Mutagenetix > Incidental Mutation

Incidental Mutation 'R7359:Npc1'

571237

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

045445-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.637) question?

Stock #

R7359 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

12322749-12369457 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 12328237 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Asparagine to Serine at position 1024 (N1024S)

Ref Sequence

ENSEMBL: ENSMUSP00000025279 (fasta)

Gene Model

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

AlphaFold

O35604

Predicted Effect

probably benign
Transcript: ENSMUST00000025279
AA Change: N1024S

PolyPhen 2 Score 0.046 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000025279
Gene: ENSMUSG00000024413
AA Change: N1024S

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: 100.0%
10x: 99.7%
20x: 98.8%

Validation Efficiency

99% (87/88)

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: 88 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2700049A03Rik	T	C	12: 71,236,348 (GRCm39)	V1233A	possibly damaging	Het
Abcc9	G	A	6: 142,617,408 (GRCm39)	T552I	probably damaging	Het
Adgrf4	T	C	17: 42,978,003 (GRCm39)	I447V	possibly damaging	Het
Akirin2	T	A	4: 34,565,944 (GRCm39)	D178E	probably damaging	Het
Arhgap12	T	C	18: 6,065,709 (GRCm39)	E359G	possibly damaging	Het
Arhgef5	A	C	6: 43,257,216 (GRCm39)	T1256P	probably damaging	Het
Avpr1a	A	C	10: 122,285,283 (GRCm39)	I192L	possibly damaging	Het
B4galnt4	A	G	7: 140,651,197 (GRCm39)	H926R	probably damaging	Het
Bean1	CT	C	8: 104,908,664 (GRCm39)		probably null	Het
Ccdc68	C	T	18: 70,089,123 (GRCm39)	A222V	probably benign	Het
Cdc23	T	C	18: 34,774,394 (GRCm39)	Y295C	probably benign	Het
Ceacam10	T	C	7: 24,480,432 (GRCm39)	Y188H	unknown	Het
Cfap57	T	A	4: 118,456,162 (GRCm39)	T511S	probably benign	Het
Cftr	T	C	6: 18,221,623 (GRCm39)	V245A	probably benign	Het
Cit	A	G	5: 116,064,633 (GRCm39)	D505G	probably damaging	Het
Cmah	T	G	13: 24,652,539 (GRCm39)	N556K	probably benign	Het
Cspg4b	T	C	13: 113,478,964 (GRCm39)	S1503P		Het
D430041D05Rik	C	A	2: 104,044,482 (GRCm39)	D839Y	probably damaging	Het
Dek	T	C	13: 47,259,065 (GRCm39)	D47G	unknown	Het
Des	C	T	1: 75,337,596 (GRCm39)	R179C	probably damaging	Het
Desi2	A	G	1: 178,015,509 (GRCm39)	N10D	probably benign	Het
Dlg5	T	C	14: 24,214,615 (GRCm39)	N679S	probably damaging	Het
Dnajc24	T	C	2: 105,832,293 (GRCm39)	Y30C	probably damaging	Het
Dock10	T	A	1: 80,687,065 (GRCm39)	H34L	probably benign	Het
Dock5	A	G	14: 68,003,337 (GRCm39)	V1586A	probably benign	Het
Dpy19l4	A	G	4: 11,273,125 (GRCm39)	V576A	probably benign	Het
Dusp6	A	G	10: 99,099,927 (GRCm39)	E125G	probably benign	Het
Dync1h1	T	C	12: 110,591,036 (GRCm39)	Y1035H	probably benign	Het
Dysf	G	A	6: 84,172,306 (GRCm39)		probably null	Het
En1	A	G	1: 120,534,817 (GRCm39)	K369E	unknown	Het
F2r	A	G	13: 95,741,194 (GRCm39)	Y114H	probably damaging	Het
Fam184a	T	C	10: 53,575,318 (GRCm39)	Y97C	probably damaging	Het
Fggy	T	C	4: 95,657,717 (GRCm39)	V286A	probably benign	Het
Flot2	T	C	11: 77,949,383 (GRCm39)	I322T	probably benign	Het
Fndc1	A	T	17: 8,032,318 (GRCm39)		probably null	Het
Frs3	A	G	17: 48,010,450 (GRCm39)	D28G	probably damaging	Het
Gimap3	C	T	6: 48,742,280 (GRCm39)	D217N	probably benign	Het
Gm128	A	G	3: 95,147,934 (GRCm39)	V120A	probably benign	Het
Gm17190	T	C	13: 96,218,970 (GRCm39)	V102A	probably damaging	Het
Gm17268	A	G	11: 81,919,057 (GRCm39)	V20A	unknown	Het
Grsf1	A	T	5: 88,813,423 (GRCm39)		probably null	Het
Hmcn2	A	T	2: 31,278,395 (GRCm39)	Y1699F	probably benign	Het
Hnmt	T	A	2: 23,938,731 (GRCm39)	M36L	probably benign	Het
Hoxd1	C	A	2: 74,594,447 (GRCm39)	T234K	probably damaging	Het
Hydin	C	G	8: 111,232,733 (GRCm39)	S1679R	probably damaging	Het
Jag1	T	C	2: 136,926,226 (GRCm39)	R1059G	probably benign	Het
Kbtbd11	T	C	8: 15,078,858 (GRCm39)	W486R	probably damaging	Het
Kcnh6	A	G	11: 105,909,789 (GRCm39)	D438G	possibly damaging	Het
Lgals4	T	G	7: 28,540,724 (GRCm39)	F276V	probably benign	Het
Lrp6	G	T	6: 134,427,923 (GRCm39)	Y1556*	probably null	Het
Mpdz	G	A	4: 81,274,632 (GRCm39)	L855F	probably benign	Het
Muc16	A	T	9: 18,554,316 (GRCm39)	D3992E	unknown	Het
Nsfl1c	A	G	2: 151,336,279 (GRCm39)	T18A	probably benign	Het
Or12e8	T	A	2: 87,188,555 (GRCm39)	L256I	possibly damaging	Het
Or12k5	A	T	2: 36,895,449 (GRCm39)	M59K	probably damaging	Het
Or2g7	G	A	17: 38,378,506 (GRCm39)	W148*	probably null	Het
Or8g31-ps1	T	C	9: 39,276,775 (GRCm39)	*307R	probably null	Het
Pcdh15	A	T	10: 74,420,048 (GRCm39)	K1235N	probably damaging	Het
Pcif1	A	G	2: 164,726,251 (GRCm39)	K51E	probably damaging	Het
Pde1b	G	A	15: 103,429,752 (GRCm39)	D82N	probably damaging	Het
Phf23	T	A	11: 69,889,467 (GRCm39)	V167E	possibly damaging	Het
Pik3c2g	T	C	6: 139,913,620 (GRCm39)	V1006A	unknown	Het
Pira12	T	A	7: 3,901,103 (GRCm39)		probably benign	Het
Pkhd1l1	G	T	15: 44,452,882 (GRCm39)	V3936F	probably damaging	Het
Pnpla1	T	C	17: 29,100,159 (GRCm39)	V342A	probably benign	Het
Ppip5k1	T	C	2: 121,171,329 (GRCm39)	D620G	possibly damaging	Het
Ppl	A	G	16: 4,907,205 (GRCm39)	L1030P	possibly damaging	Het
Prelid1	A	T	13: 55,469,088 (GRCm39)		probably benign	Het
Racgap1	C	T	15: 99,529,081 (GRCm39)	S264N	probably benign	Het
Rdh13	T	C	7: 4,430,696 (GRCm39)	D289G	probably benign	Het
Rtp3	T	C	9: 110,815,364 (GRCm39)	I334V	probably benign	Het
Setd2	A	T	9: 110,392,012 (GRCm39)	D200V		Het
Simc1	A	G	13: 54,651,731 (GRCm39)	S15G	unknown	Het
Sirpb1c	A	T	3: 15,887,389 (GRCm39)	M150K	probably benign	Het
Smoc1	T	A	12: 81,197,475 (GRCm39)	D202E	probably damaging	Het
Spata31d1b	A	G	13: 59,860,304 (GRCm39)	Y59C	probably damaging	Het
Stard9	A	G	2: 120,528,761 (GRCm39)	T1673A	probably damaging	Het
Tbc1d31	T	A	15: 57,779,504 (GRCm39)	H72Q	probably benign	Het
Tgfbrap1	C	A	1: 43,114,693 (GRCm39)	V136L	probably damaging	Het
Top2b	A	G	14: 16,407,376 (GRCm38)	N720S	probably null	Het
Vmn1r11	T	C	6: 57,115,184 (GRCm39)	S283P	probably damaging	Het
Vmn1r19	A	G	6: 57,382,080 (GRCm39)	H211R	probably damaging	Het
Vmn2r44	A	T	7: 8,370,538 (GRCm39)	M836K	probably benign	Het
Vmn2r61	A	C	7: 41,915,407 (GRCm39)	H118P	probably benign	Het
Vps33a	A	G	5: 123,696,696 (GRCm39)	I319T	probably benign	Het
Vwf	T	A	6: 125,543,220 (GRCm39)	S151T		Het
Zfp423	T	C	8: 88,508,871 (GRCm39)	N491S	possibly damaging	Het
Zfp626	T	C	7: 27,507,660 (GRCm39)	F23S	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
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'- AGGGAATACGCGGTAGTCAC -3'
(R):5'- TCTCAGCTGTGCATCATGTTTG -3'

Sequencing Primer
(F):5'- GGTAGTCACTCCCCTTAGAACG -3'
(R):5'- AACAATAGCGGCCGTGC -3'

Posted On

2019-09-13