Mutagenetix > Incidental Mutation

Incidental Mutation 'R0730:Npc1'

67516

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

038911-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.616) question?

Stock #

R0730 (G1)

Quality Score

204

Status

Validated

Chromosome

Chromosomal Location

12322749-12369457 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 12352382 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 106 (T106A)

Ref Sequence

ENSEMBL: ENSMUSP00000025279 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000025279]

AlphaFold

O35604

Predicted Effect

probably benign
Transcript: ENSMUST00000025279
AA Change: T106A

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000025279
Gene: ENSMUSG00000024413
AA Change: T106A

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: ENSMUST00000133112

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000144435

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000149211

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.4%
3x: 98.9%
10x: 97.8%
20x: 96.1%

Validation Efficiency

99% (99/100)

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: 99 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam9	A	T	8: 25,486,774 (GRCm39)	I168N	probably benign	Het
Adamts20	G	A	15: 94,245,571 (GRCm39)	A577V	probably benign	Het
Agtr1a	A	T	13: 30,565,279 (GRCm39)	S115C	probably damaging	Het
Ankrd11	T	C	8: 123,618,692 (GRCm39)	Y1720C	probably damaging	Het
Ano6	A	T	15: 95,818,252 (GRCm39)	T353S	probably damaging	Het
App	A	G	16: 84,876,840 (GRCm39)	F184L	probably damaging	Het
Arhgef38	T	A	3: 132,843,232 (GRCm39)	Y446F	probably benign	Het
Aspg	T	A	12: 112,078,693 (GRCm39)	Y57*	probably null	Het
Atp1a4	G	A	1: 172,067,774 (GRCm39)		probably benign	Het
Bdp1	G	A	13: 100,195,459 (GRCm39)		probably benign	Het
Bicd2	T	A	13: 49,531,717 (GRCm39)	S246T	possibly damaging	Het
Brd10	T	A	19: 29,695,381 (GRCm39)	I1438F	probably benign	Het
Bsn	T	A	9: 107,984,011 (GRCm39)	M3348L	unknown	Het
Cacna1c	C	T	6: 118,589,586 (GRCm39)	R1446H	probably damaging	Het
Cacna2d3	T	C	14: 28,704,322 (GRCm39)	I820V	probably benign	Het
Cdc40	A	G	10: 40,720,952 (GRCm39)		probably benign	Het
Cdh23	T	C	10: 60,159,493 (GRCm39)	E2094G	probably damaging	Het
Celsr2	T	A	3: 108,305,922 (GRCm39)	N2061Y	probably damaging	Het
Cfap206	G	A	4: 34,711,391 (GRCm39)	A502V	probably benign	Het
Cfap54	T	C	10: 92,870,599 (GRCm39)	T29A	probably benign	Het
Cfap57	T	C	4: 118,470,117 (GRCm39)		probably null	Het
Chd5	A	G	4: 152,432,441 (GRCm39)	E43G	possibly damaging	Het
Clk1	G	A	1: 58,453,558 (GRCm39)	H343Y	probably benign	Het
Cntn4	A	C	6: 106,527,447 (GRCm39)	K443T	probably damaging	Het
Csn2	G	A	5: 87,842,811 (GRCm39)	A72V	possibly damaging	Het
Ctdp1	T	A	18: 80,493,457 (GRCm39)	H346L	probably benign	Het
Ctif	A	T	18: 75,698,083 (GRCm39)	N192K	probably damaging	Het
Ddr2	G	A	1: 169,823,135 (GRCm39)	A383V	probably benign	Het
Derl3	C	T	10: 75,731,076 (GRCm39)		probably benign	Het
Dgkh	T	C	14: 78,821,919 (GRCm39)	I865V	probably damaging	Het
Dip2b	C	T	15: 100,069,532 (GRCm39)	A619V	probably damaging	Het
Elapor1	T	A	3: 108,376,851 (GRCm39)	H509L	probably benign	Het
Eml1	A	G	12: 108,496,585 (GRCm39)	T614A	possibly damaging	Het
Eogt	G	C	6: 97,092,970 (GRCm39)	Y402*	probably null	Het
Erbb4	A	G	1: 68,298,449 (GRCm39)	V647A	probably damaging	Het
Esm1	G	T	13: 113,350,036 (GRCm39)		probably null	Het
Fbxo31	A	G	8: 122,282,103 (GRCm39)		probably benign	Het
Fbxw5	T	A	2: 25,394,630 (GRCm39)	D201E	possibly damaging	Het
Fgfr1	G	A	8: 26,045,760 (GRCm39)	D123N	probably benign	Het
G530012D18Rik	A	C	1: 85,504,757 (GRCm39)		probably benign	Het
Gnat1	G	A	9: 107,556,662 (GRCm39)	T29I	probably damaging	Het
Gtf2ird2	A	T	5: 134,221,597 (GRCm39)	R67*	probably null	Het
Il22b	A	T	10: 118,130,142 (GRCm39)	D87E	probably benign	Het
Kcnq3	T	C	15: 65,867,457 (GRCm39)	T729A	probably benign	Het
Klrc2	A	T	6: 129,635,659 (GRCm39)	S156R	probably damaging	Het
Krt76	A	T	15: 101,795,784 (GRCm39)	L462Q	probably damaging	Het
Lama3	C	A	18: 12,589,907 (GRCm39)		probably benign	Het
Lin28a	A	T	4: 133,735,319 (GRCm39)	S56T	probably damaging	Het
Macf1	A	G	4: 123,276,323 (GRCm39)		probably benign	Het
Macrod2	C	T	2: 142,059,594 (GRCm39)		probably benign	Het
Mansc1	C	T	6: 134,594,424 (GRCm39)		probably benign	Het
Map1b	G	T	13: 99,566,274 (GRCm39)	S2149*	probably null	Het
Mgst1	A	T	6: 138,124,667 (GRCm39)	T34S	probably benign	Het
Mlf2	C	T	6: 124,911,354 (GRCm39)	T123M	probably damaging	Het
Mospd2	C	T	X: 163,731,253 (GRCm39)		probably benign	Het
Mrpl15	A	T	1: 4,847,834 (GRCm39)	V155E	probably damaging	Het
Mstn	A	T	1: 53,100,953 (GRCm39)	Y10F	possibly damaging	Het
Myo1g	C	T	11: 6,470,794 (GRCm39)	V21M	probably damaging	Het
Myom2	T	C	8: 15,149,326 (GRCm39)	I599T	probably benign	Het
Ndc80	A	T	17: 71,803,241 (GRCm39)	N633K	probably benign	Het
Nhs	C	A	X: 160,620,296 (GRCm39)	V1487L	possibly damaging	Het
Nup133	C	T	8: 124,675,747 (GRCm39)	V57M	probably benign	Het
Nup98	T	A	7: 101,809,923 (GRCm39)	T536S	probably damaging	Het
Oprm1	T	C	10: 6,782,652 (GRCm39)		probably benign	Het
Or5j1	T	C	2: 86,879,492 (GRCm39)	I29M	probably benign	Het
Or6c219	T	A	10: 129,780,980 (GRCm39)	H317L	probably benign	Het
Or8j3	A	G	2: 86,029,069 (GRCm39)	V9A	probably benign	Het
Ostf1	C	T	19: 18,581,571 (GRCm39)	V14I	unknown	Het
Pcdhb14	C	A	18: 37,581,921 (GRCm39)	D342E	probably damaging	Het
Pdia3	G	A	2: 121,262,858 (GRCm39)	G275S	probably damaging	Het
Pdpr	T	C	8: 111,852,387 (GRCm39)		probably null	Het
Plce1	G	A	19: 38,705,135 (GRCm39)	V847M	probably damaging	Het
Pon3	A	G	6: 5,230,444 (GRCm39)	M288T	probably benign	Het
Psd2	A	T	18: 36,111,627 (GRCm39)	D84V	possibly damaging	Het
Ptpro	T	A	6: 137,420,592 (GRCm39)	V1007D	probably damaging	Het
Ralgapa1	T	C	12: 55,712,448 (GRCm39)	K1808E	probably damaging	Het
Ramp3	T	C	11: 6,626,476 (GRCm39)		probably benign	Het
Rasgrf1	T	A	9: 89,833,062 (GRCm39)		probably benign	Het
Rictor	A	G	15: 6,803,467 (GRCm39)		probably benign	Het
Rptor	A	T	11: 119,775,780 (GRCm39)	I984F	probably benign	Het
Slc1a6	C	T	10: 78,631,842 (GRCm39)	P223S	probably benign	Het
Taar8b	A	C	10: 23,967,924 (GRCm39)	V90G	probably damaging	Het
Tbc1d21	A	G	9: 58,267,160 (GRCm39)	V327A	probably benign	Het
Tex21	T	C	12: 76,250,940 (GRCm39)	T499A	probably benign	Het
Tg	A	T	15: 66,550,638 (GRCm39)	D256V	probably damaging	Het
Tmf1	A	G	6: 97,153,453 (GRCm39)	S207P	probably benign	Het
Tpr	A	G	1: 150,269,158 (GRCm39)		probably benign	Het
Ufd1	A	G	16: 18,633,637 (GRCm39)	T21A	probably damaging	Het
Unc13a	T	C	8: 72,108,929 (GRCm39)	D115G	possibly damaging	Het
Usb1	T	A	8: 96,070,669 (GRCm39)	F198L	probably damaging	Het
Utrn	A	T	10: 12,573,902 (GRCm39)		probably benign	Het
Vars1	A	G	17: 35,233,276 (GRCm39)	N954S	probably damaging	Het
Wdr17	C	T	8: 55,146,131 (GRCm39)	A90T	possibly damaging	Het
Wdr33	C	T	18: 31,968,429 (GRCm39)		probably benign	Het
Zfp236	A	G	18: 82,658,369 (GRCm39)		probably benign	Het
Zfp445	A	T	9: 122,690,823 (GRCm39)	V124E	probably damaging	Het
Zfp616	A	T	11: 73,975,648 (GRCm39)	H639L	probably damaging	Het
Zfyve16	C	A	13: 92,657,985 (GRCm39)	S642I	probably damaging	Het
Zswim5	C	T	4: 116,842,943 (GRCm39)	T896I	possibly 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
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'- ACCCAATGTCCTGACCCAGCTT -3'
(R):5'- GTGGTCTTTGTCACATGGACACACA -3'

Sequencing Primer
(F):5'- TACTCACCATTCGCGAAGCT -3'
(R):5'- gttcacaactgcctataactcc -3'

Posted On

2013-09-03