Incidental Mutation 'R8161:Npc1'
| ID |
633549 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Npc1
|
| Ensembl Gene |
ENSMUSG00000024413 |
| Gene Name |
NPC intracellular cholesterol transporter 1 |
| Synonyms |
lcsd, nmf164, D18Ertd139e, D18Ertd723e, A430089E03Rik, C85354 |
| MMRRC Submission |
067587-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly essential
(E-score: 0.616)
|
| Stock # |
R8161 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Not validated
|
| Chromosome |
18 |
| Chromosomal Location |
12322749-12369457 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to T
at 12328129 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Isoleucine to Lysine
at position 1060
(I1060K)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000025279
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000025279]
|
| AlphaFold |
O35604 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000025279
AA Change: I1060K
PolyPhen 2
Score 0.775 (Sensitivity: 0.85; Specificity: 0.92)
|
| SMART Domains |
Protein: ENSMUSP00000025279
Gene: ENSMUSG00000024413
AA Change: I1060K
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
8 |
15 |
N/A |
INTRINSIC |
|
Pfam:NPC1_N
|
22 |
267 |
1.6e-79 |
PFAM |
|
transmembrane domain
|
269 |
291 |
N/A |
INTRINSIC |
|
transmembrane domain
|
353 |
375 |
N/A |
INTRINSIC |
|
Pfam:Patched
|
436 |
896 |
3.5e-52 |
PFAM |
|
Pfam:MMPL
|
648 |
794 |
6.3e-8 |
PFAM |
|
Pfam:Sterol-sensing
|
649 |
803 |
2.7e-56 |
PFAM |
|
Pfam:Patched
|
1023 |
1252 |
2.9e-33 |
PFAM |
|
low complexity region
|
1259 |
1273 |
N/A |
INTRINSIC |
|
| Coding Region Coverage |
- 1x: 99.9%
- 3x: 99.8%
- 10x: 99.3%
- 20x: 97.8%
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a large protein that resides in the limiting membrane of endosomes and lysosomes and mediates intracellular cholesterol trafficking via binding of cholesterol to its N-terminal domain. It is predicted to have a cytoplasmic C-terminus, 13 transmembrane domains, and 3 large loops in the lumen of the endosome - the last loop being at the N-terminus. This protein transports low-density lipoproteins to late endosomal/lysosomal compartments where they are hydrolized and released as free cholesterol. Defects in this gene cause Niemann-Pick type C disease, a rare autosomal recessive neurodegenerative disorder characterized by over accumulation of cholesterol and glycosphingolipids in late endosomal/lysosomal compartments.[provided by RefSeq, Aug 2009]
PHENOTYPE: Homozygotes for spontaneous and chemically induced mutations may exhibit lysosomal storage of non-esterified cholesterol, neurodegeneration, ataxia, presence of foam cells, sterility, and shortened lifespan. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 61 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 9630041A04Rik |
T |
C |
9: 101,815,968 (GRCm39) |
L51P |
probably damaging |
Het |
| Adgrb3 |
A |
T |
1: 25,133,003 (GRCm39) |
M1121K |
probably benign |
Het |
| Ank2 |
T |
C |
3: 126,825,778 (GRCm39) |
N371S |
|
Het |
| Arhgef5 |
T |
A |
6: 43,260,885 (GRCm39) |
C1437S |
probably damaging |
Het |
| Atp8b1 |
A |
T |
18: 64,690,058 (GRCm39) |
L558Q |
probably damaging |
Het |
| Bsn |
T |
C |
9: 108,016,729 (GRCm39) |
K94R |
probably benign |
Het |
| Cacna2d1 |
T |
A |
5: 16,519,935 (GRCm39) |
V435D |
probably damaging |
Het |
| Chd3 |
T |
C |
11: 69,241,711 (GRCm39) |
N1474S |
probably damaging |
Het |
| Chd7 |
A |
G |
4: 8,855,038 (GRCm39) |
D2089G |
probably damaging |
Het |
| Col11a2 |
T |
A |
17: 34,270,264 (GRCm39) |
M492K |
unknown |
Het |
| Col16a1 |
A |
T |
4: 129,954,262 (GRCm39) |
T502S |
unknown |
Het |
| Csl |
A |
T |
10: 99,594,182 (GRCm39) |
N294K |
probably damaging |
Het |
| Dnah5 |
T |
A |
15: 28,350,850 (GRCm39) |
M2624K |
possibly damaging |
Het |
| Dync1li1 |
C |
A |
9: 114,535,251 (GRCm39) |
H172N |
probably damaging |
Het |
| Eef1a1 |
C |
T |
9: 78,387,672 (GRCm39) |
V59I |
probably benign |
Het |
| Ephb1 |
T |
C |
9: 102,072,012 (GRCm39) |
K256E |
probably damaging |
Het |
| Erlin2 |
C |
A |
8: 27,518,970 (GRCm39) |
T78N |
probably damaging |
Het |
| Fbxo10 |
A |
G |
4: 45,044,793 (GRCm39) |
L614P |
probably damaging |
Het |
| Fer1l4 |
A |
T |
2: 155,866,555 (GRCm39) |
D1555E |
probably benign |
Het |
| Gabrr2 |
A |
G |
4: 33,082,566 (GRCm39) |
D230G |
probably damaging |
Het |
| Gen1 |
A |
T |
12: 11,291,465 (GRCm39) |
S840T |
probably benign |
Het |
| Glyctk |
G |
A |
9: 106,034,892 (GRCm39) |
T58I |
probably benign |
Het |
| Gm12258 |
G |
A |
11: 58,750,138 (GRCm39) |
A438T |
unknown |
Het |
| Gm14305 |
A |
G |
2: 176,413,298 (GRCm39) |
T397A |
probably benign |
Het |
| Hnrnpu |
G |
T |
1: 178,165,067 (GRCm39) |
R24S |
possibly damaging |
Het |
| Iffo2 |
A |
G |
4: 139,302,265 (GRCm39) |
N3D |
possibly damaging |
Het |
| Insr |
C |
T |
8: 3,308,660 (GRCm39) |
M125I |
probably damaging |
Het |
| Itsn1 |
G |
A |
16: 91,615,446 (GRCm39) |
R397H |
unknown |
Het |
| Kcnj16 |
T |
A |
11: 110,915,341 (GRCm39) |
M1K |
probably null |
Het |
| Kcns3 |
G |
A |
12: 11,169,764 (GRCm39) |
|
probably benign |
Het |
| Kmt2c |
A |
G |
5: 25,579,562 (GRCm39) |
V578A |
probably benign |
Het |
| Krt79 |
T |
C |
15: 101,839,137 (GRCm39) |
K444R |
probably damaging |
Het |
| Mtg2 |
T |
C |
2: 179,727,368 (GRCm39) |
V340A |
probably benign |
Het |
| Mtr |
A |
C |
13: 12,236,372 (GRCm39) |
L618R |
probably damaging |
Het |
| Myo6 |
T |
A |
9: 80,124,991 (GRCm39) |
D23E |
unknown |
Het |
| Nos1ap |
A |
G |
1: 170,218,328 (GRCm39) |
V27A |
probably damaging |
Het |
| Nrbp1 |
T |
A |
5: 31,401,193 (GRCm39) |
L23* |
probably null |
Het |
| Or10ag52 |
T |
C |
2: 87,044,148 (GRCm39) |
I304T |
probably damaging |
Het |
| Or1p1c |
A |
T |
11: 74,160,544 (GRCm39) |
M110L |
probably benign |
Het |
| Or6c6c |
A |
T |
10: 129,540,753 (GRCm39) |
K2I |
possibly damaging |
Het |
| Or8b3 |
C |
A |
9: 38,314,803 (GRCm39) |
T211K |
probably damaging |
Het |
| Or9s13 |
G |
A |
1: 92,548,078 (GRCm39) |
R150H |
probably benign |
Het |
| Pcdhgc5 |
A |
T |
18: 37,954,615 (GRCm39) |
T630S |
probably damaging |
Het |
| Pgm2 |
C |
A |
5: 64,269,503 (GRCm39) |
T530K |
probably damaging |
Het |
| Phf20l1 |
A |
T |
15: 66,475,922 (GRCm39) |
N185I |
probably damaging |
Het |
| Pkp2 |
A |
G |
16: 16,031,313 (GRCm39) |
D26G |
probably damaging |
Het |
| Rangap1 |
C |
T |
15: 81,594,696 (GRCm39) |
E378K |
probably benign |
Het |
| Rapgef1 |
A |
C |
2: 29,569,210 (GRCm39) |
I43L |
probably benign |
Het |
| Rbfox1 |
A |
G |
16: 7,094,892 (GRCm39) |
T111A |
|
Het |
| Rptn |
GCAAGACCAGAGTTCTCACCAGGGTCAGAAAGGCAGACAAGACCAGAGTTCTCACCAGGGTCAGAAAGGCAGACAAGACCAGAGTTCTCACCAGGGTCA |
GCAAGACCAGAGTTCTCACCAGGGTCAGAAAGGCAGACAAGACCAGAGTTCTCACCAGGGTCA |
3: 93,304,000 (GRCm39) |
|
probably benign |
Het |
| Spata16 |
A |
T |
3: 26,894,811 (GRCm39) |
M287L |
probably benign |
Het |
| Speer4a2 |
T |
C |
5: 26,289,690 (GRCm39) |
S246G |
possibly damaging |
Het |
| Stau2 |
A |
G |
1: 16,416,049 (GRCm39) |
M470T |
probably benign |
Het |
| Tcf12 |
T |
C |
9: 71,922,933 (GRCm39) |
Y70C |
probably damaging |
Het |
| Tsc22d1 |
C |
T |
14: 76,654,460 (GRCm39) |
T313M |
probably benign |
Het |
| Vmn1r52 |
T |
A |
6: 90,156,239 (GRCm39) |
M181K |
possibly damaging |
Het |
| Zbtb48 |
A |
T |
4: 152,106,567 (GRCm39) |
C345S |
probably damaging |
Het |
| Zfp628 |
G |
A |
7: 4,921,958 (GRCm39) |
R60Q |
probably damaging |
Het |
| Zfp638 |
T |
C |
6: 83,906,713 (GRCm39) |
S293P |
possibly damaging |
Het |
| Zkscan17 |
G |
A |
11: 59,393,770 (GRCm39) |
P183S |
probably benign |
Het |
| Zscan12 |
G |
T |
13: 21,547,897 (GRCm39) |
K26N |
probably benign |
Het |
|
| Other mutations in Npc1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL02347:Npc1
|
APN |
18 |
12,332,691 (GRCm39) |
missense |
probably benign |
0.45 |
|
IGL02523:Npc1
|
APN |
18 |
12,334,629 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL03018:Npc1
|
APN |
18 |
12,347,436 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL03101:Npc1
|
APN |
18 |
12,331,596 (GRCm39) |
missense |
probably benign |
0.15 |
|
IGL03151:Npc1
|
APN |
18 |
12,352,332 (GRCm39) |
missense |
probably benign |
0.05 |
|
IGL03377:Npc1
|
APN |
18 |
12,344,878 (GRCm39) |
missense |
probably benign |
|
|
PIT4354001:Npc1
|
UTSW |
18 |
12,344,592 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0068:Npc1
|
UTSW |
18 |
12,341,424 (GRCm39) |
missense |
probably benign |
0.04 |
|
R0068:Npc1
|
UTSW |
18 |
12,341,424 (GRCm39) |
missense |
probably benign |
0.04 |
|
R0190:Npc1
|
UTSW |
18 |
12,324,887 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0200:Npc1
|
UTSW |
18 |
12,352,261 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0485:Npc1
|
UTSW |
18 |
12,346,503 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0699:Npc1
|
UTSW |
18 |
12,343,632 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0730:Npc1
|
UTSW |
18 |
12,352,382 (GRCm39) |
missense |
probably benign |
0.00 |
|
R1302:Npc1
|
UTSW |
18 |
12,328,142 (GRCm39) |
missense |
probably benign |
0.00 |
|
R1442:Npc1
|
UTSW |
18 |
12,328,106 (GRCm39) |
missense |
probably benign |
|
|
R1463:Npc1
|
UTSW |
18 |
12,324,887 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1804:Npc1
|
UTSW |
18 |
12,356,145 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1808:Npc1
|
UTSW |
18 |
12,327,149 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1928:Npc1
|
UTSW |
18 |
12,346,435 (GRCm39) |
missense |
possibly damaging |
0.79 |
|
R2112:Npc1
|
UTSW |
18 |
12,346,529 (GRCm39) |
missense |
possibly damaging |
0.49 |
|
R2117:Npc1
|
UTSW |
18 |
12,329,613 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2157:Npc1
|
UTSW |
18 |
12,324,866 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R2279:Npc1
|
UTSW |
18 |
12,330,236 (GRCm39) |
splice site |
probably null |
|
|
R2311:Npc1
|
UTSW |
18 |
12,335,240 (GRCm39) |
missense |
probably benign |
|
|
R2446:Npc1
|
UTSW |
18 |
12,347,396 (GRCm39) |
missense |
probably benign |
0.01 |
|
R3004:Npc1
|
UTSW |
18 |
12,330,311 (GRCm39) |
missense |
probably benign |
0.03 |
|
R4090:Npc1
|
UTSW |
18 |
12,331,219 (GRCm39) |
splice site |
probably null |
|
|
R4304:Npc1
|
UTSW |
18 |
12,343,584 (GRCm39) |
missense |
possibly damaging |
0.77 |
|
R4308:Npc1
|
UTSW |
18 |
12,343,584 (GRCm39) |
missense |
possibly damaging |
0.77 |
|
R4564:Npc1
|
UTSW |
18 |
12,324,789 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4786:Npc1
|
UTSW |
18 |
12,332,554 (GRCm39) |
missense |
probably benign |
0.35 |
|
R5243:Npc1
|
UTSW |
18 |
12,331,688 (GRCm39) |
intron |
probably benign |
|
|
R5404:Npc1
|
UTSW |
18 |
12,346,356 (GRCm39) |
missense |
possibly damaging |
0.79 |
|
R5823:Npc1
|
UTSW |
18 |
12,324,846 (GRCm39) |
missense |
possibly damaging |
0.69 |
|
R6080:Npc1
|
UTSW |
18 |
12,352,408 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6215:Npc1
|
UTSW |
18 |
12,369,249 (GRCm39) |
small deletion |
probably benign |
|
|
R6301:Npc1
|
UTSW |
18 |
12,330,302 (GRCm39) |
missense |
probably benign |
0.00 |
|
R6476:Npc1
|
UTSW |
18 |
12,334,751 (GRCm39) |
nonsense |
probably null |
|
|
R7007:Npc1
|
UTSW |
18 |
12,343,605 (GRCm39) |
missense |
probably benign |
0.02 |
|
R7020:Npc1
|
UTSW |
18 |
12,331,594 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7048:Npc1
|
UTSW |
18 |
12,337,822 (GRCm39) |
splice site |
probably null |
|
|
R7116:Npc1
|
UTSW |
18 |
12,344,601 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7153:Npc1
|
UTSW |
18 |
12,346,348 (GRCm39) |
missense |
possibly damaging |
0.78 |
|
R7359:Npc1
|
UTSW |
18 |
12,328,237 (GRCm39) |
missense |
probably benign |
0.05 |
|
R7382:Npc1
|
UTSW |
18 |
12,334,763 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R7765:Npc1
|
UTSW |
18 |
12,328,105 (GRCm39) |
missense |
probably benign |
0.01 |
|
R8047:Npc1
|
UTSW |
18 |
12,346,374 (GRCm39) |
missense |
probably benign |
0.00 |
|
R8094:Npc1
|
UTSW |
18 |
12,327,297 (GRCm39) |
missense |
probably benign |
|
|
R8310:Npc1
|
UTSW |
18 |
12,326,455 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R8821:Npc1
|
UTSW |
18 |
12,333,877 (GRCm39) |
missense |
probably benign |
0.01 |
|
R8831:Npc1
|
UTSW |
18 |
12,333,877 (GRCm39) |
missense |
probably benign |
0.01 |
|
R8847:Npc1
|
UTSW |
18 |
12,323,987 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9022:Npc1
|
UTSW |
18 |
12,346,422 (GRCm39) |
missense |
probably benign |
|
|
R9343:Npc1
|
UTSW |
18 |
12,334,769 (GRCm39) |
missense |
possibly damaging |
0.52 |
|
R9460:Npc1
|
UTSW |
18 |
12,346,398 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
R9723:Npc1
|
UTSW |
18 |
12,343,649 (GRCm39) |
missense |
probably benign |
|
|
X0012:Npc1
|
UTSW |
18 |
12,326,368 (GRCm39) |
splice site |
probably null |
|
|
| Predicted Primers |
PCR Primer
(F):5'- CAGAGGCTAAAGACACTGGC -3'
(R):5'- CCGTGTCACAGTGCTCATATTC -3'
Sequencing Primer
(F):5'- TAAAGACACTGGCCCGCTC -3'
(R):5'- ACAGTGCTCATATTCTGCCCATAG -3'
|
| Posted On |
2020-07-13 |
Incidental Mutation