Incidental Mutation 'R1808:Npc1'
ID |
203641 |
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 |
039837-MU
|
Accession Numbers |
|
Essential gene? |
Possibly essential
(E-score: 0.616)
|
Stock # |
R1808 (G1)
|
Quality Score |
225 |
Status
|
Not validated
|
Chromosome |
18 |
Chromosomal Location |
12322749-12369457 bp(-) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
T to C
at 12327149 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Asparagine to Aspartic acid
at position 1149
(N1149D)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000025279
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000025276]
[ENSMUST00000025279]
|
AlphaFold |
O35604 |
Predicted Effect |
probably benign
Transcript: ENSMUST00000025276
|
SMART Domains |
Protein: ENSMUSP00000025276 Gene: ENSMUSG00000024410
Domain | Start | End | E-Value | Type |
SCOP:d1crza1
|
21 |
169 |
5e-4 |
SMART |
low complexity region
|
268 |
281 |
N/A |
INTRINSIC |
Pfam:Mic1
|
475 |
632 |
4.4e-73 |
PFAM |
|
Predicted Effect |
probably damaging
Transcript: ENSMUST00000025279
AA Change: N1149D
PolyPhen 2
Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
|
SMART Domains |
Protein: ENSMUSP00000025279 Gene: ENSMUSG00000024413 AA Change: N1149D
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: ENSMUST00000127123
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000134756
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000139151
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000153233
|
Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000153352
|
Coding Region Coverage |
- 1x: 97.5%
- 3x: 96.9%
- 10x: 95.1%
- 20x: 91.9%
|
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 |
1700001J03Rik |
G |
T |
5: 146,121,691 (GRCm39) |
Y69* |
probably null |
Het |
2310011J03Rik |
A |
G |
10: 80,156,015 (GRCm39) |
|
probably null |
Het |
A2ml1 |
A |
C |
6: 128,520,262 (GRCm39) |
D1367E |
probably damaging |
Het |
Adam6a |
C |
G |
12: 113,508,334 (GRCm39) |
L236V |
probably benign |
Het |
Arf3 |
T |
C |
15: 98,638,954 (GRCm39) |
N101S |
probably benign |
Het |
Arhgap42 |
T |
C |
9: 9,180,051 (GRCm39) |
E76G |
probably damaging |
Het |
Atp2a1 |
A |
G |
7: 126,052,573 (GRCm39) |
F382S |
probably damaging |
Het |
Bud13 |
T |
A |
9: 46,199,705 (GRCm39) |
F355L |
probably benign |
Het |
C2 |
G |
A |
17: 35,083,508 (GRCm39) |
P349S |
probably damaging |
Het |
Cbl |
C |
A |
9: 44,075,526 (GRCm39) |
G373V |
probably damaging |
Het |
Ccdc3 |
T |
A |
2: 5,142,896 (GRCm39) |
L51Q |
probably damaging |
Het |
Ccdc34 |
T |
A |
2: 109,874,601 (GRCm39) |
M320K |
probably benign |
Het |
Cntln |
A |
G |
4: 85,015,000 (GRCm39) |
E1097G |
probably damaging |
Het |
Ctsc |
A |
C |
7: 87,948,750 (GRCm39) |
K195Q |
possibly damaging |
Het |
Ctsf |
C |
T |
19: 4,906,562 (GRCm39) |
P163L |
probably benign |
Het |
Dcxr |
A |
T |
11: 120,616,438 (GRCm39) |
|
probably null |
Het |
Dgki |
T |
C |
6: 37,126,509 (GRCm39) |
E157G |
possibly damaging |
Het |
Dnah8 |
T |
C |
17: 30,903,160 (GRCm39) |
L933P |
probably damaging |
Het |
Dtna |
T |
C |
18: 23,702,697 (GRCm39) |
L76P |
probably damaging |
Het |
Fcgbp |
T |
A |
7: 27,784,515 (GRCm39) |
C192S |
probably benign |
Het |
Galnt5 |
T |
A |
2: 57,916,137 (GRCm39) |
D683E |
probably benign |
Het |
Greb1l |
G |
A |
18: 10,542,143 (GRCm39) |
A1297T |
probably benign |
Het |
Grik4 |
T |
C |
9: 42,540,322 (GRCm39) |
N286S |
probably benign |
Het |
Hrc |
A |
T |
7: 44,986,202 (GRCm39) |
E451V |
probably damaging |
Het |
Hrh3 |
G |
A |
2: 179,741,577 (GRCm39) |
|
probably benign |
Het |
Ints13 |
A |
G |
6: 146,455,695 (GRCm39) |
I152T |
probably damaging |
Het |
Irgm1 |
A |
T |
11: 48,757,259 (GRCm39) |
V184D |
probably damaging |
Het |
Itga5 |
C |
T |
15: 103,258,826 (GRCm39) |
A791T |
probably damaging |
Het |
Kcp |
T |
C |
6: 29,505,654 (GRCm39) |
T73A |
probably benign |
Het |
Kidins220 |
A |
G |
12: 25,053,008 (GRCm39) |
T433A |
probably benign |
Het |
Kirrel1 |
C |
T |
3: 86,996,458 (GRCm39) |
M380I |
probably null |
Het |
Kmt2d |
T |
C |
15: 98,764,567 (GRCm39) |
D12G |
probably damaging |
Het |
Mms19 |
A |
G |
19: 41,954,698 (GRCm39) |
S74P |
probably damaging |
Het |
Myh1 |
G |
T |
11: 67,102,300 (GRCm39) |
E864* |
probably null |
Het |
Nek1 |
A |
G |
8: 61,469,264 (GRCm39) |
D107G |
probably damaging |
Het |
Or14j6 |
T |
A |
17: 38,214,661 (GRCm39) |
S75T |
probably damaging |
Het |
Or3a1b |
C |
A |
11: 74,012,257 (GRCm39) |
S47R |
probably damaging |
Het |
Or4k36 |
T |
C |
2: 111,146,343 (GRCm39) |
V173A |
probably benign |
Het |
Or5p79 |
A |
C |
7: 108,221,817 (GRCm39) |
K266T |
possibly damaging |
Het |
Osbp |
T |
C |
19: 11,948,142 (GRCm39) |
S150P |
probably damaging |
Het |
Paf1 |
T |
C |
7: 28,096,247 (GRCm39) |
Y287H |
probably damaging |
Het |
Pdgfrb |
T |
C |
18: 61,201,174 (GRCm39) |
V420A |
probably benign |
Het |
Pdss1 |
G |
T |
2: 22,796,846 (GRCm39) |
E120* |
probably null |
Het |
Pink1 |
A |
T |
4: 138,044,630 (GRCm39) |
V339E |
probably damaging |
Het |
Pkn3 |
C |
T |
2: 29,969,663 (GRCm39) |
R58C |
probably damaging |
Het |
Pm20d1 |
G |
A |
1: 131,730,165 (GRCm39) |
V235I |
probably benign |
Het |
Ppp2r2a |
A |
G |
14: 67,276,412 (GRCm39) |
I31T |
probably damaging |
Het |
Rbms3 |
T |
C |
9: 116,651,894 (GRCm39) |
E152G |
probably damaging |
Het |
Rfx1 |
A |
C |
8: 84,821,677 (GRCm39) |
Q804H |
probably damaging |
Het |
Rpe |
G |
T |
1: 66,754,356 (GRCm39) |
V143L |
probably benign |
Het |
Sap30l |
G |
T |
11: 57,700,771 (GRCm39) |
V142L |
probably benign |
Het |
Sh3tc1 |
T |
C |
5: 35,863,268 (GRCm39) |
Q973R |
probably benign |
Het |
Slc10a2 |
T |
C |
8: 5,154,856 (GRCm39) |
T110A |
probably damaging |
Het |
Snrnp200 |
A |
T |
2: 127,060,947 (GRCm39) |
|
probably null |
Het |
Snrnp200 |
G |
A |
2: 127,060,948 (GRCm39) |
|
probably null |
Het |
Spaca3 |
T |
A |
11: 80,758,511 (GRCm39) |
V158E |
probably damaging |
Het |
Sprtn |
C |
A |
8: 125,629,770 (GRCm39) |
N354K |
probably benign |
Het |
Stab1 |
T |
A |
14: 30,863,101 (GRCm39) |
Y2166F |
possibly damaging |
Het |
Tmem106c |
G |
A |
15: 97,866,548 (GRCm39) |
|
probably null |
Het |
Tnc |
A |
G |
4: 63,918,168 (GRCm39) |
S1248P |
probably damaging |
Het |
Tshr |
T |
C |
12: 91,504,090 (GRCm39) |
F343L |
probably benign |
Het |
Ttn |
C |
A |
2: 76,555,698 (GRCm39) |
A30436S |
probably damaging |
Het |
Ubxn2a |
A |
T |
12: 4,935,839 (GRCm39) |
M68K |
probably benign |
Het |
Ucp2 |
T |
C |
7: 100,148,021 (GRCm39) |
V238A |
probably damaging |
Het |
Urgcp |
C |
A |
11: 5,667,242 (GRCm39) |
L365F |
probably damaging |
Het |
Vezt |
A |
T |
10: 93,826,026 (GRCm39) |
D328E |
probably damaging |
Het |
Vmn1r168 |
G |
T |
7: 23,240,184 (GRCm39) |
V14L |
probably benign |
Het |
Vps13b |
T |
C |
15: 35,792,205 (GRCm39) |
F2158L |
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 |
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 |
|
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'- CGAGTGTCTTAATGTCACTAGGC -3'
(R):5'- ACCTGACCATTATTGATGACACC -3'
Sequencing Primer
(F):5'- GTCTTAATGTCACTAGGCTACATGG -3'
(R):5'- GATGACACCATCTTTAACCTCAGTG -3'
|
Posted On |
2014-06-23 |