Incidental Mutation 'P0005:Col6a1'
| ID |
7595 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Col6a1
|
| Ensembl Gene |
ENSMUSG00000001119 |
| Gene Name |
collagen, type VI, alpha 1 |
| Synonyms |
Col6a-1 |
| MMRRC Submission |
038262-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly non essential
(E-score: 0.281)
|
| Stock # |
P0005 (G1)
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
10 |
| Chromosomal Location |
76544626-76561878 bp(-) (GRCm39) |
| Type of Mutation |
splice site |
| DNA Base Change (assembly) |
A to G
at 76553163 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000001147
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000001147]
|
| AlphaFold |
Q04857 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000001147
|
| SMART Domains |
Protein: ENSMUSP00000001147
Gene: ENSMUSG00000001119
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
19 |
N/A |
INTRINSIC |
|
VWA
|
34 |
232 |
9.55e-29 |
SMART |
|
Pfam:Collagen
|
252 |
312 |
5.6e-11 |
PFAM |
|
Pfam:Collagen
|
292 |
367 |
2e-9 |
PFAM |
|
Pfam:Collagen
|
345 |
423 |
3.6e-8 |
PFAM |
|
Pfam:Collagen
|
448 |
515 |
1.1e-8 |
PFAM |
|
Pfam:Collagen
|
499 |
563 |
1.9e-9 |
PFAM |
|
low complexity region
|
571 |
590 |
N/A |
INTRINSIC |
|
VWA
|
612 |
798 |
8.57e-31 |
SMART |
|
VWA
|
824 |
1005 |
2.6e-30 |
SMART |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000137599
|
| Coding Region Coverage |
- 1x: 85.5%
- 3x: 80.5%
- 10x: 66.1%
- 20x: 49.6%
|
| Validation Efficiency |
95% (104/109) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The collagens are a superfamily of proteins that play a role in maintaining the integrity of various tissues. Collagens are extracellular matrix proteins and have a triple-helical domain as their common structural element. Collagen VI is a major structural component of microfibrils. The basic structural unit of collagen VI is a heterotrimer of the alpha1(VI), alpha2(VI), and alpha3(VI) chains. The alpha2(VI) and alpha3(VI) chains are encoded by the COL6A2 and COL6A3 genes, respectively. The protein encoded by this gene is the alpha 1 subunit of type VI collagen (alpha1(VI) chain). Mutations in the genes that code for the collagen VI subunits result in the autosomal dominant disorder, Bethlem myopathy. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for this targeted mutation display a myopathic disorder that resembles human Bethlem myopathy. Loss of contractile strength in affected muscles is associated with an unexpected latent mitochondrial dysfunction in myofibers, as well as spontaneous apoptosis. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(5) : Targeted(5)
|
| 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 |
| 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 |
| Mmp17 |
T |
C |
5: 129,673,695 (GRCm39) |
V258A |
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 Col6a1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01327:Col6a1
|
APN |
10 |
76,546,813 (GRCm39) |
missense |
unknown |
|
|
IGL01943:Col6a1
|
APN |
10 |
76,554,957 (GRCm39) |
critical splice donor site |
probably null |
|
|
IGL02178:Col6a1
|
APN |
10 |
76,546,909 (GRCm39) |
missense |
unknown |
|
|
IGL02928:Col6a1
|
APN |
10 |
76,545,500 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
IGL03162:Col6a1
|
APN |
10 |
76,553,885 (GRCm39) |
splice site |
probably benign |
|
|
R0398:Col6a1
|
UTSW |
10 |
76,545,952 (GRCm39) |
missense |
unknown |
|
|
R0631:Col6a1
|
UTSW |
10 |
76,545,569 (GRCm39) |
missense |
probably benign |
0.03 |
|
R0698:Col6a1
|
UTSW |
10 |
76,552,114 (GRCm39) |
missense |
unknown |
|
|
R0699:Col6a1
|
UTSW |
10 |
76,552,114 (GRCm39) |
missense |
unknown |
|
|
R0848:Col6a1
|
UTSW |
10 |
76,549,458 (GRCm39) |
critical splice donor site |
probably null |
|
|
R1053:Col6a1
|
UTSW |
10 |
76,556,800 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1235:Col6a1
|
UTSW |
10 |
76,548,158 (GRCm39) |
missense |
unknown |
|
|
R1480:Col6a1
|
UTSW |
10 |
76,545,752 (GRCm39) |
missense |
unknown |
|
|
R1854:Col6a1
|
UTSW |
10 |
76,557,783 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1995:Col6a1
|
UTSW |
10 |
76,557,790 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2082:Col6a1
|
UTSW |
10 |
76,545,430 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R2122:Col6a1
|
UTSW |
10 |
76,557,332 (GRCm39) |
missense |
probably benign |
0.10 |
|
R2411:Col6a1
|
UTSW |
10 |
76,546,922 (GRCm39) |
missense |
unknown |
|
|
R3236:Col6a1
|
UTSW |
10 |
76,547,154 (GRCm39) |
missense |
unknown |
|
|
R3417:Col6a1
|
UTSW |
10 |
76,548,203 (GRCm39) |
missense |
unknown |
|
|
R3832:Col6a1
|
UTSW |
10 |
76,546,951 (GRCm39) |
missense |
unknown |
|
|
R3843:Col6a1
|
UTSW |
10 |
76,547,175 (GRCm39) |
missense |
unknown |
|
|
R3903:Col6a1
|
UTSW |
10 |
76,547,175 (GRCm39) |
missense |
unknown |
|
|
R3904:Col6a1
|
UTSW |
10 |
76,547,175 (GRCm39) |
missense |
unknown |
|
|
R4409:Col6a1
|
UTSW |
10 |
76,557,334 (GRCm39) |
missense |
probably benign |
0.17 |
|
R4418:Col6a1
|
UTSW |
10 |
76,554,239 (GRCm39) |
nonsense |
probably null |
|
|
R4568:Col6a1
|
UTSW |
10 |
76,555,031 (GRCm39) |
intron |
probably benign |
|
|
R4579:Col6a1
|
UTSW |
10 |
76,547,191 (GRCm39) |
missense |
unknown |
|
|
R4661:Col6a1
|
UTSW |
10 |
76,550,506 (GRCm39) |
missense |
unknown |
|
|
R4945:Col6a1
|
UTSW |
10 |
76,548,106 (GRCm39) |
missense |
unknown |
|
|
R4958:Col6a1
|
UTSW |
10 |
76,559,339 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5101:Col6a1
|
UTSW |
10 |
76,545,740 (GRCm39) |
missense |
unknown |
|
|
R5440:Col6a1
|
UTSW |
10 |
76,559,288 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5924:Col6a1
|
UTSW |
10 |
76,554,205 (GRCm39) |
critical splice donor site |
probably null |
|
|
R6030:Col6a1
|
UTSW |
10 |
76,545,700 (GRCm39) |
missense |
unknown |
|
|
R6030:Col6a1
|
UTSW |
10 |
76,545,700 (GRCm39) |
missense |
unknown |
|
|
R6366:Col6a1
|
UTSW |
10 |
76,546,804 (GRCm39) |
missense |
unknown |
|
|
R6435:Col6a1
|
UTSW |
10 |
76,546,957 (GRCm39) |
missense |
unknown |
|
|
R6718:Col6a1
|
UTSW |
10 |
76,560,884 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7014:Col6a1
|
UTSW |
10 |
76,557,277 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7117:Col6a1
|
UTSW |
10 |
76,560,843 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7153:Col6a1
|
UTSW |
10 |
76,546,175 (GRCm39) |
splice site |
probably null |
|
|
R7183:Col6a1
|
UTSW |
10 |
76,552,093 (GRCm39) |
critical splice donor site |
probably null |
|
|
R7244:Col6a1
|
UTSW |
10 |
76,553,242 (GRCm39) |
nonsense |
probably null |
|
|
R7625:Col6a1
|
UTSW |
10 |
76,549,760 (GRCm39) |
missense |
unknown |
|
|
R7741:Col6a1
|
UTSW |
10 |
76,545,743 (GRCm39) |
missense |
unknown |
|
|
R7774:Col6a1
|
UTSW |
10 |
76,545,710 (GRCm39) |
missense |
unknown |
|
|
R7834:Col6a1
|
UTSW |
10 |
76,545,762 (GRCm39) |
missense |
unknown |
|
|
R8145:Col6a1
|
UTSW |
10 |
76,559,305 (GRCm39) |
missense |
possibly damaging |
0.46 |
|
R8177:Col6a1
|
UTSW |
10 |
76,560,863 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8932:Col6a1
|
UTSW |
10 |
76,552,593 (GRCm39) |
missense |
unknown |
|
|
R9060:Col6a1
|
UTSW |
10 |
76,557,711 (GRCm39) |
missense |
probably benign |
0.21 |
|
R9411:Col6a1
|
UTSW |
10 |
76,547,487 (GRCm39) |
missense |
unknown |
|
|
RF019:Col6a1
|
UTSW |
10 |
76,547,449 (GRCm39) |
missense |
unknown |
|
|
X0010:Col6a1
|
UTSW |
10 |
76,559,372 (GRCm39) |
missense |
probably damaging |
1.00 |
|
X0067:Col6a1
|
UTSW |
10 |
76,545,809 (GRCm39) |
missense |
unknown |
|
|
Z1088:Col6a1
|
UTSW |
10 |
76,545,393 (GRCm39) |
makesense |
probably null |
|
|
| Protein Function and Prediction |
Col6a1 contains an N- and C-terminal globular domain that surrounds a triple helical region (Uniprot Q04857) along with three VWFA domains.
|
| Background |
Knockout animals develop normally, are fertile, and had no obvious differences from the wild-type littermates after a year [MGI: 2153356 (1)]. Disruption of Col6a1 gene expression caused myopathy (e.g., fiber necrosis and phagocytosis along with variation in muscle fiber diameter) (1). Characterization of this model determined that Col6a1 is necessary for muscle fiber maintenance. Another study found that along with muscle changes there was a concomitant change in the sarcoplasmic reticulum and mitochondria along with apoptosis (2).
Mutations in COL6A1 can lead to autosomal dominant Bethlem myopathy (OMIM: #158810), Ullrich congenital muscular dystrophy (OMIM: #254090), and ossification of the posterior longitudinal spinal ligaments (OMIM: #602475).
|
| References |
1. Bonaldo, P., Braghetta, P., Zanetti, M., Piccolo, S., Volpin, D., and Bressan, G. M. (1998) Collagen VI Deficiency Induces Early Onset Myopathy in the Mouse: An Animal Model for Bethlem Myopathy. Hum Mol Genet. 7, 2135-2140.
2. Irwin, W. A., Bergamin, N., Sabatelli, P., Reggiani, C., Megighian, A., Merlini, L., Braghetta, P., Columbaro, M., Volpin, D., Bressan, G. M., Bernardi, P., and Bonaldo, P. (2003) Mitochondrial Dysfunction and Apoptosis in Myopathic Mice with Collagen VI Deficiency. Nat Genet. 35, 367-371. |
| Posted On |
2012-10-05 |
| Science Writer |
Anne Murray |
Incidental Mutation