Incidental Mutation 'R5760:Npc1l1'
ID 445255
Institutional Source Beutler Lab
Gene Symbol Npc1l1
Ensembl Gene ENSMUSG00000020447
Gene Name NPC1 like intracellular cholesterol transporter 1
Synonyms Niemann-Pick disease, type C1, 9130221N23Rik
MMRRC Submission 043362-MU
Accession Numbers
Essential gene? Probably non essential (E-score: 0.098) question?
Stock # R5760 (G1)
Quality Score 225
Status Not validated
Chromosome 11
Chromosomal Location 6161013-6180143 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 6179031 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Histidine to Glutamine at position 126 (H126Q)
Ref Sequence ENSEMBL: ENSMUSP00000004505 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000004505]
AlphaFold no structure available at present
Predicted Effect probably benign
Transcript: ENSMUST00000004505
AA Change: H126Q

PolyPhen 2 Score 0.021 (Sensitivity: 0.95; Specificity: 0.80)
SMART Domains Protein: ENSMUSP00000004505
Gene: ENSMUSG00000020447
AA Change: H126Q

DomainStartEndE-ValueType
signal peptide 1 20 N/A INTRINSIC
Pfam:NPC1_N 28 283 8.7e-74 PFAM
low complexity region 294 307 N/A INTRINSIC
transmembrane domain 348 370 N/A INTRINSIC
Pfam:Patched 385 897 4.7e-52 PFAM
Pfam:Sterol-sensing 661 815 5.7e-55 PFAM
Pfam:MMPL 665 830 2.3e-11 PFAM
Pfam:Patched 1063 1268 6.2e-34 PFAM
Coding Region Coverage
  • 1x: 99.5%
  • 3x: 98.8%
  • 10x: 97.3%
  • 20x: 95.3%
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a multi-pass membrane protein. It contains a conserved N-terminal Niemann-Pick C1 (NPC1) domain and a putative sterol-sensing domain (SSD) which includes a YQRL motif functioning as a plasma membrane to trans-Golgi network transport signal in other proteins. This protein takes up free cholesterol into cells through vesicular endocytosis and plays a critical role in the absorption of intestinal cholesterol. It also has the ability to transport alpha-tocopherol (vitamin E). The drug ezetimibe targets this protein and inhibits the absorption of intestinal cholesterol and alpha-tocopherol. In addition, this protein may play a critical role in regulating lipid metabolism. Polymorphic variations in this gene are associated with plasma total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels and coronary heart disease (CHD) risk. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
PHENOTYPE: Mice homozygous for a targeted null mutation exhibit normal intestinal development, fertility and plasma cholesterol and triglyceride levels; however, intestinal cholesterol absorption was substantially reduced. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 47 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4930447A16Rik T C 15: 37,439,835 (GRCm39) probably benign Het
Abl2 C T 1: 156,469,427 (GRCm39) T793M probably benign Het
Accs A C 2: 93,676,105 (GRCm39) L90R probably damaging Het
Ahnak A T 19: 8,990,926 (GRCm39) D4070V probably damaging Het
Apbb2 A G 5: 66,520,100 (GRCm39) V475A probably benign Het
Atp10d T A 5: 72,418,280 (GRCm39) V602E probably benign Het
Cdh23 C T 10: 60,242,171 (GRCm39) V1088M probably damaging Het
Dennd6a A T 14: 26,333,195 (GRCm39) I144L probably damaging Het
Dnajc6 G A 4: 101,475,839 (GRCm39) A571T probably benign Het
Drap1 A G 19: 5,474,391 (GRCm39) I18T probably damaging Het
En2 C A 5: 28,371,997 (GRCm39) A158D probably benign Het
Fbn1 C T 2: 125,203,167 (GRCm39) G1219R probably damaging Het
Fkbpl G A 17: 34,864,303 (GRCm39) A24T probably benign Het
Gm7535 C T 17: 18,132,080 (GRCm39) probably benign Het
Hao2 A T 3: 98,787,748 (GRCm39) L227* probably null Het
Hdlbp C T 1: 93,368,499 (GRCm39) probably benign Het
Hivep3 A G 4: 119,952,208 (GRCm39) K175E possibly damaging Het
Hmcn2 G A 2: 31,304,580 (GRCm39) A3075T possibly damaging Het
Igkv6-15 A T 6: 70,383,516 (GRCm39) I95N probably damaging Het
Itgad A T 7: 127,802,537 (GRCm39) Q1001L probably benign Het
Jaml T A 9: 45,009,052 (GRCm39) M151K probably benign Het
Lix1 T A 17: 17,647,499 (GRCm39) V55D possibly damaging Het
Macf1 A G 4: 123,407,677 (GRCm39) S179P probably damaging Het
Matn2 T A 15: 34,355,753 (GRCm39) Q33L possibly damaging Het
Mcm3 CT CTT 1: 20,878,972 (GRCm39) probably null Het
Mroh5 A C 15: 73,693,356 (GRCm39) I28S probably damaging Het
Naip5 T G 13: 100,379,346 (GRCm39) K231N probably damaging Het
Neb A C 2: 52,073,830 (GRCm39) Y5683D probably damaging Het
Npm2 A G 14: 70,886,935 (GRCm39) F110L probably damaging Het
Nsd3 A T 8: 26,149,772 (GRCm39) H319L probably damaging Het
Nup205 G A 6: 35,224,278 (GRCm39) R2039Q probably damaging Het
Or10j7 C A 1: 173,011,318 (GRCm39) A228S probably benign Het
Or6b2b A G 1: 92,418,922 (GRCm39) L185P possibly damaging Het
Or7d10 A C 9: 19,832,050 (GRCm39) T182P probably benign Het
Pcdhac2 G A 18: 37,279,453 (GRCm39) G811E probably damaging Het
Pkhd1 T A 1: 20,143,778 (GRCm39) R3849S probably benign Het
Pmfbp1 A T 8: 110,247,655 (GRCm39) D317V probably damaging Het
Sall1 T C 8: 89,755,278 (GRCm39) N1234D possibly damaging Het
Slc12a7 T A 13: 73,961,741 (GRCm39) V1037D probably damaging Het
Slc12a8 G T 16: 33,445,155 (GRCm39) E404* probably null Het
Tchhl1 C G 3: 93,378,863 (GRCm39) S522R probably damaging Het
Tgif1 A G 17: 71,151,996 (GRCm39) V152A probably damaging Het
Tshz3 C A 7: 36,470,994 (GRCm39) H994Q probably damaging Het
Ubash3b T G 9: 40,988,719 (GRCm39) K62T probably benign Het
Ushbp1 G T 8: 71,840,012 (GRCm39) D546E probably damaging Het
Zfp458 A C 13: 67,405,853 (GRCm39) C192W probably damaging Het
Zfp808 A T 13: 62,319,740 (GRCm39) H323L probably damaging Het
Other mutations in Npc1l1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00163:Npc1l1 APN 11 6,174,199 (GRCm39) missense probably damaging 1.00
IGL01348:Npc1l1 APN 11 6,177,974 (GRCm39) missense probably damaging 1.00
IGL01891:Npc1l1 APN 11 6,164,280 (GRCm39) missense probably damaging 1.00
IGL01897:Npc1l1 APN 11 6,177,879 (GRCm39) missense probably benign
IGL02098:Npc1l1 APN 11 6,164,581 (GRCm39) missense probably damaging 0.99
IGL02121:Npc1l1 APN 11 6,178,157 (GRCm39) missense probably benign
IGL02724:Npc1l1 APN 11 6,164,684 (GRCm39) missense possibly damaging 0.88
IGL02947:Npc1l1 APN 11 6,179,246 (GRCm39) missense probably benign 0.01
IGL03328:Npc1l1 APN 11 6,168,643 (GRCm39) nonsense probably null
R0137:Npc1l1 UTSW 11 6,178,148 (GRCm39) nonsense probably null
R0322:Npc1l1 UTSW 11 6,179,042 (GRCm39) missense probably benign
R0352:Npc1l1 UTSW 11 6,173,076 (GRCm39) missense probably benign 0.00
R0492:Npc1l1 UTSW 11 6,173,040 (GRCm39) missense possibly damaging 0.82
R0918:Npc1l1 UTSW 11 6,168,239 (GRCm39) missense probably damaging 1.00
R1300:Npc1l1 UTSW 11 6,177,859 (GRCm39) missense probably damaging 1.00
R1455:Npc1l1 UTSW 11 6,178,174 (GRCm39) missense possibly damaging 0.66
R1588:Npc1l1 UTSW 11 6,167,785 (GRCm39) missense probably benign 0.01
R1803:Npc1l1 UTSW 11 6,178,846 (GRCm39) missense probably damaging 1.00
R1882:Npc1l1 UTSW 11 6,167,473 (GRCm39) splice site probably null
R1944:Npc1l1 UTSW 11 6,164,588 (GRCm39) missense possibly damaging 0.67
R1945:Npc1l1 UTSW 11 6,175,199 (GRCm39) nonsense probably null
R1945:Npc1l1 UTSW 11 6,164,588 (GRCm39) missense possibly damaging 0.67
R3155:Npc1l1 UTSW 11 6,171,840 (GRCm39) missense probably benign
R4343:Npc1l1 UTSW 11 6,167,773 (GRCm39) missense probably benign
R4504:Npc1l1 UTSW 11 6,178,741 (GRCm39) missense possibly damaging 0.61
R4610:Npc1l1 UTSW 11 6,178,215 (GRCm39) missense probably damaging 1.00
R4807:Npc1l1 UTSW 11 6,168,723 (GRCm39) missense probably damaging 1.00
R4829:Npc1l1 UTSW 11 6,164,010 (GRCm39) critical splice donor site probably null
R5135:Npc1l1 UTSW 11 6,174,245 (GRCm39) missense possibly damaging 0.94
R5290:Npc1l1 UTSW 11 6,172,221 (GRCm39) missense probably benign 0.00
R5369:Npc1l1 UTSW 11 6,167,705 (GRCm39) critical splice donor site probably null
R5388:Npc1l1 UTSW 11 6,164,733 (GRCm39) missense probably damaging 1.00
R5532:Npc1l1 UTSW 11 6,174,245 (GRCm39) missense probably damaging 0.98
R5540:Npc1l1 UTSW 11 6,164,546 (GRCm39) missense probably damaging 1.00
R5754:Npc1l1 UTSW 11 6,177,839 (GRCm39) missense probably damaging 1.00
R6057:Npc1l1 UTSW 11 6,167,806 (GRCm39) missense possibly damaging 0.66
R6388:Npc1l1 UTSW 11 6,174,145 (GRCm39) missense probably damaging 1.00
R6644:Npc1l1 UTSW 11 6,164,014 (GRCm39) missense probably damaging 0.98
R6644:Npc1l1 UTSW 11 6,164,013 (GRCm39) missense probably damaging 1.00
R6756:Npc1l1 UTSW 11 6,165,153 (GRCm39) missense probably damaging 1.00
R6790:Npc1l1 UTSW 11 6,164,260 (GRCm39) splice site probably null
R7006:Npc1l1 UTSW 11 6,167,731 (GRCm39) missense probably benign
R7062:Npc1l1 UTSW 11 6,167,807 (GRCm39) missense probably benign
R7273:Npc1l1 UTSW 11 6,168,320 (GRCm39) missense probably damaging 1.00
R7383:Npc1l1 UTSW 11 6,167,777 (GRCm39) missense probably benign 0.30
R8003:Npc1l1 UTSW 11 6,165,129 (GRCm39) missense probably benign 0.01
R8081:Npc1l1 UTSW 11 6,167,768 (GRCm39) missense probably benign 0.01
R8272:Npc1l1 UTSW 11 6,179,327 (GRCm39) nonsense probably null
R8549:Npc1l1 UTSW 11 6,168,675 (GRCm39) missense probably damaging 1.00
R8849:Npc1l1 UTSW 11 6,179,038 (GRCm39) missense probably damaging 0.97
R8887:Npc1l1 UTSW 11 6,175,665 (GRCm39) missense probably damaging 1.00
R8907:Npc1l1 UTSW 11 6,178,157 (GRCm39) missense probably benign 0.28
R9102:Npc1l1 UTSW 11 6,164,684 (GRCm39) missense possibly damaging 0.88
R9289:Npc1l1 UTSW 11 6,168,355 (GRCm39) nonsense probably null
R9626:Npc1l1 UTSW 11 6,177,854 (GRCm39) missense probably benign 0.05
R9785:Npc1l1 UTSW 11 6,180,090 (GRCm39) missense unknown
X0022:Npc1l1 UTSW 11 6,178,058 (GRCm39) missense probably damaging 1.00
Z1177:Npc1l1 UTSW 11 6,175,209 (GRCm39) missense possibly damaging 0.92
Z1177:Npc1l1 UTSW 11 6,168,681 (GRCm39) missense probably damaging 0.99
Z1177:Npc1l1 UTSW 11 6,164,343 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- TCCTTGGAAGTTGAGCCAGC -3'
(R):5'- GCTTGTCTAATACCCCAGCC -3'

Sequencing Primer
(F):5'- CGCTGAGCATTGCAGAGG -3'
(R):5'- AGCCCGCCATGTCACAG -3'
Posted On 2016-11-21