Incidental Mutation 'R1442:Npc1'
| ID |
161578 |
| 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 |
039497-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly essential
(E-score: 0.616)
|
| Stock # |
R1442 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
18 |
| Chromosomal Location |
12322749-12369457 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to A
at 12328106 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Methionine to Leucine
at position 1068
(M1068L)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000025279
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000025279]
|
| AlphaFold |
O35604 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000025279
AA Change: M1068L
PolyPhen 2
Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
|
| SMART Domains |
Protein: ENSMUSP00000025279
Gene: ENSMUSG00000024413
AA Change: M1068L
| 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 |
0.0732 |
| Coding Region Coverage |
- 1x: 98.9%
- 3x: 97.9%
- 10x: 95.0%
- 20x: 88.4%
|
| Validation Efficiency |
100% (71/71) |
| 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: 67 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 5031439G07Rik |
A |
T |
15: 84,839,833 (GRCm39) |
|
probably benign |
Het |
| Adamts7 |
T |
A |
9: 90,070,823 (GRCm39) |
I648N |
probably damaging |
Het |
| Akap13 |
T |
A |
7: 75,385,526 (GRCm39) |
F2252I |
probably damaging |
Het |
| Akr1c6 |
A |
T |
13: 4,507,159 (GRCm39) |
H314L |
probably damaging |
Het |
| Anxa3 |
T |
A |
5: 96,976,549 (GRCm39) |
|
probably null |
Het |
| Apob |
T |
G |
12: 8,036,165 (GRCm39) |
F298V |
probably benign |
Het |
| Atp8a2 |
A |
C |
14: 60,097,772 (GRCm39) |
|
probably benign |
Het |
| Atp8b5 |
A |
T |
4: 43,334,313 (GRCm39) |
T360S |
probably damaging |
Het |
| BC051665 |
A |
T |
13: 60,932,555 (GRCm39) |
N43K |
probably benign |
Het |
| Bicral |
T |
A |
17: 47,112,650 (GRCm39) |
H850L |
probably benign |
Het |
| C1qtnf1 |
A |
G |
11: 118,339,011 (GRCm39) |
D227G |
probably damaging |
Het |
| C8a |
T |
A |
4: 104,685,275 (GRCm39) |
T323S |
possibly damaging |
Het |
| Cep89 |
T |
C |
7: 35,117,636 (GRCm39) |
|
probably benign |
Het |
| Cercam |
G |
T |
2: 29,770,652 (GRCm39) |
V408L |
probably benign |
Het |
| CN725425 |
G |
A |
15: 91,123,158 (GRCm39) |
V76M |
possibly damaging |
Het |
| Cops7b |
T |
A |
1: 86,532,835 (GRCm39) |
M231K |
probably benign |
Het |
| Cpa2 |
T |
A |
6: 30,544,865 (GRCm39) |
|
probably null |
Het |
| Dab2ip |
A |
T |
2: 35,600,268 (GRCm39) |
I287F |
probably damaging |
Het |
| Defb10 |
A |
T |
8: 22,348,944 (GRCm39) |
M1L |
probably benign |
Het |
| Dscam |
C |
A |
16: 96,409,274 (GRCm39) |
R1883L |
possibly damaging |
Het |
| Dsg4 |
T |
A |
18: 20,595,717 (GRCm39) |
I640N |
possibly damaging |
Het |
| Duox2 |
G |
C |
2: 122,112,232 (GRCm39) |
P1318R |
probably benign |
Het |
| Dzip3 |
T |
C |
16: 48,765,985 (GRCm39) |
D466G |
probably benign |
Het |
| E230025N22Rik |
T |
A |
18: 36,824,462 (GRCm39) |
|
probably null |
Het |
| E2f3 |
A |
G |
13: 30,102,652 (GRCm39) |
L80P |
probably damaging |
Het |
| Eif2b2 |
T |
C |
12: 85,266,360 (GRCm39) |
S9P |
probably benign |
Het |
| Etaa1 |
A |
T |
11: 17,897,201 (GRCm39) |
D305E |
probably benign |
Het |
| Fads6 |
C |
A |
11: 115,188,235 (GRCm39) |
R23L |
probably benign |
Het |
| Flrt2 |
T |
C |
12: 95,746,979 (GRCm39) |
V439A |
probably damaging |
Het |
| Galm |
A |
C |
17: 80,452,614 (GRCm39) |
Q184P |
probably damaging |
Het |
| Gtse1 |
C |
T |
15: 85,744,303 (GRCm39) |
|
probably benign |
Het |
| Irf7 |
T |
C |
7: 140,843,935 (GRCm39) |
T246A |
probably damaging |
Het |
| Kif28 |
A |
G |
1: 179,532,697 (GRCm39) |
V639A |
possibly damaging |
Het |
| Klhdc8a |
G |
A |
1: 132,230,385 (GRCm39) |
A167T |
possibly damaging |
Het |
| Lrfn3 |
T |
C |
7: 30,059,469 (GRCm39) |
H252R |
probably benign |
Het |
| Lzts1 |
G |
T |
8: 69,591,638 (GRCm39) |
A170E |
probably damaging |
Het |
| Mphosph9 |
T |
A |
5: 124,403,461 (GRCm39) |
I856F |
possibly damaging |
Het |
| Mroh2a |
C |
T |
1: 88,160,075 (GRCm39) |
|
probably benign |
Het |
| Mroh2a |
C |
A |
1: 88,170,142 (GRCm39) |
A685D |
possibly damaging |
Het |
| Myh3 |
A |
G |
11: 66,978,103 (GRCm39) |
N392D |
possibly damaging |
Het |
| Naalad2 |
T |
C |
9: 18,262,328 (GRCm39) |
|
probably benign |
Het |
| Nup58 |
T |
A |
14: 60,469,992 (GRCm39) |
|
probably benign |
Het |
| Or10c1 |
T |
C |
17: 37,522,595 (GRCm39) |
T50A |
probably benign |
Het |
| Or4k40 |
A |
T |
2: 111,250,438 (GRCm39) |
I286N |
probably damaging |
Het |
| Or8b1 |
A |
T |
9: 38,399,939 (GRCm39) |
I205F |
probably benign |
Het |
| Or8s16 |
T |
C |
15: 98,211,068 (GRCm39) |
Y121C |
probably damaging |
Het |
| Parp2 |
T |
G |
14: 51,056,732 (GRCm39) |
|
probably null |
Het |
| Ppp4r4 |
T |
C |
12: 103,564,504 (GRCm39) |
V9A |
probably damaging |
Het |
| Ptprc |
T |
A |
1: 138,000,050 (GRCm39) |
D856V |
probably damaging |
Het |
| Ptpru |
T |
A |
4: 131,535,580 (GRCm39) |
T466S |
probably benign |
Het |
| Rhob |
A |
G |
12: 8,549,325 (GRCm39) |
V103A |
possibly damaging |
Het |
| Sec23ip |
A |
C |
7: 128,378,510 (GRCm39) |
S775R |
probably benign |
Het |
| Slit2 |
T |
G |
5: 48,395,725 (GRCm39) |
D709E |
probably damaging |
Het |
| Smok2b |
C |
G |
17: 13,454,390 (GRCm39) |
I183M |
probably damaging |
Het |
| Smtnl1 |
T |
A |
2: 84,648,780 (GRCm39) |
D158V |
probably damaging |
Het |
| Syne2 |
T |
C |
12: 75,993,489 (GRCm39) |
I2087T |
probably damaging |
Het |
| Tada1 |
G |
A |
1: 166,214,319 (GRCm39) |
R106H |
possibly damaging |
Het |
| Tecta |
T |
A |
9: 42,243,778 (GRCm39) |
I2025F |
probably damaging |
Het |
| Themis |
T |
C |
10: 28,658,131 (GRCm39) |
V386A |
probably damaging |
Het |
| Ubr5 |
G |
A |
15: 38,015,168 (GRCm39) |
|
probably benign |
Het |
| Vcl |
T |
A |
14: 21,033,446 (GRCm39) |
I134N |
probably damaging |
Het |
| Vegfa |
G |
A |
17: 46,336,418 (GRCm39) |
T56I |
possibly damaging |
Het |
| Vmn2r108 |
T |
A |
17: 20,692,623 (GRCm39) |
K78* |
probably null |
Het |
| Vmn2r82 |
A |
T |
10: 79,215,201 (GRCm39) |
T395S |
probably benign |
Het |
| Wbp2nl |
T |
C |
15: 82,198,407 (GRCm39) |
S315P |
probably benign |
Het |
| Zfp566 |
T |
C |
7: 29,777,344 (GRCm39) |
Y279C |
probably damaging |
Het |
| Zmym2 |
T |
C |
14: 57,180,784 (GRCm39) |
Y899H |
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 |
|
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 |
|
|
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'- TGGGAACTGCCCAAGAACTAGGAC -3'
(R):5'- TTCCTCAGGGGACATGCTGCTTAC -3'
Sequencing Primer
(F):5'- AGTCTGTTATCAGAGCAATGTCCC -3'
(R):5'- ACATGCTGCTTACGGTTCAG -3'
|
| Posted On |
2014-03-14 |
Incidental Mutation