Mutagenetix > Incidental Mutation

Incidental Mutation 'R0048:Ncstn'

16202

Institutional Source

Beutler Lab

Gene Symbol

Ncstn

Ensembl Gene

ENSMUSG00000003458

Gene Name

nicastrin

Synonyms

D1Dau13e, 9430068N19Rik, Nct, nicastrin

MMRRC Submission

038342-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0048 (G1)

Quality Score

Status

Validated

Chromosome

Chromosomal Location

171893580-171910356 bp(-) (GRCm39)

Type of Mutation

splice site

DNA Base Change (assembly)

A to G at 171897528 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000120663 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000003550] [ENSMUST00000140643] [ENSMUST00000146137]

AlphaFold

P57716

Predicted Effect

probably benign
Transcript: ENSMUST00000003550

SMART Domains

Protein: ENSMUSP00000003550
Gene: ENSMUSG00000003458

Domain	Start	End	E-Value	Type
signal peptide	1	32	N/A	INTRINSIC
Pfam:Peptidase_M28	254	468	2.9e-7	PFAM
Pfam:Nicastrin	273	498	1.6e-94	PFAM
transmembrane domain	669	691	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000122986

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000135928

Predicted Effect

probably benign
Transcript: ENSMUST00000140643

SMART Domains

Protein: ENSMUSP00000119128
Gene: ENSMUSG00000003458

Domain	Start	End	E-Value	Type
signal peptide	1	32	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000146137

SMART Domains

Protein: ENSMUSP00000120663
Gene: ENSMUSG00000003458

Domain	Start	End	E-Value	Type
signal peptide	1	32	N/A	INTRINSIC

Coding Region Coverage

1x: 90.1%
3x: 87.7%
10x: 82.5%
20x: 75.5%

Validation Efficiency

94% (92/98)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a type I transmembrane glycoprotein that is an integral component of the multimeric gamma-secretase complex. The encoded protein cleaves integral membrane proteins, including Notch receptors and beta-amyloid precursor protein, and may be a stabilizing cofactor required for gamma-secretase complex assembly. The cleavage of beta-amyloid precursor protein yields amyloid beta peptide, the main component of the neuritic plaque and the hallmark lesion in the brains of patients with Alzheimer's disease; however, the nature of the encoded protein's role in Alzheimer's disease is not known for certain. Mutations in this gene are associated with familial acne inversa. A pseudogene of this gene is present on chromosome 21. Alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Feb 2014]
PHENOTYPE: Homozygous mutant embryos die exhibiting morphological defects of the somites, yolk sac vasculature, neural tube, and pericardial sacs. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 69 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adgrb3	A	G	1: 25,140,563 (GRCm39)	I299T	probably benign	Het
Ankrd12	A	G	17: 66,291,798 (GRCm39)	S1212P	probably damaging	Het
Ankrd50	A	G	3: 38,537,198 (GRCm39)	S52P	probably benign	Het
Aox1	A	G	1: 58,112,371 (GRCm39)	E715G	probably damaging	Het
Arid1b	T	C	17: 5,364,309 (GRCm39)		probably null	Het
Brca1	A	G	11: 101,415,803 (GRCm39)	V777A	possibly damaging	Het
Btaf1	G	T	19: 36,980,924 (GRCm39)	A1582S	probably benign	Het
Cblif	G	A	19: 11,727,120 (GRCm39)	V110M	possibly damaging	Het
Ccdc184	G	A	15: 98,066,341 (GRCm39)	A49T	probably damaging	Het
Cd109	A	C	9: 78,587,303 (GRCm39)	Y657S	possibly damaging	Het
Cfap53	A	T	18: 74,432,244 (GRCm39)	Y44F	probably benign	Het
Cped1	T	A	6: 22,119,601 (GRCm39)	N353K	probably benign	Het
Dcaf10	T	G	4: 45,374,262 (GRCm39)	Y562*	probably null	Het
Eno4	T	C	19: 58,952,970 (GRCm39)	M328T	possibly damaging	Het
Etv3l	T	C	3: 87,462,275 (GRCm39)		noncoding transcript	Het
Eya2	T	A	2: 165,557,931 (GRCm39)	Y176N	probably damaging	Het
Fat2	G	T	11: 55,200,865 (GRCm39)	H736Q	probably benign	Het
Fgfr2	A	T	7: 129,782,218 (GRCm39)		probably benign	Het
Grhl1	A	T	12: 24,662,150 (GRCm39)		probably benign	Het
H60b	T	A	10: 22,163,130 (GRCm39)	M235K	probably benign	Het
Hal	T	A	10: 93,334,853 (GRCm39)	Y395N	probably damaging	Het
Hmcn2	T	C	2: 31,318,249 (GRCm39)	S3865P	possibly damaging	Het
Inpp5j	A	G	11: 3,451,417 (GRCm39)	V463A	probably damaging	Het
Iqgap3	A	T	3: 88,023,256 (GRCm39)	T516S	probably benign	Het
Itpr2	T	C	6: 146,133,789 (GRCm39)		probably null	Het
Jmjd4	C	A	11: 59,344,778 (GRCm39)	H244N	probably benign	Het
Klkb1	G	A	8: 45,742,233 (GRCm39)		probably benign	Het
Loxhd1	A	T	18: 77,496,474 (GRCm39)	Y1578F	probably damaging	Het
Lrp2	A	T	2: 69,295,971 (GRCm39)	D3379E	probably damaging	Het
Lrrfip1	C	T	1: 91,021,369 (GRCm39)		probably benign	Het
Mblac1	A	G	5: 138,192,727 (GRCm39)	Y23C	probably damaging	Het
Mfsd12	G	A	10: 81,198,648 (GRCm39)	V380I	possibly damaging	Het
Mroh9	G	A	1: 162,890,056 (GRCm39)	T227M	probably damaging	Het
Mtor	C	T	4: 148,623,338 (GRCm39)	Q2063*	probably null	Het
Nek9	T	C	12: 85,348,673 (GRCm39)	T954A	probably benign	Het
Nlrc5	A	T	8: 95,201,284 (GRCm39)	Y126F	possibly damaging	Het
Nr1d1	A	G	11: 98,661,304 (GRCm39)	S321P	probably benign	Het
Or13c3	C	A	4: 52,856,196 (GRCm39)	A106S	probably damaging	Het
Pkn2	T	C	3: 142,516,588 (GRCm39)	I513V	probably damaging	Het
Pls1	T	C	9: 95,669,116 (GRCm39)	E35G	probably damaging	Het
Polr3a	A	G	14: 24,519,323 (GRCm39)		probably benign	Het
Ptgfr	A	G	3: 151,540,728 (GRCm39)	V260A	possibly damaging	Het
Rabgap1l	A	G	1: 160,454,939 (GRCm39)		probably benign	Het
Raph1	T	C	1: 60,539,764 (GRCm39)	K423E	probably benign	Het
Rbm27	A	G	18: 42,431,529 (GRCm39)	D112G	probably benign	Het
Rbm46	A	T	3: 82,771,537 (GRCm39)	S359R	probably damaging	Het
Rhobtb3	A	T	13: 76,050,364 (GRCm39)	*100R	probably null	Het
Ryr2	T	C	13: 11,610,670 (GRCm39)	E4052G	probably damaging	Het
Sart3	G	T	5: 113,893,458 (GRCm39)	D346E	possibly damaging	Het
Sgsm1	A	G	5: 113,416,616 (GRCm39)	F629S	probably damaging	Het
Siglec1	T	C	2: 130,915,317 (GRCm39)	T1425A	possibly damaging	Het
Slc12a2	A	T	18: 58,048,594 (GRCm39)		probably benign	Het
Slc38a10	G	T	11: 120,001,138 (GRCm39)	P561T	probably benign	Het
Slc45a4	A	G	15: 73,477,285 (GRCm39)		probably benign	Het
Snx25	A	T	8: 46,558,146 (GRCm39)		probably benign	Het
Son	T	A	16: 91,455,865 (GRCm39)	H1537Q	possibly damaging	Het
Synpo2l	A	T	14: 20,716,340 (GRCm39)		probably benign	Het
Tarbp1	A	G	8: 127,174,269 (GRCm39)	Y846H	probably damaging	Het
Tgfb1	T	A	7: 25,393,779 (GRCm39)		probably benign	Het
Tigd2	C	A	6: 59,188,369 (GRCm39)	T412K	possibly damaging	Het
Umodl1	A	T	17: 31,187,451 (GRCm39)	N172Y	probably damaging	Het
Urah	C	T	7: 140,416,665 (GRCm39)	T46I	probably damaging	Het
Usp8	C	T	2: 126,579,809 (GRCm39)	P353L	probably damaging	Het
Vamp2	A	G	11: 68,980,585 (GRCm39)	D51G	possibly damaging	Het
Vps13a	A	T	19: 16,653,504 (GRCm39)	V1959E	probably damaging	Het
Wdr76	C	T	2: 121,365,900 (GRCm39)		probably benign	Het
Zbtb38	C	T	9: 96,569,729 (GRCm39)	V452M	probably damaging	Het
Zbtb41	A	G	1: 139,369,572 (GRCm39)	K650E	probably damaging	Het
Zfp532	A	G	18: 65,777,404 (GRCm39)	Y887C	probably damaging	Het

Other mutations in Ncstn

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00737:Ncstn	APN	1	171,901,968 (GRCm39)	missense	probably benign	0.02
IGL02030:Ncstn	APN	1	171,900,024 (GRCm39)	splice site	probably benign
IGL02470:Ncstn	APN	1	171,910,166 (GRCm39)	critical splice donor site	probably null
IGL02498:Ncstn	APN	1	171,896,159 (GRCm39)	missense	probably benign
morel	UTSW	1	171,900,043 (GRCm39)	missense	probably damaging	0.99
Pig	UTSW	1	171,899,092 (GRCm39)	missense	probably damaging	1.00
truffle	UTSW	1	171,897,576 (GRCm39)	missense	probably damaging	1.00
R0480:Ncstn	UTSW	1	171,910,159 (GRCm39)	splice site	probably benign
R0648:Ncstn	UTSW	1	171,895,454 (GRCm39)	missense	probably benign	0.01
R0792:Ncstn	UTSW	1	171,899,072 (GRCm39)	missense	possibly damaging	0.95
R1330:Ncstn	UTSW	1	171,899,092 (GRCm39)	missense	probably damaging	1.00
R1524:Ncstn	UTSW	1	171,899,716 (GRCm39)	missense	possibly damaging	0.58
R1660:Ncstn	UTSW	1	171,894,339 (GRCm39)	missense	possibly damaging	0.78
R1828:Ncstn	UTSW	1	171,899,038 (GRCm39)	frame shift	probably null
R1892:Ncstn	UTSW	1	171,899,038 (GRCm39)	frame shift	probably null
R1907:Ncstn	UTSW	1	171,899,710 (GRCm39)	missense	probably damaging	0.97
R3722:Ncstn	UTSW	1	171,895,462 (GRCm39)	missense	possibly damaging	0.50
R3876:Ncstn	UTSW	1	171,897,640 (GRCm39)	missense	probably benign	0.02
R3946:Ncstn	UTSW	1	171,895,061 (GRCm39)	missense	probably benign	0.00
R3969:Ncstn	UTSW	1	171,897,576 (GRCm39)	missense	probably damaging	1.00
R4108:Ncstn	UTSW	1	171,900,111 (GRCm39)	missense	probably damaging	1.00
R4597:Ncstn	UTSW	1	171,895,823 (GRCm39)	nonsense	probably null
R4998:Ncstn	UTSW	1	171,899,087 (GRCm39)	missense	possibly damaging	0.81
R5037:Ncstn	UTSW	1	171,896,193 (GRCm39)	missense	probably damaging	1.00
R5150:Ncstn	UTSW	1	171,895,151 (GRCm39)	intron	probably benign
R5406:Ncstn	UTSW	1	171,899,731 (GRCm39)	missense	probably benign	0.00
R5444:Ncstn	UTSW	1	171,900,406 (GRCm39)	missense	possibly damaging	0.92
R5605:Ncstn	UTSW	1	171,908,717 (GRCm39)	intron	probably benign
R6675:Ncstn	UTSW	1	171,899,095 (GRCm39)	missense	probably damaging	1.00
R7268:Ncstn	UTSW	1	171,908,830 (GRCm39)	missense	possibly damaging	0.86
R7290:Ncstn	UTSW	1	171,900,373 (GRCm39)	missense	probably benign
R7871:Ncstn	UTSW	1	171,903,023 (GRCm39)	missense	probably benign	0.00
R8238:Ncstn	UTSW	1	171,900,043 (GRCm39)	missense	probably damaging	0.99
R9462:Ncstn	UTSW	1	171,899,707 (GRCm39)	missense	probably damaging	1.00

Posted On

2013-01-08