Incidental Mutation 'R0918:Npc1l1'
| ID |
81548 |
| 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 |
039068-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably non essential
(E-score: 0.098)
|
| Stock # |
R0918 (G1)
|
| Quality Score |
225 |
|
Status
|
Not validated
|
| Chromosome |
11 |
| Chromosomal Location |
6161013-6180143 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
G to A
at 6168239 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Threonine to Methionine
at position 984
(T984M)
|
| 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: T984M
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000004505
Gene: ENSMUSG00000020447
AA Change: T984M
| 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: 98.7%
- 10x: 96.2%
- 20x: 90.0%
|
| 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: 38 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Aadac |
T |
G |
3: 59,946,953 (GRCm39) |
I217R |
probably damaging |
Het |
| Acp1 |
G |
T |
12: 30,955,126 (GRCm39) |
S20* |
probably null |
Het |
| Adcy3 |
A |
G |
12: 4,248,360 (GRCm39) |
D474G |
probably benign |
Het |
| Apob |
T |
C |
12: 8,033,941 (GRCm39) |
I217T |
probably benign |
Het |
| Cdh12 |
G |
A |
15: 21,492,685 (GRCm39) |
V235I |
probably damaging |
Het |
| Cdhr5 |
T |
A |
7: 140,852,062 (GRCm39) |
T197S |
probably damaging |
Het |
| Cerkl |
A |
G |
2: 79,163,973 (GRCm39) |
I449T |
probably benign |
Het |
| Cpz |
A |
G |
5: 35,674,998 (GRCm39) |
Y84H |
probably damaging |
Het |
| Drosha |
T |
C |
15: 12,842,619 (GRCm39) |
|
probably null |
Het |
| Fbxo11 |
A |
T |
17: 88,305,031 (GRCm39) |
N613K |
probably damaging |
Het |
| Fes |
G |
T |
7: 80,030,953 (GRCm39) |
T536K |
probably damaging |
Het |
| Gm13941 |
G |
C |
2: 110,930,945 (GRCm39) |
T76R |
unknown |
Het |
| Lrp1 |
T |
C |
10: 127,429,834 (GRCm39) |
E412G |
probably damaging |
Het |
| Map3k12 |
T |
C |
15: 102,412,287 (GRCm39) |
I285V |
probably damaging |
Het |
| Map3k13 |
G |
A |
16: 21,744,990 (GRCm39) |
D850N |
probably damaging |
Het |
| Mapk4 |
C |
T |
18: 74,103,408 (GRCm39) |
V34M |
probably damaging |
Het |
| Morn1 |
T |
A |
4: 155,171,928 (GRCm39) |
W43R |
probably damaging |
Het |
| Ncan |
T |
G |
8: 70,561,039 (GRCm39) |
M643L |
possibly damaging |
Het |
| Or14c44 |
A |
G |
7: 86,062,403 (GRCm39) |
T278A |
probably benign |
Het |
| Or5a3 |
A |
G |
19: 12,400,599 (GRCm39) |
K309E |
probably benign |
Het |
| Or5ak4 |
A |
G |
2: 85,162,276 (GRCm39) |
|
probably benign |
Het |
| Or5p5 |
T |
C |
7: 107,414,418 (GRCm39) |
I209T |
probably benign |
Het |
| Pcdhb22 |
T |
C |
18: 37,653,067 (GRCm39) |
F255L |
probably damaging |
Het |
| Pi4ka |
T |
C |
16: 17,103,124 (GRCm39) |
D1697G |
possibly damaging |
Het |
| Pla2g12b |
A |
G |
10: 59,257,306 (GRCm39) |
D163G |
probably damaging |
Het |
| Pot1a |
G |
A |
6: 25,756,267 (GRCm39) |
T359M |
possibly damaging |
Het |
| Sass6 |
G |
A |
3: 116,397,172 (GRCm39) |
|
probably null |
Het |
| Scn1a |
C |
T |
2: 66,153,651 (GRCm39) |
|
probably null |
Het |
| Slc38a1 |
A |
G |
15: 96,507,743 (GRCm39) |
L103P |
probably damaging |
Het |
| Slc38a6 |
T |
A |
12: 73,391,559 (GRCm39) |
|
probably null |
Het |
| Smarca4 |
C |
T |
9: 21,547,511 (GRCm39) |
P265S |
probably benign |
Het |
| Snrpa1 |
A |
G |
7: 65,720,363 (GRCm39) |
T189A |
probably benign |
Het |
| Snx11 |
G |
A |
11: 96,660,104 (GRCm39) |
P195L |
possibly damaging |
Het |
| Spen |
T |
G |
4: 141,212,875 (GRCm39) |
I584L |
unknown |
Het |
| Sult2a5 |
T |
A |
7: 13,359,334 (GRCm39) |
H103Q |
probably benign |
Het |
| Syce1 |
T |
C |
7: 140,360,436 (GRCm39) |
K50E |
probably damaging |
Het |
| Timm21 |
G |
C |
18: 84,967,387 (GRCm39) |
L130V |
probably damaging |
Het |
| Tmem132a |
A |
G |
19: 10,835,477 (GRCm39) |
S1018P |
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 |
|
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 |
|
| Predicted Primers |
PCR Primer
(F):5'- TCCAGGGGACACTGATAGTGTGAG -3'
(R):5'- ACAACTTTTCCACCGAGGCAGG -3'
Sequencing Primer
(F):5'- ACTGATAGTGTGAGTGCCTAACC -3'
(R):5'- CAGGCATGAACGCCATTTG -3'
|
| Posted On |
2013-11-07 |
Incidental Mutation