Incidental Mutation 'R6644:Npc1l1'
ID |
526025 |
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 |
044765-MU
|
Accession Numbers |
|
Essential gene? |
Probably non essential
(E-score: 0.098)
|
Stock # |
R6644 (G1)
|
Quality Score |
138.008 |
Status
|
Validated
|
Chromosome |
11 |
Chromosomal Location |
6161013-6180143 bp(-) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
G to T
at 6164014 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Leucine to Methionine
at position 1266
(L1266M)
|
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: L1266M
PolyPhen 2
Score 0.983 (Sensitivity: 0.75; Specificity: 0.96)
|
SMART Domains |
Protein: ENSMUSP00000004505 Gene: ENSMUSG00000020447 AA Change: L1266M
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 |
0.6467 |
Coding Region Coverage |
- 1x: 99.9%
- 3x: 99.5%
- 10x: 97.5%
- 20x: 92.3%
|
Validation Efficiency |
100% (50/50) |
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: 49 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
Abca7 |
C |
T |
10: 79,844,598 (GRCm39) |
P1461L |
probably damaging |
Het |
Abhd14a |
T |
C |
9: 106,321,472 (GRCm39) |
Y10C |
probably damaging |
Het |
Adcy2 |
C |
T |
13: 68,816,671 (GRCm39) |
V772M |
possibly damaging |
Het |
Apob |
A |
G |
12: 8,059,077 (GRCm39) |
M2487V |
probably damaging |
Het |
B4galnt1 |
T |
C |
10: 127,007,662 (GRCm39) |
|
probably null |
Het |
Cabp7 |
C |
T |
11: 4,690,396 (GRCm39) |
V76I |
probably benign |
Het |
Cbr3 |
A |
G |
16: 93,487,399 (GRCm39) |
Y194C |
probably damaging |
Het |
Cdk18 |
G |
A |
1: 132,049,807 (GRCm39) |
Q58* |
probably null |
Het |
Cryba4 |
T |
C |
5: 112,394,628 (GRCm39) |
D167G |
probably damaging |
Het |
Czib |
T |
G |
4: 107,752,119 (GRCm39) |
I130S |
probably damaging |
Het |
Dner |
T |
C |
1: 84,373,428 (GRCm39) |
N588S |
probably damaging |
Het |
Dnm1l |
T |
C |
16: 16,147,737 (GRCm39) |
I343V |
probably benign |
Het |
Eif1ad16 |
A |
G |
12: 87,985,460 (GRCm39) |
F28L |
probably benign |
Het |
Fam168b |
C |
A |
1: 34,875,822 (GRCm39) |
G21V |
probably damaging |
Het |
Fbxw17 |
G |
A |
13: 50,577,255 (GRCm39) |
R49Q |
probably damaging |
Het |
Garin2 |
T |
A |
12: 78,762,060 (GRCm39) |
D241E |
probably damaging |
Het |
Gm10332 |
T |
A |
14: 55,057,616 (GRCm39) |
F59I |
probably damaging |
Het |
Gnai3 |
A |
G |
3: 108,030,852 (GRCm39) |
|
probably null |
Het |
Helz |
T |
A |
11: 107,523,087 (GRCm39) |
M75K |
possibly damaging |
Het |
Hnrnph3 |
C |
T |
10: 62,854,672 (GRCm39) |
|
probably benign |
Het |
Ifi211 |
C |
T |
1: 173,733,118 (GRCm39) |
C181Y |
probably benign |
Het |
Immp1l |
A |
G |
2: 105,767,390 (GRCm39) |
K83R |
probably damaging |
Het |
Itga6 |
G |
A |
2: 71,671,468 (GRCm39) |
G740R |
probably damaging |
Het |
Klhl1 |
T |
C |
14: 96,755,354 (GRCm39) |
T134A |
probably benign |
Het |
Klhl7 |
A |
G |
5: 24,354,244 (GRCm39) |
D353G |
probably damaging |
Het |
Map3k1 |
A |
G |
13: 111,888,983 (GRCm39) |
S1325P |
probably benign |
Het |
Map3k4 |
A |
G |
17: 12,451,297 (GRCm39) |
|
probably null |
Het |
Meioc |
G |
A |
11: 102,559,286 (GRCm39) |
|
probably null |
Het |
Mfap5 |
T |
C |
6: 122,497,555 (GRCm39) |
F26L |
probably damaging |
Het |
Myo5a |
A |
G |
9: 75,054,249 (GRCm39) |
T386A |
probably damaging |
Het |
Or4c116 |
A |
G |
2: 88,942,325 (GRCm39) |
M177T |
probably benign |
Het |
Or51aa2 |
C |
A |
7: 103,188,265 (GRCm39) |
V59F |
possibly damaging |
Het |
Pbld1 |
T |
A |
10: 62,910,842 (GRCm39) |
S233T |
probably damaging |
Het |
Phf12 |
A |
G |
11: 77,916,918 (GRCm39) |
*789W |
probably null |
Het |
Sf3b2 |
A |
T |
19: 5,329,992 (GRCm39) |
|
probably null |
Het |
Slc23a3 |
A |
G |
1: 75,105,191 (GRCm39) |
I459T |
probably damaging |
Het |
Spata31e4 |
A |
G |
13: 50,856,071 (GRCm39) |
T570A |
possibly damaging |
Het |
Sptbn2 |
C |
G |
19: 4,799,040 (GRCm39) |
R2037G |
probably benign |
Het |
Stard9 |
A |
C |
2: 120,526,253 (GRCm39) |
M837L |
probably benign |
Het |
Stx5a |
A |
T |
19: 8,732,612 (GRCm39) |
|
probably benign |
Het |
Tmc7 |
A |
G |
7: 118,137,385 (GRCm39) |
V719A |
probably benign |
Het |
Trank1 |
T |
A |
9: 111,193,902 (GRCm39) |
I642K |
possibly damaging |
Het |
Trim34a |
T |
C |
7: 103,910,244 (GRCm39) |
Y349H |
probably damaging |
Het |
Uba7 |
A |
G |
9: 107,858,671 (GRCm39) |
Y834C |
possibly damaging |
Het |
Ube2d1 |
A |
G |
10: 71,092,530 (GRCm39) |
S105P |
possibly damaging |
Het |
Vps13a |
A |
G |
19: 16,722,283 (GRCm39) |
V343A |
possibly damaging |
Het |
Zbtb37 |
G |
A |
1: 160,859,643 (GRCm39) |
Q221* |
probably null |
Het |
Zfp119b |
T |
C |
17: 56,246,148 (GRCm39) |
N346S |
probably benign |
Het |
Zfp708 |
G |
T |
13: 67,218,785 (GRCm39) |
T358K |
possibly 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 |
6,164,013 (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'- GCAGCCCACACAGTGTTTAAG -3'
(R):5'- GATCCACCTGAGCCTTTATGTC -3'
Sequencing Primer
(F):5'- TGTTTAAGACACAATCAACTCACAG -3'
(R):5'- TGCTGACTCCTGGCTGTGAC -3'
|
Posted On |
2018-06-22 |