Incidental Mutation 'R0190:Npc1'
| ID |
43524 |
| 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 |
038451-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly essential
(E-score: 0.637)
|
| Stock # |
R0190 (G1)
|
| Quality Score |
82 |
|
Status
|
Not validated
|
| Chromosome |
18 |
| Chromosomal Location |
12322749-12369457 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
G to A
at 12324887 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Threonine to Isoleucine
at position 1202
(T1202I)
|
| 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: T1202I
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000025279
Gene: ENSMUSG00000024413
AA Change: T1202I
| 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 |
0.9320 |
| Coding Region Coverage |
- 1x: 98.8%
- 3x: 97.6%
- 10x: 91.6%
- 20x: 72.5%
|
| Validation Efficiency |
75% (45/60) |
| 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: 61 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Acsl1 |
T |
C |
8: 46,966,429 (GRCm39) |
|
probably null |
Het |
| Aff2 |
CA |
CAAA |
X: 68,892,711 (GRCm39) |
|
probably null |
Het |
| Ankrd34a |
A |
G |
3: 96,505,105 (GRCm39) |
D103G |
probably damaging |
Het |
| Atp1b2 |
T |
C |
11: 69,492,388 (GRCm39) |
D224G |
probably damaging |
Het |
| Atxn10 |
A |
G |
15: 85,220,730 (GRCm39) |
D22G |
possibly damaging |
Het |
| Btbd9 |
C |
T |
17: 30,493,916 (GRCm39) |
D492N |
possibly damaging |
Het |
| Caskin1 |
C |
T |
17: 24,723,596 (GRCm39) |
L795F |
possibly damaging |
Het |
| Cdk12 |
T |
C |
11: 98,132,657 (GRCm39) |
|
probably null |
Het |
| Crtc2 |
A |
G |
3: 90,166,716 (GRCm39) |
H91R |
probably damaging |
Het |
| Dbt |
A |
G |
3: 116,332,736 (GRCm39) |
|
probably null |
Het |
| Dda1 |
C |
A |
8: 71,924,877 (GRCm39) |
Y41* |
probably null |
Het |
| Dnah2 |
T |
A |
11: 69,326,075 (GRCm39) |
D3692V |
probably damaging |
Het |
| Dpep1 |
A |
G |
8: 123,927,447 (GRCm39) |
T334A |
probably benign |
Het |
| Enthd1 |
C |
T |
15: 80,418,695 (GRCm39) |
|
probably null |
Het |
| Fpr-rs6 |
T |
A |
17: 20,402,741 (GRCm39) |
I207F |
probably benign |
Het |
| Fsip2 |
T |
A |
2: 82,815,521 (GRCm39) |
S3751R |
possibly damaging |
Het |
| Gigyf2 |
A |
T |
1: 87,356,410 (GRCm39) |
|
probably benign |
Het |
| Gtf3c4 |
C |
A |
2: 28,730,140 (GRCm39) |
D34Y |
probably benign |
Het |
| Iftap |
G |
A |
2: 101,416,775 (GRCm39) |
S58L |
probably benign |
Het |
| Igfn1 |
A |
T |
1: 135,889,790 (GRCm39) |
V2419E |
probably damaging |
Het |
| Kank1 |
A |
T |
19: 25,386,647 (GRCm39) |
I79L |
probably benign |
Het |
| Kif21b |
A |
G |
1: 136,098,957 (GRCm39) |
H1415R |
probably benign |
Het |
| Mad2l1 |
T |
C |
6: 66,516,862 (GRCm39) |
S185P |
possibly damaging |
Het |
| Mettl18 |
A |
G |
1: 163,823,991 (GRCm39) |
E104G |
probably damaging |
Het |
| Mrgprb2 |
G |
A |
7: 48,202,525 (GRCm39) |
H67Y |
possibly damaging |
Het |
| Mrgprd |
G |
A |
7: 144,875,439 (GRCm39) |
M103I |
probably benign |
Het |
| Nanos3 |
C |
T |
8: 84,902,763 (GRCm39) |
R133Q |
probably damaging |
Het |
| Nucks1 |
A |
G |
1: 131,852,329 (GRCm39) |
D60G |
probably damaging |
Het |
| Or10g7 |
A |
G |
9: 39,905,840 (GRCm39) |
I245V |
probably benign |
Het |
| Or13f5 |
G |
C |
4: 52,825,613 (GRCm39) |
W72S |
probably damaging |
Het |
| Or4a72 |
T |
A |
2: 89,405,302 (GRCm39) |
Y256F |
probably damaging |
Het |
| Paqr8 |
A |
G |
1: 21,005,271 (GRCm39) |
T142A |
probably benign |
Het |
| Pdss1 |
T |
C |
2: 22,796,843 (GRCm39) |
S119P |
probably damaging |
Het |
| Plcl2 |
A |
G |
17: 50,914,671 (GRCm39) |
D560G |
probably benign |
Het |
| Ppm1b |
T |
A |
17: 85,301,531 (GRCm39) |
V137E |
probably damaging |
Het |
| Ppp1r16b |
A |
C |
2: 158,537,983 (GRCm39) |
K35Q |
probably damaging |
Het |
| Prkd2 |
A |
T |
7: 16,603,815 (GRCm39) |
E832V |
probably damaging |
Het |
| Rab34 |
G |
T |
11: 78,082,232 (GRCm39) |
K191N |
possibly damaging |
Het |
| Rad51ap2 |
A |
C |
12: 11,508,540 (GRCm39) |
T821P |
probably benign |
Het |
| Rbm19 |
A |
G |
5: 120,282,111 (GRCm39) |
T823A |
probably benign |
Het |
| Rpf2 |
T |
G |
10: 40,103,597 (GRCm39) |
H106P |
probably damaging |
Het |
| Schip1 |
A |
G |
3: 68,533,177 (GRCm39) |
M453V |
probably benign |
Het |
| Sema5a |
T |
A |
15: 32,562,920 (GRCm39) |
N310K |
possibly damaging |
Het |
| Sf3b1 |
T |
C |
1: 55,029,465 (GRCm39) |
D1179G |
probably damaging |
Het |
| Skint2 |
A |
T |
4: 112,473,729 (GRCm39) |
T4S |
possibly damaging |
Het |
| Slc22a5 |
A |
T |
11: 53,760,241 (GRCm39) |
Y358* |
probably null |
Het |
| Slc34a1 |
T |
C |
13: 55,556,914 (GRCm39) |
M251T |
probably benign |
Het |
| Slc44a5 |
A |
G |
3: 153,944,755 (GRCm39) |
D124G |
probably null |
Het |
| Slc9b1 |
G |
A |
3: 135,063,434 (GRCm39) |
E73K |
unknown |
Het |
| Ssbp2 |
T |
C |
13: 91,817,829 (GRCm39) |
L156P |
probably damaging |
Het |
| Taar2 |
G |
A |
10: 23,817,393 (GRCm39) |
R311H |
probably benign |
Het |
| Trim47 |
A |
G |
11: 115,997,053 (GRCm39) |
V568A |
probably damaging |
Het |
| Ttn |
A |
T |
2: 76,718,324 (GRCm39) |
|
probably benign |
Het |
| Ttpa |
A |
T |
4: 20,021,260 (GRCm39) |
I74F |
probably damaging |
Het |
| Vmn2r52 |
T |
C |
7: 9,905,315 (GRCm39) |
I175V |
probably benign |
Het |
| Wrn |
C |
T |
8: 33,731,011 (GRCm39) |
C1350Y |
probably benign |
Het |
| Zfp11 |
C |
T |
5: 129,735,302 (GRCm39) |
G53E |
possibly damaging |
Het |
| Zfp422 |
A |
T |
6: 116,603,572 (GRCm39) |
D142E |
probably damaging |
Het |
| Zfp473 |
A |
T |
7: 44,382,612 (GRCm39) |
C574S |
probably damaging |
Het |
| Zfp638 |
T |
A |
6: 83,905,946 (GRCm39) |
M37K |
probably damaging |
Het |
| Zfp976 |
C |
A |
7: 42,291,948 (GRCm39) |
|
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 |
|
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 |
|
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'- TCCAGGATGCCTAAGGAAATGCCC -3'
(R):5'- TGCTCATAAAGCAGCAGGCCAG -3'
Sequencing Primer
(F):5'- ccatcctgcttccactcc -3'
(R):5'- GCCAGACAGTTTGGGTACG -3'
|
| Posted On |
2013-05-24 |
Incidental Mutation