Incidental Mutation 'R4564:Npc1'
| ID |
343272 |
| 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 |
041789-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly essential
(E-score: 0.616)
|
| Stock # |
R4564 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
18 |
| Chromosomal Location |
12322749-12369457 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
C to T
at 12324789 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Glycine to Arginine
at position 1235
(G1235R)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000025279
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000025276]
[ENSMUST00000025279]
[ENSMUST00000138866]
|
| 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: G1235R
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000025279
Gene: ENSMUSG00000024413
AA Change: G1235R
| 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 |
probably benign
Transcript: ENSMUST00000138866
|
| SMART Domains |
Protein: ENSMUSP00000121414
Gene: ENSMUSG00000024410
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
37 |
50 |
N/A |
INTRINSIC |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000139151
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000153233
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000153352
|
| Meta Mutation Damage Score |
0.9706 |
| Coding Region Coverage |
- 1x: 99.3%
- 3x: 98.5%
- 10x: 97.0%
- 20x: 94.6%
|
| Validation Efficiency |
97% (58/60) |
| 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: 52 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Atad3a |
C |
T |
4: 155,831,766 (GRCm39) |
|
probably null |
Het |
| Bach2 |
T |
G |
4: 32,563,338 (GRCm39) |
S602A |
probably damaging |
Het |
| Ccl19 |
G |
T |
4: 42,756,295 (GRCm39) |
S12R |
probably damaging |
Het |
| Cfap54 |
T |
C |
10: 92,675,402 (GRCm39) |
|
probably benign |
Het |
| Cndp1 |
T |
A |
18: 84,640,411 (GRCm39) |
I265F |
probably damaging |
Het |
| Cnot3 |
G |
A |
7: 3,656,257 (GRCm39) |
R181H |
probably damaging |
Het |
| Dicer1 |
T |
A |
12: 104,671,010 (GRCm39) |
K1011* |
probably null |
Het |
| Dip2b |
G |
A |
15: 100,055,139 (GRCm39) |
W99* |
probably null |
Het |
| Fpr-rs6 |
A |
T |
17: 20,403,168 (GRCm39) |
Y64* |
probably null |
Het |
| Fubp1 |
C |
A |
3: 151,928,573 (GRCm39) |
Y480* |
probably null |
Het |
| Gfra1 |
T |
C |
19: 58,227,682 (GRCm39) |
|
probably null |
Het |
| Gm10770 |
T |
C |
2: 150,020,831 (GRCm39) |
T229A |
probably benign |
Het |
| Gm826 |
A |
C |
2: 160,153,913 (GRCm39) |
|
probably benign |
Het |
| Gpd2 |
G |
A |
2: 57,197,095 (GRCm39) |
V217I |
possibly damaging |
Het |
| Hectd4 |
T |
C |
5: 121,488,494 (GRCm39) |
I3595T |
probably benign |
Het |
| Lmln |
A |
G |
16: 32,930,226 (GRCm39) |
E561G |
probably benign |
Het |
| Lrrc71 |
T |
A |
3: 87,652,715 (GRCm39) |
|
probably benign |
Het |
| Man2a2 |
T |
A |
7: 80,018,586 (GRCm39) |
Y91F |
probably benign |
Het |
| Map4k4 |
A |
G |
1: 40,028,135 (GRCm39) |
T319A |
probably damaging |
Het |
| Mcm6 |
G |
T |
1: 128,271,196 (GRCm39) |
H474Q |
probably damaging |
Het |
| Mn1 |
C |
G |
5: 111,568,533 (GRCm39) |
N834K |
possibly damaging |
Het |
| Mslnl |
G |
A |
17: 25,961,908 (GRCm39) |
V128M |
probably damaging |
Het |
| Niban3 |
T |
C |
8: 72,057,704 (GRCm39) |
|
probably benign |
Het |
| Npas2 |
A |
G |
1: 39,326,647 (GRCm39) |
D44G |
probably damaging |
Het |
| Olfml2a |
C |
T |
2: 38,850,306 (GRCm39) |
T674I |
probably benign |
Het |
| Or4f58 |
A |
G |
2: 111,852,112 (GRCm39) |
L29P |
possibly damaging |
Het |
| Pgap6 |
A |
G |
17: 26,336,837 (GRCm39) |
R252G |
possibly damaging |
Het |
| Plxnb1 |
C |
T |
9: 108,942,488 (GRCm39) |
A1779V |
probably benign |
Het |
| Ppil3 |
T |
A |
1: 58,470,481 (GRCm39) |
D123V |
probably damaging |
Het |
| Prr23a3 |
A |
G |
9: 98,747,190 (GRCm39) |
E48G |
probably damaging |
Het |
| Prr5l |
T |
C |
2: 101,577,094 (GRCm39) |
E110G |
probably damaging |
Het |
| Ptgir |
A |
G |
7: 16,640,794 (GRCm39) |
M29V |
possibly damaging |
Het |
| R3hdm1 |
C |
T |
1: 128,149,396 (GRCm39) |
T839M |
probably benign |
Het |
| Rasgrf2 |
G |
A |
13: 92,033,773 (GRCm39) |
Q544* |
probably null |
Het |
| Riok3 |
C |
A |
18: 12,281,936 (GRCm39) |
R302S |
probably damaging |
Het |
| Rnf145 |
A |
G |
11: 44,439,635 (GRCm39) |
K144E |
probably benign |
Het |
| Sin3b |
A |
C |
8: 73,480,209 (GRCm39) |
T904P |
probably damaging |
Het |
| Skint4 |
C |
T |
4: 111,977,066 (GRCm39) |
T152M |
probably damaging |
Het |
| Slc22a2 |
A |
G |
17: 12,828,943 (GRCm39) |
I350V |
probably benign |
Het |
| Slc6a11 |
G |
T |
6: 114,108,323 (GRCm39) |
G29V |
probably benign |
Het |
| Speg |
A |
C |
1: 75,368,478 (GRCm39) |
H676P |
probably damaging |
Het |
| St6gal2 |
T |
A |
17: 55,789,648 (GRCm39) |
H227Q |
probably damaging |
Het |
| Strn3 |
A |
G |
12: 51,680,404 (GRCm39) |
S399P |
probably benign |
Het |
| Tbc1d1 |
A |
G |
5: 64,330,827 (GRCm39) |
E2G |
probably damaging |
Het |
| Tecpr2 |
T |
A |
12: 110,921,219 (GRCm39) |
M1264K |
probably benign |
Het |
| Trpm6 |
T |
C |
19: 18,809,961 (GRCm39) |
L1119P |
possibly damaging |
Het |
| Upf2 |
A |
C |
2: 6,032,123 (GRCm39) |
T890P |
unknown |
Het |
| Upk1b |
T |
A |
16: 38,600,469 (GRCm39) |
K170N |
probably benign |
Het |
| Vmn1r78 |
A |
T |
7: 11,886,485 (GRCm39) |
Y32F |
probably damaging |
Het |
| Vps11 |
A |
G |
9: 44,272,894 (GRCm39) |
F12S |
probably damaging |
Het |
| Zfp318 |
T |
A |
17: 46,723,741 (GRCm39) |
C1915S |
possibly damaging |
Het |
| Zfp346 |
A |
C |
13: 55,261,520 (GRCm39) |
R103S |
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 |
|
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'- AGCTAGCTGTCAGTACAAACTC -3'
(R):5'- ACTGCTGAGGAAGGTTTGCG -3'
Sequencing Primer
(F):5'- CCAGGGTCTTTTAGCTTAGGTTAAAC -3'
(R):5'- CTCCAGGTATTCAGTGGA -3'
|
| Posted On |
2015-09-24 |
Incidental Mutation