Incidental Mutation 'R0068:Npc1'
| ID |
18016 |
| 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 |
038359-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly essential
(E-score: 0.637)
|
| Stock # |
R0068 (G1)
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
18 |
| Chromosomal Location |
12322749-12369457 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
G to C
at 12341424 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Proline to Alanine
at position 532
(P532A)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000025279
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000025279]
|
| AlphaFold |
O35604 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000025279
AA Change: P532A
PolyPhen 2
Score 0.039 (Sensitivity: 0.94; Specificity: 0.83)
|
| SMART Domains |
Protein: ENSMUSP00000025279
Gene: ENSMUSG00000024413
AA Change: P532A
| 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: ENSMUST00000145771
|
| Meta Mutation Damage Score |
0.2178 |
| Coding Region Coverage |
- 1x: 89.9%
- 3x: 97.6%
- 10x: 82.1%
- 20x: 74.0%
|
| Validation Efficiency |
94% (83/88) |
| 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: 57 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abca9 |
T |
C |
11: 110,036,405 (GRCm39) |
N568S |
probably damaging |
Het |
| Aldoart2 |
G |
T |
12: 55,612,233 (GRCm39) |
E53* |
probably null |
Het |
| Ankra2 |
C |
T |
13: 98,409,891 (GRCm39) |
Q137* |
probably null |
Het |
| Arpc1a |
C |
T |
5: 145,028,054 (GRCm39) |
T21I |
possibly damaging |
Het |
| Arvcf |
T |
C |
16: 18,214,819 (GRCm39) |
|
probably benign |
Het |
| Ash1l |
C |
A |
3: 88,914,624 (GRCm39) |
S1751R |
probably benign |
Het |
| Bltp1 |
A |
G |
3: 37,006,370 (GRCm39) |
T1675A |
probably benign |
Het |
| Bsn |
C |
A |
9: 107,989,336 (GRCm39) |
G2139C |
probably damaging |
Het |
| Cbl |
A |
T |
9: 44,065,491 (GRCm39) |
S22T |
probably damaging |
Het |
| Ccdc148 |
T |
C |
2: 58,717,629 (GRCm39) |
E530G |
probably benign |
Het |
| Cct3 |
A |
G |
3: 88,225,772 (GRCm39) |
D365G |
probably benign |
Het |
| Cep85 |
A |
T |
4: 133,881,606 (GRCm39) |
H332Q |
probably benign |
Het |
| Cwf19l1 |
A |
T |
19: 44,119,938 (GRCm39) |
Y68N |
probably damaging |
Het |
| Dlc1 |
T |
A |
8: 37,404,875 (GRCm39) |
M305L |
probably benign |
Het |
| Dnm1l |
C |
A |
16: 16,141,883 (GRCm39) |
G288C |
probably damaging |
Het |
| Exoc7 |
T |
C |
11: 116,195,732 (GRCm39) |
Y83C |
probably damaging |
Het |
| Fignl2 |
A |
T |
15: 100,952,129 (GRCm39) |
I51N |
probably damaging |
Het |
| Flnb |
A |
G |
14: 7,915,290 (GRCm38) |
N1474D |
possibly damaging |
Het |
| Ghrhr |
C |
T |
6: 55,357,849 (GRCm39) |
|
probably benign |
Het |
| Gucy1b1 |
T |
C |
3: 81,942,185 (GRCm39) |
T525A |
probably benign |
Het |
| Hhip |
T |
G |
8: 80,715,885 (GRCm39) |
D557A |
probably damaging |
Het |
| Hps5 |
A |
G |
7: 46,426,466 (GRCm39) |
|
probably benign |
Het |
| Igsf10 |
A |
T |
3: 59,238,045 (GRCm39) |
V712D |
probably damaging |
Het |
| Irf6 |
G |
T |
1: 192,848,067 (GRCm39) |
|
probably benign |
Het |
| Itpr3 |
T |
C |
17: 27,323,034 (GRCm39) |
|
probably benign |
Het |
| Jag2 |
A |
G |
12: 112,878,813 (GRCm39) |
|
probably benign |
Het |
| Kansl1l |
A |
G |
1: 66,760,047 (GRCm39) |
V911A |
probably benign |
Het |
| Kdm3b |
C |
T |
18: 34,957,827 (GRCm39) |
T1064I |
probably benign |
Het |
| Lrriq1 |
T |
A |
10: 102,899,279 (GRCm39) |
Q1654L |
probably benign |
Het |
| Ltbp1 |
A |
G |
17: 75,666,404 (GRCm39) |
T1366A |
probably damaging |
Het |
| Mroh1 |
A |
G |
15: 76,330,892 (GRCm39) |
|
probably benign |
Het |
| Napb |
G |
A |
2: 148,540,843 (GRCm39) |
|
probably benign |
Het |
| Nebl |
T |
A |
2: 17,439,782 (GRCm39) |
R164* |
probably null |
Het |
| Nrp2 |
G |
T |
1: 62,784,536 (GRCm39) |
K228N |
possibly damaging |
Het |
| Or13f5 |
T |
A |
4: 52,825,503 (GRCm39) |
Y35* |
probably null |
Het |
| Plekhg1 |
A |
T |
10: 3,890,502 (GRCm39) |
Y386F |
probably damaging |
Het |
| Pmfbp1 |
G |
C |
8: 110,269,011 (GRCm39) |
|
probably benign |
Het |
| Poln |
T |
C |
5: 34,234,432 (GRCm39) |
|
probably benign |
Het |
| Polr1c |
A |
G |
17: 46,555,829 (GRCm39) |
V200A |
probably benign |
Het |
| Ppil1 |
A |
T |
17: 29,471,230 (GRCm39) |
F92I |
probably damaging |
Het |
| Ptchd3 |
T |
G |
11: 121,733,798 (GRCm39) |
L896R |
probably damaging |
Het |
| Rev3l |
A |
G |
10: 39,700,827 (GRCm39) |
N1775D |
possibly damaging |
Het |
| Robo4 |
G |
A |
9: 37,315,773 (GRCm39) |
R342Q |
probably benign |
Het |
| Rusc2 |
T |
C |
4: 43,424,100 (GRCm39) |
|
probably benign |
Het |
| S100pbp |
T |
C |
4: 129,038,249 (GRCm39) |
|
probably benign |
Het |
| Slc25a48 |
T |
C |
13: 56,599,024 (GRCm39) |
V118A |
probably damaging |
Het |
| Slc38a10 |
T |
C |
11: 120,025,679 (GRCm39) |
D219G |
probably damaging |
Het |
| Slc38a2 |
C |
T |
15: 96,589,173 (GRCm39) |
|
probably null |
Het |
| Slc39a12 |
A |
G |
2: 14,440,489 (GRCm39) |
E480G |
probably benign |
Het |
| Tab2 |
C |
A |
10: 7,795,441 (GRCm39) |
R347L |
probably damaging |
Het |
| Tas2r123 |
T |
C |
6: 132,824,955 (GRCm39) |
I284T |
possibly damaging |
Het |
| Tex9 |
A |
G |
9: 72,394,051 (GRCm39) |
|
probably benign |
Het |
| Tifab |
A |
G |
13: 56,324,218 (GRCm39) |
L75P |
probably damaging |
Het |
| Tmc5 |
T |
A |
7: 118,233,460 (GRCm39) |
D91E |
probably benign |
Het |
| Tnks1bp1 |
T |
A |
2: 84,892,696 (GRCm39) |
D212E |
probably benign |
Het |
| Ugcg |
A |
G |
4: 59,217,130 (GRCm39) |
D218G |
probably benign |
Het |
| Zfp451 |
A |
T |
1: 33,816,706 (GRCm39) |
L198I |
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 |
|
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 |
|
|
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 |
|
|
| Posted On |
2013-03-25 |
Incidental Mutation