Incidental Mutation 'R3946:Ncstn'
ID |
307684 |
Institutional Source |
Beutler Lab
|
Gene Symbol |
Ncstn
|
Ensembl Gene |
ENSMUSG00000003458 |
Gene Name |
nicastrin |
Synonyms |
D1Dau13e, 9430068N19Rik, Nct, nicastrin |
MMRRC Submission |
040827-MU
|
Accession Numbers |
|
Essential gene? |
Essential
(E-score: 1.000)
|
Stock # |
R3946 (G1)
|
Quality Score |
223 |
Status
|
Validated
|
Chromosome |
1 |
Chromosomal Location |
171893580-171910356 bp(-) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
T to C
at 171895061 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Glutamic Acid to Glycine
at position 614
(E614G)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000003550
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000003550]
[ENSMUST00000140643]
[ENSMUST00000146137]
|
AlphaFold |
P57716 |
Predicted Effect |
probably benign
Transcript: ENSMUST00000003550
AA Change: E614G
PolyPhen 2
Score 0.004 (Sensitivity: 0.98; Specificity: 0.59)
|
SMART Domains |
Protein: ENSMUSP00000003550 Gene: ENSMUSG00000003458 AA Change: E614G
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 |
|
Meta Mutation Damage Score |
0.0898 |
Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.6%
- 10x: 97.0%
- 20x: 94.1%
|
Validation Efficiency |
98% (60/61) |
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: 61 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
Abi2 |
A |
G |
1: 60,492,913 (GRCm39) |
Q328R |
probably damaging |
Het |
Agr3 |
C |
A |
12: 35,997,512 (GRCm39) |
|
probably benign |
Het |
Brca2 |
T |
A |
5: 150,460,169 (GRCm39) |
S481R |
probably damaging |
Het |
Cabin1 |
T |
G |
10: 75,581,093 (GRCm39) |
Q411P |
probably damaging |
Het |
Calr3 |
A |
G |
8: 73,197,464 (GRCm39) |
Y22H |
probably damaging |
Het |
Caprin1 |
T |
A |
2: 103,627,111 (GRCm39) |
I59F |
probably damaging |
Het |
Cdk5rap1 |
T |
C |
2: 154,190,636 (GRCm39) |
T442A |
probably damaging |
Het |
Chn2 |
T |
C |
6: 54,246,411 (GRCm39) |
|
probably benign |
Het |
Cic |
C |
A |
7: 24,971,771 (GRCm39) |
R501S |
possibly damaging |
Het |
Coch |
A |
G |
12: 51,648,595 (GRCm39) |
|
probably null |
Het |
Defa25 |
G |
A |
8: 21,574,506 (GRCm39) |
V17I |
probably null |
Het |
Dglucy |
T |
C |
12: 100,804,959 (GRCm39) |
|
probably null |
Het |
Dtx1 |
T |
G |
5: 120,819,351 (GRCm39) |
T616P |
possibly damaging |
Het |
Eef1g |
T |
C |
19: 8,947,341 (GRCm39) |
L171P |
probably benign |
Het |
Fam135a |
A |
G |
1: 24,069,475 (GRCm39) |
S465P |
probably damaging |
Het |
Gm14412 |
A |
T |
2: 177,006,478 (GRCm39) |
C472* |
probably null |
Het |
Gm7104 |
T |
C |
12: 88,252,812 (GRCm39) |
|
noncoding transcript |
Het |
Got2 |
A |
G |
8: 96,614,858 (GRCm39) |
S26P |
probably benign |
Het |
H2-M11 |
A |
G |
17: 36,860,123 (GRCm39) |
I329M |
probably damaging |
Het |
Hmcn2 |
T |
A |
2: 31,272,406 (GRCm39) |
D1295E |
possibly damaging |
Het |
Hoxd12 |
G |
T |
2: 74,505,771 (GRCm39) |
R114L |
probably damaging |
Het |
Ilkap |
A |
C |
1: 91,314,972 (GRCm39) |
D124E |
probably damaging |
Het |
Maco1 |
A |
G |
4: 134,531,792 (GRCm39) |
Y626H |
probably damaging |
Het |
Med6 |
T |
C |
12: 81,628,625 (GRCm39) |
Y88C |
probably damaging |
Het |
Mep1a |
A |
T |
17: 43,785,932 (GRCm39) |
L719* |
probably null |
Het |
Mmp23 |
T |
C |
4: 155,736,480 (GRCm39) |
Y187C |
probably damaging |
Het |
Myo1g |
A |
G |
11: 6,470,760 (GRCm39) |
M32T |
possibly damaging |
Het |
Nr2c2 |
C |
T |
6: 92,140,119 (GRCm39) |
R464W |
probably damaging |
Het |
Or4f15 |
G |
A |
2: 111,813,642 (GRCm39) |
T259M |
possibly damaging |
Het |
Otub2 |
T |
A |
12: 103,359,085 (GRCm39) |
L58* |
probably null |
Het |
Pcdhga12 |
G |
A |
18: 37,900,682 (GRCm39) |
V505I |
probably benign |
Het |
Pcdhga9 |
T |
A |
18: 37,870,897 (GRCm39) |
V242D |
probably damaging |
Het |
Pex1 |
C |
T |
5: 3,676,084 (GRCm39) |
L891F |
probably damaging |
Het |
Pgm2 |
C |
T |
5: 64,269,404 (GRCm39) |
T497I |
probably benign |
Het |
Pikfyve |
T |
C |
1: 65,235,840 (GRCm39) |
F171L |
probably damaging |
Het |
Pilrb1 |
T |
G |
5: 137,855,654 (GRCm39) |
K79T |
probably benign |
Het |
Pin1 |
C |
T |
9: 20,566,660 (GRCm39) |
R21W |
probably damaging |
Het |
Prxl2c |
T |
C |
13: 64,456,912 (GRCm39) |
I104V |
probably damaging |
Het |
Ptprq |
A |
G |
10: 107,522,253 (GRCm39) |
|
probably benign |
Het |
Rad17 |
G |
A |
13: 100,759,371 (GRCm39) |
A552V |
possibly damaging |
Het |
Rbbp8 |
A |
G |
18: 11,851,925 (GRCm39) |
T249A |
probably benign |
Het |
Rtkn |
A |
T |
6: 83,112,957 (GRCm39) |
I10F |
probably benign |
Het |
Scube2 |
T |
A |
7: 109,456,797 (GRCm39) |
I103F |
possibly damaging |
Het |
Sec23b |
A |
G |
2: 144,423,893 (GRCm39) |
H514R |
probably benign |
Het |
Serbp1 |
T |
A |
6: 67,249,204 (GRCm39) |
D223E |
probably benign |
Het |
Slc14a1 |
C |
A |
18: 78,154,607 (GRCm39) |
V260L |
probably benign |
Het |
Slc22a23 |
A |
G |
13: 34,367,109 (GRCm39) |
I633T |
probably damaging |
Het |
Stk19 |
A |
T |
17: 35,043,723 (GRCm39) |
|
probably benign |
Het |
Svs5 |
T |
C |
2: 164,079,047 (GRCm39) |
M287V |
probably benign |
Het |
Syne3 |
T |
A |
12: 104,924,325 (GRCm39) |
Q358L |
probably damaging |
Het |
Synj1 |
A |
G |
16: 90,806,984 (GRCm39) |
F58L |
possibly damaging |
Het |
Tg |
T |
C |
15: 66,545,872 (GRCm39) |
V198A |
probably damaging |
Het |
Tle4 |
A |
T |
19: 14,574,752 (GRCm39) |
Y9N |
probably damaging |
Het |
Tmx3 |
G |
A |
18: 90,542,459 (GRCm39) |
A186T |
possibly damaging |
Het |
Traf3 |
G |
A |
12: 111,221,679 (GRCm39) |
S280N |
possibly damaging |
Het |
Trmt13 |
A |
G |
3: 116,375,167 (GRCm39) |
F447S |
probably damaging |
Het |
Trp53bp1 |
T |
A |
2: 121,059,107 (GRCm39) |
H918L |
probably damaging |
Het |
Ush2a |
T |
G |
1: 188,460,701 (GRCm39) |
V2654G |
probably benign |
Het |
Vinac1 |
A |
G |
2: 128,881,521 (GRCm39) |
L135P |
probably damaging |
Het |
Vmn2r25 |
A |
G |
6: 123,817,057 (GRCm39) |
Y175H |
probably damaging |
Het |
Zfp335 |
T |
C |
2: 164,734,109 (GRCm39) |
D1330G |
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 |
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 |
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'- TCTGGGGACAAATGAGCAAC -3'
(R):5'- TGGGATGAAGAGTTGCAGCC -3'
Sequencing Primer
(F):5'- CTGACAGACCACAGGCAGG -3'
(R):5'- TGAAGAGTTGCAGCCAGTTG -3'
|
Posted On |
2015-04-17 |