Incidental Mutation 'R5369:Npc1l1'
ID |
429558 |
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 |
042946-MU
|
Accession Numbers |
|
Essential gene? |
Probably non essential
(E-score: 0.098)
|
Stock # |
R5369 (G1)
|
Quality Score |
225 |
Status
|
Validated
|
Chromosome |
11 |
Chromosomal Location |
6161013-6180143 bp(-) (GRCm39) |
Type of Mutation |
critical splice donor site (2 bp from exon) |
DNA Base Change (assembly) |
A to G
at 6167705 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
|
Ref Sequence |
ENSEMBL: ENSMUSP00000004505
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000004505]
|
AlphaFold |
no structure available at present |
Predicted Effect |
probably null
Transcript: ENSMUST00000004505
|
SMART Domains |
Protein: ENSMUSP00000004505 Gene: ENSMUSG00000020447
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 |
0.9485 |
Coding Region Coverage |
- 1x: 99.3%
- 3x: 98.7%
- 10x: 97.4%
- 20x: 95.6%
|
Validation Efficiency |
99% (77/78) |
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: 74 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
A2ml1 |
T |
C |
6: 128,545,796 (GRCm39) |
T444A |
probably damaging |
Het |
A330070K13Rik |
G |
A |
5: 130,407,932 (GRCm39) |
|
probably benign |
Het |
Abcb8 |
C |
T |
5: 24,605,137 (GRCm39) |
R108C |
possibly damaging |
Het |
Acbd5 |
T |
A |
2: 23,002,522 (GRCm39) |
L508Q |
probably damaging |
Het |
Asb15 |
T |
C |
6: 24,562,563 (GRCm39) |
V175A |
probably benign |
Het |
B3galnt2 |
T |
C |
13: 14,169,010 (GRCm39) |
|
probably null |
Het |
BC024139 |
A |
C |
15: 76,004,422 (GRCm39) |
S711R |
probably benign |
Het |
Bod1l |
A |
G |
5: 41,984,526 (GRCm39) |
I508T |
probably damaging |
Het |
Btnl6 |
T |
A |
17: 34,726,959 (GRCm39) |
R524* |
probably null |
Het |
C3 |
C |
A |
17: 57,528,159 (GRCm39) |
D687Y |
probably benign |
Het |
Ccbe1 |
G |
A |
18: 66,194,485 (GRCm39) |
A367V |
probably benign |
Het |
Ccr1 |
A |
T |
9: 123,764,326 (GRCm39) |
M68K |
probably damaging |
Het |
Cd27 |
T |
A |
6: 125,211,327 (GRCm39) |
|
probably benign |
Het |
Celf2 |
C |
A |
2: 7,085,892 (GRCm39) |
|
probably benign |
Het |
Cfap54 |
T |
C |
10: 92,897,119 (GRCm39) |
|
probably benign |
Het |
Cfap97 |
A |
G |
8: 46,622,687 (GRCm39) |
K26E |
probably damaging |
Het |
Clcn4 |
T |
A |
7: 7,299,032 (GRCm39) |
I48F |
probably benign |
Het |
Cnot7 |
A |
T |
8: 40,947,061 (GRCm39) |
N238K |
probably benign |
Het |
Colec12 |
A |
G |
18: 9,866,750 (GRCm39) |
I654V |
unknown |
Het |
Dip2a |
A |
G |
10: 76,128,194 (GRCm39) |
I22T |
probably damaging |
Het |
Eif4g3 |
C |
T |
4: 137,910,645 (GRCm39) |
T1375M |
possibly damaging |
Het |
Eml5 |
C |
T |
12: 98,825,042 (GRCm39) |
G725D |
probably damaging |
Het |
F12 |
T |
C |
13: 55,566,304 (GRCm39) |
E496G |
probably benign |
Het |
Fam227a |
A |
T |
15: 79,499,637 (GRCm39) |
S573T |
probably benign |
Het |
Fnip1 |
T |
C |
11: 54,393,415 (GRCm39) |
V593A |
probably benign |
Het |
Focad |
T |
A |
4: 88,039,610 (GRCm39) |
|
probably benign |
Het |
Frem1 |
A |
G |
4: 82,919,976 (GRCm39) |
I460T |
possibly damaging |
Het |
Galnt10 |
T |
G |
11: 57,656,573 (GRCm39) |
|
probably null |
Het |
Gm5592 |
A |
T |
7: 40,867,635 (GRCm39) |
|
probably benign |
Het |
Gm6185 |
A |
T |
1: 161,037,330 (GRCm39) |
|
noncoding transcript |
Het |
Gm7935 |
A |
T |
15: 73,952,963 (GRCm39) |
|
noncoding transcript |
Het |
Grb14 |
C |
T |
2: 64,747,653 (GRCm39) |
V369I |
probably benign |
Het |
Gstm5 |
G |
A |
3: 107,805,782 (GRCm39) |
A198T |
probably damaging |
Het |
Herc2 |
T |
A |
7: 55,832,448 (GRCm39) |
V3048D |
probably damaging |
Het |
Htra4 |
T |
G |
8: 25,523,585 (GRCm39) |
I327L |
possibly damaging |
Het |
Ifi209 |
T |
C |
1: 173,464,873 (GRCm39) |
M1T |
probably null |
Het |
Ints6 |
T |
C |
14: 62,981,384 (GRCm39) |
T135A |
probably damaging |
Het |
Itpr1 |
T |
A |
6: 108,496,385 (GRCm39) |
I2604N |
probably damaging |
Het |
Krt6a |
T |
A |
15: 101,600,993 (GRCm39) |
M268L |
probably benign |
Het |
Lrp1b |
G |
T |
2: 40,894,625 (GRCm39) |
S2201* |
probably null |
Het |
Lrp2 |
T |
C |
2: 69,289,904 (GRCm39) |
N3645S |
probably benign |
Het |
Lrrc15 |
A |
T |
16: 30,091,722 (GRCm39) |
I539N |
possibly damaging |
Het |
Map3k6 |
T |
C |
4: 132,974,992 (GRCm39) |
I675T |
probably damaging |
Het |
Map3k9 |
T |
A |
12: 81,768,826 (GRCm39) |
E1074V |
probably damaging |
Het |
Med13l |
T |
A |
5: 118,862,075 (GRCm39) |
S339R |
probably benign |
Het |
Mrps18a |
T |
C |
17: 46,436,552 (GRCm39) |
|
probably benign |
Het |
Mtcl2 |
T |
C |
2: 156,882,654 (GRCm39) |
E466G |
probably damaging |
Het |
Nat8f2 |
G |
T |
6: 85,844,854 (GRCm39) |
Y169* |
probably null |
Het |
Nlrp1b |
A |
G |
11: 71,072,625 (GRCm39) |
I406T |
probably benign |
Het |
Or10z1 |
A |
G |
1: 174,078,007 (GRCm39) |
V162A |
probably damaging |
Het |
Or5ac20 |
A |
T |
16: 59,104,743 (GRCm39) |
M39K |
probably damaging |
Het |
Ostf1 |
C |
T |
19: 18,558,689 (GRCm39) |
G198E |
probably benign |
Het |
Pcsk5 |
A |
G |
19: 17,558,619 (GRCm39) |
V596A |
probably damaging |
Het |
Pde4c |
T |
C |
8: 71,202,754 (GRCm39) |
*647Q |
probably null |
Het |
Pkm |
A |
T |
9: 59,577,917 (GRCm39) |
I245F |
probably damaging |
Het |
Prss3b |
T |
A |
6: 41,009,940 (GRCm39) |
R131S |
probably benign |
Het |
Ptprj |
T |
C |
2: 90,299,985 (GRCm39) |
H179R |
probably benign |
Het |
Rapgef2 |
A |
T |
3: 78,976,739 (GRCm39) |
S1356T |
probably benign |
Het |
Rbm45 |
T |
A |
2: 76,200,594 (GRCm39) |
L41Q |
probably damaging |
Het |
Rsf1 |
ATGGCG |
ATGGCGACGGTGGCG |
7: 97,229,111 (GRCm39) |
|
probably benign |
Het |
Scara5 |
CG |
C |
14: 65,997,111 (GRCm39) |
|
probably null |
Het |
Scel |
A |
T |
14: 103,823,929 (GRCm39) |
I386F |
probably benign |
Het |
Serpinb5 |
A |
T |
1: 106,809,487 (GRCm39) |
N298Y |
possibly damaging |
Het |
Sirt3 |
A |
T |
7: 140,449,406 (GRCm39) |
L180Q |
probably damaging |
Het |
Slc24a2 |
C |
T |
4: 86,909,625 (GRCm39) |
V698I |
probably damaging |
Het |
Slc43a3 |
A |
T |
2: 84,788,067 (GRCm39) |
H483L |
probably damaging |
Het |
Snrnp35 |
A |
G |
5: 124,628,262 (GRCm39) |
D25G |
probably benign |
Het |
Snrnp40 |
T |
C |
4: 130,256,439 (GRCm39) |
S55P |
probably damaging |
Het |
Snx9 |
T |
A |
17: 5,970,855 (GRCm39) |
C399S |
probably damaging |
Het |
Ttbk2 |
T |
C |
2: 120,655,743 (GRCm39) |
|
probably benign |
Het |
Vmn1r1 |
A |
G |
1: 181,985,341 (GRCm39) |
V108A |
possibly damaging |
Het |
Vmn1r201 |
T |
A |
13: 22,659,672 (GRCm39) |
N295K |
probably benign |
Het |
Zfp292 |
G |
A |
4: 34,807,491 (GRCm39) |
P1851L |
possibly damaging |
Het |
Zfp472 |
A |
T |
17: 33,196,717 (GRCm39) |
D264V |
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 |
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'- GAGGTTCTATACGCTGCTAGG -3'
(R):5'- TTGGGCACAGAATGGGAGTC -3'
Sequencing Primer
(F):5'- TATACGCTGCTAGGCCCCTG -3'
(R):5'- AGTCAGGACAGGAGCTGCC -3'
|
Posted On |
2016-09-06 |