Incidental Mutation 'IGL02121:Npc1l1'
| ID |
280606 |
| Institutional Source |
Australian Phenomics Network
(link to record)
|
| Gene Symbol |
Npc1l1
|
| Ensembl Gene |
ENSMUSG00000020447 |
| Gene Name |
NPC1 like intracellular cholesterol transporter 1 |
| Synonyms |
Niemann-Pick disease, type C1, 9130221N23Rik |
| Accession Numbers |
|
| Essential gene? |
Probably non essential
(E-score: 0.082)
|
| Stock # |
IGL02121
|
| Quality Score |
|
|
Status
|
|
| Chromosome |
11 |
| Chromosomal Location |
6161013-6180143 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 6178157 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Serine to Proline
at position 418
(S418P)
|
| 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: S418P
PolyPhen 2
Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
|
| SMART Domains |
Protein: ENSMUSP00000004505
Gene: ENSMUSG00000020447
AA Change: S418P
| 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 |
|
| 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: 65 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 1700029F12Rik |
A |
T |
13: 97,159,038 (GRCm39) |
V122D |
unknown |
Het |
| 4930579F01Rik |
T |
G |
3: 137,870,134 (GRCm39) |
Y199S |
possibly damaging |
Het |
| Abca6 |
T |
A |
11: 110,073,750 (GRCm39) |
I1434F |
probably benign |
Het |
| Acsm1 |
T |
C |
7: 119,257,635 (GRCm39) |
V467A |
possibly damaging |
Het |
| Alg3 |
T |
C |
16: 20,425,285 (GRCm39) |
T260A |
possibly damaging |
Het |
| Aoc1 |
A |
G |
6: 48,883,254 (GRCm39) |
|
probably null |
Het |
| Ap5b1 |
C |
T |
19: 5,620,815 (GRCm39) |
T745I |
possibly damaging |
Het |
| Atp6v1c2 |
T |
G |
12: 17,341,441 (GRCm39) |
K272Q |
possibly damaging |
Het |
| Brd8 |
C |
T |
18: 34,735,780 (GRCm39) |
S899N |
probably damaging |
Het |
| Cert1 |
T |
G |
13: 96,735,982 (GRCm39) |
Y181D |
probably benign |
Het |
| Clcn7 |
C |
T |
17: 25,372,058 (GRCm39) |
A426V |
possibly damaging |
Het |
| Clec14a |
T |
C |
12: 58,315,223 (GRCm39) |
E133G |
probably damaging |
Het |
| Dst |
T |
A |
1: 34,267,738 (GRCm39) |
V2720E |
probably damaging |
Het |
| Efr3a |
C |
T |
15: 65,742,999 (GRCm39) |
|
probably benign |
Het |
| Fam83g |
T |
C |
11: 61,575,609 (GRCm39) |
S84P |
probably benign |
Het |
| Gm7251 |
T |
C |
13: 49,959,382 (GRCm39) |
|
noncoding transcript |
Het |
| Gnptab |
T |
G |
10: 88,265,323 (GRCm39) |
S312A |
possibly damaging |
Het |
| Grap2 |
C |
A |
15: 80,532,076 (GRCm39) |
S230R |
possibly damaging |
Het |
| Grm6 |
T |
A |
11: 50,750,483 (GRCm39) |
C549S |
probably damaging |
Het |
| Gtf3c1 |
A |
T |
7: 125,245,903 (GRCm39) |
L1504* |
probably null |
Het |
| Iars1 |
A |
G |
13: 49,878,172 (GRCm39) |
M899V |
probably benign |
Het |
| Il1rl1 |
T |
A |
1: 40,481,463 (GRCm39) |
|
probably benign |
Het |
| Kcna4 |
T |
C |
2: 107,126,963 (GRCm39) |
Y566H |
possibly damaging |
Het |
| Kcnn2 |
T |
C |
18: 45,694,340 (GRCm39) |
I175T |
probably damaging |
Het |
| Kcnt1 |
C |
T |
2: 25,791,877 (GRCm39) |
T609I |
probably damaging |
Het |
| Kif3b |
A |
G |
2: 153,159,194 (GRCm39) |
R332G |
probably damaging |
Het |
| Mansc1 |
T |
C |
6: 134,598,800 (GRCm39) |
D39G |
probably damaging |
Het |
| Med12 |
T |
C |
X: 100,331,948 (GRCm39) |
|
probably benign |
Het |
| Mmp1b |
G |
T |
9: 7,384,935 (GRCm39) |
T238K |
probably benign |
Het |
| Nav3 |
A |
G |
10: 109,594,897 (GRCm39) |
S1435P |
probably damaging |
Het |
| Or14j1 |
T |
C |
17: 38,146,832 (GRCm39) |
V314A |
probably benign |
Het |
| Or2ab1 |
T |
C |
11: 58,488,408 (GRCm39) |
V62A |
possibly damaging |
Het |
| Or3a1b |
A |
G |
11: 74,012,113 (GRCm39) |
|
probably benign |
Het |
| Or52a24 |
A |
G |
7: 103,381,676 (GRCm39) |
Y181C |
probably damaging |
Het |
| Or52h1 |
A |
C |
7: 103,829,432 (GRCm39) |
M61R |
probably damaging |
Het |
| Or6ae1 |
G |
T |
7: 139,742,607 (GRCm39) |
D85E |
probably benign |
Het |
| Or8b3b |
T |
C |
9: 38,584,711 (GRCm39) |
T23A |
probably damaging |
Het |
| Otoa |
A |
G |
7: 120,721,247 (GRCm39) |
T421A |
probably benign |
Het |
| Otulin |
G |
A |
15: 27,608,823 (GRCm39) |
A42V |
probably damaging |
Het |
| Pcdhb1 |
T |
A |
18: 37,398,838 (GRCm39) |
V263E |
probably benign |
Het |
| Pfkfb4 |
C |
T |
9: 108,854,178 (GRCm39) |
R351W |
probably damaging |
Het |
| Phip |
A |
T |
9: 82,775,423 (GRCm39) |
V1053D |
probably damaging |
Het |
| Pkd1 |
G |
A |
17: 24,794,901 (GRCm39) |
R2196H |
probably benign |
Het |
| Plin4 |
T |
A |
17: 56,409,131 (GRCm39) |
Q1363L |
probably damaging |
Het |
| Pp2d1 |
C |
A |
17: 53,814,949 (GRCm39) |
V592L |
probably damaging |
Het |
| Pramel51 |
T |
C |
12: 88,145,242 (GRCm39) |
D28G |
possibly damaging |
Het |
| Prkdc |
T |
G |
16: 15,535,048 (GRCm39) |
M1649R |
probably benign |
Het |
| Ptk2b |
T |
C |
14: 66,450,931 (GRCm39) |
K12E |
probably benign |
Het |
| Rars2 |
G |
A |
4: 34,657,219 (GRCm39) |
V522I |
probably damaging |
Het |
| Rpgrip1 |
T |
A |
14: 52,384,831 (GRCm39) |
N646K |
possibly damaging |
Het |
| Sars2 |
A |
G |
7: 28,451,950 (GRCm39) |
|
probably benign |
Het |
| Sgo2b |
T |
C |
8: 64,384,316 (GRCm39) |
T227A |
possibly damaging |
Het |
| Smc1b |
T |
C |
15: 84,982,186 (GRCm39) |
T703A |
probably benign |
Het |
| Stk32a |
G |
T |
18: 43,446,572 (GRCm39) |
D341Y |
probably benign |
Het |
| Thap11 |
T |
C |
8: 106,582,546 (GRCm39) |
V185A |
possibly damaging |
Het |
| Ttll10 |
C |
A |
4: 156,132,890 (GRCm39) |
V65F |
probably benign |
Het |
| Ube2q1 |
T |
A |
3: 89,687,769 (GRCm39) |
N111K |
possibly damaging |
Het |
| Upf2 |
C |
A |
2: 6,031,134 (GRCm39) |
|
probably benign |
Het |
| Utp25 |
A |
T |
1: 192,800,586 (GRCm39) |
D411E |
probably benign |
Het |
| Vasp |
T |
A |
7: 18,991,637 (GRCm39) |
|
probably benign |
Het |
| Vmn2r104 |
C |
T |
17: 20,262,056 (GRCm39) |
W358* |
probably null |
Het |
| Vmn2r9 |
G |
A |
5: 108,991,502 (GRCm39) |
L620F |
probably damaging |
Het |
| Wdfy3 |
C |
T |
5: 102,046,376 (GRCm39) |
G1826R |
possibly damaging |
Het |
| Wdr7 |
T |
A |
18: 63,910,616 (GRCm39) |
Y669* |
probably null |
Het |
| Wdr72 |
T |
A |
9: 74,189,011 (GRCm39) |
|
probably benign |
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 |
|
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 |
|
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 |
|
| Posted On |
2015-04-16 |
Incidental Mutation