Incidental Mutation 'R5037:Ncstn'
| ID |
389557 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Ncstn
|
| Ensembl Gene |
ENSMUSG00000003458 |
| Gene Name |
nicastrin |
| Synonyms |
D1Dau13e, 9430068N19Rik, Nct, nicastrin |
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R5037 (G1)
|
| Quality Score |
225 |
|
Status
|
Not validated
|
| Chromosome |
1 |
| Chromosomal Location |
171893580-171910356 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
C to T
at 171896193 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Arginine to Histidine
at position 495
(R495H)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000003550
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000003550]
[ENSMUST00000140643]
[ENSMUST00000146137]
|
| AlphaFold |
P57716 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000003550
AA Change: R495H
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000003550
Gene: ENSMUSG00000003458
AA Change: R495H
| 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: 99.2%
- 3x: 98.4%
- 10x: 96.6%
- 20x: 93.3%
|
| 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: 50 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Btaf1 |
T |
C |
19: 36,980,931 (GRCm39) |
V1584A |
probably damaging |
Het |
| Ccdc136 |
A |
T |
6: 29,417,122 (GRCm39) |
S648C |
probably damaging |
Het |
| Ccna2 |
A |
G |
3: 36,625,152 (GRCm39) |
|
probably benign |
Het |
| Cdc23 |
C |
A |
18: 34,784,742 (GRCm39) |
V7L |
unknown |
Het |
| Cenpf |
T |
C |
1: 189,416,043 (GRCm39) |
E94G |
probably damaging |
Het |
| Clic1 |
G |
A |
17: 35,274,235 (GRCm39) |
V139I |
probably benign |
Het |
| Coasy |
A |
G |
11: 100,975,648 (GRCm39) |
E327G |
probably damaging |
Het |
| Col6a5 |
C |
T |
9: 105,805,337 (GRCm39) |
E1190K |
unknown |
Het |
| Cyp2c70 |
A |
G |
19: 40,172,441 (GRCm39) |
V67A |
possibly damaging |
Het |
| Dglucy |
A |
G |
12: 100,801,500 (GRCm39) |
S52G |
probably benign |
Het |
| Dync1h1 |
A |
G |
12: 110,607,341 (GRCm39) |
N2644S |
probably benign |
Het |
| Eif4g2 |
A |
T |
7: 110,676,239 (GRCm39) |
N347K |
probably benign |
Het |
| Epha10 |
T |
C |
4: 124,809,178 (GRCm39) |
|
probably benign |
Het |
| Epm2aip1 |
T |
C |
9: 111,101,218 (GRCm39) |
F64L |
probably benign |
Het |
| Eri2 |
G |
A |
7: 119,384,897 (GRCm39) |
L535F |
probably benign |
Het |
| Garin5b |
T |
G |
7: 4,761,575 (GRCm39) |
K379T |
possibly damaging |
Het |
| Gm17430 |
T |
C |
18: 9,726,561 (GRCm39) |
E37G |
probably benign |
Het |
| Heatr5b |
T |
A |
17: 79,131,939 (GRCm39) |
Q388L |
probably benign |
Het |
| Htr1f |
A |
G |
16: 64,746,291 (GRCm39) |
W334R |
probably damaging |
Het |
| Icam4 |
A |
T |
9: 20,940,937 (GRCm39) |
C717* |
probably null |
Het |
| Iqgap1 |
A |
C |
7: 80,383,848 (GRCm39) |
L1072W |
probably damaging |
Het |
| Kbtbd11 |
G |
T |
8: 15,077,886 (GRCm39) |
A162S |
probably benign |
Het |
| Kif13b |
T |
G |
14: 64,996,038 (GRCm39) |
Y941* |
probably null |
Het |
| Kndc1 |
T |
C |
7: 139,490,371 (GRCm39) |
V291A |
possibly damaging |
Het |
| Lrrn3 |
A |
T |
12: 41,503,594 (GRCm39) |
I241N |
probably damaging |
Het |
| Macf1 |
A |
G |
4: 123,349,312 (GRCm39) |
S2387P |
probably damaging |
Het |
| Msh5 |
A |
G |
17: 35,251,369 (GRCm39) |
L451S |
possibly damaging |
Het |
| Mthfd1 |
T |
G |
12: 76,340,914 (GRCm39) |
F258V |
probably damaging |
Het |
| Or4k2 |
T |
G |
14: 50,423,745 (GRCm39) |
T310P |
probably benign |
Het |
| Pkd1l3 |
T |
A |
8: 110,392,268 (GRCm39) |
I1954N |
probably damaging |
Het |
| Ppox |
C |
A |
1: 171,105,169 (GRCm39) |
V340L |
probably damaging |
Het |
| Prkag1 |
T |
C |
15: 98,713,768 (GRCm39) |
T21A |
possibly damaging |
Het |
| Pygo1 |
C |
A |
9: 72,852,199 (GRCm39) |
H129N |
probably damaging |
Het |
| Rad9a |
A |
T |
19: 4,247,173 (GRCm39) |
C271S |
probably benign |
Het |
| Raph1 |
T |
C |
1: 60,535,381 (GRCm39) |
|
probably null |
Het |
| Reln |
A |
G |
5: 22,153,510 (GRCm39) |
F2265L |
probably damaging |
Het |
| Shc4 |
A |
G |
2: 125,471,647 (GRCm39) |
I304T |
probably damaging |
Het |
| Slc35f3 |
T |
A |
8: 127,116,011 (GRCm39) |
L313M |
probably damaging |
Het |
| Spata31g1 |
T |
A |
4: 42,972,195 (GRCm39) |
H509Q |
probably benign |
Het |
| Spef1l |
A |
T |
7: 139,558,587 (GRCm39) |
S3R |
possibly damaging |
Het |
| Sycp2l |
T |
A |
13: 41,283,337 (GRCm39) |
M191K |
possibly damaging |
Het |
| Tmem132c |
C |
A |
5: 127,630,199 (GRCm39) |
Q579K |
probably benign |
Het |
| Trbj2-5 |
A |
G |
6: 41,520,394 (GRCm39) |
|
probably benign |
Het |
| Ttc38 |
A |
G |
15: 85,728,741 (GRCm39) |
E231G |
probably benign |
Het |
| Utp20 |
A |
G |
10: 88,611,192 (GRCm39) |
V1375A |
probably benign |
Het |
| Vcan |
T |
A |
13: 89,852,096 (GRCm39) |
T955S |
probably damaging |
Het |
| Vmn1r89 |
T |
C |
7: 12,953,314 (GRCm39) |
C17R |
possibly damaging |
Het |
| Wnk1 |
A |
G |
6: 119,942,696 (GRCm39) |
|
probably benign |
Het |
| Zfp667 |
T |
G |
7: 6,308,949 (GRCm39) |
I539S |
possibly damaging |
Het |
| Zfp738 |
T |
A |
13: 67,818,320 (GRCm39) |
H557L |
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 |
|
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 |
|
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'- GGGGCATGCTAAATCCCAAAG -3'
(R):5'- ACCAGAGCATTTATGACACGG -3'
Sequencing Primer
(F):5'- CAAAGTTTGGGAAGTTGGCAC -3'
(R):5'- CATTAATGTGACCTATCCTGAGTGGC -3'
|
| Posted On |
2016-06-06 |
Incidental Mutation