Incidental Mutation 'R1588:Npc1l1'
ID |
177649 |
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 |
039625-MU
|
Accession Numbers |
|
Essential gene? |
Probably non essential
(E-score: 0.098)
|
Stock # |
R1588 (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 G
at 6167785 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Valine to Alanine
at position 1002
(V1002A)
|
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: V1002A
PolyPhen 2
Score 0.012 (Sensitivity: 0.96; Specificity: 0.78)
|
SMART Domains |
Protein: ENSMUSP00000004505 Gene: ENSMUSG00000020447 AA Change: V1002A
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: 98.0%
- 10x: 95.0%
- 20x: 87.7%
|
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: 56 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
Abcc4 |
A |
G |
14: 118,771,484 (GRCm39) |
V869A |
probably benign |
Het |
Ablim1 |
C |
T |
19: 57,071,979 (GRCm39) |
M1I |
probably null |
Het |
Adamts13 |
A |
T |
2: 26,865,687 (GRCm39) |
I81F |
probably benign |
Het |
Akap11 |
A |
T |
14: 78,747,685 (GRCm39) |
N1567K |
possibly damaging |
Het |
Arrdc4 |
G |
A |
7: 68,391,484 (GRCm39) |
T261M |
possibly damaging |
Het |
C4b |
T |
C |
17: 34,959,999 (GRCm39) |
I326V |
probably benign |
Het |
Casp8ap2 |
G |
A |
4: 32,640,541 (GRCm39) |
A532T |
probably benign |
Het |
Ccdc134 |
A |
G |
15: 82,019,337 (GRCm39) |
T187A |
probably benign |
Het |
Cdh8 |
T |
C |
8: 99,917,039 (GRCm39) |
N359D |
probably damaging |
Het |
Cep97 |
A |
G |
16: 55,748,184 (GRCm39) |
L82P |
probably damaging |
Het |
Cfap53 |
A |
T |
18: 74,440,444 (GRCm39) |
R404S |
probably benign |
Het |
Chrng |
C |
A |
1: 87,135,229 (GRCm39) |
F179L |
probably damaging |
Het |
Ddi1 |
A |
T |
9: 6,265,391 (GRCm39) |
I326K |
probably damaging |
Het |
Decr2 |
T |
C |
17: 26,302,002 (GRCm39) |
T243A |
possibly damaging |
Het |
Dip2c |
T |
C |
13: 9,715,900 (GRCm39) |
V1502A |
probably damaging |
Het |
Edem1 |
T |
C |
6: 108,818,640 (GRCm39) |
V216A |
probably damaging |
Het |
Fat2 |
A |
C |
11: 55,174,230 (GRCm39) |
V2161G |
probably damaging |
Het |
Fbn1 |
T |
C |
2: 125,161,034 (GRCm39) |
T2169A |
probably benign |
Het |
Fmn1 |
T |
C |
2: 113,196,043 (GRCm39) |
V581A |
unknown |
Het |
Hip1r |
A |
T |
5: 124,134,638 (GRCm39) |
D350V |
probably damaging |
Het |
Ift140 |
G |
A |
17: 25,306,959 (GRCm39) |
R898H |
probably damaging |
Het |
Il12a |
A |
G |
3: 68,602,896 (GRCm39) |
I159V |
probably benign |
Het |
Itprid1 |
A |
G |
6: 55,955,488 (GRCm39) |
E1032G |
possibly damaging |
Het |
Kl |
A |
G |
5: 150,906,097 (GRCm39) |
E489G |
probably benign |
Het |
Klhl3 |
T |
C |
13: 58,161,712 (GRCm39) |
E461G |
probably damaging |
Het |
Masp1 |
T |
C |
16: 23,313,404 (GRCm39) |
Y177C |
probably damaging |
Het |
Nop58 |
T |
A |
1: 59,742,031 (GRCm39) |
Y187N |
probably damaging |
Het |
Ntaq1 |
T |
A |
15: 58,021,285 (GRCm39) |
|
probably null |
Het |
Ntrk1 |
A |
T |
3: 87,687,384 (GRCm39) |
Y683* |
probably null |
Het |
Or11g26 |
A |
G |
14: 50,753,584 (GRCm39) |
I308V |
probably benign |
Het |
Or13j1 |
C |
T |
4: 43,705,923 (GRCm39) |
C215Y |
probably damaging |
Het |
Or2w4 |
C |
T |
13: 21,796,083 (GRCm39) |
D19N |
probably benign |
Het |
Or8k21 |
T |
C |
2: 86,144,874 (GRCm39) |
Y252C |
probably damaging |
Het |
Osbpl6 |
T |
C |
2: 76,409,560 (GRCm39) |
V367A |
probably benign |
Het |
Phip |
A |
G |
9: 82,782,881 (GRCm39) |
W855R |
probably damaging |
Het |
Phlpp1 |
A |
G |
1: 106,308,115 (GRCm39) |
S1131G |
probably damaging |
Het |
Pkdrej |
A |
T |
15: 85,701,442 (GRCm39) |
V1498E |
probably benign |
Het |
Pramel22 |
G |
T |
4: 143,382,121 (GRCm39) |
L192M |
probably damaging |
Het |
Prkaa2 |
T |
C |
4: 104,908,420 (GRCm39) |
N152D |
probably damaging |
Het |
Ptpro |
T |
A |
6: 137,420,592 (GRCm39) |
V1007D |
probably damaging |
Het |
Pxdn |
G |
A |
12: 30,052,558 (GRCm39) |
V732M |
probably damaging |
Het |
Rccd1 |
C |
T |
7: 79,969,859 (GRCm39) |
W223* |
probably null |
Het |
Riox2 |
T |
A |
16: 59,295,946 (GRCm39) |
S16T |
possibly damaging |
Het |
Scn5a |
C |
T |
9: 119,350,367 (GRCm39) |
V836I |
probably damaging |
Het |
Serpinf1 |
G |
A |
11: 75,301,076 (GRCm39) |
R380C |
probably damaging |
Het |
Sf3b1 |
A |
T |
1: 55,036,336 (GRCm39) |
N912K |
probably benign |
Het |
Shprh |
T |
A |
10: 11,040,488 (GRCm39) |
C134S |
probably damaging |
Het |
Skint8 |
T |
A |
4: 111,785,924 (GRCm39) |
C123* |
probably null |
Het |
Slc16a13 |
G |
T |
11: 70,109,421 (GRCm39) |
S360* |
probably null |
Het |
Srr |
A |
G |
11: 74,799,629 (GRCm39) |
I282T |
possibly damaging |
Het |
Trpm1 |
T |
C |
7: 63,873,565 (GRCm39) |
F607L |
possibly damaging |
Het |
Ttn |
T |
C |
2: 76,539,870 (GRCm39) |
D34372G |
probably benign |
Het |
Tub |
C |
T |
7: 108,628,888 (GRCm39) |
T401I |
probably damaging |
Het |
Wdhd1 |
T |
C |
14: 47,493,693 (GRCm39) |
E9G |
probably damaging |
Het |
Yipf3 |
T |
A |
17: 46,561,787 (GRCm39) |
F198Y |
possibly damaging |
Het |
Zfp955a |
C |
T |
17: 33,460,791 (GRCm39) |
R447K |
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 |
R1455:Npc1l1
|
UTSW |
11 |
6,178,174 (GRCm39) |
missense |
possibly damaging |
0.66 |
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'- AACGAGACCTTGTCCTGTCAGTCC -3'
(R):5'- TCACACTATCAGTGTCCCCTGGAG -3'
Sequencing Primer
(F):5'- TCACTGTGCCCCAGAAAGG -3'
(R):5'- CTATGGCCCTGCATATGGAG -3'
|
Posted On |
2014-04-24 |