Incidental Mutation 'R3155:Npc1l1'
ID |
263469 |
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 |
040606-MU
|
Accession Numbers |
|
Essential gene? |
Probably non essential
(E-score: 0.098)
|
Stock # |
R3155 (G1)
|
Quality Score |
225 |
Status
|
Validated
|
Chromosome |
11 |
Chromosomal Location |
6161013-6180143 bp(-) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
A to C
at 6171840 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Aspartic acid to Glutamic Acid
at position 874
(D874E)
|
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: D874E
PolyPhen 2
Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
|
SMART Domains |
Protein: ENSMUSP00000004505 Gene: ENSMUSG00000020447 AA Change: D874E
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 |
0.0898 |
Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.6%
- 10x: 97.4%
- 20x: 95.5%
|
Validation Efficiency |
100% (39/39) |
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: 39 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
4933407L21Rik |
T |
C |
1: 85,859,104 (GRCm39) |
|
probably benign |
Het |
Aco1 |
T |
C |
4: 40,182,915 (GRCm39) |
V487A |
probably damaging |
Het |
Adh1 |
A |
G |
3: 137,986,250 (GRCm39) |
E79G |
probably damaging |
Het |
Aebp1 |
A |
G |
11: 5,821,425 (GRCm39) |
N608S |
probably benign |
Het |
Ahctf1 |
G |
A |
1: 179,583,148 (GRCm39) |
R43C |
probably damaging |
Het |
Ahnak |
A |
T |
19: 8,987,541 (GRCm39) |
I2942L |
possibly damaging |
Het |
Anxa9 |
A |
T |
3: 95,209,716 (GRCm39) |
D134E |
probably benign |
Het |
Ccdc14 |
A |
G |
16: 34,544,222 (GRCm39) |
D860G |
probably damaging |
Het |
Cdhr3 |
T |
A |
12: 33,099,152 (GRCm39) |
I480F |
possibly damaging |
Het |
Cldn34a |
C |
T |
X: 151,346,840 (GRCm39) |
H171Y |
probably benign |
Het |
Cyp2d9 |
T |
A |
15: 82,336,843 (GRCm39) |
|
probably null |
Het |
Dmbt1 |
T |
A |
7: 130,651,887 (GRCm39) |
Y376* |
probably null |
Het |
Fancm |
T |
C |
12: 65,163,195 (GRCm39) |
I1453T |
probably benign |
Het |
Fbxw11 |
A |
G |
11: 32,689,244 (GRCm39) |
I456V |
possibly damaging |
Het |
Fut2 |
A |
T |
7: 45,300,091 (GRCm39) |
L227Q |
probably damaging |
Het |
Gbp5 |
T |
C |
3: 142,208,888 (GRCm39) |
|
probably null |
Het |
Glrp1 |
C |
A |
1: 88,430,976 (GRCm39) |
Q131H |
unknown |
Het |
Gm6871 |
T |
C |
7: 41,223,079 (GRCm39) |
N3S |
probably benign |
Het |
H2-Eb1 |
C |
A |
17: 34,533,348 (GRCm39) |
T190K |
probably damaging |
Het |
Kdr |
T |
A |
5: 76,129,065 (GRCm39) |
I194F |
probably benign |
Het |
Klhdc7a |
A |
G |
4: 139,694,500 (GRCm39) |
V149A |
probably benign |
Het |
Lrit3 |
A |
G |
3: 129,585,044 (GRCm39) |
F238S |
probably benign |
Het |
Map10 |
A |
T |
8: 126,398,313 (GRCm39) |
I569F |
possibly damaging |
Het |
Myh6 |
A |
G |
14: 55,182,125 (GRCm39) |
I1761T |
probably damaging |
Het |
Or4k15c |
T |
C |
14: 50,321,982 (GRCm39) |
D52G |
probably benign |
Het |
Or8c17 |
T |
A |
9: 38,179,836 (GRCm39) |
M1K |
probably null |
Het |
Pawr |
A |
G |
10: 108,245,370 (GRCm39) |
T193A |
probably benign |
Het |
Ppp2r3d |
T |
C |
9: 101,089,559 (GRCm39) |
K255E |
possibly damaging |
Het |
Rbp3 |
A |
T |
14: 33,679,071 (GRCm39) |
K1006N |
probably damaging |
Het |
Rif1 |
GCCACCA |
GCCA |
2: 52,000,336 (GRCm39) |
|
probably benign |
Het |
Rin2 |
A |
G |
2: 145,702,771 (GRCm39) |
K489R |
probably benign |
Het |
Rlf |
A |
G |
4: 121,006,529 (GRCm39) |
V817A |
probably damaging |
Het |
Rusc1 |
T |
C |
3: 88,999,038 (GRCm39) |
D248G |
probably benign |
Het |
Slc15a4 |
A |
G |
5: 127,681,600 (GRCm39) |
|
probably null |
Het |
Stk4 |
T |
A |
2: 163,993,663 (GRCm39) |
M98K |
probably benign |
Het |
Taf15 |
T |
A |
11: 83,393,599 (GRCm39) |
H307Q |
probably benign |
Het |
Urgcp |
A |
T |
11: 5,666,327 (GRCm39) |
F670L |
probably damaging |
Het |
Vmn2r76 |
T |
C |
7: 85,874,959 (GRCm39) |
T673A |
probably damaging |
Het |
Zfp324 |
G |
A |
7: 12,702,817 (GRCm39) |
M60I |
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 |
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'- CGCTCACACTTACAACATGGATG -3'
(R):5'- AGAGCTTGAGCCTGTCCAAC -3'
Sequencing Primer
(F):5'- CACACTTACAACATGGATGTGCTTTC -3'
(R):5'- AACTCTAGGACGTTTCCCAGGATG -3'
|
Posted On |
2015-02-05 |