Incidental Mutation 'R0352:Npc1l1'
ID |
29717 |
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 |
038558-MU
|
Accession Numbers |
|
Essential gene? |
Probably non essential
(E-score: 0.098)
|
Stock # |
R0352 (G1)
|
Quality Score |
225 |
Status
|
Validated
|
Chromosome |
11 |
Chromosomal Location |
6161013-6180143 bp(-) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
T to C
at 6173076 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Methionine to Valine
at position 788
(M788V)
|
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: M788V
PolyPhen 2
Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)
|
SMART Domains |
Protein: ENSMUSP00000004505 Gene: ENSMUSG00000020447 AA Change: M788V
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 |
0.0715 |
Coding Region Coverage |
- 1x: 99.0%
- 3x: 97.9%
- 10x: 95.4%
- 20x: 90.0%
|
Validation Efficiency |
100% (70/70) |
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: 67 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
2700049A03Rik |
C |
T |
12: 71,184,804 (GRCm39) |
T64M |
possibly damaging |
Het |
3110040N11Rik |
G |
T |
7: 81,438,208 (GRCm39) |
N49K |
probably benign |
Het |
Adrb1 |
T |
A |
19: 56,711,293 (GRCm39) |
F164I |
probably damaging |
Het |
Aplf |
C |
T |
6: 87,630,866 (GRCm39) |
V190I |
probably benign |
Het |
Aqr |
A |
G |
2: 114,000,533 (GRCm39) |
Y50H |
probably damaging |
Het |
Arfgef3 |
A |
C |
10: 18,537,135 (GRCm39) |
I182R |
probably benign |
Het |
Cacna1b |
G |
A |
2: 24,515,244 (GRCm39) |
|
probably benign |
Het |
Casp9 |
A |
G |
4: 141,532,841 (GRCm39) |
T246A |
probably damaging |
Het |
Clcn6 |
A |
G |
4: 148,099,063 (GRCm39) |
S427P |
probably damaging |
Het |
Cnga1 |
T |
C |
5: 72,761,846 (GRCm39) |
N556S |
possibly damaging |
Het |
Cntnap2 |
G |
A |
6: 45,969,018 (GRCm39) |
|
probably null |
Het |
Col11a2 |
T |
G |
17: 34,261,501 (GRCm39) |
V120G |
probably benign |
Het |
Cux2 |
A |
C |
5: 122,022,802 (GRCm39) |
|
probably benign |
Het |
Dmrt2 |
T |
C |
19: 25,656,026 (GRCm39) |
S542P |
probably damaging |
Het |
Dnah7b |
A |
G |
1: 46,316,286 (GRCm39) |
H3133R |
probably damaging |
Het |
Drosha |
G |
A |
15: 12,837,374 (GRCm39) |
R286Q |
unknown |
Het |
Eipr1 |
A |
G |
12: 28,816,784 (GRCm39) |
D47G |
probably damaging |
Het |
Fras1 |
T |
G |
5: 96,874,399 (GRCm39) |
Y2275D |
probably damaging |
Het |
Grm4 |
C |
T |
17: 27,670,865 (GRCm39) |
|
probably benign |
Het |
Hebp1 |
A |
G |
6: 135,129,918 (GRCm39) |
V100A |
possibly damaging |
Het |
Hivep2 |
G |
A |
10: 14,019,039 (GRCm39) |
V1937I |
possibly damaging |
Het |
Hs3st6 |
T |
C |
17: 24,977,168 (GRCm39) |
V216A |
probably damaging |
Het |
Hsd17b4 |
T |
C |
18: 50,324,851 (GRCm39) |
I688T |
probably benign |
Het |
Hydin |
T |
C |
8: 111,296,533 (GRCm39) |
|
probably null |
Het |
Iws1 |
A |
G |
18: 32,217,258 (GRCm39) |
E426G |
probably damaging |
Het |
Klrb1f |
T |
C |
6: 129,030,680 (GRCm39) |
S64P |
probably damaging |
Het |
Lacc1 |
C |
T |
14: 77,272,629 (GRCm39) |
G56R |
probably damaging |
Het |
Lcmt2 |
A |
G |
2: 120,969,377 (GRCm39) |
S569P |
probably benign |
Het |
Lipm |
C |
T |
19: 34,090,275 (GRCm39) |
|
probably benign |
Het |
Lum |
A |
G |
10: 97,404,471 (GRCm39) |
H122R |
probably damaging |
Het |
Magi2 |
A |
G |
5: 20,270,664 (GRCm39) |
Y15C |
probably damaging |
Het |
Mal |
A |
T |
2: 127,482,286 (GRCm39) |
I39N |
probably damaging |
Het |
Mgme1 |
A |
G |
2: 144,118,319 (GRCm39) |
H197R |
probably benign |
Het |
Mmrn1 |
A |
T |
6: 60,921,955 (GRCm39) |
K137N |
probably benign |
Het |
Myh3 |
T |
A |
11: 66,981,254 (GRCm39) |
C706S |
possibly damaging |
Het |
Myo18b |
A |
T |
5: 113,022,389 (GRCm39) |
|
probably benign |
Het |
Myom1 |
A |
G |
17: 71,352,744 (GRCm39) |
E356G |
possibly damaging |
Het |
Nfib |
A |
G |
4: 82,422,954 (GRCm39) |
|
probably benign |
Het |
Or9a2 |
C |
T |
6: 41,749,058 (GRCm39) |
M58I |
probably damaging |
Het |
Pdha2 |
A |
G |
3: 140,917,457 (GRCm39) |
V17A |
probably benign |
Het |
Pgap1 |
A |
T |
1: 54,525,617 (GRCm39) |
|
probably benign |
Het |
Polr1a |
G |
T |
6: 71,897,747 (GRCm39) |
|
probably benign |
Het |
Ppp1r16a |
C |
T |
15: 76,574,999 (GRCm39) |
|
probably benign |
Het |
Pramel20 |
A |
T |
4: 143,297,878 (GRCm39) |
|
probably benign |
Het |
Pramel21 |
A |
T |
4: 143,342,559 (GRCm39) |
D222V |
possibly damaging |
Het |
Prmt2 |
A |
T |
10: 76,044,337 (GRCm39) |
V405D |
possibly damaging |
Het |
Psg26 |
T |
A |
7: 18,209,181 (GRCm39) |
Y409F |
probably benign |
Het |
Psme3ip1 |
A |
G |
8: 95,314,639 (GRCm39) |
F73S |
probably damaging |
Het |
Ptges |
G |
T |
2: 30,793,144 (GRCm39) |
Y29* |
probably null |
Het |
Ptrhd1 |
A |
G |
12: 4,286,399 (GRCm39) |
T97A |
probably benign |
Het |
Ripk3 |
T |
A |
14: 56,024,200 (GRCm39) |
|
probably benign |
Het |
Rnf114 |
A |
T |
2: 167,353,136 (GRCm39) |
I136F |
probably benign |
Het |
Serinc5 |
A |
G |
13: 92,844,497 (GRCm39) |
|
probably null |
Het |
Slc17a3 |
C |
T |
13: 24,039,841 (GRCm39) |
S293F |
probably damaging |
Het |
Slc23a2 |
C |
A |
2: 131,902,716 (GRCm39) |
M495I |
probably benign |
Het |
Slc52a3 |
T |
A |
2: 151,849,433 (GRCm39) |
L360* |
probably null |
Het |
Snapc1 |
C |
T |
12: 74,021,806 (GRCm39) |
R81C |
probably damaging |
Het |
Syt5 |
A |
G |
7: 4,544,170 (GRCm39) |
V290A |
probably benign |
Het |
Szt2 |
G |
A |
4: 118,239,790 (GRCm39) |
A1931V |
unknown |
Het |
Tasp1 |
A |
G |
2: 139,793,378 (GRCm39) |
|
probably null |
Het |
Tcp10a |
C |
A |
17: 7,593,805 (GRCm39) |
D43E |
probably damaging |
Het |
Tnfsf11 |
A |
T |
14: 78,516,408 (GRCm39) |
Y187N |
probably benign |
Het |
Tppp2 |
T |
A |
14: 52,156,807 (GRCm39) |
N61K |
possibly damaging |
Het |
Wwtr1 |
A |
T |
3: 57,482,548 (GRCm39) |
W100R |
probably damaging |
Het |
Zfp623 |
A |
G |
15: 75,820,433 (GRCm39) |
D463G |
probably benign |
Het |
Zfp990 |
A |
G |
4: 145,263,174 (GRCm39) |
I57M |
probably damaging |
Het |
Zmat5 |
G |
A |
11: 4,672,413 (GRCm39) |
C10Y |
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 |
|
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'- ATTGGTGAGCACAGAGCCCCAAAC -3'
(R):5'- TCTTTCTAGGTGAGCAAGGGCTGTC -3'
Sequencing Primer
(F):5'- AAACATTCTCTCTCAGAATACTGTCC -3'
(R):5'- AGCCCAGGCTTTCAGAAG -3'
|
Posted On |
2013-04-24 |