Incidental Mutation 'R8549:Npc1l1'
| ID |
659783 |
| 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 |
068514-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably non essential
(E-score: 0.098)
|
| Stock # |
R8549 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
11 |
| Chromosomal Location |
6161013-6180143 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 6168675 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Phenylalanine to Serine
at position 902
(F902S)
|
| 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: F902S
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000004505
Gene: ENSMUSG00000020447
AA Change: F902S
| 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 |
0.9516 |
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 99.9%
- 10x: 99.6%
- 20x: 98.7%
|
| Validation Efficiency |
100% (45/45) |
| 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: 48 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4930562C15Rik |
T |
C |
16: 4,681,061 (GRCm39) |
|
probably null |
Het |
| Aadacl4 |
G |
A |
4: 144,349,726 (GRCm39) |
V328I |
probably benign |
Het |
| Adcy7 |
A |
T |
8: 89,052,818 (GRCm39) |
H968L |
probably benign |
Het |
| Ahnak |
G |
A |
19: 8,988,847 (GRCm39) |
G3377E |
probably damaging |
Het |
| Ank3 |
A |
G |
10: 69,818,012 (GRCm39) |
T56A |
possibly damaging |
Het |
| Anpep |
A |
G |
7: 79,490,644 (GRCm39) |
S291P |
probably benign |
Het |
| Arap3 |
G |
A |
18: 38,106,365 (GRCm39) |
P1493S |
probably benign |
Het |
| Bsn |
G |
A |
9: 107,988,651 (GRCm39) |
A2367V |
probably benign |
Het |
| C1rb |
T |
C |
6: 124,551,498 (GRCm39) |
Y203H |
probably benign |
Het |
| Caprin1 |
G |
T |
2: 103,599,862 (GRCm39) |
N604K |
probably damaging |
Het |
| Chrd |
A |
G |
16: 20,560,027 (GRCm39) |
E898G |
probably benign |
Het |
| Cobll1 |
T |
C |
2: 64,928,794 (GRCm39) |
D881G |
probably damaging |
Het |
| Cyp39a1 |
T |
A |
17: 44,041,886 (GRCm39) |
D364E |
possibly damaging |
Het |
| Defb33 |
G |
A |
8: 21,387,594 (GRCm39) |
G44R |
probably damaging |
Het |
| Efcab3 |
A |
T |
11: 104,890,521 (GRCm39) |
E4201V |
probably damaging |
Het |
| Ehhadh |
A |
T |
16: 21,585,168 (GRCm39) |
S238T |
probably benign |
Het |
| Eif5b |
G |
A |
1: 38,076,288 (GRCm39) |
R612Q |
possibly damaging |
Het |
| Eps8l1 |
G |
T |
7: 4,473,853 (GRCm39) |
R220L |
probably damaging |
Het |
| Frmd8 |
A |
G |
19: 5,919,565 (GRCm39) |
Y161H |
possibly damaging |
Het |
| Gad2 |
T |
A |
2: 22,525,059 (GRCm39) |
|
probably null |
Het |
| Gm4553 |
ACCCTTGCAGCCACCACAGGAGCCACAGCCCCCACAGGAGCTACAGCCTCCCTTGCAGCCACCACAGGAGCCACAGCCCCCACAGGAGCTACAGCCTCCCTTGCAGCCCCCACAGGAGCCACAGCC |
ACCCTTGCAGCCACCACAGGAGCCACAGCCCCCACAGGAGCTACAGCCTCCCTTGCAGCCCCCACAGGAGCCACAGCC |
7: 141,719,157 (GRCm39) |
|
probably benign |
Het |
| Gm5460 |
T |
C |
14: 33,758,892 (GRCm39) |
F184L |
possibly damaging |
Het |
| Grip2 |
C |
A |
6: 91,750,769 (GRCm39) |
|
probably null |
Het |
| Hrh4 |
T |
C |
18: 13,155,115 (GRCm39) |
F218S |
possibly damaging |
Het |
| Ippk |
T |
C |
13: 49,615,177 (GRCm39) |
V520A |
probably benign |
Het |
| Kif15 |
T |
A |
9: 122,815,236 (GRCm39) |
Y189N |
probably benign |
Het |
| Kif9 |
T |
G |
9: 110,343,487 (GRCm39) |
|
probably null |
Het |
| L1td1 |
T |
C |
4: 98,626,280 (GRCm39) |
F825S |
probably damaging |
Het |
| Mcm6 |
C |
T |
1: 128,273,685 (GRCm39) |
E382K |
possibly damaging |
Het |
| Nalcn |
T |
C |
14: 123,607,448 (GRCm39) |
T674A |
probably benign |
Het |
| Nbeal1 |
G |
A |
1: 60,274,721 (GRCm39) |
|
probably null |
Het |
| Nip7 |
C |
A |
8: 107,784,605 (GRCm39) |
|
probably null |
Het |
| Or4k48 |
C |
T |
2: 111,479,512 (GRCm39) |
|
probably benign |
Het |
| Pcdha6 |
T |
G |
18: 37,101,594 (GRCm39) |
I262M |
possibly damaging |
Het |
| Pcdhga1 |
T |
A |
18: 37,966,386 (GRCm39) |
*56R |
probably null |
Het |
| Plcb1 |
A |
G |
2: 135,206,853 (GRCm39) |
Y959C |
probably benign |
Het |
| Rnase9 |
T |
A |
14: 51,276,448 (GRCm39) |
I177L |
probably benign |
Het |
| Rtn3 |
T |
C |
19: 7,434,624 (GRCm39) |
N437S |
probably benign |
Het |
| Rufy3 |
T |
A |
5: 88,795,073 (GRCm39) |
|
probably null |
Het |
| Snx29 |
T |
C |
16: 11,532,920 (GRCm39) |
|
probably null |
Het |
| Szt2 |
C |
A |
4: 118,229,878 (GRCm39) |
R2751L |
unknown |
Het |
| Tagap |
A |
G |
17: 8,152,797 (GRCm39) |
T661A |
probably benign |
Het |
| Tcp10b |
T |
A |
17: 13,281,915 (GRCm39) |
I95K |
probably benign |
Het |
| Topbp1 |
T |
C |
9: 103,201,577 (GRCm39) |
F637L |
probably damaging |
Het |
| Yju2b |
A |
T |
8: 84,985,399 (GRCm39) |
V290E |
probably benign |
Het |
| Zfp41 |
C |
T |
15: 75,490,540 (GRCm39) |
T164M |
probably benign |
Het |
| Zfp707 |
T |
A |
15: 75,846,547 (GRCm39) |
I126N |
probably benign |
Het |
| Zfp957 |
T |
C |
14: 79,451,346 (GRCm39) |
E151G |
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 |
|
R8081:Npc1l1
|
UTSW |
11 |
6,167,768 (GRCm39) |
missense |
probably benign |
0.01 |
|
R8272:Npc1l1
|
UTSW |
11 |
6,179,327 (GRCm39) |
nonsense |
probably null |
|
|
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'- GCTGCAGAAACAGAGCATGC -3'
(R):5'- CGTGTACCTCTGAGTGTGTC -3'
Sequencing Primer
(F):5'- CAGAAACAGAGCATGCAGGAAG -3'
(R):5'- GAGTGTGTCTTCTGCTTCCAGATAC -3'
|
| Posted On |
2021-01-18 |
Incidental Mutation