Incidental Mutation 'R7007:Npc1'
| ID |
544802 |
| 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 |
045109-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly essential
(E-score: 0.616)
|
| Stock # |
R7007 (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 C
at 12343605 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Threonine to Alanine
at position 463
(T463A)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000025279
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000025279]
|
| AlphaFold |
O35604 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000025279
AA Change: T463A
PolyPhen 2
Score 0.017 (Sensitivity: 0.95; Specificity: 0.80)
|
| SMART Domains |
Protein: ENSMUSP00000025279
Gene: ENSMUSG00000024413
AA Change: T463A
| 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: 100.0%
- 10x: 99.7%
- 20x: 99.0%
|
| Validation Efficiency |
95% (63/66) |
| 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: 66 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4930474N05Rik |
C |
T |
14: 35,817,121 (GRCm39) |
T57I |
probably benign |
Het |
| Adcy8 |
T |
C |
15: 64,576,565 (GRCm39) |
N999S |
possibly damaging |
Het |
| Adgrv1 |
T |
A |
13: 81,684,483 (GRCm39) |
I1073F |
possibly damaging |
Het |
| Akap3 |
A |
G |
6: 126,843,439 (GRCm39) |
D686G |
probably damaging |
Het |
| Alg2 |
A |
T |
4: 47,471,881 (GRCm39) |
I309N |
probably benign |
Het |
| Ankrd36 |
A |
G |
11: 5,639,168 (GRCm39) |
E1360G |
probably benign |
Het |
| Aox1 |
C |
A |
1: 58,370,051 (GRCm39) |
Q788K |
probably damaging |
Het |
| Apoc2 |
A |
T |
7: 19,407,282 (GRCm39) |
D26E |
possibly damaging |
Het |
| Bbx |
G |
A |
16: 50,022,851 (GRCm39) |
T703I |
possibly damaging |
Het |
| C2cd4d |
T |
C |
3: 94,271,378 (GRCm39) |
Y215H |
probably benign |
Het |
| C3 |
C |
T |
17: 57,525,809 (GRCm39) |
E858K |
probably benign |
Het |
| Ciita |
T |
C |
16: 10,329,171 (GRCm39) |
L482P |
probably damaging |
Het |
| Cldn9 |
T |
C |
17: 23,902,052 (GRCm39) |
E191G |
probably benign |
Het |
| Cnst |
T |
A |
1: 179,438,133 (GRCm39) |
S566T |
probably damaging |
Het |
| Col5a2 |
A |
G |
1: 45,417,609 (GRCm39) |
I1322T |
possibly damaging |
Het |
| Cp |
G |
A |
3: 20,024,137 (GRCm39) |
V326M |
probably damaging |
Het |
| Cyp7b1 |
G |
A |
3: 18,151,782 (GRCm39) |
Q144* |
probably null |
Het |
| Dnah10 |
T |
C |
5: 124,864,490 (GRCm39) |
S2232P |
probably damaging |
Het |
| Dnah17 |
T |
C |
11: 118,009,697 (GRCm39) |
E625G |
possibly damaging |
Het |
| Dnah7c |
T |
A |
1: 46,571,910 (GRCm39) |
D794E |
probably benign |
Het |
| Dusp10 |
G |
A |
1: 183,769,414 (GRCm39) |
V127M |
probably benign |
Het |
| Dysf |
G |
C |
6: 84,090,962 (GRCm39) |
W1015C |
probably damaging |
Het |
| Fbxw17 |
T |
C |
13: 50,577,808 (GRCm39) |
Y104H |
probably damaging |
Het |
| Gm6408 |
G |
A |
5: 146,420,647 (GRCm39) |
E176K |
probably damaging |
Het |
| Gp1bb |
T |
A |
16: 18,439,689 (GRCm39) |
D135V |
possibly damaging |
Het |
| Gprin1 |
C |
T |
13: 54,886,069 (GRCm39) |
C735Y |
probably damaging |
Het |
| Heatr9 |
T |
A |
11: 83,411,446 (GRCm39) |
M30L |
possibly damaging |
Het |
| Hhat |
G |
A |
1: 192,376,134 (GRCm39) |
T333I |
possibly damaging |
Het |
| Htr5b |
A |
G |
1: 121,438,223 (GRCm39) |
F336S |
probably damaging |
Het |
| Ippk |
T |
G |
13: 49,590,181 (GRCm39) |
|
probably null |
Het |
| Jph1 |
T |
A |
1: 17,074,410 (GRCm39) |
H11L |
possibly damaging |
Het |
| Kif12 |
T |
A |
4: 63,084,717 (GRCm39) |
I534L |
probably benign |
Het |
| Lemd3 |
A |
T |
10: 120,788,137 (GRCm39) |
F523I |
probably benign |
Het |
| Lgsn |
C |
A |
1: 31,229,508 (GRCm39) |
H76Q |
probably benign |
Het |
| Lipm |
T |
A |
19: 34,089,497 (GRCm39) |
W152R |
probably damaging |
Het |
| Mei1 |
A |
T |
15: 81,978,200 (GRCm39) |
R216W |
probably damaging |
Het |
| Mybpc1 |
C |
T |
10: 88,389,274 (GRCm39) |
G379S |
probably damaging |
Het |
| Myh8 |
A |
G |
11: 67,179,142 (GRCm39) |
T512A |
probably benign |
Het |
| Nf1 |
A |
G |
11: 79,337,849 (GRCm39) |
|
probably null |
Het |
| Or12e10 |
A |
G |
2: 87,640,230 (GRCm39) |
N22S |
probably damaging |
Het |
| Or2y13 |
G |
A |
11: 49,415,011 (GRCm39) |
V154M |
probably benign |
Het |
| Or6c7 |
A |
T |
10: 129,323,277 (GRCm39) |
I133F |
probably damaging |
Het |
| Osbpl11 |
T |
G |
16: 33,047,309 (GRCm39) |
I424R |
possibly damaging |
Het |
| Pnma8b |
A |
T |
7: 16,680,181 (GRCm39) |
K388N |
possibly damaging |
Het |
| Ppp1r26 |
A |
T |
2: 28,341,171 (GRCm39) |
K267I |
probably damaging |
Het |
| Psmb5 |
A |
T |
14: 54,854,166 (GRCm39) |
M104K |
probably damaging |
Het |
| Ptges2 |
T |
C |
2: 32,292,318 (GRCm39) |
V378A |
probably benign |
Het |
| Rcan2 |
C |
T |
17: 44,147,216 (GRCm39) |
S18F |
probably benign |
Het |
| Saxo5 |
A |
T |
8: 3,526,309 (GRCm39) |
D154V |
probably damaging |
Het |
| Sf3b2 |
C |
T |
19: 5,324,545 (GRCm39) |
R859Q |
probably benign |
Het |
| Slc7a1 |
G |
A |
5: 148,289,256 (GRCm39) |
|
|
Het |
| Spata31d1a |
T |
A |
13: 59,851,448 (GRCm39) |
T227S |
probably benign |
Het |
| Sptbn2 |
T |
A |
19: 4,794,173 (GRCm39) |
V1459E |
possibly damaging |
Het |
| Srgap2 |
T |
C |
1: 131,247,275 (GRCm39) |
I586V |
probably benign |
Het |
| St6galnac1 |
G |
A |
11: 116,657,833 (GRCm39) |
R356* |
probably null |
Het |
| Taf5 |
T |
A |
19: 47,059,650 (GRCm39) |
F265I |
probably damaging |
Het |
| Tkfc |
T |
A |
19: 10,573,727 (GRCm39) |
I229L |
probably benign |
Het |
| Tmem132c |
T |
A |
5: 127,436,679 (GRCm39) |
L56Q |
probably damaging |
Het |
| Togaram2 |
C |
T |
17: 72,016,638 (GRCm39) |
A665V |
probably damaging |
Het |
| Ttn |
G |
A |
2: 76,537,390 (GRCm39) |
T34846I |
probably benign |
Het |
| Tyr |
G |
A |
7: 87,142,548 (GRCm39) |
A4V |
probably benign |
Het |
| Ubap2 |
A |
C |
4: 41,206,221 (GRCm39) |
F549L |
probably damaging |
Het |
| Usp2 |
T |
C |
9: 44,001,339 (GRCm39) |
S294P |
probably damaging |
Het |
| Vrk3 |
A |
G |
7: 44,407,187 (GRCm39) |
N53D |
probably damaging |
Het |
| Zfp324 |
T |
C |
7: 12,705,142 (GRCm39) |
S444P |
probably damaging |
Het |
| Zfp597 |
T |
C |
16: 3,683,791 (GRCm39) |
I322V |
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 |
|
|
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'- ACATCTGGTTCCATCTACTGGGTC -3'
(R):5'- AAGTATGCCCTCCGAGCATC -3'
Sequencing Primer
(F):5'- CATCTACTGGGTCTCCATATGTATG -3'
(R):5'- GAGCATCCTTCTCGCCCG -3'
|
| Posted On |
2019-05-13 |
Incidental Mutation