Incidental Mutation 'R0050:Stx2'
| ID |
16087 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Stx2
|
| Ensembl Gene |
ENSMUSG00000029428 |
| Gene Name |
syntaxin 2 |
| Synonyms |
repro34, G1-536-1, Syn-2, Epim |
| MMRRC Submission |
038344-MU
|
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
R0050 (G1)
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
5 |
| Chromosomal Location |
129061621-129085638 bp(-) (GRCm39) |
| Type of Mutation |
critical splice donor site (2 bp from exon) |
| DNA Base Change (assembly) |
A to G
at 129076572 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000118220
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000031378]
[ENSMUST00000100680]
[ENSMUST00000149877]
[ENSMUST00000149877]
[ENSMUST00000195906]
|
| AlphaFold |
no structure available at present |
| Predicted Effect |
probably null
Transcript: ENSMUST00000031378
|
| SMART Domains |
Protein: ENSMUSP00000031378
Gene: ENSMUSG00000029428
| Domain | Start | End | E-Value | Type |
|---|
|
SynN
|
25 |
146 |
1.33e-40 |
SMART |
|
low complexity region
|
159 |
170 |
N/A |
INTRINSIC |
|
low complexity region
|
175 |
185 |
N/A |
INTRINSIC |
|
t_SNARE
|
187 |
254 |
1.74e-19 |
SMART |
|
transmembrane domain
|
266 |
288 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably null
Transcript: ENSMUST00000100680
|
| SMART Domains |
Protein: ENSMUSP00000098247
Gene: ENSMUSG00000029428
| Domain | Start | End | E-Value | Type |
|---|
|
SynN
|
25 |
146 |
1.33e-40 |
SMART |
|
low complexity region
|
159 |
170 |
N/A |
INTRINSIC |
|
low complexity region
|
175 |
185 |
N/A |
INTRINSIC |
|
t_SNARE
|
187 |
254 |
1.74e-19 |
SMART |
|
transmembrane domain
|
265 |
287 |
N/A |
INTRINSIC |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000141492
|
| Predicted Effect |
probably null
Transcript: ENSMUST00000149877
|
| SMART Domains |
Protein: ENSMUSP00000118220
Gene: ENSMUSG00000029428
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Syntaxin
|
1 |
85 |
1.3e-28 |
PFAM |
|
| Predicted Effect |
probably null
Transcript: ENSMUST00000149877
|
| SMART Domains |
Protein: ENSMUSP00000118220
Gene: ENSMUSG00000029428
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Syntaxin
|
1 |
85 |
1.3e-28 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000151712
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000195906
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000199813
|
| Meta Mutation Damage Score |
0.9485 |
| Coding Region Coverage |
- 1x: 88.6%
- 3x: 85.4%
- 10x: 76.7%
- 20x: 62.7%
|
| Validation Efficiency |
90% (86/96) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The product of this gene belongs to the syntaxin/epimorphin family of proteins. The syntaxins are a large protein family implicated in the targeting and fusion of intracellular transport vesicles. The product of this gene regulates epithelial-mesenchymal interactions and epithelial cell morphogenesis and activation. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a null allele display male infertility associated with abnormal testicular development and impaired spermatogenesis, increased intestinal growth due to enhanced crypt cell proliferation and crypt fission, and decreased susceptibility to induced colitis. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(10) : Targeted(4) Gene trapped(5) Chemically induced(1)
|
| Other mutations in this stock |
Total: 52 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abca1 |
A |
G |
4: 53,069,910 (GRCm39) |
|
probably benign |
Het |
| Abca9 |
C |
T |
11: 110,036,417 (GRCm39) |
C564Y |
probably damaging |
Het |
| Abhd14a |
A |
T |
9: 106,318,082 (GRCm39) |
|
probably benign |
Het |
| Acnat2 |
G |
A |
4: 49,380,586 (GRCm39) |
T264I |
probably benign |
Het |
| Adamts2 |
T |
C |
11: 50,666,222 (GRCm39) |
V406A |
probably damaging |
Het |
| Adcy5 |
A |
G |
16: 35,124,673 (GRCm39) |
|
probably benign |
Het |
| Akr1c13 |
T |
C |
13: 4,244,669 (GRCm39) |
|
probably benign |
Het |
| Ankar |
T |
A |
1: 72,695,323 (GRCm39) |
E1093D |
probably damaging |
Het |
| Arhgef38 |
C |
A |
3: 132,837,957 (GRCm39) |
D75Y |
probably damaging |
Het |
| Asns |
T |
C |
6: 7,676,019 (GRCm39) |
I484V |
probably benign |
Het |
| Astn1 |
T |
C |
1: 158,407,294 (GRCm39) |
|
probably benign |
Het |
| Atg4b |
T |
A |
1: 93,715,440 (GRCm39) |
|
probably benign |
Het |
| Cadm2 |
A |
G |
16: 66,750,154 (GRCm39) |
|
probably benign |
Het |
| Ces2c |
T |
A |
8: 105,574,831 (GRCm39) |
M96K |
probably benign |
Het |
| Cpd |
T |
A |
11: 76,683,685 (GRCm39) |
T1025S |
possibly damaging |
Het |
| Daw1 |
T |
C |
1: 83,158,086 (GRCm39) |
V45A |
probably benign |
Het |
| Dmrt3 |
C |
A |
19: 25,599,953 (GRCm39) |
P266H |
probably damaging |
Het |
| Dnah10 |
A |
G |
5: 124,907,808 (GRCm39) |
T4416A |
probably benign |
Het |
| Dock9 |
A |
G |
14: 121,844,637 (GRCm39) |
V1124A |
probably benign |
Het |
| Ermp1 |
C |
A |
19: 29,606,184 (GRCm39) |
A190S |
probably damaging |
Het |
| Gm10267 |
T |
A |
18: 44,289,520 (GRCm39) |
|
probably benign |
Het |
| Golga2 |
T |
A |
2: 32,182,139 (GRCm39) |
V29D |
probably damaging |
Het |
| Gprc6a |
T |
A |
10: 51,491,485 (GRCm39) |
M755L |
probably damaging |
Het |
| H1f8 |
G |
T |
6: 115,924,729 (GRCm39) |
K78N |
probably damaging |
Het |
| Lama1 |
A |
T |
17: 68,089,051 (GRCm39) |
D1574V |
possibly damaging |
Het |
| Lama3 |
T |
A |
18: 12,537,160 (GRCm39) |
H268Q |
probably damaging |
Het |
| Lmntd1 |
T |
C |
6: 145,363,202 (GRCm39) |
D107G |
probably damaging |
Het |
| Lrriq1 |
A |
G |
10: 102,904,792 (GRCm39) |
V1614A |
probably damaging |
Het |
| Mmp12 |
A |
G |
9: 7,350,152 (GRCm39) |
|
probably benign |
Het |
| Mre11a |
A |
G |
9: 14,742,269 (GRCm39) |
|
probably benign |
Het |
| Mtrf1l |
T |
C |
10: 5,765,553 (GRCm39) |
|
silent |
Het |
| Oaz2 |
A |
G |
9: 65,595,084 (GRCm39) |
E61G |
probably damaging |
Het |
| Parp3 |
A |
T |
9: 106,348,600 (GRCm39) |
D473E |
possibly damaging |
Het |
| Pear1 |
G |
T |
3: 87,663,294 (GRCm39) |
Y441* |
probably null |
Het |
| Pkhd1l1 |
A |
T |
15: 44,437,203 (GRCm39) |
T3493S |
possibly damaging |
Het |
| Ppp3cb |
A |
G |
14: 20,581,820 (GRCm39) |
V65A |
possibly damaging |
Het |
| Rheb |
A |
T |
5: 25,022,832 (GRCm39) |
|
probably benign |
Het |
| Ros1 |
G |
A |
10: 51,977,899 (GRCm39) |
T1449M |
probably damaging |
Het |
| Scn4a |
C |
G |
11: 106,211,682 (GRCm39) |
R1445P |
probably damaging |
Het |
| Sema3d |
T |
A |
5: 12,634,920 (GRCm39) |
M662K |
probably benign |
Het |
| Skp2 |
A |
G |
15: 9,125,178 (GRCm39) |
F134L |
probably benign |
Het |
| Slc6a12 |
T |
C |
6: 121,337,378 (GRCm39) |
|
probably benign |
Het |
| Slc8a3 |
T |
C |
12: 81,362,039 (GRCm39) |
Y260C |
probably damaging |
Het |
| Spin1 |
T |
A |
13: 51,304,454 (GRCm39) |
|
probably benign |
Het |
| Sycp2 |
A |
T |
2: 178,006,504 (GRCm39) |
V863D |
probably damaging |
Het |
| Tgfb3 |
T |
A |
12: 86,116,658 (GRCm39) |
I127F |
possibly damaging |
Het |
| Tgif1 |
T |
G |
17: 71,157,879 (GRCm39) |
K2Q |
probably damaging |
Het |
| Trmt2a |
A |
T |
16: 18,068,707 (GRCm39) |
E234D |
probably damaging |
Het |
| Trps1 |
A |
T |
15: 50,628,921 (GRCm39) |
S696T |
probably benign |
Het |
| Ucp1 |
A |
G |
8: 84,020,857 (GRCm39) |
E191G |
probably damaging |
Het |
| Usp48 |
C |
A |
4: 137,341,114 (GRCm39) |
D371E |
probably damaging |
Het |
| Usp54 |
A |
T |
14: 20,623,823 (GRCm39) |
|
probably benign |
Het |
|
| Other mutations in Stx2 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01729:Stx2
|
APN |
5 |
129,068,042 (GRCm39) |
missense |
probably benign |
0.01 |
|
IGL01951:Stx2
|
APN |
5 |
129,069,329 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02348:Stx2
|
APN |
5 |
129,065,894 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02902:Stx2
|
APN |
5 |
129,069,285 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0050:Stx2
|
UTSW |
5 |
129,076,572 (GRCm39) |
critical splice donor site |
probably null |
|
|
R0277:Stx2
|
UTSW |
5 |
129,065,967 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0323:Stx2
|
UTSW |
5 |
129,065,967 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0419:Stx2
|
UTSW |
5 |
129,070,641 (GRCm39) |
splice site |
probably benign |
|
|
R0843:Stx2
|
UTSW |
5 |
129,076,612 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1346:Stx2
|
UTSW |
5 |
129,065,852 (GRCm39) |
unclassified |
probably benign |
|
|
R1631:Stx2
|
UTSW |
5 |
129,069,289 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1920:Stx2
|
UTSW |
5 |
129,065,903 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5350:Stx2
|
UTSW |
5 |
129,068,155 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6877:Stx2
|
UTSW |
5 |
129,064,884 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7379:Stx2
|
UTSW |
5 |
129,064,863 (GRCm39) |
missense |
possibly damaging |
0.68 |
|
R7391:Stx2
|
UTSW |
5 |
129,065,867 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7747:Stx2
|
UTSW |
5 |
129,063,481 (GRCm39) |
missense |
probably benign |
0.39 |
|
R7803:Stx2
|
UTSW |
5 |
129,070,627 (GRCm39) |
nonsense |
probably null |
|
|
R8354:Stx2
|
UTSW |
5 |
129,071,932 (GRCm39) |
missense |
probably benign |
0.00 |
|
R8725:Stx2
|
UTSW |
5 |
129,070,564 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R9348:Stx2
|
UTSW |
5 |
129,076,601 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9768:Stx2
|
UTSW |
5 |
129,063,422 (GRCm39) |
missense |
unknown |
|
|
| Protein Function and Prediction |
Stx2 encodes epimorphin, a member of the syntaxin family of membrane-bound, intracellular vesicle-docking proteins (1). It functions as a mesenchymal signal factor that is proposed to function in maintaining normal tissue structure and interactions between mesenchymal tissue and epithelial tissue (2). Studies have shown that epimorphin has morphogenetic effects in multiple epithelial tissues, including intestine, pancreas, mammary gland, lung, gallbladder, and liver (3-6). Epimorphin induces epithelial branching morphogenesis (7). Epimorphin plays a central role in epithelial-mesenchymal interactions (3). Horikoshi et al. proposed that epimorphin functions in the development of the kidney and in the differentiation of fibroblast and mesangial cells (7). An antibody to epimorphin inhibited epithelial morphogenesis in such processes as hair follicle growth and lung epithelial tubular formation (3). Transfection of sense or antisense epimorphin constructs into myofibroblasts affects the morphology of cocultured epithelial cells and promotes the growth and spreading of the cells (8). Overexpression of epimorphin in myofibroblasts induces the formation of round epithelial colonies that develop small lumens (1).
|
| Expression/Localization |
In mouse embryonic tissues, epimorphin is expressed on the surface of mesenchymal cells (3;7;9). Epimorphin is expressed in fibroblasts and myofibroblasts surrounding the epithelium (1;5). Epimorphin widely distributed in all human organs and is ubiquitously expressed in normal skin and is upregulated in diseased human skin (2). Epimorphin is localized in the connective tissue adjacent to or around various epithelial tissues, muscles, and vessels (2). Epimorphin is expressed in glomerular mesangial cells and interstitial fibroblasts of the kidney during gestation (7) as well as in intestinal myofibroblasts (8). In fetal gut mesenchyme, epimorphin is abundantly expressed during villus morphogenesis (1;9).
|
| Background |
Stx2tm1Dcru/tm1Dcru; MGI:3526405
involves: 129X1/SvJ
Platelets from homozygous animals exhibit normal exocytosis (10).
Stx2tm1Dcru/tm1Dcru; MGI:3526405
involves: 129X1/SvJ * C57BL/6J
In this genetic background, mice homozygous for a null mutation display male infertility, azoospermia, reduced litter size, reduced severity of dextran sodium sulfate-induced chemical colitis, increased liver weight, and abnormal small intestine, colon, and crypts of Lieberkuhn morphology (11).
|
| References |
1. Qin, J., Takahashi, Y., Isuzugawa, K., Imai, M., Yamamoto, S., Hirai, Y., and Imakawa, K. (2005) Regulation of Embryo Outgrowth by a Morphogenic Factor, Epimorphin, in the Mouse. Mol Reprod Dev. 70, 455-463.
3. Hirai, Y., Takebe, K., Takashina, M., Kobayashi, S., and Takeichi, M. (1992) Epimorphin: A Mesenchymal Protein Essential for Epithelial Morphogenesis. Cell. 69, 471-481.
4. Hirai, Y., Lochter, A., Galosy, S., Koshida, S., Niwa, S., and Bissell, M. J. (1998) Epimorphin Functions as a Key Morphoregulator for Mammary Epithelial Cells. J Cell Biol. 140, 159-169.
5. Lehnert, L., Lerch, M. M., Hirai, Y., Kruse, M. L., Schmiegel, W., and Kalthoff, H. (2001) Autocrine Stimulation of Human Pancreatic Duct-Like Development by Soluble Isoforms of Epimorphin in Vitro. J Cell Biol. 152, 911-922.
6. Miura, K., Nagai, H., Ueno, Y., Goto, T., Mikami, K., Nakane, K., Yoneyama, K., Watanabe, D., Terada, K., Sugiyama, T., Imai, K., Senoo, H., and Watanabe, S. (2003) Epimorphin is Involved in Differentiation of Rat Hepatic Stem-Like Cells through Cell-Cell Contact. Biochem Biophys Res Commun. 311, 415-423.
7. Horikoshi, S., Yoshikawa, M., Shibata, T., Takahashi, K., Shirato, I., and Tomino, Y. (2001) Protein Localization and mRNA Expression of Epimorphin in Mouse and Human Kidneys. Exp Nephrol. 9, 412-419.
8. Fritsch, C., Swietlicki, E. A., Lefebvre, O., Kedinger, M., Iordanov, H., Levin, M. S., and Rubin, D. C. (2002) Epimorphin Expression in Intestinal Myofibroblasts Induces Epithelial Morphogenesis. J Clin Invest. 110, 1629-1641.
9. Goyal, A., Singh, R., Swietlicki, E. A., Levin, M. S., and Rubin, D. C. (1998) Characterization of Rat epimorphin/syntaxin 2 Expression Suggests a Role in Crypt-Villus Morphogenesis. Am J Physiol. 275, G114-24.
10. Ye, S., Karim, Z. A., Al Hawas, R., Pessin, J. E., Filipovich, A. H., and Whiteheart, S. W. (2012) Syntaxin-11, but Not Syntaxin-2 Or Syntaxin-4, is Required for Platelet Secretion. Blood. 120, 2484-2492.
11. Wang, Y., Wang, L., Iordanov, H., Swietlicki, E. A., Zheng, Q., Jiang, S., Tang, Y., Levin, M. S., and Rubin, D. C. (2006) Epimorphin(-/-) Mice have Increased Intestinal Growth, Decreased Susceptibility to Dextran Sodium Sulfate Colitis, and Impaired Spermatogenesis. J Clin Invest. 116, 1535-1546. |
| Posted On |
2013-01-08 |
| Science Writer |
Anne Murray |
Incidental Mutation