Incidental Mutation 'R6721:Ctsd'
| ID |
529588 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Ctsd
|
| Ensembl Gene |
ENSMUSG00000007891 |
| Gene Name |
cathepsin D |
| Synonyms |
CatD, CD |
| MMRRC Submission |
044839-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R6721 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
7 |
| Chromosomal Location |
141929647-141941564 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
G to A
at 141930590 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Proline to Serine
at position 349
(P349S)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000121203
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000059223]
[ENSMUST00000066401]
[ENSMUST00000084412]
[ENSMUST00000105988]
[ENSMUST00000151120]
|
| AlphaFold |
P18242 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000059223
|
| SMART Domains |
Protein: ENSMUSP00000062728
Gene: ENSMUSG00000045777
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Dispanin
|
38 |
108 |
6.5e-12 |
PFAM |
|
| Predicted Effect |
unknown
Transcript: ENSMUST00000066401
AA Change: P343S
|
| SMART Domains |
Protein: ENSMUSP00000063904
Gene: ENSMUSG00000007891
AA Change: P343S
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:A1_Propeptide
|
21 |
49 |
1.7e-11 |
PFAM |
|
Pfam:Asp
|
78 |
274 |
1.6e-75 |
PFAM |
|
Pfam:TAXi_N
|
79 |
246 |
2.5e-11 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000084412
|
| SMART Domains |
Protein: ENSMUSP00000081450
Gene: ENSMUSG00000045777
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Dispanin
|
38 |
121 |
9e-24 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000105988
|
| SMART Domains |
Protein: ENSMUSP00000101608
Gene: ENSMUSG00000045777
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
53 |
74 |
N/A |
INTRINSIC |
|
Pfam:CD225
|
115 |
191 |
2.4e-23 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000123543
|
| Predicted Effect |
unknown
Transcript: ENSMUST00000133843
AA Change: P217S
|
| SMART Domains |
Protein: ENSMUSP00000117247
Gene: ENSMUSG00000110040
AA Change: P217S
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Asp
|
1 |
249 |
4.5e-74 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000140032
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000151120
AA Change: P349S
PolyPhen 2
Score 0.770 (Sensitivity: 0.85; Specificity: 0.92)
|
| SMART Domains |
Protein: ENSMUSP00000121203
Gene: ENSMUSG00000007891
AA Change: P349S
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
20 |
N/A |
INTRINSIC |
|
Pfam:A1_Propeptide
|
21 |
48 |
6.9e-11 |
PFAM |
|
Pfam:Asp
|
78 |
407 |
4.7e-123 |
PFAM |
|
Pfam:TAXi_N
|
79 |
247 |
2.1e-10 |
PFAM |
|
Pfam:TAXi_C
|
326 |
406 |
6.4e-9 |
PFAM |
|
| Predicted Effect |
unknown
Transcript: ENSMUST00000209263
AA Change: P149S
|
| Meta Mutation Damage Score |
0.3333 |
| Coding Region Coverage |
- 1x: 99.9%
- 3x: 99.6%
- 10x: 98.2%
- 20x: 95.0%
|
| Validation Efficiency |
100% (44/44) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the A1 family of peptidases. The encoded preproprotein is proteolytically processed to generate multiple protein products. These products include the cathepsin D light and heavy chains, which heterodimerize to form the mature enzyme. This enzyme exhibits pepsin-like activity and plays a role in protein turnover and in the proteolytic activation of hormones and growth factors. Mutations in this gene play a causal role in neuronal ceroid lipofuscinosis-10 and may be involved in the pathogenesis of several other diseases, including breast cancer and possibly Alzheimer's disease. [provided by RefSeq, Nov 2015]
PHENOTYPE: Mice homozygous for a null mutation die in a state of anorexia at ~P26, displaying severe atrophy of the intestinal mucosa, and massive destruction of the thymus and spleen with loss of T and B cells; near the terminal stage, affected mice have seizures,display retinal atrophy, and become blind. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 44 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Adgrv1 |
A |
G |
13: 81,629,634 (GRCm39) |
L3588S |
probably benign |
Het |
| Ankrd27 |
T |
C |
7: 35,311,976 (GRCm39) |
F402S |
probably damaging |
Het |
| Aplp1 |
T |
C |
7: 30,139,720 (GRCm39) |
Q359R |
probably null |
Het |
| Arhgef10l |
T |
C |
4: 140,297,655 (GRCm39) |
Y546C |
probably damaging |
Het |
| Bltp2 |
T |
C |
11: 78,170,625 (GRCm39) |
Y1615H |
probably damaging |
Het |
| Cd46 |
T |
C |
1: 194,765,939 (GRCm39) |
Y142C |
probably damaging |
Het |
| Cfap418 |
A |
G |
4: 10,874,744 (GRCm39) |
N44D |
probably benign |
Het |
| Chd3 |
T |
C |
11: 69,260,045 (GRCm39) |
|
probably benign |
Het |
| Cmtm2b |
A |
G |
8: 105,049,077 (GRCm39) |
S31G |
possibly damaging |
Het |
| CN725425 |
A |
G |
15: 91,115,821 (GRCm39) |
K21R |
possibly damaging |
Het |
| Cngb1 |
T |
C |
8: 95,997,516 (GRCm39) |
T560A |
probably benign |
Het |
| Creb3l3 |
T |
C |
10: 80,926,977 (GRCm39) |
D151G |
probably damaging |
Het |
| Cts7 |
A |
T |
13: 61,504,108 (GRCm39) |
V124E |
probably damaging |
Het |
| Ern1 |
A |
G |
11: 106,302,478 (GRCm39) |
W459R |
probably damaging |
Het |
| Faxc |
A |
T |
4: 21,982,672 (GRCm39) |
|
probably null |
Het |
| Gabbr1 |
T |
C |
17: 37,365,084 (GRCm39) |
I239T |
probably damaging |
Het |
| Galnt12 |
T |
A |
4: 47,122,529 (GRCm39) |
C269* |
probably null |
Het |
| Gmpr2 |
A |
T |
14: 55,910,191 (GRCm39) |
D7V |
probably damaging |
Het |
| Hivep3 |
T |
A |
4: 119,952,296 (GRCm39) |
I204N |
possibly damaging |
Het |
| Il16 |
A |
T |
7: 83,312,270 (GRCm39) |
|
probably null |
Het |
| Jag1 |
T |
C |
2: 136,936,394 (GRCm39) |
T367A |
probably benign |
Het |
| Lefty2 |
T |
C |
1: 180,722,166 (GRCm39) |
V168A |
probably damaging |
Het |
| Mecom |
T |
C |
3: 30,034,023 (GRCm39) |
E227G |
probably damaging |
Het |
| Muc5ac |
T |
A |
7: 141,352,729 (GRCm39) |
C739S |
possibly damaging |
Het |
| Npy1r |
T |
A |
8: 67,156,941 (GRCm39) |
C120* |
probably null |
Het |
| Nup153 |
A |
G |
13: 46,854,502 (GRCm39) |
V530A |
probably damaging |
Het |
| Ogfr |
T |
A |
2: 180,237,221 (GRCm39) |
L602Q |
possibly damaging |
Het |
| Or10g7 |
C |
T |
9: 39,905,603 (GRCm39) |
P166S |
possibly damaging |
Het |
| Or10h5 |
C |
T |
17: 33,434,508 (GRCm39) |
G270E |
probably benign |
Het |
| Or7e178 |
A |
C |
9: 20,225,576 (GRCm39) |
D213E |
probably benign |
Het |
| Perm1 |
G |
T |
4: 156,302,776 (GRCm39) |
R440L |
probably benign |
Het |
| Plcb4 |
T |
C |
2: 135,752,157 (GRCm39) |
V121A |
probably benign |
Het |
| Plxna4 |
C |
T |
6: 32,177,794 (GRCm39) |
V1036M |
probably benign |
Het |
| Ppl |
A |
T |
16: 4,925,333 (GRCm39) |
M102K |
probably damaging |
Het |
| Prop1 |
T |
C |
11: 50,844,213 (GRCm39) |
S7G |
probably benign |
Het |
| Rabggta |
A |
G |
14: 55,954,660 (GRCm39) |
L507P |
probably damaging |
Het |
| Sfmbt2 |
A |
G |
2: 10,547,836 (GRCm39) |
T473A |
probably damaging |
Het |
| Spc25 |
A |
C |
2: 69,027,517 (GRCm39) |
M125R |
possibly damaging |
Het |
| Taok3 |
T |
C |
5: 117,393,928 (GRCm39) |
M567T |
probably benign |
Het |
| Tlr3 |
A |
G |
8: 45,851,917 (GRCm39) |
Y327H |
probably benign |
Het |
| Tmem209 |
A |
G |
6: 30,497,174 (GRCm39) |
F339L |
probably benign |
Het |
| U2surp |
T |
C |
9: 95,373,157 (GRCm39) |
N279S |
probably damaging |
Het |
| Ythdf3 |
G |
A |
3: 16,258,025 (GRCm39) |
M61I |
possibly damaging |
Het |
| Zfp647 |
T |
C |
15: 76,796,076 (GRCm39) |
I195V |
probably benign |
Het |
|
| Other mutations in Ctsd |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00841:Ctsd
|
APN |
7 |
141,936,418 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01963:Ctsd
|
APN |
7 |
141,930,336 (GRCm39) |
critical splice donor site |
probably null |
|
|
IGL02021:Ctsd
|
APN |
7 |
141,939,213 (GRCm39) |
missense |
probably damaging |
0.99 |
|
twiggy
|
UTSW |
7 |
141,930,881 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5161:Ctsd
|
UTSW |
7 |
141,930,881 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5533:Ctsd
|
UTSW |
7 |
141,931,070 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5762:Ctsd
|
UTSW |
7 |
141,937,266 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5933:Ctsd
|
UTSW |
7 |
141,930,316 (GRCm39) |
missense |
probably benign |
0.00 |
|
R6031:Ctsd
|
UTSW |
7 |
141,930,451 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6365:Ctsd
|
UTSW |
7 |
141,939,314 (GRCm39) |
missense |
probably benign |
0.37 |
|
R7426:Ctsd
|
UTSW |
7 |
141,937,278 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R7499:Ctsd
|
UTSW |
7 |
141,937,149 (GRCm39) |
splice site |
probably null |
|
|
R7829:Ctsd
|
UTSW |
7 |
141,930,879 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8322:Ctsd
|
UTSW |
7 |
141,939,197 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R9242:Ctsd
|
UTSW |
7 |
141,937,280 (GRCm39) |
critical splice acceptor site |
probably null |
|
|
R9423:Ctsd
|
UTSW |
7 |
141,939,212 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9601:Ctsd
|
UTSW |
7 |
141,936,373 (GRCm39) |
missense |
probably damaging |
1.00 |
|
X0025:Ctsd
|
UTSW |
7 |
141,930,581 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Z1088:Ctsd
|
UTSW |
7 |
141,930,334 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- ATGAAGACATCGCCCAGGATC -3'
(R):5'- TCTTATCCAGGGTGAGGTAAGC -3'
Sequencing Primer
(F):5'- ATCGCCCAGGATCCAGAG -3'
(R):5'- CTTATCCAGGGTGAGGTAAGCTACTG -3'
|
| Posted On |
2018-08-01 |
Incidental Mutation