Incidental Mutation 'R5243:Npc1'
| ID |
401018 |
| 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 |
042814-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly essential
(E-score: 0.616)
|
| Stock # |
R5243 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
18 |
| Chromosomal Location |
12322749-12369457 bp(-) (GRCm39) |
| Type of Mutation |
intron |
| DNA Base Change (assembly) |
T to A
at 12331688 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000025279
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000025279]
|
| AlphaFold |
O35604 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000025279
|
| SMART Domains |
Protein: ENSMUSP00000025279
Gene: ENSMUSG00000024413
| 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 |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000153352
|
| Meta Mutation Damage Score |
0.0846 |
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.6%
- 10x: 97.1%
- 20x: 95.0%
|
| Validation Efficiency |
95% (62/65) |
| 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: 60 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4930447C04Rik |
A |
T |
12: 72,956,543 (GRCm39) |
|
probably null |
Het |
| Aatk |
A |
G |
11: 119,907,594 (GRCm39) |
L78P |
probably damaging |
Het |
| Acadsb |
T |
A |
7: 131,045,972 (GRCm39) |
I412K |
probably damaging |
Het |
| Acer3 |
T |
C |
7: 97,867,277 (GRCm39) |
R246G |
possibly damaging |
Het |
| Atp1a3 |
T |
A |
7: 24,693,994 (GRCm39) |
I387F |
probably damaging |
Het |
| Atp6v1b2 |
A |
T |
8: 69,556,391 (GRCm39) |
M300L |
probably benign |
Het |
| Aurkb |
T |
A |
11: 68,936,752 (GRCm39) |
|
probably benign |
Het |
| Card10 |
C |
A |
15: 78,664,872 (GRCm39) |
G694V |
possibly damaging |
Het |
| Ccdc171 |
A |
G |
4: 83,522,344 (GRCm39) |
N336S |
probably damaging |
Het |
| Copg2 |
T |
C |
6: 30,750,626 (GRCm39) |
T720A |
probably benign |
Het |
| Coro2a |
A |
T |
4: 46,545,620 (GRCm39) |
W272R |
probably damaging |
Het |
| Cpne6 |
T |
A |
14: 55,750,204 (GRCm39) |
C112S |
probably damaging |
Het |
| Ddx21 |
A |
G |
10: 62,437,992 (GRCm39) |
M1T |
probably null |
Het |
| Dohh |
A |
G |
10: 81,223,203 (GRCm39) |
R161G |
probably benign |
Het |
| Dsc1 |
A |
C |
18: 20,232,216 (GRCm39) |
V264G |
probably damaging |
Het |
| E4f1 |
A |
T |
17: 24,666,292 (GRCm39) |
C198S |
probably damaging |
Het |
| Evpl |
T |
A |
11: 116,113,795 (GRCm39) |
E1298D |
probably damaging |
Het |
| Grid2ip |
A |
T |
5: 143,363,260 (GRCm39) |
I246F |
probably damaging |
Het |
| H2-M1 |
A |
G |
17: 36,982,193 (GRCm39) |
F136S |
possibly damaging |
Het |
| Hck |
T |
C |
2: 152,986,412 (GRCm39) |
V387A |
probably damaging |
Het |
| Hdac1 |
G |
A |
4: 129,410,646 (GRCm39) |
|
probably benign |
Het |
| Hydin |
A |
C |
8: 111,232,380 (GRCm39) |
Q1633P |
possibly damaging |
Het |
| Igkv12-41 |
A |
G |
6: 69,835,686 (GRCm39) |
I22T |
probably damaging |
Het |
| Ints3 |
CA |
CAA |
3: 90,308,451 (GRCm39) |
|
probably null |
Het |
| Itpr2 |
C |
G |
6: 146,089,044 (GRCm39) |
W2188C |
probably damaging |
Het |
| Kcnt1 |
A |
G |
2: 25,798,086 (GRCm39) |
E899G |
probably damaging |
Het |
| Lgals8 |
C |
A |
13: 12,469,645 (GRCm39) |
V12L |
probably benign |
Het |
| Lgr6 |
T |
C |
1: 135,037,010 (GRCm39) |
|
probably benign |
Het |
| Lrrc8b |
T |
G |
5: 105,628,812 (GRCm39) |
I386S |
probably damaging |
Het |
| Mks1 |
T |
C |
11: 87,747,504 (GRCm39) |
|
probably benign |
Het |
| Mon1b |
A |
G |
8: 114,364,553 (GRCm39) |
D110G |
possibly damaging |
Het |
| Mpdz |
G |
T |
4: 81,225,116 (GRCm39) |
A1437E |
probably damaging |
Het |
| Nbeal1 |
T |
A |
1: 60,309,487 (GRCm39) |
N1753K |
probably damaging |
Het |
| Nceh1 |
T |
C |
3: 27,295,837 (GRCm39) |
V366A |
probably damaging |
Het |
| Ncor1 |
A |
T |
11: 62,229,788 (GRCm39) |
D893E |
probably damaging |
Het |
| Or1j15 |
T |
C |
2: 36,458,655 (GRCm39) |
L15P |
probably damaging |
Het |
| Or9i1b |
A |
G |
19: 13,897,025 (GRCm39) |
I214V |
probably damaging |
Het |
| Podxl2 |
T |
C |
6: 88,826,356 (GRCm39) |
T317A |
probably benign |
Het |
| Prl8a9 |
T |
G |
13: 27,746,446 (GRCm39) |
Q54P |
probably damaging |
Het |
| Prpf31 |
C |
T |
7: 3,641,753 (GRCm39) |
R351* |
probably null |
Het |
| Pspc1 |
C |
T |
14: 57,001,648 (GRCm39) |
G242D |
probably damaging |
Het |
| Rbmxl2 |
G |
C |
7: 106,809,044 (GRCm39) |
G110R |
probably damaging |
Het |
| Rif1 |
T |
A |
2: 52,001,836 (GRCm39) |
H1763Q |
possibly damaging |
Het |
| Rpusd3 |
T |
C |
6: 113,395,025 (GRCm39) |
T85A |
probably benign |
Het |
| Rttn |
A |
G |
18: 89,126,187 (GRCm39) |
I1853M |
possibly damaging |
Het |
| Sacs |
T |
A |
14: 61,443,406 (GRCm39) |
C1817* |
probably null |
Het |
| Scrib |
A |
T |
15: 75,937,101 (GRCm39) |
V335E |
probably benign |
Het |
| Sdk2 |
A |
G |
11: 113,715,912 (GRCm39) |
L1549P |
possibly damaging |
Het |
| Slc25a11 |
C |
T |
11: 70,536,924 (GRCm39) |
G44S |
probably damaging |
Het |
| Slc6a3 |
A |
G |
13: 73,719,570 (GRCm39) |
Y533C |
possibly damaging |
Het |
| Slc7a5 |
A |
G |
8: 122,623,274 (GRCm39) |
V191A |
probably damaging |
Het |
| Son |
A |
G |
16: 91,451,621 (GRCm39) |
K123E |
probably damaging |
Het |
| Tcstv3 |
T |
A |
13: 120,779,125 (GRCm39) |
M8K |
probably benign |
Het |
| Tie1 |
A |
G |
4: 118,339,548 (GRCm39) |
V411A |
probably damaging |
Het |
| Upk3bl |
C |
A |
5: 136,088,977 (GRCm39) |
D1E |
possibly damaging |
Het |
| Vmn2r5 |
T |
C |
3: 64,411,497 (GRCm39) |
D357G |
probably damaging |
Het |
| Vmn2r75 |
T |
C |
7: 85,813,447 (GRCm39) |
N452D |
probably damaging |
Het |
| Wnk2 |
T |
A |
13: 49,226,054 (GRCm39) |
N1043I |
possibly damaging |
Het |
| Zfp407 |
A |
T |
18: 84,579,216 (GRCm39) |
H632Q |
probably damaging |
Het |
| Zfp423 |
T |
C |
8: 88,500,275 (GRCm39) |
K1174R |
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 |
|
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 |
|
|
R8161:Npc1
|
UTSW |
18 |
12,328,129 (GRCm39) |
missense |
possibly damaging |
0.77 |
|
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'- CATGATTTGCATTCAGAAGCAAGC -3'
(R):5'- AAAGCCCTGTAGGTGCTGTAC -3'
Sequencing Primer
(F):5'- TGCATTCAGAAGCAAGCATTAAC -3'
(R):5'- AAGCCCTGTAGGTGCTGTACTATAAG -3'
|
| Posted On |
2016-07-06 |
Incidental Mutation