Incidental Mutation 'R6476:Npc1'
| ID |
516817 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Npc1
|
| Ensembl Gene |
ENSMUSG00000024413 |
| Gene Name |
NPC intracellular cholesterol transporter 1 |
| Synonyms |
lcsd, nmf164, D18Ertd139e, D18Ertd723e, A430089E03Rik, C85354 |
| Accession Numbers |
|
| Essential gene? |
Possibly essential
(E-score: 0.616)
|
| Stock # |
R6476 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Not validated
|
| Chromosome |
18 |
| Chromosomal Location |
12322749-12369457 bp(-) (GRCm39) |
| Type of Mutation |
nonsense |
| DNA Base Change (assembly) |
G to T
at 12334751 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Serine to Stop codon
at position 667
(S667*)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000025279
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000025279]
|
| AlphaFold |
O35604 |
| Predicted Effect |
probably null
Transcript: ENSMUST00000025279
AA Change: S667*
|
| SMART Domains |
Protein: ENSMUSP00000025279
Gene: ENSMUSG00000024413
AA Change: S667*
| 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
|
| Coding Region Coverage |
- 1x: 99.9%
- 3x: 99.6%
- 10x: 98.3%
- 20x: 95.3%
|
| 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: 68 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| a |
T |
C |
2: 154,892,699 (GRCm39) |
V126A |
probably benign |
Het |
| Adamts20 |
T |
C |
15: 94,259,691 (GRCm39) |
Q336R |
probably benign |
Het |
| Ankrd36 |
A |
G |
11: 5,578,753 (GRCm39) |
T6A |
probably benign |
Het |
| Arhgap33 |
A |
G |
7: 30,223,837 (GRCm39) |
S731P |
probably damaging |
Het |
| Arhgef10l |
G |
C |
4: 140,338,693 (GRCm39) |
P23R |
probably damaging |
Het |
| Atf7 |
T |
C |
15: 102,502,147 (GRCm39) |
D3G |
probably benign |
Het |
| Caps2 |
A |
G |
10: 112,011,465 (GRCm39) |
T30A |
possibly damaging |
Het |
| Ccdc15 |
A |
T |
9: 37,253,715 (GRCm39) |
I191N |
probably benign |
Het |
| Cep170 |
A |
T |
1: 176,607,917 (GRCm39) |
S180T |
possibly damaging |
Het |
| Chd1 |
G |
A |
17: 17,601,250 (GRCm39) |
|
probably null |
Het |
| Col6a3 |
A |
T |
1: 90,709,534 (GRCm39) |
N1887K |
unknown |
Het |
| Csgalnact1 |
C |
T |
8: 68,913,761 (GRCm39) |
S148N |
probably damaging |
Het |
| Csgalnact1 |
T |
A |
8: 68,913,762 (GRCm39) |
S148C |
probably damaging |
Het |
| Dnah14 |
A |
G |
1: 181,572,333 (GRCm39) |
E2888G |
probably benign |
Het |
| Dnah7b |
T |
A |
1: 46,281,364 (GRCm39) |
Y2808* |
probably null |
Het |
| Dock10 |
A |
C |
1: 80,518,959 (GRCm39) |
L1254* |
probably null |
Het |
| Eml2 |
T |
C |
7: 18,930,236 (GRCm39) |
V511A |
probably benign |
Het |
| Eml6 |
A |
G |
11: 29,741,971 (GRCm39) |
|
probably null |
Het |
| Erbin |
C |
A |
13: 103,977,755 (GRCm39) |
D601Y |
probably damaging |
Het |
| Farsa |
A |
G |
8: 85,583,809 (GRCm39) |
E49G |
probably damaging |
Het |
| Fzd7 |
A |
G |
1: 59,523,154 (GRCm39) |
M346V |
probably damaging |
Het |
| Gatd3a |
T |
C |
10: 78,003,347 (GRCm39) |
N102D |
probably damaging |
Het |
| Glg1 |
A |
C |
8: 111,926,806 (GRCm39) |
S170A |
possibly damaging |
Het |
| Gpx3 |
A |
T |
11: 54,798,025 (GRCm39) |
I54F |
probably damaging |
Het |
| H6pd |
G |
A |
4: 150,067,184 (GRCm39) |
H401Y |
probably damaging |
Het |
| Hspb8 |
A |
G |
5: 116,560,457 (GRCm39) |
S28P |
probably damaging |
Het |
| Iqub |
T |
A |
6: 24,449,744 (GRCm39) |
N707I |
probably damaging |
Het |
| Krt9 |
A |
T |
11: 100,081,640 (GRCm39) |
D296E |
probably damaging |
Het |
| Lcor |
C |
T |
19: 41,571,518 (GRCm39) |
T237I |
probably benign |
Het |
| Lnx1 |
A |
G |
5: 74,768,541 (GRCm39) |
V349A |
possibly damaging |
Het |
| Map3k6 |
A |
T |
4: 132,977,397 (GRCm39) |
S915C |
probably damaging |
Het |
| Mecom |
C |
A |
3: 30,034,717 (GRCm39) |
A510S |
possibly damaging |
Het |
| Mettl14 |
A |
G |
3: 123,167,686 (GRCm39) |
I224T |
probably damaging |
Het |
| Mme |
T |
C |
3: 63,251,056 (GRCm39) |
|
probably null |
Het |
| Nbea |
T |
A |
3: 55,912,227 (GRCm39) |
T1187S |
probably benign |
Het |
| Ndor1 |
T |
C |
2: 25,138,154 (GRCm39) |
T444A |
possibly damaging |
Het |
| Nhlrc1 |
A |
G |
13: 47,167,657 (GRCm39) |
L200P |
possibly damaging |
Het |
| Nscme3l |
A |
C |
19: 5,553,253 (GRCm39) |
I176S |
probably damaging |
Het |
| Or14a256 |
C |
T |
7: 86,265,218 (GRCm39) |
V212I |
probably benign |
Het |
| Or1l8 |
T |
A |
2: 36,817,595 (GRCm39) |
H177L |
possibly damaging |
Het |
| Or4c109 |
T |
A |
2: 88,817,721 (GRCm39) |
D275V |
probably benign |
Het |
| Or51d1 |
T |
A |
7: 102,348,310 (GRCm39) |
N288K |
possibly damaging |
Het |
| Or5g9 |
T |
A |
2: 85,551,928 (GRCm39) |
Y60N |
probably damaging |
Het |
| Pds5a |
A |
C |
5: 65,791,630 (GRCm39) |
I773R |
possibly damaging |
Het |
| Pgr |
T |
A |
9: 8,964,839 (GRCm39) |
|
probably null |
Het |
| Plscr4 |
A |
T |
9: 92,372,819 (GRCm39) |
M314L |
probably benign |
Het |
| Polr2m |
A |
G |
9: 71,390,752 (GRCm39) |
V46A |
probably benign |
Het |
| Ptk2b |
T |
A |
14: 66,424,923 (GRCm39) |
M174L |
possibly damaging |
Het |
| Sec31a |
A |
T |
5: 100,534,008 (GRCm39) |
F521I |
probably benign |
Het |
| Serpinb3d |
T |
C |
1: 107,011,071 (GRCm39) |
N47S |
probably benign |
Het |
| Shld2 |
T |
C |
14: 33,989,971 (GRCm39) |
S312G |
probably benign |
Het |
| Slc24a3 |
T |
A |
2: 145,448,750 (GRCm39) |
D431E |
probably benign |
Het |
| Slc34a1 |
C |
A |
13: 23,996,569 (GRCm39) |
H25N |
probably damaging |
Het |
| Slc9a9 |
T |
C |
9: 94,567,191 (GRCm39) |
F87L |
probably benign |
Het |
| Spata31 |
T |
A |
13: 65,065,456 (GRCm39) |
S54T |
possibly damaging |
Het |
| Spata6 |
T |
C |
4: 111,632,020 (GRCm39) |
S144P |
probably damaging |
Het |
| Sppl2c |
A |
G |
11: 104,077,595 (GRCm39) |
N132D |
probably benign |
Het |
| Ssu2 |
C |
T |
6: 112,351,793 (GRCm39) |
G311S |
probably damaging |
Het |
| Syne1 |
T |
A |
10: 5,104,531 (GRCm39) |
Q6328L |
possibly damaging |
Het |
| Tie1 |
T |
C |
4: 118,330,062 (GRCm39) |
T1054A |
possibly damaging |
Het |
| Tnfaip6 |
T |
G |
2: 51,942,328 (GRCm39) |
D212E |
probably benign |
Het |
| Tnxb |
A |
G |
17: 34,909,166 (GRCm39) |
T1442A |
probably damaging |
Het |
| Trim35 |
C |
T |
14: 66,546,244 (GRCm39) |
T337M |
probably damaging |
Het |
| Vipr1 |
T |
C |
9: 121,498,489 (GRCm39) |
V413A |
probably benign |
Het |
| Vmn1r19 |
C |
G |
6: 57,381,578 (GRCm39) |
Q44E |
probably damaging |
Het |
| Zfp1002 |
T |
C |
2: 150,097,246 (GRCm39) |
D61G |
probably benign |
Het |
| Zfp266 |
G |
T |
9: 20,410,577 (GRCm39) |
H533Q |
probably damaging |
Het |
| Zfp689 |
T |
C |
7: 127,043,896 (GRCm39) |
S245G |
probably damaging |
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 |
|
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'- CAGTGCTGAGCAGTCACTTAG -3'
(R):5'- TTGTTGCTAGGGAGAAACCTGC -3'
Sequencing Primer
(F):5'- TCACTGAGTGCTTAGACAGACGC -3'
(R):5'- AAACCTGCAAGTTTCTTCTGTG -3'
|
| Posted On |
2018-05-21 |
Incidental Mutation