Incidental Mutation 'IGL03101:Npc1'
ID418718
Institutional Source Australian Phenomics Network (link to record)
Gene Symbol Npc1
Ensembl Gene ENSMUSG00000024413
Gene NameNPC intracellular cholesterol transporter 1
Synonymsnmf164, A430089E03Rik, D18Ertd723e, C85354, D18Ertd139e, lcsd
Accession Numbers
Is this an essential gene? Possibly essential (E-score: 0.680) question?
Stock #IGL03101
Quality Score
Status
Chromosome18
Chromosomal Location12189693-12236400 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) A to G at 12198539 bp
ZygosityHeterozygous
Amino Acid Change Isoleucine to Threonine at position 858 (I858T)
Ref Sequence ENSEMBL: ENSMUSP00000025279 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000025279]
Predicted Effect probably benign
Transcript: ENSMUST00000025279
AA Change: I858T

PolyPhen 2 Score 0.148 (Sensitivity: 0.92; Specificity: 0.87)
SMART Domains Protein: ENSMUSP00000025279
Gene: ENSMUSG00000024413
AA Change: I858T

DomainStartEndE-ValueType
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: ENSMUST00000153352
Coding Region Coverage
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: 32 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
AA474408 A T 7: 110,060,970 probably benign Het
Abcc1 T A 16: 14,389,868 V23D probably damaging Het
Adam8 G T 7: 139,988,543 N260K possibly damaging Het
Ap3b1 A T 13: 94,455,398 I457L probably benign Het
Apaf1 T C 10: 91,031,559 N808S possibly damaging Het
Arhgef26 A G 3: 62,419,661 T532A possibly damaging Het
Cfap65 G T 1: 74,928,433 T162N possibly damaging Het
Clec12b A G 6: 129,379,517 probably null Het
Creb3 T C 4: 43,563,081 V60A probably benign Het
Cyp11b1 A G 15: 74,835,854 F469L probably benign Het
Defb28 A T 2: 152,520,127 E69V possibly damaging Het
Etnppl T C 3: 130,622,318 L118S probably damaging Het
Fsip1 T C 2: 118,241,663 Y213C probably damaging Het
Glb1l2 A G 9: 26,765,125 W480R probably damaging Het
Gm12394 T C 4: 42,793,424 D236G possibly damaging Het
Herc1 A T 9: 66,487,997 M4205L probably benign Het
Kif5a A T 10: 127,235,609 probably benign Het
Lmbrd2 C T 15: 9,186,608 R557C probably damaging Het
Map4k3 A G 17: 80,655,855 probably null Het
Olfr866 T C 9: 20,027,429 T170A probably benign Het
Pecam1 A G 11: 106,697,351 V92A probably damaging Het
Rbm43 A T 2: 51,926,745 I70N probably benign Het
Rps6kb1 T C 11: 86,502,882 Y474C probably benign Het
Slco2a1 G A 9: 103,077,006 G459R possibly damaging Het
Snca T A 6: 60,827,611 probably benign Het
Stap2 T A 17: 56,002,029 I113F probably damaging Het
Tas2r137 T C 6: 40,491,830 M198T probably benign Het
Trim9 T C 12: 70,346,654 E172G probably damaging Het
Ttll7 T C 3: 146,896,690 V81A possibly damaging Het
Vmn2r103 A G 17: 19,773,520 Y53C probably damaging Het
Vmn2r22 C A 6: 123,637,336 A432S probably benign Het
Zfp943 T C 17: 21,992,175 S81P probably damaging Het
Other mutations in Npc1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02347:Npc1 APN 18 12199634 missense probably benign 0.45
IGL02523:Npc1 APN 18 12201572 missense probably benign 0.00
IGL03018:Npc1 APN 18 12214379 missense probably damaging 0.99
IGL03151:Npc1 APN 18 12219275 missense probably benign 0.05
IGL03377:Npc1 APN 18 12211821 missense probably benign
PIT4354001:Npc1 UTSW 18 12211535 missense probably benign 0.00
R0068:Npc1 UTSW 18 12208367 missense probably benign 0.04
R0068:Npc1 UTSW 18 12208367 missense probably benign 0.04
R0190:Npc1 UTSW 18 12191830 missense probably damaging 1.00
R0200:Npc1 UTSW 18 12219204 missense probably damaging 1.00
R0485:Npc1 UTSW 18 12213446 missense probably benign 0.00
R0699:Npc1 UTSW 18 12210575 missense probably benign 0.00
R0730:Npc1 UTSW 18 12219325 missense probably benign 0.00
R1302:Npc1 UTSW 18 12195085 missense probably benign 0.00
R1442:Npc1 UTSW 18 12195049 missense probably benign
R1463:Npc1 UTSW 18 12191830 missense probably damaging 1.00
R1804:Npc1 UTSW 18 12223088 missense probably damaging 1.00
R1808:Npc1 UTSW 18 12194092 missense probably damaging 1.00
R1928:Npc1 UTSW 18 12213378 missense possibly damaging 0.79
R2112:Npc1 UTSW 18 12213472 missense possibly damaging 0.49
R2117:Npc1 UTSW 18 12196556 missense probably damaging 1.00
R2157:Npc1 UTSW 18 12191809 missense probably damaging 0.98
R2279:Npc1 UTSW 18 12197179 splice site probably null
R2311:Npc1 UTSW 18 12202183 missense probably benign
R2446:Npc1 UTSW 18 12214339 missense probably benign 0.01
R3004:Npc1 UTSW 18 12197254 missense probably benign 0.03
R4090:Npc1 UTSW 18 12198162 splice site probably null
R4304:Npc1 UTSW 18 12210527 missense possibly damaging 0.77
R4308:Npc1 UTSW 18 12210527 missense possibly damaging 0.77
R4564:Npc1 UTSW 18 12191732 missense probably damaging 1.00
R4786:Npc1 UTSW 18 12199497 missense probably benign 0.35
R5243:Npc1 UTSW 18 12198631 intron probably benign
R5404:Npc1 UTSW 18 12213299 missense possibly damaging 0.79
R5823:Npc1 UTSW 18 12191789 missense possibly damaging 0.69
R6080:Npc1 UTSW 18 12219351 missense probably damaging 1.00
R6215:Npc1 UTSW 18 12236192 small deletion probably benign
R6301:Npc1 UTSW 18 12197245 missense probably benign 0.00
R6476:Npc1 UTSW 18 12201694 nonsense probably null
R7007:Npc1 UTSW 18 12210548 missense probably benign 0.02
R7020:Npc1 UTSW 18 12198537 missense probably damaging 1.00
R7048:Npc1 UTSW 18 12204765 splice site probably null
R7116:Npc1 UTSW 18 12211544 missense probably damaging 1.00
R7153:Npc1 UTSW 18 12213291 missense possibly damaging 0.78
R7359:Npc1 UTSW 18 12195180 missense probably benign 0.05
R7382:Npc1 UTSW 18 12201706 missense probably damaging 0.99
R7765:Npc1 UTSW 18 12195048 missense probably benign 0.01
X0012:Npc1 UTSW 18 12193311 unclassified probably null
Posted On2016-08-02