Incidental Mutation 'R8821:Npc1'
| ID |
673084 |
| 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 |
068654-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly essential
(E-score: 0.637)
|
| Stock # |
R8821 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
18 |
| Chromosomal Location |
12322749-12369457 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to A
at 12333877 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Methionine to Leucine
at position 735
(M735L)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000025279
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000025279]
|
| AlphaFold |
O35604 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000025279
AA Change: M735L
PolyPhen 2
Score 0.008 (Sensitivity: 0.96; Specificity: 0.76)
|
| SMART Domains |
Protein: ENSMUSP00000025279
Gene: ENSMUSG00000024413
AA Change: M735L
| 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 |
|
| Meta Mutation Damage Score |
0.1097 |
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 99.9%
- 10x: 99.7%
- 20x: 99.1%
|
| Validation Efficiency |
100% (74/74) |
| 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: 76 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| A230072I06Rik |
A |
T |
8: 12,329,688 (GRCm39) |
I48L |
unknown |
Het |
| Abca8a |
A |
T |
11: 109,949,362 (GRCm39) |
I927K |
probably damaging |
Het |
| Abcc3 |
A |
C |
11: 94,241,787 (GRCm39) |
C1415G |
probably damaging |
Het |
| Abcf3 |
C |
T |
16: 20,369,214 (GRCm39) |
R205C |
probably damaging |
Het |
| Aldh3a1 |
A |
G |
11: 61,107,142 (GRCm39) |
Y282C |
probably damaging |
Het |
| Alyref |
CCCGCGCGGCGGCCTGCACTGCGCCGCCGCGGCCGCCCTGGGAGCCGGCCCTGCCGCG |
CCCGCG |
11: 120,489,023 (GRCm39) |
|
probably null |
Het |
| Arfgef3 |
A |
G |
10: 18,528,491 (GRCm39) |
S299P |
possibly damaging |
Het |
| Asic2 |
A |
T |
11: 81,858,726 (GRCm39) |
N95K |
probably damaging |
Het |
| Atp2c2 |
A |
G |
8: 120,476,033 (GRCm39) |
|
probably null |
Het |
| Btbd18 |
A |
G |
2: 84,497,601 (GRCm39) |
D413G |
probably damaging |
Het |
| C8b |
A |
G |
4: 104,647,874 (GRCm39) |
Y355C |
probably damaging |
Het |
| Carm1 |
A |
G |
9: 21,491,663 (GRCm39) |
E244G |
probably damaging |
Het |
| Castor2 |
T |
A |
5: 134,164,092 (GRCm39) |
V96E |
possibly damaging |
Het |
| Catsperg1 |
A |
T |
7: 28,904,361 (GRCm39) |
|
probably benign |
Het |
| Cish |
T |
A |
9: 107,177,671 (GRCm39) |
F116I |
probably damaging |
Het |
| Ckmt1 |
G |
A |
2: 121,191,302 (GRCm39) |
|
probably benign |
Het |
| Clasrp |
C |
T |
7: 19,320,362 (GRCm39) |
R432H |
unknown |
Het |
| Clstn1 |
G |
A |
4: 149,730,780 (GRCm39) |
R837Q |
probably benign |
Het |
| Col27a1 |
A |
G |
4: 63,143,148 (GRCm39) |
T279A |
probably benign |
Het |
| Cox10 |
A |
G |
11: 63,855,306 (GRCm39) |
F325S |
probably damaging |
Het |
| Cpne5 |
T |
C |
17: 29,430,668 (GRCm39) |
I81V |
probably benign |
Het |
| Ctps1 |
A |
T |
4: 120,424,507 (GRCm39) |
S36T |
possibly damaging |
Het |
| Dchs2 |
T |
C |
3: 83,192,670 (GRCm39) |
L1705P |
probably benign |
Het |
| Dcstamp |
A |
G |
15: 39,618,185 (GRCm39) |
H198R |
probably benign |
Het |
| Dhx58 |
T |
A |
11: 100,594,806 (GRCm39) |
K30M |
probably damaging |
Het |
| Dnah1 |
C |
T |
14: 31,018,455 (GRCm39) |
A1392T |
probably benign |
Het |
| Dnah14 |
C |
A |
1: 181,619,569 (GRCm39) |
Y3964* |
probably null |
Het |
| Dnah8 |
T |
C |
17: 31,013,712 (GRCm39) |
S3818P |
probably damaging |
Het |
| Dnmt3b |
T |
A |
2: 153,518,734 (GRCm39) |
N632K |
probably benign |
Het |
| Drc7 |
G |
A |
8: 95,788,845 (GRCm39) |
R301Q |
probably damaging |
Het |
| Dsg1a |
T |
C |
18: 20,453,365 (GRCm39) |
V21A |
probably damaging |
Het |
| Dtd1 |
T |
C |
2: 144,459,261 (GRCm39) |
L95P |
probably benign |
Het |
| Efhb |
A |
T |
17: 53,707,772 (GRCm39) |
|
probably benign |
Het |
| Fam186b |
T |
A |
15: 99,178,733 (GRCm39) |
M198L |
possibly damaging |
Het |
| Fam193a |
A |
G |
5: 34,616,374 (GRCm39) |
T850A |
probably benign |
Het |
| Fan1 |
G |
A |
7: 64,004,249 (GRCm39) |
P739L |
probably damaging |
Het |
| Flii |
A |
T |
11: 60,616,074 (GRCm39) |
N28K |
probably benign |
Het |
| Fmo3 |
T |
C |
1: 162,796,407 (GRCm39) |
Y55C |
probably damaging |
Het |
| Gfi1 |
G |
A |
5: 107,868,138 (GRCm39) |
R377C |
probably damaging |
Het |
| Gm9195 |
C |
T |
14: 72,717,536 (GRCm39) |
E266K |
possibly damaging |
Het |
| Hdac1-ps |
T |
A |
17: 78,799,969 (GRCm39) |
L320Q |
probably damaging |
Het |
| Helz |
A |
T |
11: 107,525,919 (GRCm39) |
M825L |
probably damaging |
Het |
| Hsd3b9 |
A |
T |
3: 98,354,047 (GRCm39) |
W151R |
probably benign |
Het |
| Ift80 |
G |
A |
3: 68,869,583 (GRCm39) |
A236V |
probably damaging |
Het |
| Il1rn |
A |
T |
2: 24,239,505 (GRCm39) |
T134S |
possibly damaging |
Het |
| Imp4 |
T |
C |
1: 34,483,445 (GRCm39) |
M257T |
probably benign |
Het |
| Impdh2 |
T |
C |
9: 108,441,957 (GRCm39) |
L377S |
probably damaging |
Het |
| Kcnrg |
T |
C |
14: 61,844,981 (GRCm39) |
V7A |
possibly damaging |
Het |
| Kdm1b |
C |
A |
13: 47,217,617 (GRCm39) |
L359I |
possibly damaging |
Het |
| Lima1 |
T |
A |
15: 99,704,306 (GRCm39) |
T288S |
probably benign |
Het |
| Lrrc37 |
A |
T |
11: 103,510,470 (GRCm39) |
D499E |
unknown |
Het |
| Lrrc4c |
A |
T |
2: 97,460,040 (GRCm39) |
D222V |
possibly damaging |
Het |
| Mybpc3 |
T |
A |
2: 90,948,524 (GRCm39) |
V4E |
probably null |
Het |
| Ncor1 |
A |
T |
11: 62,260,234 (GRCm39) |
D505E |
probably benign |
Het |
| Nell1 |
A |
G |
7: 50,476,097 (GRCm39) |
S579G |
probably damaging |
Het |
| Or1j13 |
G |
A |
2: 36,369,794 (GRCm39) |
T116I |
possibly damaging |
Het |
| Or2at4 |
A |
G |
7: 99,384,893 (GRCm39) |
H181R |
possibly damaging |
Het |
| Or4a73 |
A |
G |
2: 89,420,880 (GRCm39) |
I193T |
probably damaging |
Het |
| Pcdhb12 |
A |
G |
18: 37,570,386 (GRCm39) |
M511V |
probably benign |
Het |
| Peli2 |
G |
A |
14: 48,490,130 (GRCm39) |
E201K |
possibly damaging |
Het |
| Phf3 |
T |
A |
1: 30,860,347 (GRCm39) |
K828* |
probably null |
Het |
| Pih1d1 |
A |
G |
7: 44,806,196 (GRCm39) |
D44G |
possibly damaging |
Het |
| Prag1 |
A |
T |
8: 36,613,891 (GRCm39) |
T1148S |
probably benign |
Het |
| Ptpn18 |
A |
T |
1: 34,511,271 (GRCm39) |
R338W |
probably null |
Het |
| Slc7a6os |
A |
T |
8: 106,937,189 (GRCm39) |
D90E |
probably benign |
Het |
| Sp7 |
T |
A |
15: 102,267,227 (GRCm39) |
H211L |
possibly damaging |
Het |
| Ssh3 |
A |
G |
19: 4,319,053 (GRCm39) |
V19A |
possibly damaging |
Het |
| Tcp11l2 |
A |
G |
10: 84,449,522 (GRCm39) |
I496V |
probably damaging |
Het |
| Tenm3 |
C |
T |
8: 48,729,417 (GRCm39) |
A1530T |
|
Het |
| Tmem232 |
A |
G |
17: 65,743,367 (GRCm39) |
L308P |
probably damaging |
Het |
| Tulp4 |
A |
G |
17: 6,189,409 (GRCm39) |
N77S |
probably damaging |
Het |
| Unc13d |
AATGCCTCCCATGCC |
AATGCCTCCCATGCCTCCCATGCC |
11: 115,958,998 (GRCm39) |
|
probably benign |
Het |
| Usp48 |
A |
T |
4: 137,341,080 (GRCm39) |
D360V |
probably damaging |
Het |
| Vmn2r84 |
G |
A |
10: 130,226,968 (GRCm39) |
A290V |
probably benign |
Het |
| Zfp1007 |
A |
T |
5: 109,824,174 (GRCm39) |
S425R |
probably benign |
Het |
| Zfp512b |
T |
C |
2: 181,228,525 (GRCm39) |
N738S |
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 |
|
|
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 |
|
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'- CTAGCCCAGCATCAGTACTG -3'
(R):5'- TAACGGCATTAGTCAGCTGC -3'
Sequencing Primer
(F):5'- AGCATCAGTACTGTGCTGGGAC -3'
(R):5'- GCATTAGTCAGCTGCTGCAG -3'
|
| Posted On |
2021-04-30 |
Incidental Mutation