Mutagenetix > Incidental Mutation

Incidental Mutation 'R1660:Ncstn'

186635

Institutional Source

Beutler Lab

Gene Symbol

Ncstn

Ensembl Gene

ENSMUSG00000003458

Gene Name

nicastrin

Synonyms

D1Dau13e, 9430068N19Rik, Nct, nicastrin

MMRRC Submission

039696-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1660 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

171893580-171910356 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 171894339 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Cysteine at position 677 (S677C)

Ref Sequence

ENSEMBL: ENSMUSP00000003550 (fasta)

Gene Model

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

AlphaFold

P57716

Predicted Effect

possibly damaging
Transcript: ENSMUST00000003550
AA Change: S677C

PolyPhen 2 Score 0.783 (Sensitivity: 0.85; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000003550
Gene: ENSMUSG00000003458
AA Change: S677C

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: 99.1%
3x: 98.4%
10x: 96.4%
20x: 92.9%

Validation Efficiency

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: 66 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A1cf	C	A	19: 31,870,507 (GRCm39)	S3*	probably null	Het
Adgrv1	C	T	13: 81,624,750 (GRCm39)	V3740I	probably benign	Het
Aida	T	C	1: 183,079,127 (GRCm39)	F22S	probably damaging	Het
Ankrd65	A	T	4: 155,876,528 (GRCm39)	D220V	probably damaging	Het
Antxr2	A	T	5: 98,123,209 (GRCm39)	C279*	probably null	Het
Ap3b1	T	C	13: 94,545,320 (GRCm39)	V191A	probably damaging	Het
Arhgef28	T	C	13: 98,117,884 (GRCm39)	K595E	probably benign	Het
Atp12a	A	G	14: 56,608,305 (GRCm39)	T98A	probably benign	Het
Cdcp1	A	T	9: 123,014,427 (GRCm39)	S116T	probably benign	Het
Chrm1	T	C	19: 8,656,582 (GRCm39)	F429S	possibly damaging	Het
Ckap5	C	A	2: 91,393,303 (GRCm39)	Q395K	possibly damaging	Het
Cntn4	T	A	6: 106,656,258 (GRCm39)	I853K	probably benign	Het
Cyp2g1	G	A	7: 26,509,107 (GRCm39)		probably null	Het
Dhx57	C	T	17: 80,553,157 (GRCm39)	V1257I	possibly damaging	Het
Disp1	A	T	1: 182,869,306 (GRCm39)	V1038D	probably damaging	Het
Dmxl2	A	T	9: 54,358,314 (GRCm39)	S462T	possibly damaging	Het
Dnaaf10	A	T	11: 17,177,183 (GRCm39)	E180D	probably benign	Het
Exoc3l	A	G	8: 106,019,692 (GRCm39)		probably null	Het
Fam210a	T	C	18: 68,409,167 (GRCm39)	T48A	probably benign	Het
Fbxw5	G	A	2: 25,393,286 (GRCm39)		probably null	Het
Fkbp9	T	C	6: 56,850,434 (GRCm39)	C437R	probably damaging	Het
Gpc5	A	G	14: 115,636,691 (GRCm39)	K458R	probably benign	Het
Grik2	C	A	10: 49,120,439 (GRCm39)	G56*	probably null	Het
Igsf10	T	C	3: 59,238,706 (GRCm39)	T492A	probably damaging	Het
Kif1c	C	T	11: 70,619,223 (GRCm39)	L953F	probably damaging	Het
Lrrc51	T	C	7: 101,562,645 (GRCm39)	Y145C	probably damaging	Het
Lsmem1	GTACATACATACATACATACATACATACA	GTACATACATACATACATACATACATACATACA	12: 40,235,260 (GRCm39)		probably null	Het
Mapkbp1	A	T	2: 119,849,029 (GRCm39)	I682F	possibly damaging	Het
Mttp	A	T	3: 137,808,954 (GRCm39)	V718D	probably damaging	Het
Myt1l	T	A	12: 29,945,272 (GRCm39)	D1012E	unknown	Het
Nbn	G	A	4: 15,971,771 (GRCm39)	G301D	probably benign	Het
Nod1	C	A	6: 54,921,218 (GRCm39)		probably null	Het
Nos1ap	A	G	1: 170,342,206 (GRCm39)	V52A	possibly damaging	Het
Or51f2	T	G	7: 102,526,863 (GRCm39)	Y179D	probably damaging	Het
Or52z14	T	A	7: 103,252,882 (GRCm39)	L7*	probably null	Het
Or5b98	T	A	19: 12,931,055 (GRCm39)	I34N	probably damaging	Het
Or5h23	T	A	16: 58,906,706 (GRCm39)	I47F	probably benign	Het
Phf13	T	C	4: 152,076,962 (GRCm39)	I77V	probably benign	Het
Pias2	A	G	18: 77,207,825 (GRCm39)	K230E	probably damaging	Het
Poli	A	G	18: 70,642,535 (GRCm39)	L469P	probably damaging	Het
Prag1	A	T	8: 36,607,177 (GRCm39)	T973S	possibly damaging	Het
Prpf40b	C	A	15: 99,203,442 (GRCm39)	H101Q	probably damaging	Het
Prss50	T	C	9: 110,691,557 (GRCm39)	V287A	possibly damaging	Het
Rbm25	C	T	12: 83,714,924 (GRCm39)		probably benign	Het
Rcor2	T	C	19: 7,246,337 (GRCm39)	V4A	probably damaging	Het
Rnf180	T	C	13: 105,407,499 (GRCm39)	T17A	probably benign	Het
Robo3	A	T	9: 37,340,440 (GRCm39)	V179E	probably damaging	Het
Sacs	T	A	14: 61,446,458 (GRCm39)	S2835T	probably damaging	Het
Serpinb3c	T	A	1: 107,199,432 (GRCm39)	H363L	probably damaging	Het
Setd1a	T	C	7: 127,395,841 (GRCm39)		probably benign	Het
Skp2	A	C	15: 9,125,201 (GRCm39)	V126G	probably benign	Het
Snph	G	A	2: 151,436,398 (GRCm39)	Q108*	probably null	Het
Snrpa1	T	A	7: 65,719,246 (GRCm39)	V144E	probably damaging	Het
Tifab	T	C	13: 56,324,248 (GRCm39)	E65G	probably damaging	Het
Tmem201	A	T	4: 149,804,032 (GRCm39)	Y468N	probably damaging	Het
Tpcn1	T	C	5: 120,687,580 (GRCm39)	N388S	possibly damaging	Het
Tssk4	A	G	14: 55,888,029 (GRCm39)	Q75R	probably null	Het
Tuba4a	T	C	1: 75,192,547 (GRCm39)	N356D	probably benign	Het
Ugt2b5	T	A	5: 87,287,477 (GRCm39)	D230V	probably benign	Het
Ush2a	T	C	1: 188,648,261 (GRCm39)	V4622A	probably benign	Het
Vmn2r11	T	G	5: 109,201,724 (GRCm39)	Y260S	possibly damaging	Het
Vmn2r89	C	A	14: 51,693,693 (GRCm39)	H348N	possibly damaging	Het
Vmn2r96	A	T	17: 18,817,988 (GRCm39)	M714L	probably benign	Het
Zbtb18	T	C	1: 177,275,329 (GRCm39)	S221P	probably benign	Het
Zfp418	A	G	7: 7,184,789 (GRCm39)	T251A	probably benign	Het
Zmynd15	A	G	11: 70,354,328 (GRCm39)	Y267C	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
R0048:Ncstn	UTSW	1	171,897,528 (GRCm39)	splice site	probably benign
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
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

Predicted Primers

PCR Primer
(F):5'- GTGTGTCAATCCCCGTCTAAGCAG -3'
(R):5'- AGCAGAACCAGTGCAGTGTGTG -3'

Sequencing Primer
(F):5'- CAGTCCAGTGACAAATTAGTGG -3'
(R):5'- GAGCCCCTGTTATAAGTAAGTCAC -3'

Posted On

2014-05-09