |
A |
T |
7: 84,595,756 (GRCm39) |
N309K |
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 |
|
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 |
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'- ATTGCAGAGGGCAGAGCCATACAC -3'
(R):5'- TTGGCACCCTAAGCATAGCACG -3'
Sequencing Primer
(F):5'- ATGCTGCCCACAGCCAG -3'
(R):5'- TGTGCCAACCAGCCTTAG -3'
|
Posted On |
2013-04-16 |