Incidental Mutation 'R7116:Npc1'
| ID |
551803 |
| 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 |
045207-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly essential
(E-score: 0.616)
|
| Stock # |
R7116 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Not validated
|
| Chromosome |
18 |
| Chromosomal Location |
12322749-12369457 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 12344601 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Tyrosine to Cysteine
at position 423
(Y423C)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000025279
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000025279]
|
| AlphaFold |
O35604 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000025279
AA Change: Y423C
PolyPhen 2
Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000025279
Gene: ENSMUSG00000024413
AA Change: Y423C
| 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 |
|
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 99.9%
- 10x: 99.6%
- 20x: 98.8%
|
| Validation Efficiency |
|
| 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: 59 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Actn1 |
A |
G |
12: 80,251,751 (GRCm39) |
S109P |
probably damaging |
Het |
| Afg3l1 |
T |
G |
8: 124,216,601 (GRCm39) |
L280R |
probably damaging |
Het |
| Akap13 |
T |
A |
7: 75,369,943 (GRCm39) |
S129T |
probably benign |
Het |
| Ankrd11 |
A |
G |
8: 123,622,869 (GRCm39) |
S328P |
probably damaging |
Het |
| Aox3 |
A |
T |
1: 58,192,689 (GRCm39) |
E554D |
probably benign |
Het |
| Bcl11a |
T |
C |
11: 24,113,839 (GRCm39) |
V394A |
probably damaging |
Het |
| Cass4 |
A |
G |
2: 172,269,889 (GRCm39) |
Y657C |
unknown |
Het |
| Ccdc88a |
C |
T |
11: 29,454,051 (GRCm39) |
A1738V |
probably benign |
Het |
| Cfap74 |
T |
C |
4: 155,539,518 (GRCm39) |
F948L |
unknown |
Het |
| Chgb |
A |
T |
2: 132,623,237 (GRCm39) |
|
probably benign |
Het |
| Coro1c |
C |
T |
5: 113,990,267 (GRCm39) |
W138* |
probably null |
Het |
| Dgkb |
A |
G |
12: 38,031,989 (GRCm39) |
Q17R |
probably benign |
Het |
| Esco2 |
A |
G |
14: 66,064,006 (GRCm39) |
Y393H |
probably damaging |
Het |
| Eya3 |
T |
A |
4: 132,422,110 (GRCm39) |
D228E |
probably benign |
Het |
| Fat2 |
T |
C |
11: 55,173,162 (GRCm39) |
D2517G |
probably damaging |
Het |
| Fry |
T |
A |
5: 150,319,334 (GRCm39) |
|
probably null |
Het |
| Gal3st2b |
A |
T |
1: 93,868,498 (GRCm39) |
Q243L |
possibly damaging |
Het |
| Gimap9 |
C |
T |
6: 48,654,989 (GRCm39) |
A192V |
probably benign |
Het |
| Glg1 |
T |
A |
8: 111,905,589 (GRCm39) |
Q564L |
probably benign |
Het |
| H2-Aa |
A |
T |
17: 34,502,601 (GRCm39) |
Y188* |
probably null |
Het |
| Hira |
T |
C |
16: 18,730,864 (GRCm39) |
Y188H |
probably damaging |
Het |
| Ighv8-8 |
C |
T |
12: 115,257,814 (GRCm39) |
D76N |
probably benign |
Het |
| Irf6 |
T |
C |
1: 192,849,905 (GRCm39) |
F276L |
probably damaging |
Het |
| Itpr1 |
T |
C |
6: 108,458,229 (GRCm39) |
C2000R |
probably damaging |
Het |
| Jakmip3 |
T |
C |
7: 138,621,979 (GRCm39) |
V293A |
possibly damaging |
Het |
| Kcnh7 |
A |
G |
2: 62,707,614 (GRCm39) |
V132A |
probably benign |
Het |
| Kcnj1 |
A |
G |
9: 32,308,277 (GRCm39) |
T234A |
possibly damaging |
Het |
| Kpna3 |
T |
A |
14: 61,605,635 (GRCm39) |
N470I |
probably benign |
Het |
| Lamb2 |
T |
C |
9: 108,364,522 (GRCm39) |
F1121L |
probably damaging |
Het |
| Lingo1 |
T |
C |
9: 56,527,911 (GRCm39) |
D232G |
probably benign |
Het |
| Lpxn |
T |
A |
19: 12,788,622 (GRCm39) |
N70K |
probably benign |
Het |
| Ltbp4 |
T |
A |
7: 27,004,852 (GRCm39) |
H1657L |
probably damaging |
Het |
| Luzp2 |
C |
A |
7: 54,915,078 (GRCm39) |
F334L |
possibly damaging |
Het |
| Mgat5b |
A |
T |
11: 116,835,785 (GRCm39) |
S142C |
possibly damaging |
Het |
| Mroh7 |
G |
A |
4: 106,568,517 (GRCm39) |
T396I |
probably benign |
Het |
| Muc5b |
T |
C |
7: 141,417,487 (GRCm39) |
S3478P |
probably benign |
Het |
| Nfatc2 |
A |
T |
2: 168,349,269 (GRCm39) |
M626K |
probably benign |
Het |
| Nlrp14 |
A |
G |
7: 106,782,255 (GRCm39) |
D484G |
possibly damaging |
Het |
| Nrsn1 |
A |
G |
13: 25,437,388 (GRCm39) |
I180T |
probably damaging |
Het |
| Or11g25 |
A |
T |
14: 50,723,025 (GRCm39) |
I37F |
probably benign |
Het |
| Or51a8 |
T |
A |
7: 102,549,842 (GRCm39) |
N89K |
probably benign |
Het |
| Osbpl6 |
A |
T |
2: 76,426,225 (GRCm39) |
I935F |
probably benign |
Het |
| Otog |
T |
C |
7: 45,947,689 (GRCm39) |
F96L |
probably damaging |
Het |
| Pde1b |
T |
C |
15: 103,436,745 (GRCm39) |
L534P |
possibly damaging |
Het |
| Pdzd8 |
C |
T |
19: 59,288,125 (GRCm39) |
E1092K |
probably damaging |
Het |
| Pfkl |
T |
C |
10: 77,837,249 (GRCm39) |
H108R |
probably benign |
Het |
| Pkhd1l1 |
G |
A |
15: 44,421,372 (GRCm39) |
V3047I |
probably benign |
Het |
| Plag1 |
A |
T |
4: 3,904,812 (GRCm39) |
C126* |
probably null |
Het |
| Pphln1 |
T |
A |
15: 93,353,406 (GRCm39) |
S229T |
probably benign |
Het |
| Pramel5 |
C |
T |
4: 144,000,451 (GRCm39) |
D42N |
possibly damaging |
Het |
| Psd3 |
A |
G |
8: 68,166,390 (GRCm39) |
V915A |
probably benign |
Het |
| Ptdss1 |
T |
A |
13: 67,093,391 (GRCm39) |
I77N |
probably benign |
Het |
| Rsbn1 |
T |
A |
3: 103,821,892 (GRCm39) |
C3* |
probably null |
Het |
| Shank1 |
C |
T |
7: 43,976,585 (GRCm39) |
A561V |
unknown |
Het |
| Stip1 |
C |
T |
19: 6,999,178 (GRCm39) |
G467S |
possibly damaging |
Het |
| Sv2c |
A |
T |
13: 96,113,152 (GRCm39) |
V599E |
probably damaging |
Het |
| Vmn2r37 |
T |
C |
7: 9,220,898 (GRCm39) |
T322A |
probably benign |
Het |
| Vmn2r60 |
T |
A |
7: 41,786,487 (GRCm39) |
M430K |
probably benign |
Het |
| Wipf3 |
T |
A |
6: 54,458,904 (GRCm39) |
|
probably null |
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 |
|
|
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'- ACTGGGAGTAACGCTGTGTG -3'
(R):5'- ATCACTGTGTGCTCTTCTGG -3'
Sequencing Primer
(F):5'- AAGCAGGCTGCCTTCAAGTTC -3'
(R):5'- GCTCTTCTGGCCTGGTATTTGTC -3'
|
| Posted On |
2019-05-15 |
Incidental Mutation