Incidental Mutation 'R5532:Npc1l1'
| ID |
436233 |
| 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 |
043090-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably non essential
(E-score: 0.098)
|
| Stock # |
R5532 (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 6174245 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Tyrosine to Histidine
at position 687
(Y687H)
|
| 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: Y687H
PolyPhen 2
Score 0.978 (Sensitivity: 0.76; Specificity: 0.96)
|
| SMART Domains |
Protein: ENSMUSP00000004505
Gene: ENSMUSG00000020447
AA Change: Y687H
| 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: 99.9%
- 3x: 99.6%
- 10x: 98.1%
- 20x: 94.4%
|
| 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: 44 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| A2ml1 |
T |
A |
6: 128,530,293 (GRCm39) |
|
probably null |
Het |
| Adsl |
C |
G |
15: 80,848,110 (GRCm39) |
P118A |
probably damaging |
Het |
| Ano6 |
C |
T |
15: 95,860,122 (GRCm39) |
P748L |
probably damaging |
Het |
| Arhgap10 |
A |
T |
8: 78,146,701 (GRCm39) |
N234K |
probably benign |
Het |
| Arhgap18 |
T |
A |
10: 26,722,104 (GRCm39) |
I25K |
possibly damaging |
Het |
| AW551984 |
T |
C |
9: 39,508,481 (GRCm39) |
Y345C |
probably damaging |
Het |
| Ccdc146 |
A |
G |
5: 21,510,329 (GRCm39) |
V561A |
probably benign |
Het |
| Cenpv |
G |
A |
11: 62,418,398 (GRCm39) |
T185M |
probably damaging |
Het |
| Fat2 |
T |
A |
11: 55,153,163 (GRCm39) |
D3683V |
probably damaging |
Het |
| Galns |
T |
C |
8: 123,311,765 (GRCm39) |
D415G |
possibly damaging |
Het |
| Gatad2a |
G |
A |
8: 70,369,070 (GRCm39) |
T259M |
probably damaging |
Het |
| Gja8 |
T |
C |
3: 96,827,648 (GRCm39) |
S5G |
probably benign |
Het |
| Ifi209 |
T |
C |
1: 173,466,542 (GRCm39) |
S125P |
probably damaging |
Het |
| Iigp1c |
A |
G |
18: 60,379,142 (GRCm39) |
I226V |
probably benign |
Het |
| Il12rb2 |
G |
A |
6: 67,269,246 (GRCm39) |
R856W |
probably damaging |
Het |
| Kcnq3 |
A |
T |
15: 65,869,622 (GRCm39) |
Y605* |
probably null |
Het |
| Klk1b16 |
T |
C |
7: 43,790,950 (GRCm39) |
S251P |
probably benign |
Het |
| Map2 |
A |
G |
1: 66,453,779 (GRCm39) |
N890D |
probably damaging |
Het |
| Map4 |
T |
A |
9: 109,863,746 (GRCm39) |
S324T |
probably benign |
Het |
| Mmp28 |
T |
C |
11: 83,333,684 (GRCm39) |
D419G |
probably damaging |
Het |
| Mtnr1b |
A |
G |
9: 15,774,210 (GRCm39) |
L283P |
probably benign |
Het |
| Ndufb7 |
T |
A |
8: 84,298,063 (GRCm39) |
Y95N |
probably damaging |
Het |
| Nfrkb |
C |
T |
9: 31,309,075 (GRCm39) |
R280W |
probably damaging |
Het |
| Or6f1 |
A |
C |
7: 85,970,879 (GRCm39) |
F94V |
possibly damaging |
Het |
| Or8b40 |
C |
T |
9: 38,027,923 (GRCm39) |
T277I |
probably benign |
Het |
| Or8g51 |
T |
C |
9: 38,608,943 (GRCm39) |
T240A |
probably damaging |
Het |
| Or8h9 |
T |
A |
2: 86,788,924 (GRCm39) |
R293* |
probably null |
Het |
| Pabpc4l |
T |
C |
3: 46,401,044 (GRCm39) |
D200G |
probably benign |
Het |
| Plekhg6 |
T |
C |
6: 125,349,514 (GRCm39) |
E361G |
possibly damaging |
Het |
| Pramel31 |
A |
T |
4: 144,090,061 (GRCm39) |
D367V |
probably damaging |
Het |
| Rictor |
A |
G |
15: 6,819,046 (GRCm39) |
Y1423C |
probably damaging |
Het |
| Rsf1 |
G |
A |
7: 97,329,902 (GRCm39) |
D1143N |
probably damaging |
Het |
| Spsb4 |
C |
T |
9: 96,877,627 (GRCm39) |
|
probably null |
Het |
| Strada |
G |
T |
11: 106,061,843 (GRCm39) |
A136E |
probably damaging |
Het |
| Syce2 |
A |
T |
8: 85,610,131 (GRCm39) |
Q73L |
probably damaging |
Het |
| Teddm2 |
A |
T |
1: 153,726,130 (GRCm39) |
V195D |
probably benign |
Het |
| Tex36 |
A |
T |
7: 133,203,712 (GRCm39) |
N12K |
probably benign |
Het |
| Ubtf |
A |
G |
11: 102,199,785 (GRCm39) |
S484P |
probably benign |
Het |
| Ufd1 |
T |
G |
16: 18,636,680 (GRCm39) |
L66R |
probably damaging |
Het |
| Vmn2r74 |
C |
T |
7: 85,601,197 (GRCm39) |
A814T |
probably benign |
Het |
| Vmn2r98 |
T |
C |
17: 19,287,645 (GRCm39) |
S493P |
possibly damaging |
Het |
| Xrcc1 |
T |
A |
7: 24,267,353 (GRCm39) |
|
probably null |
Het |
| Zfp277 |
A |
C |
12: 40,385,308 (GRCm39) |
C305G |
probably damaging |
Het |
| Zfp998 |
A |
T |
13: 66,579,740 (GRCm39) |
C248S |
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 |
|
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'- AATGAATTTGTGCCAACCCAGG -3'
(R):5'- TGAGCACCAATGATGCCTGC -3'
Sequencing Primer
(F):5'- ACCAGAATTCCAGTGAGTCTGTGC -3'
(R):5'- AATGATGCCTGCCCACTC -3'
|
| Posted On |
2016-10-24 |
Incidental Mutation