Incidental Mutation 'P0005:Mmp17'
| ID |
7616 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Mmp17
|
| Ensembl Gene |
ENSMUSG00000029436 |
| Gene Name |
matrix metallopeptidase 17 |
| Synonyms |
MT4-MMP, membrane type-4 matrix metalloproteinase |
| MMRRC Submission |
038262-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably non essential
(E-score: 0.078)
|
| Stock # |
P0005 (G1)
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
5 |
| Chromosomal Location |
129661233-129688163 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 129673695 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Valine to Alanine
at position 258
(V258A)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000031390
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000031390]
|
| AlphaFold |
Q9R0S3 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000031390
AA Change: V258A
PolyPhen 2
Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)
|
| SMART Domains |
Protein: ENSMUSP00000031390
Gene: ENSMUSG00000029436
AA Change: V258A
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
39 |
N/A |
INTRINSIC |
|
Pfam:PG_binding_1
|
44 |
104 |
5e-15 |
PFAM |
|
ZnMc
|
128 |
295 |
8.26e-47 |
SMART |
|
low complexity region
|
308 |
320 |
N/A |
INTRINSIC |
|
HX
|
340 |
384 |
3.17e-8 |
SMART |
|
HX
|
389 |
432 |
2.59e-13 |
SMART |
|
HX
|
435 |
481 |
6.39e-13 |
SMART |
|
HX
|
483 |
527 |
1.1e-7 |
SMART |
|
low complexity region
|
563 |
578 |
N/A |
INTRINSIC |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000177802
|
| Meta Mutation Damage Score |
0.0894 |
| Coding Region Coverage |
- 1x: 85.5%
- 3x: 80.5%
- 10x: 66.1%
- 20x: 49.6%
|
| Validation Efficiency |
95% (104/109) |
| MGI Phenotype |
FUNCTION: This gene encodes a member of the matrix metalloproteinase family of extracellular matrix-degrading enzymes that are involved in tissue remodeling, wound repair, progression of atherosclerosis and tumor invasion. The encoded preproprotein undergoes proteolytic processing to generate a mature, zinc-dependent endopeptidase enzyme. Mice lacking the encoded protein exhibit dysfunctional vascular smooth muscle cells and altered extracellular matrix in the vessel wall leading to an increased susceptibility to angiotensin-II-induced thoracic aortic aneurysm. [provided by RefSeq, Feb 2016]
PHENOTYPE: Mice homozygous for a reporter allele exhibit normal morphology, clinical chemistry, hematology and behavior. Mice homozygous for a reporter/null allele exhibit normal growth, fertility, and lifespan but show subtle renal developmental defects, hypodipsia, and elevated urine osmolarity. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(2) : Targeted(2)
|
| Other mutations in this stock |
Total: 20 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Atp13a1 |
T |
C |
8: 70,256,397 (GRCm39) |
V845A |
possibly damaging |
Het |
| Casp6 |
T |
C |
3: 129,705,792 (GRCm39) |
V153A |
probably benign |
Het |
| Col6a1 |
A |
G |
10: 76,553,163 (GRCm39) |
|
probably benign |
Het |
| Dars2 |
A |
G |
1: 160,881,509 (GRCm39) |
|
probably null |
Het |
| Hmgcll1 |
T |
A |
9: 75,982,041 (GRCm39) |
M162K |
possibly damaging |
Het |
| Hydin |
A |
T |
8: 111,220,921 (GRCm39) |
|
probably null |
Het |
| Ift74 |
A |
G |
4: 94,550,813 (GRCm39) |
|
probably benign |
Het |
| Itpr1 |
A |
T |
6: 108,358,218 (GRCm39) |
I595F |
probably damaging |
Het |
| Mgat4f |
T |
A |
1: 134,315,646 (GRCm39) |
M15K |
probably benign |
Het |
| Nek6 |
T |
C |
2: 38,459,749 (GRCm39) |
|
probably null |
Het |
| Nomo1 |
A |
T |
7: 45,686,981 (GRCm39) |
|
probably null |
Het |
| Nudt3 |
A |
G |
17: 27,815,689 (GRCm39) |
|
probably benign |
Het |
| Pramel32 |
A |
G |
4: 88,546,187 (GRCm39) |
L385P |
probably damaging |
Het |
| Prkg2 |
A |
C |
5: 99,117,806 (GRCm39) |
F512V |
probably damaging |
Het |
| Ptp4a3 |
T |
A |
15: 73,627,160 (GRCm39) |
D72E |
possibly damaging |
Het |
| Rpgrip1l |
A |
T |
8: 92,025,853 (GRCm39) |
|
probably benign |
Het |
| Rrp9 |
G |
A |
9: 106,358,376 (GRCm39) |
R101H |
probably benign |
Het |
| Slc7a6os |
T |
C |
8: 106,931,154 (GRCm39) |
I161V |
probably benign |
Het |
| Tex15 |
T |
C |
8: 34,060,896 (GRCm39) |
F109L |
probably benign |
Het |
| Tns2 |
A |
G |
15: 102,022,491 (GRCm39) |
Q1188R |
probably damaging |
Het |
|
| Other mutations in Mmp17 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01473:Mmp17
|
APN |
5 |
129,683,472 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL01602:Mmp17
|
APN |
5 |
129,679,008 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL01605:Mmp17
|
APN |
5 |
129,679,008 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL01782:Mmp17
|
APN |
5 |
129,679,205 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01986:Mmp17
|
APN |
5 |
129,673,692 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02096:Mmp17
|
APN |
5 |
129,675,752 (GRCm39) |
nonsense |
probably null |
|
|
IGL02160:Mmp17
|
APN |
5 |
129,672,633 (GRCm39) |
missense |
possibly damaging |
0.91 |
|
IGL03075:Mmp17
|
APN |
5 |
129,672,138 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0125:Mmp17
|
UTSW |
5 |
129,671,646 (GRCm39) |
missense |
possibly damaging |
0.88 |
|
R0553:Mmp17
|
UTSW |
5 |
129,675,734 (GRCm39) |
missense |
probably benign |
0.30 |
|
R1521:Mmp17
|
UTSW |
5 |
129,672,152 (GRCm39) |
splice site |
probably null |
|
|
R1938:Mmp17
|
UTSW |
5 |
129,679,190 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2151:Mmp17
|
UTSW |
5 |
129,682,725 (GRCm39) |
missense |
probably benign |
0.01 |
|
R4908:Mmp17
|
UTSW |
5 |
129,682,730 (GRCm39) |
nonsense |
probably null |
|
|
R4970:Mmp17
|
UTSW |
5 |
129,679,229 (GRCm39) |
missense |
possibly damaging |
0.51 |
|
R5096:Mmp17
|
UTSW |
5 |
129,682,627 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5112:Mmp17
|
UTSW |
5 |
129,679,229 (GRCm39) |
missense |
possibly damaging |
0.51 |
|
R5178:Mmp17
|
UTSW |
5 |
129,672,122 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5304:Mmp17
|
UTSW |
5 |
129,671,678 (GRCm39) |
missense |
probably null |
0.89 |
|
R5341:Mmp17
|
UTSW |
5 |
129,679,193 (GRCm39) |
missense |
possibly damaging |
0.50 |
|
R6341:Mmp17
|
UTSW |
5 |
129,679,019 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R6501:Mmp17
|
UTSW |
5 |
129,683,469 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7257:Mmp17
|
UTSW |
5 |
129,672,697 (GRCm39) |
missense |
probably benign |
0.03 |
|
R7371:Mmp17
|
UTSW |
5 |
129,682,836 (GRCm39) |
missense |
probably null |
0.98 |
|
R7546:Mmp17
|
UTSW |
5 |
129,673,653 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8026:Mmp17
|
UTSW |
5 |
129,672,148 (GRCm39) |
critical splice donor site |
probably null |
|
|
R8370:Mmp17
|
UTSW |
5 |
129,682,642 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8525:Mmp17
|
UTSW |
5 |
129,679,271 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8708:Mmp17
|
UTSW |
5 |
129,672,486 (GRCm39) |
missense |
possibly damaging |
0.67 |
|
R8803:Mmp17
|
UTSW |
5 |
129,675,773 (GRCm39) |
nonsense |
probably null |
|
|
R8878:Mmp17
|
UTSW |
5 |
129,683,378 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8882:Mmp17
|
UTSW |
5 |
129,679,008 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9399:Mmp17
|
UTSW |
5 |
129,671,686 (GRCm39) |
nonsense |
probably null |
|
|
R9404:Mmp17
|
UTSW |
5 |
129,682,741 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
R9528:Mmp17
|
UTSW |
5 |
129,683,392 (GRCm39) |
missense |
probably benign |
0.00 |
|
W0251:Mmp17
|
UTSW |
5 |
129,672,591 (GRCm39) |
missense |
probably benign |
0.09 |
|
Y5377:Mmp17
|
UTSW |
5 |
129,672,594 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Y5380:Mmp17
|
UTSW |
5 |
129,672,594 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Z1177:Mmp17
|
UTSW |
5 |
129,672,725 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
| Protein Function and Prediction |
Matrix metalloproteinases (MMPs) are zinc-binding endopeptidases that degrade various components of the extracellular matrix. They have been implicated in normal and pathologic processes including tissue remodeling, wound healing, angiogenesis, and tumor invasion (OMIM *602285).
|
| Expression/Localization |
MMP17 gene is expressed as a major 2.7-kb transcript in brain, leukocytes, colon, ovary, and testis (1).
|
| Background |
Mmp17tm1Dgen/tm1Dgen; MGI:3604575
involves: 129P2/OlaHsd * C57BL/6
In this targeted (reporter) model, insertion of lacZ into the gene had not detrimental affects and no abnormal phenotype was reported (MGI).
Mmp17tm1Ski/tm1Ski; MGI:3777020
involves: B6.Cg-Mmp17tm1Ski
In this knockout model, Srichai et al. report that loss of Mmp17 leads to increased urine osmolality, abnormal kidney collecting duct and papilla morphology, and oliguria (2). The animals had decreased drinking behavior and increased urinary osmolarity is due to hypodipsia (2). The animals had no defects in life span (3).
|
| References |
1. Puente, X. S., Pendas, A. M., Llano, E., Velasco, G., and Lopez-Otin, C. (1996) Molecular Cloning of a Novel Membrane-Type Matrix Metalloproteinase from a Human Breast Carcinoma. Cancer Res. 56, 944-949.
2. Srichai, M. B., Colleta, H., Gewin, L., Matrisian, L., Abel, T. W., Koshikawa, N., Seiki, M., Pozzi, A., Harris, R. C., and Zent, R. (2011) Membrane-Type 4 Matrix Metalloproteinase (MT4-MMP) Modulates Water Homeostasis in Mice. PLoS One. 6, e17099.
3. Rikimaru, A., Komori, K., Sakamoto, T., Ichise, H., Yoshida, N., Yana, I., and Seiki, M. (2007) Establishment of an MT4-MMP-Deficient Mouse Strain Representing an Efficient Tracking System for MT4-MMP/MMP-17 Expression in Vivo using Beta-Galactosidase. Genes Cells. 12, 1091-1100. |
| Posted On |
2012-10-05 |
| Science Writer |
Anne Murray |
Incidental Mutation