Incidental Mutation 'F6893:Lamb2'
| ID |
193 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Lamb2
|
| Ensembl Gene |
ENSMUSG00000052911 |
| Gene Name |
laminin, beta 2 |
| Synonyms |
Lams, npht, Lamb-2 |
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.854)
|
| Stock # |
F6893 (G3)
of strain
busy
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
9 |
| Chromosomal Location |
108357080-108367729 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 108359755 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Valine to Alanine
at position 365
(V365A)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000069087
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000065014]
[ENSMUST00000194147]
[ENSMUST00000195058]
[ENSMUST00000195483]
|
| AlphaFold |
Q61292 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000065014
AA Change: V365A
PolyPhen 2
Score 0.116 (Sensitivity: 0.93; Specificity: 0.86)
|
| SMART Domains |
Protein: ENSMUSP00000069087
Gene: ENSMUSG00000052911
AA Change: V365A
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
35 |
N/A |
INTRINSIC |
|
LamNT
|
44 |
284 |
1.9e-102 |
SMART |
|
EGF_Lam
|
286 |
347 |
1.34e-6 |
SMART |
|
EGF_Lam
|
350 |
410 |
6.1e-10 |
SMART |
|
EGF_Lam
|
413 |
470 |
2.98e-13 |
SMART |
|
EGF_Lam
|
473 |
522 |
7.93e-9 |
SMART |
|
EGF_Lam
|
525 |
569 |
1.01e-10 |
SMART |
|
EGF_Lam
|
784 |
829 |
3.42e-13 |
SMART |
|
EGF_Lam
|
832 |
875 |
6.54e-10 |
SMART |
|
EGF_Lam
|
878 |
925 |
1.34e-6 |
SMART |
|
EGF_Lam
|
928 |
984 |
4.74e-7 |
SMART |
|
EGF_Lam
|
987 |
1036 |
1.53e-10 |
SMART |
|
EGF_Lam
|
1039 |
1093 |
6.29e-12 |
SMART |
|
EGF_Lam
|
1096 |
1141 |
1.79e-7 |
SMART |
|
EGF_Lam
|
1144 |
1188 |
6.64e-11 |
SMART |
|
coiled coil region
|
1261 |
1299 |
N/A |
INTRINSIC |
|
low complexity region
|
1445 |
1458 |
N/A |
INTRINSIC |
|
coiled coil region
|
1473 |
1527 |
N/A |
INTRINSIC |
|
low complexity region
|
1609 |
1625 |
N/A |
INTRINSIC |
|
SCOP:d1eq1a_
|
1632 |
1786 |
5e-17 |
SMART |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000191864
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000194147
|
| SMART Domains |
Protein: ENSMUSP00000141562
Gene: ENSMUSG00000052911
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
59 |
79 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000195058
|
| SMART Domains |
Protein: ENSMUSP00000141757
Gene: ENSMUSG00000052911
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
35 |
N/A |
INTRINSIC |
|
Pfam:Laminin_N
|
50 |
102 |
6.2e-16 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000195483
|
| SMART Domains |
Protein: ENSMUSP00000142304
Gene: ENSMUSG00000052911
| Domain | Start | End | E-Value | Type |
|---|
|
signal peptide
|
1 |
35 |
N/A |
INTRINSIC |
|
LamNT
|
44 |
125 |
3e-3 |
SMART |
|
| Meta Mutation Damage Score |
0.4671 |
| Coding Region Coverage |
|
| Validation Efficiency |
88% (165/188) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins, composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively), form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the beta chain isoform laminin, beta 2. The beta 2 chain contains the 7 structural domains typical of beta chains of laminin, including the short alpha region. However, unlike beta 1 chain, beta 2 has a more restricted tissue distribution. It is enriched in the basement membrane of muscles at the neuromuscular junctions, kidney glomerulus and vascular smooth muscle. Transgenic mice in which the beta 2 chain gene was inactivated by homologous recombination, showed defects in the maturation of neuromuscular junctions and impairment of glomerular filtration. Alternative splicing involving a non consensus 5' splice site (gc) in the 5' UTR of this gene has been reported. It was suggested that inefficient splicing of this first intron, which does not change the protein sequence, results in a greater abundance of the unspliced form of the transcript than the spliced form. The full-length nature of the spliced transcript is not known. [provided by RefSeq, Aug 2011]
PHENOTYPE: Homozygotes for a targeted null mutation exhibit small size, severe proteinuria due to a defect in glomerular filtration, abnormalities of the retina and skeletal neuromuscular synapses, and lethality by 30 days of age. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(5) : Targeted, knock-out(2) Gene trapped(3)
|
| Other mutations in this stock |
Total: 35 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abca14 |
G |
A |
7: 119,924,261 (GRCm39) |
V1638M |
probably damaging |
Het |
| Agrn |
C |
T |
4: 156,258,636 (GRCm39) |
R972Q |
probably benign |
Het |
| Anxa3 |
T |
C |
5: 96,972,853 (GRCm39) |
|
probably benign |
Het |
| Bpifa6 |
G |
T |
2: 153,829,078 (GRCm39) |
D202Y |
probably damaging |
Het |
| Ccdc15 |
G |
A |
9: 37,226,936 (GRCm39) |
T346I |
probably damaging |
Homo |
| Celsr3 |
G |
A |
9: 108,712,266 (GRCm39) |
R1731H |
probably benign |
Het |
| Ces4a |
A |
G |
8: 105,873,859 (GRCm39) |
R443G |
possibly damaging |
Het |
| Chd2 |
T |
C |
7: 73,157,620 (GRCm39) |
Q175R |
possibly damaging |
Het |
| Dpyd |
T |
A |
3: 118,597,783 (GRCm39) |
|
probably null |
Het |
| Dscam |
G |
T |
16: 96,857,660 (GRCm39) |
H117N |
possibly damaging |
Het |
| F13a1 |
A |
G |
13: 37,155,999 (GRCm39) |
Y205H |
probably damaging |
Het |
| Fat3 |
A |
C |
9: 15,918,085 (GRCm39) |
L1446R |
probably damaging |
Homo |
| Golga4 |
T |
C |
9: 118,382,525 (GRCm39) |
L515S |
probably damaging |
Het |
| Hoxb1 |
A |
T |
11: 96,256,728 (GRCm39) |
T26S |
probably benign |
Het |
| Igsf10 |
T |
G |
3: 59,238,481 (GRCm39) |
T567P |
probably damaging |
Het |
| Mepe |
A |
G |
5: 104,485,242 (GRCm39) |
I127M |
possibly damaging |
Het |
| Mpi |
A |
T |
9: 57,453,832 (GRCm39) |
M230K |
probably benign |
Homo |
| Myh4 |
A |
G |
11: 67,146,283 (GRCm39) |
D1447G |
probably null |
Homo |
| Or1f19 |
A |
G |
16: 3,411,027 (GRCm39) |
I256V |
possibly damaging |
Het |
| Or1j4 |
A |
G |
2: 36,740,819 (GRCm39) |
T254A |
probably benign |
Het |
| Panx2 |
T |
C |
15: 88,952,213 (GRCm39) |
Y227H |
probably damaging |
Homo |
| Pdzd7 |
A |
G |
19: 45,025,173 (GRCm39) |
W441R |
probably damaging |
Het |
| Poldip2 |
A |
G |
11: 78,410,020 (GRCm39) |
I267M |
probably damaging |
Homo |
| Pros1 |
T |
A |
16: 62,745,002 (GRCm39) |
V539E |
probably damaging |
Het |
| Sacs |
T |
C |
14: 61,450,425 (GRCm39) |
M4157T |
probably benign |
Het |
| Slc45a3 |
A |
G |
1: 131,909,075 (GRCm39) |
E424G |
probably benign |
Homo |
| Slc9a1 |
A |
G |
4: 133,149,457 (GRCm39) |
E761G |
probably benign |
Homo |
| Stab2 |
G |
A |
10: 86,691,035 (GRCm39) |
P2178L |
probably damaging |
Het |
| Syt4 |
C |
T |
18: 31,577,274 (GRCm39) |
V27I |
possibly damaging |
Homo |
| Thumpd1 |
T |
A |
7: 119,319,799 (GRCm39) |
K56* |
probably null |
Het |
| Tpr |
A |
G |
1: 150,269,313 (GRCm39) |
K19E |
possibly damaging |
Homo |
| Ttll10 |
A |
G |
4: 156,132,775 (GRCm39) |
I74T |
probably benign |
Het |
| Txnrd1 |
C |
T |
10: 82,702,823 (GRCm39) |
Q95* |
probably null |
Homo |
| Zc3h7b |
A |
G |
15: 81,662,872 (GRCm39) |
E421G |
possibly damaging |
Homo |
| Zc3hc1 |
G |
T |
6: 30,387,525 (GRCm39) |
D51E |
probably benign |
Homo |
|
| Other mutations in Lamb2 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01370:Lamb2
|
APN |
9 |
108,364,932 (GRCm39) |
splice site |
probably null |
|
|
IGL02072:Lamb2
|
APN |
9 |
108,359,107 (GRCm39) |
nonsense |
probably null |
|
|
IGL02079:Lamb2
|
APN |
9 |
108,359,312 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02087:Lamb2
|
APN |
9 |
108,364,318 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
IGL02193:Lamb2
|
APN |
9 |
108,366,559 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL02199:Lamb2
|
APN |
9 |
108,357,824 (GRCm39) |
missense |
possibly damaging |
0.49 |
|
IGL02201:Lamb2
|
APN |
9 |
108,364,741 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02468:Lamb2
|
APN |
9 |
108,364,348 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0053:Lamb2
|
UTSW |
9 |
108,363,936 (GRCm39) |
nonsense |
probably null |
|
|
R0053:Lamb2
|
UTSW |
9 |
108,363,936 (GRCm39) |
nonsense |
probably null |
|
|
R0122:Lamb2
|
UTSW |
9 |
108,363,713 (GRCm39) |
missense |
probably benign |
0.01 |
|
R0452:Lamb2
|
UTSW |
9 |
108,363,553 (GRCm39) |
unclassified |
probably benign |
|
|
R0524:Lamb2
|
UTSW |
9 |
108,361,571 (GRCm39) |
missense |
possibly damaging |
0.90 |
|
R0605:Lamb2
|
UTSW |
9 |
108,363,304 (GRCm39) |
unclassified |
probably benign |
|
|
R0737:Lamb2
|
UTSW |
9 |
108,360,993 (GRCm39) |
missense |
probably benign |
0.03 |
|
R1083:Lamb2
|
UTSW |
9 |
108,360,892 (GRCm39) |
missense |
probably benign |
|
|
R1159:Lamb2
|
UTSW |
9 |
108,358,607 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1283:Lamb2
|
UTSW |
9 |
108,359,007 (GRCm39) |
missense |
possibly damaging |
0.46 |
|
R1507:Lamb2
|
UTSW |
9 |
108,367,581 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1547:Lamb2
|
UTSW |
9 |
108,359,824 (GRCm39) |
missense |
probably benign |
0.00 |
|
R1576:Lamb2
|
UTSW |
9 |
108,357,506 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R1647:Lamb2
|
UTSW |
9 |
108,358,622 (GRCm39) |
critical splice donor site |
probably null |
|
|
R1678:Lamb2
|
UTSW |
9 |
108,360,885 (GRCm39) |
critical splice acceptor site |
probably null |
|
|
R1740:Lamb2
|
UTSW |
9 |
108,359,127 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1803:Lamb2
|
UTSW |
9 |
108,365,298 (GRCm39) |
missense |
probably benign |
|
|
R1846:Lamb2
|
UTSW |
9 |
108,364,586 (GRCm39) |
missense |
probably benign |
0.00 |
|
R1863:Lamb2
|
UTSW |
9 |
108,358,583 (GRCm39) |
missense |
probably benign |
0.13 |
|
R2184:Lamb2
|
UTSW |
9 |
108,357,752 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2262:Lamb2
|
UTSW |
9 |
108,357,809 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2338:Lamb2
|
UTSW |
9 |
108,359,340 (GRCm39) |
missense |
probably benign |
0.20 |
|
R2483:Lamb2
|
UTSW |
9 |
108,357,758 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4084:Lamb2
|
UTSW |
9 |
108,365,217 (GRCm39) |
missense |
probably benign |
0.17 |
|
R4164:Lamb2
|
UTSW |
9 |
108,367,497 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4295:Lamb2
|
UTSW |
9 |
108,363,410 (GRCm39) |
missense |
probably benign |
0.42 |
|
R4422:Lamb2
|
UTSW |
9 |
108,360,754 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R4497:Lamb2
|
UTSW |
9 |
108,363,997 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4880:Lamb2
|
UTSW |
9 |
108,361,226 (GRCm39) |
splice site |
probably null |
|
|
R4935:Lamb2
|
UTSW |
9 |
108,364,700 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
R4977:Lamb2
|
UTSW |
9 |
108,364,846 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R5152:Lamb2
|
UTSW |
9 |
108,364,937 (GRCm39) |
missense |
probably benign |
|
|
R5499:Lamb2
|
UTSW |
9 |
108,365,001 (GRCm39) |
missense |
possibly damaging |
0.50 |
|
R5724:Lamb2
|
UTSW |
9 |
108,357,950 (GRCm39) |
splice site |
probably null |
|
|
R5932:Lamb2
|
UTSW |
9 |
108,357,810 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5997:Lamb2
|
UTSW |
9 |
108,357,587 (GRCm39) |
missense |
possibly damaging |
0.65 |
|
R6052:Lamb2
|
UTSW |
9 |
108,364,811 (GRCm39) |
nonsense |
probably null |
|
|
R6142:Lamb2
|
UTSW |
9 |
108,362,817 (GRCm39) |
nonsense |
probably null |
|
|
R6245:Lamb2
|
UTSW |
9 |
108,365,398 (GRCm39) |
splice site |
probably null |
|
|
R6531:Lamb2
|
UTSW |
9 |
108,360,925 (GRCm39) |
missense |
possibly damaging |
0.78 |
|
R6557:Lamb2
|
UTSW |
9 |
108,365,599 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6562:Lamb2
|
UTSW |
9 |
108,364,207 (GRCm39) |
missense |
possibly damaging |
0.56 |
|
R6997:Lamb2
|
UTSW |
9 |
108,358,496 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7024:Lamb2
|
UTSW |
9 |
108,366,687 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7116:Lamb2
|
UTSW |
9 |
108,364,522 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7146:Lamb2
|
UTSW |
9 |
108,361,283 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R7261:Lamb2
|
UTSW |
9 |
108,358,496 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7288:Lamb2
|
UTSW |
9 |
108,365,523 (GRCm39) |
missense |
probably benign |
0.20 |
|
R7404:Lamb2
|
UTSW |
9 |
108,364,782 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7456:Lamb2
|
UTSW |
9 |
108,362,979 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R7472:Lamb2
|
UTSW |
9 |
108,363,347 (GRCm39) |
missense |
probably benign |
0.01 |
|
R7623:Lamb2
|
UTSW |
9 |
108,366,423 (GRCm39) |
missense |
possibly damaging |
0.62 |
|
R8125:Lamb2
|
UTSW |
9 |
108,364,722 (GRCm39) |
missense |
probably benign |
|
|
R8153:Lamb2
|
UTSW |
9 |
108,357,845 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R8154:Lamb2
|
UTSW |
9 |
108,357,845 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R8155:Lamb2
|
UTSW |
9 |
108,357,845 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R8156:Lamb2
|
UTSW |
9 |
108,357,845 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R8157:Lamb2
|
UTSW |
9 |
108,357,845 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R8419:Lamb2
|
UTSW |
9 |
108,365,563 (GRCm39) |
missense |
probably benign |
0.00 |
|
R8695:Lamb2
|
UTSW |
9 |
108,363,365 (GRCm39) |
missense |
probably benign |
0.08 |
|
R8825:Lamb2
|
UTSW |
9 |
108,362,460 (GRCm39) |
missense |
probably benign |
0.01 |
|
R9005:Lamb2
|
UTSW |
9 |
108,361,370 (GRCm39) |
critical splice donor site |
probably null |
|
|
R9315:Lamb2
|
UTSW |
9 |
108,364,366 (GRCm39) |
missense |
possibly damaging |
0.77 |
|
R9398:Lamb2
|
UTSW |
9 |
108,364,366 (GRCm39) |
missense |
possibly damaging |
0.77 |
|
R9419:Lamb2
|
UTSW |
9 |
108,356,959 (GRCm39) |
missense |
unknown |
|
|
R9450:Lamb2
|
UTSW |
9 |
108,357,760 (GRCm39) |
nonsense |
probably null |
|
|
R9495:Lamb2
|
UTSW |
9 |
108,358,006 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9514:Lamb2
|
UTSW |
9 |
108,358,006 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9529:Lamb2
|
UTSW |
9 |
108,363,477 (GRCm39) |
missense |
probably benign |
0.05 |
|
R9532:Lamb2
|
UTSW |
9 |
108,365,830 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9534:Lamb2
|
UTSW |
9 |
108,365,830 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9734:Lamb2
|
UTSW |
9 |
108,365,830 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Z1176:Lamb2
|
UTSW |
9 |
108,360,100 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Nature of Mutation |
 DNA sequencing using the SOLiD technique identified a T to C transition at position 1208 of the Lamb2 transcript in exon 10 of 33 total exons. The mutated nucleotide causes a valine to alanine substitution at amino acid 365 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
|
| Protein Function and Prediction |
The Lamb2 gene encodes a 1799 amino acid secreted protein that is a laminin subunit and mediates the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. Laminin β2 contains 13 laminin EGF-like domains, one laminin IV type B domain, and one Laminin N-terminal domain (Uniprot Q61292). Homozygotes for a targeted null mutation exhibit small size, severe proteinuria due to a defect in glomerular filtration, abnormalities of the retina and skeletal neuromuscular synapses, and lethality by 30 days of age. Humans with mutations in this gene display Pierson syndrome comprising congenital nephrotic syndrome with diffuse mesangial sclerosis and distinct ocular anomalies with microcoria (OMIM #609049).
The V365A change occurs in the second EGF-like domain, and is predicted to be benign by the PolyPhen program. |
| Posted On |
2010-05-03 |
Incidental Mutation