Incidental Mutation 'R5760:Npc1l1'
ID |
445255 |
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 |
043362-MU
|
Accession Numbers |
|
Essential gene? |
Probably non essential
(E-score: 0.098)
|
Stock # |
R5760 (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 T
at 6179031 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Histidine to Glutamine
at position 126
(H126Q)
|
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: H126Q
PolyPhen 2
Score 0.021 (Sensitivity: 0.95; Specificity: 0.80)
|
SMART Domains |
Protein: ENSMUSP00000004505 Gene: ENSMUSG00000020447 AA Change: H126Q
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: 99.5%
- 3x: 98.8%
- 10x: 97.3%
- 20x: 95.3%
|
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: 47 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
4930447A16Rik |
T |
C |
15: 37,439,835 (GRCm39) |
|
probably benign |
Het |
Abl2 |
C |
T |
1: 156,469,427 (GRCm39) |
T793M |
probably benign |
Het |
Accs |
A |
C |
2: 93,676,105 (GRCm39) |
L90R |
probably damaging |
Het |
Ahnak |
A |
T |
19: 8,990,926 (GRCm39) |
D4070V |
probably damaging |
Het |
Apbb2 |
A |
G |
5: 66,520,100 (GRCm39) |
V475A |
probably benign |
Het |
Atp10d |
T |
A |
5: 72,418,280 (GRCm39) |
V602E |
probably benign |
Het |
Cdh23 |
C |
T |
10: 60,242,171 (GRCm39) |
V1088M |
probably damaging |
Het |
Dennd6a |
A |
T |
14: 26,333,195 (GRCm39) |
I144L |
probably damaging |
Het |
Dnajc6 |
G |
A |
4: 101,475,839 (GRCm39) |
A571T |
probably benign |
Het |
Drap1 |
A |
G |
19: 5,474,391 (GRCm39) |
I18T |
probably damaging |
Het |
En2 |
C |
A |
5: 28,371,997 (GRCm39) |
A158D |
probably benign |
Het |
Fbn1 |
C |
T |
2: 125,203,167 (GRCm39) |
G1219R |
probably damaging |
Het |
Fkbpl |
G |
A |
17: 34,864,303 (GRCm39) |
A24T |
probably benign |
Het |
Gm7535 |
C |
T |
17: 18,132,080 (GRCm39) |
|
probably benign |
Het |
Hao2 |
A |
T |
3: 98,787,748 (GRCm39) |
L227* |
probably null |
Het |
Hdlbp |
C |
T |
1: 93,368,499 (GRCm39) |
|
probably benign |
Het |
Hivep3 |
A |
G |
4: 119,952,208 (GRCm39) |
K175E |
possibly damaging |
Het |
Hmcn2 |
G |
A |
2: 31,304,580 (GRCm39) |
A3075T |
possibly damaging |
Het |
Igkv6-15 |
A |
T |
6: 70,383,516 (GRCm39) |
I95N |
probably damaging |
Het |
Itgad |
A |
T |
7: 127,802,537 (GRCm39) |
Q1001L |
probably benign |
Het |
Jaml |
T |
A |
9: 45,009,052 (GRCm39) |
M151K |
probably benign |
Het |
Lix1 |
T |
A |
17: 17,647,499 (GRCm39) |
V55D |
possibly damaging |
Het |
Macf1 |
A |
G |
4: 123,407,677 (GRCm39) |
S179P |
probably damaging |
Het |
Matn2 |
T |
A |
15: 34,355,753 (GRCm39) |
Q33L |
possibly damaging |
Het |
Mcm3 |
CT |
CTT |
1: 20,878,972 (GRCm39) |
|
probably null |
Het |
Mroh5 |
A |
C |
15: 73,693,356 (GRCm39) |
I28S |
probably damaging |
Het |
Naip5 |
T |
G |
13: 100,379,346 (GRCm39) |
K231N |
probably damaging |
Het |
Neb |
A |
C |
2: 52,073,830 (GRCm39) |
Y5683D |
probably damaging |
Het |
Npm2 |
A |
G |
14: 70,886,935 (GRCm39) |
F110L |
probably damaging |
Het |
Nsd3 |
A |
T |
8: 26,149,772 (GRCm39) |
H319L |
probably damaging |
Het |
Nup205 |
G |
A |
6: 35,224,278 (GRCm39) |
R2039Q |
probably damaging |
Het |
Or10j7 |
C |
A |
1: 173,011,318 (GRCm39) |
A228S |
probably benign |
Het |
Or6b2b |
A |
G |
1: 92,418,922 (GRCm39) |
L185P |
possibly damaging |
Het |
Or7d10 |
A |
C |
9: 19,832,050 (GRCm39) |
T182P |
probably benign |
Het |
Pcdhac2 |
G |
A |
18: 37,279,453 (GRCm39) |
G811E |
probably damaging |
Het |
Pkhd1 |
T |
A |
1: 20,143,778 (GRCm39) |
R3849S |
probably benign |
Het |
Pmfbp1 |
A |
T |
8: 110,247,655 (GRCm39) |
D317V |
probably damaging |
Het |
Sall1 |
T |
C |
8: 89,755,278 (GRCm39) |
N1234D |
possibly damaging |
Het |
Slc12a7 |
T |
A |
13: 73,961,741 (GRCm39) |
V1037D |
probably damaging |
Het |
Slc12a8 |
G |
T |
16: 33,445,155 (GRCm39) |
E404* |
probably null |
Het |
Tchhl1 |
C |
G |
3: 93,378,863 (GRCm39) |
S522R |
probably damaging |
Het |
Tgif1 |
A |
G |
17: 71,151,996 (GRCm39) |
V152A |
probably damaging |
Het |
Tshz3 |
C |
A |
7: 36,470,994 (GRCm39) |
H994Q |
probably damaging |
Het |
Ubash3b |
T |
G |
9: 40,988,719 (GRCm39) |
K62T |
probably benign |
Het |
Ushbp1 |
G |
T |
8: 71,840,012 (GRCm39) |
D546E |
probably damaging |
Het |
Zfp458 |
A |
C |
13: 67,405,853 (GRCm39) |
C192W |
probably damaging |
Het |
Zfp808 |
A |
T |
13: 62,319,740 (GRCm39) |
H323L |
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 |
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 |
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'- TCCTTGGAAGTTGAGCCAGC -3'
(R):5'- GCTTGTCTAATACCCCAGCC -3'
Sequencing Primer
(F):5'- CGCTGAGCATTGCAGAGG -3'
(R):5'- AGCCCGCCATGTCACAG -3'
|
Posted On |
2016-11-21 |