Incidental Mutation 'I2289:Ibsp'
| ID |
606 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Ibsp
|
| Ensembl Gene |
ENSMUSG00000029306 |
| Gene Name |
integrin binding sialoprotein |
| Synonyms |
Bsp2, bone sialoprotein, BSP, Bsp |
| Accession Numbers |
|
| Essential gene? |
Probably non essential
(E-score: 0.084)
|
| Stock # |
I2289 (G3)
of strain
633
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
5 |
| Chromosomal Location |
104447153-104459338 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
G to A
at 104450353 bp (GRCm39)
|
| Zygosity |
Homozygous |
| Amino Acid Change |
Arginine to Glutamine
at position 57
(R57Q)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000031246
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000031246]
|
| AlphaFold |
Q61711 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000031246
AA Change: R57Q
PolyPhen 2
Score 0.643 (Sensitivity: 0.87; Specificity: 0.91)
|
| SMART Domains |
Protein: ENSMUSP00000031246
Gene: ENSMUSG00000029306
AA Change: R57Q
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
16 |
N/A |
INTRINSIC |
|
Pfam:BSP_II
|
17 |
321 |
2.8e-127 |
PFAM |
|
| Meta Mutation Damage Score |
0.1465 |
| Coding Region Coverage |
|
| Het Detection Efficiency |
55.8% |
| Validation Efficiency |
88% (46/52) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a major structural protein of the bone matrix. It constitutes approximately 12% of the noncollagenous proteins in human bone and is synthesized by skeletal-associated cell types, including hypertrophic chondrocytes, osteoblasts, osteocytes, and osteoclasts. The only extraskeletal site of its synthesis is the trophoblast. This protein binds to calcium and hydroxyapatite via its acidic amino acid clusters, and mediates cell attachment through an RGD sequence that recognizes the vitronectin receptor. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a knock-out allele show reduced body weight/size, delayed long bone growth and mineralization with low bone turn over due to reduced osteoclast formation, delayed intramembranous ossification, progressive periodontal breakdown, and severe alveolar and mandibular bone loss. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(3) : Targeted, knock-out(1) Targeted, other(2)
|
| Other mutations in this stock |
Total: 21 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Adamts12 |
T |
A |
15: 11,071,894 (GRCm39) |
L146Q |
probably benign |
Homo |
| Adgrv1 |
A |
G |
13: 81,585,643 (GRCm39) |
L4607P |
probably damaging |
Het |
| Amelx |
A |
G |
X: 167,961,009 (GRCm39) |
|
probably null |
Homo |
| Ankfy1 |
A |
G |
11: 72,621,311 (GRCm39) |
K199R |
probably benign |
Het |
| Arfgef1 |
T |
C |
1: 10,243,478 (GRCm39) |
K1024E |
probably damaging |
Het |
| Bank1 |
T |
A |
3: 135,760,179 (GRCm39) |
D782V |
probably damaging |
Homo |
| Csmd1 |
A |
T |
8: 15,962,381 (GRCm39) |
I3271K |
probably benign |
Homo |
| Fat1 |
A |
G |
8: 45,478,033 (GRCm39) |
I2360V |
probably benign |
Homo |
| Gldc |
G |
A |
19: 30,124,576 (GRCm39) |
R241* |
probably null |
Het |
| Golgb1 |
A |
G |
16: 36,718,904 (GRCm39) |
H270R |
probably benign |
Het |
| Heg1 |
T |
C |
16: 33,583,829 (GRCm39) |
I1212T |
probably damaging |
Het |
| Hes1 |
T |
A |
16: 29,884,699 (GRCm39) |
S53R |
probably damaging |
Het |
| Lrp1b |
A |
T |
2: 41,012,944 (GRCm39) |
I2001K |
probably damaging |
Het |
| Nf1 |
G |
A |
11: 79,438,602 (GRCm39) |
R2181H |
probably damaging |
Het |
| Nrcam |
C |
A |
12: 44,611,098 (GRCm39) |
H567Q |
probably benign |
Homo |
| Or51a10 |
T |
C |
7: 103,698,961 (GRCm39) |
Y200C |
probably damaging |
Homo |
| Or5bw2 |
A |
T |
7: 6,573,818 (GRCm39) |
Y276F |
probably damaging |
Het |
| Rraga |
T |
C |
4: 86,494,522 (GRCm39) |
F123L |
probably damaging |
Het |
| Spam1 |
A |
G |
6: 24,796,477 (GRCm39) |
I143V |
probably benign |
Het |
| Synj2 |
A |
G |
17: 6,072,542 (GRCm39) |
|
probably benign |
Homo |
| T |
A |
T |
17: 8,657,474 (GRCm39) |
T112S |
probably benign |
Homo |
|
| Other mutations in Ibsp |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00687:Ibsp
|
APN |
5 |
104,457,934 (GRCm39) |
missense |
probably benign |
0.27 |
|
IGL02317:Ibsp
|
APN |
5 |
104,450,332 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02539:Ibsp
|
APN |
5 |
104,450,149 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL03236:Ibsp
|
APN |
5 |
104,453,871 (GRCm39) |
missense |
probably benign |
0.30 |
|
crunch
|
UTSW |
5 |
104,457,148 (GRCm39) |
missense |
probably damaging |
1.00 |
|
PIT4445001:Ibsp
|
UTSW |
5 |
104,450,170 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R0049:Ibsp
|
UTSW |
5 |
104,450,024 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0049:Ibsp
|
UTSW |
5 |
104,450,024 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0234:Ibsp
|
UTSW |
5 |
104,457,935 (GRCm39) |
small deletion |
probably benign |
|
|
R0610:Ibsp
|
UTSW |
5 |
104,458,000 (GRCm39) |
missense |
probably benign |
0.07 |
|
R0656:Ibsp
|
UTSW |
5 |
104,457,886 (GRCm39) |
critical splice acceptor site |
probably null |
|
|
R1168:Ibsp
|
UTSW |
5 |
104,450,018 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1440:Ibsp
|
UTSW |
5 |
104,458,405 (GRCm39) |
missense |
unknown |
|
|
R1569:Ibsp
|
UTSW |
5 |
104,458,017 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1921:Ibsp
|
UTSW |
5 |
104,458,078 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2172:Ibsp
|
UTSW |
5 |
104,458,296 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2879:Ibsp
|
UTSW |
5 |
104,458,260 (GRCm39) |
missense |
possibly damaging |
0.88 |
|
R4399:Ibsp
|
UTSW |
5 |
104,457,148 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4517:Ibsp
|
UTSW |
5 |
104,453,863 (GRCm39) |
nonsense |
probably null |
|
|
R5417:Ibsp
|
UTSW |
5 |
104,458,335 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R5575:Ibsp
|
UTSW |
5 |
104,457,925 (GRCm39) |
missense |
possibly damaging |
0.78 |
|
R6183:Ibsp
|
UTSW |
5 |
104,453,896 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R6273:Ibsp
|
UTSW |
5 |
104,458,167 (GRCm39) |
missense |
probably benign |
0.15 |
|
R6295:Ibsp
|
UTSW |
5 |
104,449,987 (GRCm39) |
splice site |
probably null |
|
|
R7061:Ibsp
|
UTSW |
5 |
104,457,768 (GRCm39) |
splice site |
probably null |
|
|
R7133:Ibsp
|
UTSW |
5 |
104,450,172 (GRCm39) |
nonsense |
probably null |
|
|
R7202:Ibsp
|
UTSW |
5 |
104,450,027 (GRCm39) |
missense |
probably benign |
0.02 |
|
R7205:Ibsp
|
UTSW |
5 |
104,458,297 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R7769:Ibsp
|
UTSW |
5 |
104,458,050 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R7769:Ibsp
|
UTSW |
5 |
104,453,871 (GRCm39) |
missense |
probably benign |
0.15 |
|
R8506:Ibsp
|
UTSW |
5 |
104,457,947 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8840:Ibsp
|
UTSW |
5 |
104,458,006 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9396:Ibsp
|
UTSW |
5 |
104,458,297 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9431:Ibsp
|
UTSW |
5 |
104,457,167 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Nature of Mutation |
 DNA sequencing using the SOLiD technique identified a G to A transition at position 251 of the Ibsp transcript in exon 4 of 7 exons using Genbank record NM_008318.3. The mutated nucleotide causes an arginine to glutamine substitution at amino acid 57 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method.
|
| Protein Function and Prediction |
The Ibsp gene encodes a 324 amino acid integrin binding sialoprotein. IBSB is a bone glycoprotein that forms an integral part of the mineralized matrix and is produced by skeletal-associated cell types. The protein promotes Arg-Gly-Asp-dependent cell attachment. This motif occurs at residues 293-295 (Uniprot Q61711). Mice homozygous for a knock-out allele exhibit reduced body weight/size and impaired long bone growth and mineralization, concomitant with severely reduced bone formation.
|
| Posted On |
2011-03-03 |
Incidental Mutation