Incidental Mutation 'R7765:Npc1'
ID |
598213 |
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 |
045821-MU
|
Accession Numbers |
|
Essential gene? |
Possibly essential
(E-score: 0.616)
|
Stock # |
R7765 (G1)
|
Quality Score |
225.009 |
Status
|
Validated
|
Chromosome |
18 |
Chromosomal Location |
12322749-12369457 bp(-) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
A to T
at 12328105 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Methionine to Lysine
at position 1068
(M1068K)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000025279
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000025279]
|
AlphaFold |
O35604 |
Predicted Effect |
probably benign
Transcript: ENSMUST00000025279
AA Change: M1068K
PolyPhen 2
Score 0.006 (Sensitivity: 0.97; Specificity: 0.75)
|
SMART Domains |
Protein: ENSMUSP00000025279 Gene: ENSMUSG00000024413 AA Change: M1068K
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 |
0.3290 |
Coding Region Coverage |
- 1x: 100.0%
- 3x: 100.0%
- 10x: 99.7%
- 20x: 99.0%
|
Validation Efficiency |
100% (62/62) |
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: 62 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
Adam2 |
T |
C |
14: 66,297,345 (GRCm39) |
E187G |
probably damaging |
Het |
Adam28 |
C |
T |
14: 68,846,555 (GRCm39) |
|
probably null |
Het |
Ap2a1 |
G |
A |
7: 44,559,160 (GRCm39) |
T189M |
probably damaging |
Het |
Apaf1 |
A |
G |
10: 90,859,644 (GRCm39) |
Y845H |
probably benign |
Het |
Asb14 |
G |
T |
14: 26,619,718 (GRCm39) |
V55F |
probably benign |
Het |
Brap |
A |
T |
5: 121,800,192 (GRCm39) |
D71V |
probably damaging |
Het |
Ccdc93 |
T |
G |
1: 121,427,042 (GRCm39) |
F610V |
probably damaging |
Het |
Cfap46 |
T |
G |
7: 139,231,480 (GRCm39) |
D911A |
|
Het |
Chn2 |
T |
C |
6: 54,275,137 (GRCm39) |
|
probably null |
Het |
Cib3 |
A |
G |
8: 72,958,269 (GRCm39) |
F156S |
probably damaging |
Het |
Csnk2a1-ps3 |
G |
A |
1: 156,352,354 (GRCm39) |
G185D |
possibly damaging |
Het |
Ctif |
A |
T |
18: 75,738,715 (GRCm39) |
V164D |
probably damaging |
Het |
Ddx27 |
T |
A |
2: 166,869,879 (GRCm39) |
F405I |
probably damaging |
Het |
Dnttip2 |
A |
G |
3: 122,069,594 (GRCm39) |
T270A |
probably benign |
Het |
Dst |
T |
A |
1: 34,314,775 (GRCm39) |
S4455T |
probably damaging |
Het |
Efcab8 |
A |
G |
2: 153,685,110 (GRCm39) |
K47R |
|
Het |
Efhd2 |
T |
C |
4: 141,601,886 (GRCm39) |
E98G |
probably damaging |
Het |
Fcmr |
T |
A |
1: 130,802,025 (GRCm39) |
L93Q |
probably damaging |
Het |
Fhdc1 |
T |
A |
3: 84,351,906 (GRCm39) |
E1106D |
probably benign |
Het |
Gcnt1 |
C |
T |
19: 17,306,723 (GRCm39) |
G334D |
probably damaging |
Het |
Hltf |
T |
C |
3: 20,145,647 (GRCm39) |
F488L |
probably benign |
Het |
Hmgxb4 |
C |
A |
8: 75,727,436 (GRCm39) |
H140N |
probably damaging |
Het |
Ifi214 |
A |
T |
1: 173,352,402 (GRCm39) |
F342L |
probably damaging |
Het |
Ip6k1 |
A |
G |
9: 107,909,288 (GRCm39) |
D105G |
possibly damaging |
Het |
Kank1 |
GCGAACG |
GCG |
19: 25,388,569 (GRCm39) |
|
probably null |
Het |
Kif18a |
G |
A |
2: 109,137,285 (GRCm39) |
D506N |
probably benign |
Het |
Klf17 |
T |
A |
4: 117,617,812 (GRCm39) |
M182L |
probably benign |
Het |
Kmt2d |
A |
G |
15: 98,750,215 (GRCm39) |
F2493L |
unknown |
Het |
Lefty1 |
A |
G |
1: 180,764,112 (GRCm39) |
E84G |
probably damaging |
Het |
Lyst |
T |
G |
13: 13,884,117 (GRCm39) |
L2975R |
possibly damaging |
Het |
Magea5 |
G |
A |
X: 153,837,174 (GRCm39) |
P73S |
possibly damaging |
Het |
Mctp2 |
T |
C |
7: 71,740,079 (GRCm39) |
|
probably null |
Het |
Mprip |
C |
T |
11: 59,649,047 (GRCm39) |
T917M |
possibly damaging |
Het |
Myh8 |
T |
A |
11: 67,194,481 (GRCm39) |
I1564N |
probably benign |
Het |
Nr2e1 |
A |
G |
10: 42,450,433 (GRCm39) |
C60R |
probably benign |
Het |
Nrxn3 |
A |
G |
12: 89,780,254 (GRCm39) |
I29V |
probably benign |
Het |
Ntsr1 |
T |
A |
2: 180,180,610 (GRCm39) |
H305Q |
probably damaging |
Het |
Or2y1e |
A |
G |
11: 49,218,571 (GRCm39) |
E111G |
probably damaging |
Het |
Or8g35 |
A |
G |
9: 39,381,612 (GRCm39) |
S137P |
probably benign |
Het |
Or8h10 |
T |
A |
2: 86,808,538 (GRCm39) |
I201F |
probably damaging |
Het |
Pate2 |
A |
C |
9: 35,581,197 (GRCm39) |
E22D |
probably benign |
Het |
Pcdhb22 |
A |
G |
18: 37,652,158 (GRCm39) |
T209A |
probably damaging |
Het |
Pdss2 |
C |
T |
10: 43,340,628 (GRCm39) |
S352F |
probably benign |
Het |
Pfn3 |
T |
A |
13: 55,562,900 (GRCm39) |
D27V |
probably damaging |
Het |
Pigg |
T |
G |
5: 108,461,920 (GRCm39) |
S84A |
probably benign |
Het |
Prm3 |
CTCTTCTTCTTCTTC |
CTCTTCTTCTTC |
16: 10,608,565 (GRCm39) |
|
probably benign |
Het |
Prss22 |
C |
T |
17: 24,213,592 (GRCm39) |
G233E |
probably damaging |
Het |
Rad51b |
T |
C |
12: 79,850,044 (GRCm39) |
|
probably null |
Het |
Scn10a |
A |
G |
9: 119,438,970 (GRCm39) |
V1632A |
possibly damaging |
Het |
Serpinb3d |
T |
G |
1: 107,007,512 (GRCm39) |
D158A |
probably damaging |
Het |
Sh3yl1 |
T |
C |
12: 31,008,868 (GRCm39) |
L266P |
probably damaging |
Het |
Sidt2 |
A |
T |
9: 45,852,873 (GRCm39) |
|
probably null |
Het |
Stox1 |
C |
T |
10: 62,501,778 (GRCm39) |
V261M |
probably benign |
Het |
Taf7l2 |
T |
A |
10: 115,949,158 (GRCm39) |
K123* |
probably null |
Het |
Tll1 |
A |
G |
8: 64,504,483 (GRCm39) |
Y638H |
probably damaging |
Het |
Tst |
A |
T |
15: 78,289,816 (GRCm39) |
M73K |
possibly damaging |
Het |
Tuba4a |
C |
T |
1: 75,193,003 (GRCm39) |
V232M |
probably benign |
Het |
Unk |
T |
A |
11: 115,943,908 (GRCm39) |
V343D |
probably benign |
Het |
Usf3 |
T |
C |
16: 44,039,426 (GRCm39) |
V1302A |
probably benign |
Het |
Usp32 |
A |
T |
11: 84,885,234 (GRCm39) |
L1271H |
probably damaging |
Het |
Vwa5b2 |
C |
T |
16: 20,413,361 (GRCm39) |
P192L |
probably benign |
Het |
Zfp995 |
A |
G |
17: 22,100,984 (GRCm39) |
Y38H |
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 |
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 |
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'- CAGAGGCTAAAGACACTGGC -3'
(R):5'- CGTGTCACAGTGCTCATATTC -3'
Sequencing Primer
(F):5'- TAAAGACACTGGCCCGCTC -3'
(R):5'- ACAGTGCTCATATTCTGCCCATAG -3'
|
Posted On |
2019-11-26 |