Incidental Mutation 'R9343:Npc1'
| ID |
716004 |
| 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 |
|
| Accession Numbers |
|
| Essential gene? |
Possibly essential
(E-score: 0.637)
|
| Stock # |
R9343 (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 G
at 12334769 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Isoleucine to Threonine
at position 661
(I661T)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000025279
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000025279]
|
| AlphaFold |
O35604 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000025279
AA Change: I661T
PolyPhen 2
Score 0.521 (Sensitivity: 0.88; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000025279
Gene: ENSMUSG00000024413
AA Change: I661T
| 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: 98.7%
|
| Validation Efficiency |
100% (45/45) |
| 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: 45 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abtb2 |
A |
G |
2: 103,547,505 (GRCm39) |
I960V |
probably benign |
Het |
| Alpk3 |
A |
G |
7: 80,742,079 (GRCm39) |
D632G |
probably benign |
Het |
| Aplp2 |
A |
T |
9: 31,122,935 (GRCm39) |
L30Q |
unknown |
Het |
| Axl |
A |
T |
7: 25,473,544 (GRCm39) |
Y361N |
probably damaging |
Het |
| Brinp2 |
A |
T |
1: 158,077,090 (GRCm39) |
|
probably benign |
Het |
| Bsn |
T |
C |
9: 107,992,701 (GRCm39) |
D1017G |
probably damaging |
Het |
| Cc2d2a |
A |
T |
5: 43,875,999 (GRCm39) |
D1046V |
probably damaging |
Het |
| Cdc42bpg |
G |
A |
19: 6,364,553 (GRCm39) |
G594S |
probably damaging |
Het |
| Clcn6 |
A |
G |
4: 148,098,458 (GRCm39) |
S519P |
probably benign |
Het |
| Cnot2 |
T |
G |
10: 116,346,326 (GRCm39) |
H92P |
|
Het |
| Col2a1 |
T |
C |
15: 97,877,775 (GRCm39) |
D1049G |
probably damaging |
Het |
| Creld1 |
C |
T |
6: 113,466,728 (GRCm39) |
A237V |
probably benign |
Het |
| Csf2rb2 |
A |
T |
15: 78,171,287 (GRCm39) |
|
probably benign |
Het |
| Csmd3 |
G |
A |
15: 48,015,001 (GRCm39) |
T643I |
probably damaging |
Het |
| Fam186b |
G |
A |
15: 99,177,616 (GRCm39) |
A570V |
probably damaging |
Het |
| Fcmr |
A |
T |
1: 130,802,072 (GRCm39) |
T109S |
|
Het |
| Grap |
C |
A |
11: 61,562,551 (GRCm39) |
P174Q |
possibly damaging |
Het |
| Itgb5 |
T |
A |
16: 33,730,826 (GRCm39) |
|
probably benign |
Het |
| Kidins220 |
A |
G |
12: 25,058,078 (GRCm39) |
N561S |
probably damaging |
Het |
| Mri1 |
A |
T |
8: 84,983,796 (GRCm39) |
S32T |
probably benign |
Het |
| Mrtfb |
T |
C |
16: 13,218,791 (GRCm39) |
V479A |
probably benign |
Het |
| Muc4 |
A |
T |
16: 32,569,971 (GRCm39) |
T344S |
possibly damaging |
Het |
| Npy1r |
A |
G |
8: 67,156,751 (GRCm39) |
N57S |
probably damaging |
Het |
| Pds5b |
A |
G |
5: 150,704,186 (GRCm39) |
D863G |
probably damaging |
Het |
| Phf14 |
T |
A |
6: 11,961,563 (GRCm39) |
V400D |
probably damaging |
Het |
| Polr2l |
A |
G |
7: 141,053,246 (GRCm39) |
I56T |
probably benign |
Het |
| Ppat |
A |
G |
5: 77,063,884 (GRCm39) |
I422T |
probably benign |
Het |
| Prkcg |
T |
A |
7: 3,359,124 (GRCm39) |
S110R |
possibly damaging |
Het |
| Rab7b |
A |
T |
1: 131,639,540 (GRCm39) |
|
probably benign |
Het |
| Rnf152 |
A |
T |
1: 105,212,251 (GRCm39) |
L102Q |
|
Het |
| Samd12 |
A |
G |
15: 53,583,088 (GRCm39) |
V82A |
probably damaging |
Het |
| Serpina1e |
T |
A |
12: 103,917,299 (GRCm39) |
R123S |
probably benign |
Het |
| Slit1 |
T |
A |
19: 41,615,737 (GRCm39) |
N794I |
probably damaging |
Het |
| Surf6 |
T |
C |
2: 26,783,006 (GRCm39) |
K154R |
probably damaging |
Het |
| Tln2 |
C |
T |
9: 67,230,353 (GRCm39) |
A71T |
probably benign |
Het |
| Trim3 |
A |
G |
7: 105,260,673 (GRCm39) |
Y649H |
probably benign |
Het |
| Ttll7 |
T |
A |
3: 146,667,497 (GRCm39) |
W808R |
probably damaging |
Het |
| Tvp23a |
T |
C |
16: 10,245,287 (GRCm39) |
D104G |
probably damaging |
Het |
| Upp2 |
A |
G |
2: 58,645,339 (GRCm39) |
|
probably benign |
Het |
| Vipr1 |
G |
A |
9: 121,471,993 (GRCm39) |
|
probably null |
Het |
| Vmn1r119 |
A |
G |
7: 20,746,358 (GRCm39) |
V8A |
probably benign |
Het |
| Vmn1r209 |
T |
A |
13: 22,990,546 (GRCm39) |
H48L |
probably damaging |
Het |
| Wdr11 |
T |
C |
7: 129,232,523 (GRCm39) |
|
probably null |
Het |
| Zcchc17 |
T |
C |
4: 130,210,546 (GRCm39) |
D207G |
probably damaging |
Het |
| Zfp78 |
T |
C |
7: 6,381,942 (GRCm39) |
S331P |
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 |
|
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 |
|
|
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'- CAGTGCTGAGCAGTCACTTAG -3'
(R):5'- TTGTTGCTAGGGAGAAACCTGC -3'
Sequencing Primer
(F):5'- TCACTGAGTGCTTAGACAGACGC -3'
(R):5'- AAACCTGCAAGTTTCTTCTGTG -3'
|
| Posted On |
2022-06-15 |
Incidental Mutation