Incidental Mutation 'R4504:Npc1l1'
| ID |
331937 |
| 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 |
041755-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably non essential
(E-score: 0.082)
|
| Stock # |
R4504 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
11 |
| Chromosomal Location |
6161013-6180143 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 6178741 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Leucine to Serine
at position 223
(L223S)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000004505
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000004505]
|
| AlphaFold |
no structure available at present |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000004505
AA Change: L223S
PolyPhen 2
Score 0.605 (Sensitivity: 0.87; Specificity: 0.91)
|
| SMART Domains |
Protein: ENSMUSP00000004505
Gene: ENSMUSG00000020447
AA Change: L223S
| 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 |
0.1250 |
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.6%
- 10x: 97.3%
- 20x: 95.4%
|
| Validation Efficiency |
100% (45/45) |
| 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: 41 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4930503E14Rik |
A |
G |
14: 44,407,899 (GRCm39) |
S45P |
probably damaging |
Het |
| Adgrg4 |
C |
T |
X: 55,961,802 (GRCm39) |
R1124C |
possibly damaging |
Het |
| Anxa13 |
T |
C |
15: 58,228,052 (GRCm39) |
|
noncoding transcript |
Het |
| Arhgap32 |
C |
A |
9: 32,093,135 (GRCm39) |
|
probably null |
Het |
| Carm1 |
T |
C |
9: 21,480,822 (GRCm39) |
F99L |
probably damaging |
Het |
| Dennd1b |
A |
G |
1: 139,013,665 (GRCm39) |
E253G |
possibly damaging |
Het |
| Dsg4 |
A |
G |
18: 20,594,493 (GRCm39) |
I541V |
probably benign |
Het |
| Dstyk |
A |
G |
1: 132,362,127 (GRCm39) |
T186A |
possibly damaging |
Het |
| Ear1 |
A |
T |
14: 44,056,721 (GRCm39) |
V49D |
probably benign |
Het |
| Epha10 |
A |
G |
4: 124,809,480 (GRCm39) |
|
probably benign |
Het |
| Fbh1 |
A |
G |
2: 11,753,828 (GRCm39) |
V838A |
possibly damaging |
Het |
| Fndc8 |
T |
A |
11: 82,783,226 (GRCm39) |
M69K |
probably benign |
Het |
| Golga1 |
T |
C |
2: 38,913,466 (GRCm39) |
I482V |
probably benign |
Het |
| Hivep3 |
G |
A |
4: 119,590,990 (GRCm39) |
|
probably benign |
Het |
| Igkv13-85 |
A |
G |
6: 68,907,356 (GRCm39) |
F82L |
probably damaging |
Het |
| Itih1 |
G |
A |
14: 30,657,842 (GRCm39) |
R410C |
probably damaging |
Het |
| Kcnc2 |
T |
C |
10: 112,291,699 (GRCm39) |
W296R |
probably damaging |
Het |
| Kcnq3 |
A |
T |
15: 65,867,191 (GRCm39) |
Y817* |
probably null |
Het |
| Kif3b |
T |
C |
2: 153,165,564 (GRCm39) |
|
probably null |
Het |
| Krtcap2 |
A |
G |
3: 89,153,563 (GRCm39) |
|
probably benign |
Het |
| Lhx5 |
C |
A |
5: 120,578,073 (GRCm39) |
H298N |
possibly damaging |
Het |
| Notch1 |
A |
G |
2: 26,362,189 (GRCm39) |
V1022A |
probably benign |
Het |
| Or11m3 |
T |
C |
15: 98,396,015 (GRCm39) |
F221L |
probably benign |
Het |
| Or4c10 |
C |
T |
2: 89,760,695 (GRCm39) |
P181S |
possibly damaging |
Het |
| Or8a1b |
C |
T |
9: 37,622,760 (GRCm39) |
V272I |
probably benign |
Het |
| Pbxip1 |
A |
G |
3: 89,353,690 (GRCm39) |
D281G |
possibly damaging |
Het |
| Pcdhga8 |
G |
C |
18: 37,949,816 (GRCm39) |
V411L |
probably damaging |
Het |
| Pcsk5 |
C |
T |
19: 17,429,319 (GRCm39) |
C1553Y |
probably damaging |
Het |
| Pdgfc |
A |
C |
3: 81,082,298 (GRCm39) |
M164L |
probably benign |
Het |
| Pdzd8 |
T |
C |
19: 59,333,880 (GRCm39) |
Y47C |
probably damaging |
Het |
| Pip5k1c |
T |
A |
10: 81,150,945 (GRCm39) |
I633N |
probably damaging |
Het |
| Pkn1 |
G |
A |
8: 84,419,556 (GRCm39) |
R16* |
probably null |
Het |
| Pole2 |
A |
G |
12: 69,269,242 (GRCm39) |
V85A |
probably benign |
Het |
| Ppp4c |
A |
C |
7: 126,386,637 (GRCm39) |
L150R |
probably damaging |
Het |
| Pramel25 |
G |
C |
4: 143,520,553 (GRCm39) |
E102Q |
probably benign |
Het |
| Ric8a |
A |
G |
7: 140,438,429 (GRCm39) |
I223V |
probably benign |
Het |
| Rnf144a |
T |
A |
12: 26,377,302 (GRCm39) |
R92S |
probably benign |
Het |
| Sbno2 |
C |
A |
10: 79,896,326 (GRCm39) |
R898L |
possibly damaging |
Het |
| Scnn1b |
A |
C |
7: 121,511,698 (GRCm39) |
N370T |
probably damaging |
Het |
| Taar3 |
A |
G |
10: 23,825,471 (GRCm39) |
I6V |
possibly damaging |
Het |
| Vps13a |
T |
C |
19: 16,672,866 (GRCm39) |
E1302G |
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 |
|
|
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'- GATGATGATGAGAGCCAGCC -3'
(R):5'- TATGAGGCCTTTTATCAACGCAG -3'
Sequencing Primer
(F):5'- AGCCTGGCATTCGACCCATG -3'
(R):5'- CAGTTTTGCAGAGAAGGCCTATG -3'
|
| Posted On |
2015-07-21 |
Incidental Mutation