Incidental Mutation 'R7006:Npc1l1'
| ID |
544726 |
| 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 |
045011-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably non essential
(E-score: 0.082)
|
| Stock # |
R7006 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Not validated
|
| Chromosome |
11 |
| Chromosomal Location |
6161013-6180143 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
G to A
at 6167731 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Threonine to Methionine
at position 1020
(T1020M)
|
| 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: T1020M
PolyPhen 2
Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
|
| SMART Domains |
Protein: ENSMUSP00000004505
Gene: ENSMUSG00000020447
AA Change: T1020M
| 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: 99.7%
- 20x: 99.0%
|
| 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: 45 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| AAdacl4fm3 |
A |
G |
4: 144,447,853 (GRCm39) |
V41A |
probably benign |
Het |
| Adcy2 |
G |
A |
13: 69,036,139 (GRCm39) |
T174M |
probably damaging |
Het |
| Ankfy1 |
T |
A |
11: 72,631,290 (GRCm39) |
I412N |
probably benign |
Het |
| AW146154 |
T |
C |
7: 41,130,648 (GRCm39) |
E156G |
possibly damaging |
Het |
| B4galnt1 |
T |
C |
10: 127,005,700 (GRCm39) |
L267P |
probably benign |
Het |
| Bod1l |
T |
C |
5: 41,989,895 (GRCm39) |
E276G |
probably damaging |
Het |
| Ccdc187 |
T |
C |
2: 26,171,102 (GRCm39) |
T459A |
probably benign |
Het |
| Ccdc196 |
T |
A |
12: 78,255,702 (GRCm39) |
*177R |
probably null |
Het |
| Cep72 |
G |
A |
13: 74,198,427 (GRCm39) |
Q311* |
probably null |
Het |
| Cir1 |
T |
C |
2: 73,140,834 (GRCm39) |
Q45R |
probably damaging |
Het |
| Ciz1 |
T |
C |
2: 32,261,127 (GRCm39) |
|
probably null |
Het |
| Crtap |
G |
T |
9: 114,215,391 (GRCm39) |
A166E |
probably damaging |
Het |
| Dipk1a |
A |
G |
5: 108,058,027 (GRCm39) |
V132A |
probably benign |
Het |
| Dmp1 |
A |
G |
5: 104,360,188 (GRCm39) |
D288G |
probably benign |
Het |
| Fhad1 |
CGG |
CG |
4: 141,645,602 (GRCm39) |
|
probably null |
Het |
| Fmnl2 |
C |
A |
2: 52,998,266 (GRCm39) |
Q544K |
probably benign |
Het |
| Gpsm1 |
T |
C |
2: 26,212,572 (GRCm39) |
L72P |
probably damaging |
Het |
| Gys1 |
G |
A |
7: 45,089,437 (GRCm39) |
A199T |
probably damaging |
Het |
| Kcnq3 |
A |
C |
15: 65,892,165 (GRCm39) |
Y403* |
probably null |
Het |
| Kcp |
A |
C |
6: 29,499,169 (GRCm39) |
Y298D |
probably damaging |
Het |
| Kif5c |
T |
C |
2: 49,625,526 (GRCm39) |
S599P |
probably damaging |
Het |
| Krt20 |
A |
T |
11: 99,328,587 (GRCm39) |
Y113N |
probably benign |
Het |
| Mcm8 |
T |
G |
2: 132,665,181 (GRCm39) |
V191G |
probably damaging |
Het |
| Msr1 |
T |
A |
8: 40,042,423 (GRCm39) |
D384V |
probably damaging |
Het |
| Mtpap |
A |
C |
18: 4,380,873 (GRCm39) |
S184R |
possibly damaging |
Het |
| Nphp4 |
A |
G |
4: 152,573,259 (GRCm39) |
T66A |
probably benign |
Het |
| Or1o3 |
T |
A |
17: 37,573,625 (GRCm39) |
*310L |
probably null |
Het |
| Or4f14 |
C |
A |
2: 111,742,601 (GRCm39) |
V225L |
probably benign |
Het |
| Or8h10 |
G |
A |
2: 86,808,303 (GRCm39) |
T279I |
probably damaging |
Het |
| Or8k18 |
T |
A |
2: 86,085,572 (GRCm39) |
Q155L |
probably benign |
Het |
| Phf11d |
G |
T |
14: 59,590,823 (GRCm39) |
T178K |
probably benign |
Het |
| Ppm1d |
A |
G |
11: 85,227,977 (GRCm39) |
K298E |
possibly damaging |
Het |
| Rab2b |
A |
T |
14: 52,503,690 (GRCm39) |
I144K |
probably benign |
Het |
| Stoml1 |
A |
G |
9: 58,167,523 (GRCm39) |
D5G |
probably damaging |
Het |
| Styxl2 |
T |
C |
1: 165,926,663 (GRCm39) |
N983S |
probably benign |
Het |
| Tanc1 |
T |
C |
2: 59,626,188 (GRCm39) |
V515A |
probably damaging |
Het |
| Tas1r3 |
A |
G |
4: 155,947,361 (GRCm39) |
V108A |
possibly damaging |
Het |
| Tifab |
T |
C |
13: 56,324,059 (GRCm39) |
Y128C |
probably benign |
Het |
| Tmc6 |
G |
T |
11: 117,665,083 (GRCm39) |
R397S |
probably damaging |
Het |
| Tnpo3 |
C |
T |
6: 29,589,162 (GRCm39) |
A63T |
probably damaging |
Het |
| Trgc4 |
T |
A |
13: 19,528,995 (GRCm39) |
|
probably benign |
Het |
| Usp16 |
G |
T |
16: 87,268,724 (GRCm39) |
C284F |
probably damaging |
Het |
| Wipf1 |
T |
C |
2: 73,267,441 (GRCm39) |
D319G |
probably damaging |
Het |
| Xpnpep3 |
T |
A |
15: 81,326,649 (GRCm39) |
W347R |
probably damaging |
Het |
| Zfp180 |
G |
T |
7: 23,804,537 (GRCm39) |
E319* |
probably null |
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 |
|
|
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'- AGAGGTTCTATACGCTGCTAGGC -3'
(R):5'- TTGGGCACAGAATGGGAGTC -3'
Sequencing Primer
(F):5'- TATACGCTGCTAGGCCCCTG -3'
(R):5'- AGTCAGGACAGGAGCTGCC -3'
|
| Posted On |
2019-05-13 |
Incidental Mutation