Incidental Mutation 'R6301:Npc1'
| ID |
509129 |
| 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 |
044466-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly essential
(E-score: 0.616)
|
| Stock # |
R6301 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
18 |
| Chromosomal Location |
12322749-12369457 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
C to T
at 12330302 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Valine to Isoleucine
at position 950
(V950I)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000025279
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000025279]
|
| AlphaFold |
O35604 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000025279
AA Change: V950I
PolyPhen 2
Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
|
| SMART Domains |
Protein: ENSMUSP00000025279
Gene: ENSMUSG00000024413
AA Change: V950I
| 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 |
0.0898 |
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 99.9%
- 10x: 99.5%
- 20x: 98.5%
|
| Validation Efficiency |
100% (66/66) |
| 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: 61 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Aadacl4fm2 |
C |
T |
4: 144,285,224 (GRCm39) |
A138T |
probably damaging |
Het |
| Acot10 |
T |
C |
15: 20,666,348 (GRCm39) |
N131S |
probably benign |
Het |
| Agbl5 |
A |
G |
5: 31,049,177 (GRCm39) |
Y220C |
probably damaging |
Het |
| Ankdd1a |
C |
T |
9: 65,415,343 (GRCm39) |
A227T |
possibly damaging |
Het |
| Ap3b1 |
A |
T |
13: 94,664,803 (GRCm39) |
Q914L |
unknown |
Het |
| Arhgef25 |
T |
C |
10: 127,021,751 (GRCm39) |
D216G |
possibly damaging |
Het |
| Bcas2 |
T |
A |
3: 103,079,187 (GRCm39) |
|
probably benign |
Het |
| Bpifb5 |
A |
C |
2: 154,072,139 (GRCm39) |
H282P |
possibly damaging |
Het |
| Ccdc121rt2 |
A |
T |
5: 112,598,334 (GRCm39) |
I294F |
possibly damaging |
Het |
| Ccdc167 |
A |
G |
17: 29,924,556 (GRCm39) |
I15T |
probably damaging |
Het |
| Cd248 |
A |
G |
19: 5,120,009 (GRCm39) |
N619S |
probably benign |
Het |
| Chrna1 |
A |
G |
2: 73,400,828 (GRCm39) |
F234S |
possibly damaging |
Het |
| Clcc1 |
T |
G |
3: 108,580,682 (GRCm39) |
M332R |
probably damaging |
Het |
| Cmklr1 |
T |
A |
5: 113,752,999 (GRCm39) |
M1L |
possibly damaging |
Het |
| Cntnap5c |
A |
G |
17: 58,199,032 (GRCm39) |
M109V |
probably benign |
Het |
| Coq2 |
A |
G |
5: 100,809,729 (GRCm39) |
I18T |
possibly damaging |
Het |
| Crybg3 |
T |
C |
16: 59,350,701 (GRCm39) |
S880G |
probably damaging |
Het |
| Cubn |
A |
G |
2: 13,482,889 (GRCm39) |
C286R |
probably damaging |
Het |
| Defa24 |
T |
C |
8: 22,225,299 (GRCm39) |
V63A |
probably benign |
Het |
| Dnah6 |
C |
T |
6: 73,063,200 (GRCm39) |
R2634H |
probably damaging |
Het |
| Dusp8 |
T |
A |
7: 141,636,756 (GRCm39) |
|
probably null |
Het |
| Elac1 |
T |
C |
18: 73,871,939 (GRCm39) |
D352G |
probably damaging |
Het |
| Ermap |
A |
T |
4: 119,042,800 (GRCm39) |
V241E |
probably damaging |
Het |
| Fgf10 |
T |
A |
13: 118,852,047 (GRCm39) |
M43K |
probably benign |
Het |
| Gabrd |
A |
G |
4: 155,471,724 (GRCm39) |
V193A |
probably damaging |
Het |
| Hectd4 |
T |
G |
5: 121,392,283 (GRCm39) |
C182W |
possibly damaging |
Het |
| Hook3 |
C |
T |
8: 26,524,968 (GRCm39) |
W26* |
probably null |
Het |
| Kif1a |
C |
A |
1: 92,982,663 (GRCm39) |
E714* |
probably null |
Het |
| Krt6b |
T |
C |
15: 101,587,386 (GRCm39) |
E236G |
probably damaging |
Het |
| Large2 |
A |
G |
2: 92,199,861 (GRCm39) |
L209P |
probably damaging |
Het |
| Lats1 |
A |
G |
10: 7,578,871 (GRCm39) |
N665S |
probably benign |
Het |
| Lrrc37 |
A |
T |
11: 103,509,756 (GRCm39) |
|
probably benign |
Het |
| Lrrtm3 |
T |
C |
10: 63,925,001 (GRCm39) |
I55M |
probably benign |
Het |
| Ltk |
A |
G |
2: 119,582,238 (GRCm39) |
S838P |
probably damaging |
Het |
| Ltn1 |
T |
C |
16: 87,217,194 (GRCm39) |
I348V |
probably benign |
Het |
| Mag |
T |
A |
7: 30,600,104 (GRCm39) |
S559C |
probably damaging |
Het |
| Mink1 |
A |
G |
11: 70,503,120 (GRCm39) |
H1072R |
possibly damaging |
Het |
| Mycbp2 |
T |
A |
14: 103,392,862 (GRCm39) |
Q833L |
probably damaging |
Het |
| Myh4 |
G |
A |
11: 67,146,159 (GRCm39) |
E1406K |
possibly damaging |
Het |
| Npl |
A |
G |
1: 153,394,627 (GRCm39) |
|
probably null |
Het |
| Or10w3 |
A |
G |
19: 13,703,753 (GRCm39) |
I43V |
probably benign |
Het |
| Or11g27 |
T |
A |
14: 50,771,711 (GRCm39) |
F281I |
probably benign |
Het |
| Or2m13 |
A |
T |
16: 19,226,167 (GRCm39) |
F200I |
possibly damaging |
Het |
| Or8b36 |
ATTGCTGTTT |
ATTGCTGTTTGCTGTTT |
9: 37,937,836 (GRCm39) |
|
probably null |
Het |
| Oxsm |
A |
T |
14: 16,242,220 (GRCm38) |
I183N |
probably damaging |
Het |
| Pde7a |
T |
C |
3: 19,297,327 (GRCm39) |
I108V |
probably benign |
Het |
| Pgghg |
A |
T |
7: 140,526,289 (GRCm39) |
T585S |
probably damaging |
Het |
| Pkhd1l1 |
G |
A |
15: 44,452,921 (GRCm39) |
D3949N |
probably damaging |
Het |
| Ralgapa2 |
A |
T |
2: 146,169,331 (GRCm39) |
H1777Q |
possibly damaging |
Het |
| Rela |
G |
A |
19: 5,695,438 (GRCm39) |
|
probably null |
Het |
| Rilpl1 |
C |
A |
5: 124,652,602 (GRCm39) |
G41W |
probably damaging |
Het |
| Rp1 |
T |
C |
1: 4,417,477 (GRCm39) |
K1212E |
probably benign |
Het |
| Sgca |
A |
C |
11: 94,863,393 (GRCm39) |
L28V |
probably damaging |
Het |
| Ssmem1 |
A |
G |
6: 30,519,758 (GRCm39) |
R148G |
probably damaging |
Het |
| St8sia5 |
A |
T |
18: 77,333,836 (GRCm39) |
N165Y |
probably damaging |
Het |
| Tbl2 |
A |
T |
5: 135,188,223 (GRCm39) |
H339L |
probably benign |
Het |
| Tcof1 |
G |
A |
18: 60,961,897 (GRCm39) |
P718L |
probably damaging |
Het |
| Trim72 |
A |
T |
7: 127,603,786 (GRCm39) |
E44V |
possibly damaging |
Het |
| Try10 |
T |
A |
6: 41,332,523 (GRCm39) |
S60T |
probably benign |
Het |
| Usp31 |
A |
T |
7: 121,247,499 (GRCm39) |
S1315T |
possibly damaging |
Het |
| Xrn2 |
A |
G |
2: 146,905,262 (GRCm39) |
I856V |
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 |
|
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 |
|
|
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'- TTGACGCAGCTCTGAGAGTC -3'
(R):5'- CTCATTGGCCATGGGTTTTC -3'
Sequencing Primer
(F):5'- ACGTGTGTGACTGAGCAC -3'
(R):5'- CTTGAAGGTTTGGTCAGTAGTATAGC -3'
|
| Posted On |
2018-04-02 |
Incidental Mutation