Incidental Mutation 'R7383:Npc1l1'
ID |
572888 |
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 |
045465-MU
|
Accession Numbers |
|
Essential gene? |
Probably non essential
(E-score: 0.098)
|
Stock # |
R7383 (G1)
|
Quality Score |
225.009 |
Status
|
Not validated
|
Chromosome |
11 |
Chromosomal Location |
6161013-6180143 bp(-) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
T to C
at 6167777 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Threonine to Alanine
at position 1005
(T1005A)
|
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: T1005A
PolyPhen 2
Score 0.304 (Sensitivity: 0.90; Specificity: 0.89)
|
SMART Domains |
Protein: ENSMUSP00000004505 Gene: ENSMUSG00000020447 AA Change: T1005A
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: 100.0%
- 3x: 100.0%
- 10x: 99.8%
- 20x: 99.3%
|
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: 71 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
Aebp1 |
T |
A |
11: 5,818,548 (GRCm39) |
I511N |
probably damaging |
Het |
Ap5m1 |
T |
G |
14: 49,311,653 (GRCm39) |
V241G |
possibly damaging |
Het |
BC049715 |
T |
A |
6: 136,817,453 (GRCm39) |
I231N |
probably damaging |
Het |
Bckdhb |
T |
G |
9: 83,835,766 (GRCm39) |
V90G |
possibly damaging |
Het |
Cep20 |
TTGTG |
TTG |
16: 14,118,009 (GRCm39) |
|
probably null |
Het |
Chd8 |
T |
C |
14: 52,452,776 (GRCm39) |
I1248V |
probably damaging |
Het |
Ckap2l |
A |
T |
2: 129,111,172 (GRCm39) |
M675K |
possibly damaging |
Het |
Ckap4 |
A |
T |
10: 84,364,148 (GRCm39) |
V305E |
probably damaging |
Het |
Clasrp |
C |
A |
7: 19,319,198 (GRCm39) |
R489L |
unknown |
Het |
Col24a1 |
A |
G |
3: 145,004,599 (GRCm39) |
I26V |
probably benign |
Het |
Cort |
C |
T |
4: 149,209,861 (GRCm39) |
A64T |
possibly damaging |
Het |
Dmkn |
T |
A |
7: 30,464,793 (GRCm39) |
N255K |
unknown |
Het |
Dph2 |
A |
T |
4: 117,748,566 (GRCm39) |
L69Q |
probably damaging |
Het |
Fbxo11 |
A |
G |
17: 88,310,282 (GRCm39) |
I432T |
|
Het |
Fgd3 |
T |
C |
13: 49,421,785 (GRCm39) |
K531R |
possibly damaging |
Het |
Fgd5 |
A |
G |
6: 91,964,099 (GRCm39) |
K111E |
probably benign |
Het |
Gdf6 |
T |
A |
4: 9,859,537 (GRCm39) |
D206E |
probably benign |
Het |
Gtpbp1 |
T |
A |
15: 79,600,354 (GRCm39) |
L429Q |
probably damaging |
Het |
Hk2 |
A |
G |
6: 82,726,276 (GRCm39) |
F90S |
probably damaging |
Het |
Hrnr |
A |
T |
3: 93,239,098 (GRCm39) |
Q3112L |
unknown |
Het |
Hsd17b4 |
A |
C |
18: 50,297,917 (GRCm39) |
K402T |
probably benign |
Het |
Htr1f |
T |
C |
16: 64,747,206 (GRCm39) |
T29A |
probably benign |
Het |
Ikbkb |
C |
A |
8: 23,159,066 (GRCm39) |
A471S |
probably benign |
Het |
Inpp5f |
A |
G |
7: 128,296,310 (GRCm39) |
D887G |
probably damaging |
Het |
Ipo9 |
A |
G |
1: 135,316,411 (GRCm39) |
L805P |
probably damaging |
Het |
Jmjd1c |
A |
T |
10: 67,025,537 (GRCm39) |
N118I |
probably benign |
Het |
Kif26b |
T |
G |
1: 178,358,275 (GRCm39) |
C129G |
probably damaging |
Het |
Mga |
G |
A |
2: 119,790,821 (GRCm39) |
A2236T |
probably damaging |
Het |
Micu2 |
T |
C |
14: 58,154,810 (GRCm39) |
Q405R |
possibly damaging |
Het |
Myo1e |
T |
A |
9: 70,204,577 (GRCm39) |
V59D |
probably damaging |
Het |
Nav3 |
A |
G |
10: 109,552,532 (GRCm39) |
I1770T |
probably damaging |
Het |
Ndufa10 |
A |
T |
1: 92,392,183 (GRCm39) |
I190N |
probably damaging |
Het |
Niban3 |
A |
C |
8: 72,056,470 (GRCm39) |
E390A |
possibly damaging |
Het |
Npat |
T |
A |
9: 53,474,078 (GRCm39) |
H623Q |
probably benign |
Het |
Or10ag58 |
A |
G |
2: 87,265,721 (GRCm39) |
S297G |
possibly damaging |
Het |
Or14c39 |
A |
T |
7: 86,343,960 (GRCm39) |
I99F |
probably damaging |
Het |
Or1e22 |
A |
G |
11: 73,376,715 (GRCm39) |
*312Q |
probably null |
Het |
Or2b4 |
A |
G |
17: 38,116,972 (GRCm39) |
K312R |
probably benign |
Het |
Or2w3 |
T |
C |
11: 58,557,011 (GRCm39) |
S209P |
possibly damaging |
Het |
Or5t7 |
A |
G |
2: 86,507,263 (GRCm39) |
V138A |
possibly damaging |
Het |
Or8s8 |
C |
G |
15: 98,354,578 (GRCm39) |
P129R |
probably damaging |
Het |
Pafah1b2 |
C |
T |
9: 45,880,147 (GRCm39) |
G177R |
probably benign |
Het |
Phc1 |
A |
G |
6: 122,300,317 (GRCm39) |
S521P |
unknown |
Het |
Plpp2 |
A |
T |
10: 79,366,841 (GRCm39) |
L25Q |
probably null |
Het |
Plxna4 |
A |
G |
6: 32,129,734 (GRCm39) |
|
probably null |
Het |
Ppl |
G |
T |
16: 4,915,835 (GRCm39) |
P576Q |
probably damaging |
Het |
Rab38 |
T |
C |
7: 88,079,637 (GRCm39) |
Y10H |
possibly damaging |
Het |
Rbfox1 |
G |
A |
16: 6,887,899 (GRCm39) |
G13S |
probably benign |
Het |
Rhot1 |
C |
G |
11: 80,114,760 (GRCm39) |
P56R |
probably damaging |
Het |
Sipa1l2 |
A |
G |
8: 126,174,385 (GRCm39) |
W1298R |
probably damaging |
Het |
Slc16a14 |
G |
A |
1: 84,890,292 (GRCm39) |
H338Y |
probably damaging |
Het |
Slc8a3 |
T |
G |
12: 81,362,579 (GRCm39) |
Y80S |
probably damaging |
Het |
Slco6c1 |
A |
T |
1: 97,003,608 (GRCm39) |
Y513* |
probably null |
Het |
Smarcd2 |
A |
G |
11: 106,155,602 (GRCm39) |
C405R |
probably damaging |
Het |
Szt2 |
G |
A |
4: 118,222,411 (GRCm39) |
R3198* |
probably null |
Het |
Tmeff1 |
T |
A |
4: 48,636,841 (GRCm39) |
C180S |
probably damaging |
Het |
Tmem132a |
A |
T |
19: 10,844,358 (GRCm39) |
M80K |
probably benign |
Het |
Tnfsf12 |
A |
G |
11: 69,577,892 (GRCm39) |
V175A |
probably damaging |
Het |
Tnpo2 |
G |
A |
8: 85,776,748 (GRCm39) |
R485H |
probably damaging |
Het |
Togaram2 |
A |
T |
17: 72,007,512 (GRCm39) |
I354F |
probably damaging |
Het |
Uchl5 |
T |
A |
1: 143,659,753 (GRCm39) |
S42R |
probably benign |
Het |
Virma |
C |
A |
4: 11,514,026 (GRCm39) |
L627I |
probably damaging |
Het |
Vmn2r12 |
A |
T |
5: 109,240,684 (GRCm39) |
I143K |
probably benign |
Het |
Vmn2r95 |
T |
G |
17: 18,660,734 (GRCm39) |
V382G |
probably benign |
Het |
Wipf3 |
G |
T |
6: 54,462,263 (GRCm39) |
A158S |
probably benign |
Het |
Ylpm1 |
T |
G |
12: 85,091,242 (GRCm39) |
S1809A |
possibly damaging |
Het |
Zdhhc5 |
A |
T |
2: 84,524,748 (GRCm39) |
C191S |
probably benign |
Het |
Zer1 |
G |
A |
2: 30,001,253 (GRCm39) |
R84C |
probably damaging |
Het |
Zfhx2 |
A |
T |
14: 55,305,710 (GRCm39) |
V991D |
probably benign |
Het |
Zscan4b |
C |
A |
7: 10,637,960 (GRCm39) |
M61I |
possibly damaging |
Het |
Zswim2 |
A |
T |
2: 83,745,672 (GRCm39) |
S589T |
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 |
6,164,014 (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 |
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'- AGACCTTGTCCTGTCAGTCC -3'
(R):5'- CATTTCTTGACCCCACAACTGG -3'
Sequencing Primer
(F):5'- TCACTGTGCCCCAGAAAGG -3'
(R):5'- GGGGTGGCAGGTGTAAACCTC -3'
|
Posted On |
2019-09-13 |