Incidental Mutation 'R5540:Npc1l1'
ID |
435901 |
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 |
043098-MU
|
Accession Numbers |
|
Essential gene? |
Probably non essential
(E-score: 0.098)
|
Stock # |
R5540 (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 G
at 6164546 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Serine to Proline
at position 1168
(S1168P)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000004505
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000004505]
|
AlphaFold |
no structure available at present |
Predicted Effect |
probably damaging
Transcript: ENSMUST00000004505
AA Change: S1168P
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
SMART Domains |
Protein: ENSMUSP00000004505 Gene: ENSMUSG00000020447 AA Change: S1168P
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: 99.9%
- 3x: 99.7%
- 10x: 98.6%
- 20x: 96.1%
|
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: 74 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
1700008O03Rik |
A |
G |
7: 44,012,371 (GRCm39) |
S15P |
probably damaging |
Het |
Actl7a |
A |
T |
4: 56,744,388 (GRCm39) |
H305L |
probably benign |
Het |
Adam26b |
C |
A |
8: 43,974,654 (GRCm39) |
C116F |
probably damaging |
Het |
Adgrl2 |
A |
G |
3: 148,543,198 (GRCm39) |
|
probably null |
Het |
Akr1b10 |
A |
G |
6: 34,371,047 (GRCm39) |
T238A |
probably damaging |
Het |
Akr1c18 |
A |
G |
13: 4,187,178 (GRCm39) |
V186A |
probably benign |
Het |
Alpk3 |
G |
A |
7: 80,745,184 (GRCm39) |
V1311M |
probably damaging |
Het |
Aox1 |
A |
G |
1: 58,143,569 (GRCm39) |
N1229S |
probably benign |
Het |
Apobec3 |
T |
A |
15: 79,782,120 (GRCm39) |
N43K |
probably benign |
Het |
Arid1a |
A |
C |
4: 133,407,765 (GRCm39) |
D2247E |
unknown |
Het |
Asph |
A |
G |
4: 9,635,906 (GRCm39) |
L77S |
probably damaging |
Het |
Cd300ld |
T |
A |
11: 114,878,231 (GRCm39) |
T94S |
probably damaging |
Het |
Celf2 |
T |
C |
2: 6,558,743 (GRCm39) |
T382A |
probably benign |
Het |
Cfap54 |
C |
T |
10: 92,808,470 (GRCm39) |
A1402T |
possibly damaging |
Het |
Chrnb1 |
A |
T |
11: 69,686,476 (GRCm39) |
V48E |
probably benign |
Het |
Col6a5 |
T |
A |
9: 105,739,975 (GRCm39) |
E2548V |
probably benign |
Het |
Crebrf |
A |
G |
17: 26,961,071 (GRCm39) |
D56G |
possibly damaging |
Het |
Dctn5 |
A |
G |
7: 121,734,275 (GRCm39) |
T40A |
probably benign |
Het |
Dmxl2 |
A |
T |
9: 54,301,141 (GRCm39) |
N2323K |
probably benign |
Het |
Dync1h1 |
A |
G |
12: 110,627,384 (GRCm39) |
Q4021R |
probably benign |
Het |
Dyrk1a |
T |
G |
16: 94,486,202 (GRCm39) |
|
probably null |
Het |
Ephb3 |
T |
A |
16: 21,039,610 (GRCm39) |
F454Y |
probably damaging |
Het |
Fbxo38 |
A |
G |
18: 62,647,864 (GRCm39) |
|
probably null |
Het |
Flg |
T |
C |
3: 93,184,923 (GRCm39) |
F15S |
probably damaging |
Het |
Fndc3b |
G |
A |
3: 27,555,651 (GRCm39) |
P301L |
probably damaging |
Het |
Fpr-rs7 |
C |
T |
17: 20,334,356 (GRCm39) |
G45R |
probably damaging |
Het |
Garin3 |
A |
G |
11: 46,295,715 (GRCm39) |
N29S |
probably damaging |
Het |
Gfi1 |
T |
A |
5: 107,867,991 (GRCm39) |
T360S |
probably damaging |
Het |
Grik4 |
T |
C |
9: 42,432,243 (GRCm39) |
H918R |
probably damaging |
Het |
Hpx |
A |
G |
7: 105,241,119 (GRCm39) |
S385P |
possibly damaging |
Het |
Kdm5b |
A |
G |
1: 134,558,979 (GRCm39) |
D1501G |
probably damaging |
Het |
Kif20b |
A |
T |
19: 34,915,860 (GRCm39) |
M546L |
probably benign |
Het |
Map3k9 |
G |
T |
12: 81,819,587 (GRCm39) |
N222K |
probably damaging |
Het |
Me1 |
A |
G |
9: 86,561,926 (GRCm39) |
L53P |
possibly damaging |
Het |
Mis18bp1 |
T |
C |
12: 65,195,520 (GRCm39) |
E748G |
possibly damaging |
Het |
Morc3 |
T |
A |
16: 93,644,268 (GRCm39) |
N186K |
probably benign |
Het |
Mtor |
A |
G |
4: 148,539,165 (GRCm39) |
T221A |
probably benign |
Het |
Muc6 |
A |
G |
7: 141,235,850 (GRCm39) |
|
probably null |
Het |
Myh8 |
C |
A |
11: 67,177,266 (GRCm39) |
T444N |
probably benign |
Het |
Myo7b |
A |
G |
18: 32,140,143 (GRCm39) |
Y216H |
probably damaging |
Het |
Myom1 |
G |
A |
17: 71,416,782 (GRCm39) |
V1382M |
probably damaging |
Het |
Nbeal2 |
A |
T |
9: 110,460,801 (GRCm39) |
Y1718N |
probably damaging |
Het |
Or4c58 |
A |
G |
2: 89,675,011 (GRCm39) |
F102S |
probably damaging |
Het |
Or4d2 |
T |
A |
11: 87,784,511 (GRCm39) |
K80* |
probably null |
Het |
Or51f5 |
C |
T |
7: 102,424,136 (GRCm39) |
A135V |
probably benign |
Het |
Or5an9 |
T |
A |
19: 12,187,824 (GRCm39) |
I298N |
probably damaging |
Het |
Or6c8b |
G |
T |
10: 128,882,364 (GRCm39) |
D189E |
probably damaging |
Het |
Pcdha4 |
C |
A |
18: 37,087,890 (GRCm39) |
A691E |
probably benign |
Het |
Pde6a |
T |
G |
18: 61,364,438 (GRCm39) |
F165V |
probably damaging |
Het |
Ptpn14 |
A |
T |
1: 189,578,561 (GRCm39) |
M340L |
probably benign |
Het |
Rnasel |
G |
T |
1: 153,630,890 (GRCm39) |
E469* |
probably null |
Het |
Rsph3a |
T |
G |
17: 8,164,790 (GRCm39) |
L50R |
probably benign |
Het |
Rusc2 |
A |
G |
4: 43,423,975 (GRCm39) |
Y1043C |
probably damaging |
Het |
Serpinb6b |
A |
T |
13: 33,161,541 (GRCm39) |
K86* |
probably null |
Het |
Serpine1 |
T |
C |
5: 137,092,063 (GRCm39) |
T392A |
probably benign |
Het |
Shcbp1 |
A |
T |
8: 4,794,529 (GRCm39) |
D421E |
probably damaging |
Het |
Slc24a1 |
A |
G |
9: 64,855,863 (GRCm39) |
V348A |
unknown |
Het |
Slc26a7 |
A |
G |
4: 14,506,621 (GRCm39) |
F605L |
probably benign |
Het |
Slc66a1 |
A |
T |
4: 139,027,655 (GRCm39) |
L229Q |
probably damaging |
Het |
Spag17 |
A |
C |
3: 99,963,588 (GRCm39) |
E1102A |
possibly damaging |
Het |
Stab2 |
A |
G |
10: 86,683,989 (GRCm39) |
V2390A |
probably benign |
Het |
Stk11 |
A |
G |
10: 79,961,883 (GRCm39) |
I35V |
probably benign |
Het |
Stk24 |
T |
C |
14: 121,531,693 (GRCm39) |
D321G |
possibly damaging |
Het |
Tbx4 |
A |
T |
11: 85,801,994 (GRCm39) |
N209I |
possibly damaging |
Het |
Tmem225 |
T |
C |
9: 40,060,681 (GRCm39) |
L80P |
probably damaging |
Het |
Tnfrsf4 |
C |
T |
4: 156,098,380 (GRCm39) |
T17I |
probably benign |
Het |
Traf3ip1 |
G |
A |
1: 91,429,037 (GRCm39) |
R268Q |
probably benign |
Het |
Trhde |
T |
A |
10: 114,636,497 (GRCm39) |
I237F |
probably benign |
Het |
Ugt2a1 |
A |
T |
5: 87,633,915 (GRCm39) |
W231R |
probably damaging |
Het |
Vash1 |
ACTGCTGCTGCTGCTGCTGC |
ACTGCTGCTGCTGCTGC |
12: 86,726,831 (GRCm39) |
|
probably benign |
Het |
Vps16 |
T |
A |
2: 130,284,305 (GRCm39) |
D685E |
probably benign |
Het |
Washc4 |
A |
G |
10: 83,409,657 (GRCm39) |
D602G |
probably damaging |
Het |
Wdr59 |
A |
G |
8: 112,211,816 (GRCm39) |
L377P |
possibly damaging |
Het |
Wdr81 |
T |
C |
11: 75,339,896 (GRCm39) |
E1364G |
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 |
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'- CCTACAGGCAAGAGAAATGAACTTC -3'
(R):5'- ACCACACCCTGATCTTTGGC -3'
Sequencing Primer
(F):5'- GCAAGAGAAATGAACTTCAGGAAAC -3'
(R):5'- AGGATCTCCAATGTGTTCTACCAG -3'
|
Posted On |
2016-10-24 |