Incidental Mutation 'R6328:Lmna'
| ID |
510796 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Lmna
|
| Ensembl Gene |
ENSMUSG00000028063 |
| Gene Name |
lamin A |
| Synonyms |
lamin A/C, Dhe |
| MMRRC Submission |
044482-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R6328 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
3 |
| Chromosomal Location |
88388455-88413842 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 88393813 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Glutamine to Arginine
at position 255
(Q255R)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000113093
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000029699]
[ENSMUST00000036252]
[ENSMUST00000120377]
|
| AlphaFold |
P48678 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000029699
AA Change: Q255R
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000029699
Gene: ENSMUSG00000028063
AA Change: Q255R
| Domain | Start | End | E-Value | Type |
|---|
|
Filament
|
30 |
386 |
4.38e-45 |
SMART |
|
low complexity region
|
395 |
414 |
N/A |
INTRINSIC |
|
low complexity region
|
422 |
431 |
N/A |
INTRINSIC |
|
Pfam:LTD
|
433 |
544 |
4e-15 |
PFAM |
|
low complexity region
|
551 |
562 |
N/A |
INTRINSIC |
|
low complexity region
|
565 |
576 |
N/A |
INTRINSIC |
|
low complexity region
|
600 |
639 |
N/A |
INTRINSIC |
|
low complexity region
|
651 |
663 |
N/A |
INTRINSIC |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000036252
AA Change: Q143R
PolyPhen 2
Score 0.953 (Sensitivity: 0.79; Specificity: 0.95)
|
| SMART Domains |
Protein: ENSMUSP00000040265
Gene: ENSMUSG00000028063
AA Change: Q143R
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Filament
|
2 |
274 |
5.6e-66 |
PFAM |
|
low complexity region
|
283 |
302 |
N/A |
INTRINSIC |
|
Pfam:LTD
|
317 |
436 |
1.2e-22 |
PFAM |
|
low complexity region
|
439 |
450 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000120377
AA Change: Q255R
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000113093
Gene: ENSMUSG00000028063
AA Change: Q255R
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Filament
|
30 |
386 |
1.3e-95 |
PFAM |
|
low complexity region
|
395 |
414 |
N/A |
INTRINSIC |
|
Pfam:LTD
|
429 |
548 |
1.7e-22 |
PFAM |
|
low complexity region
|
551 |
562 |
N/A |
INTRINSIC |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000135494
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000147537
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000150496
|
| Meta Mutation Damage Score |
0.2463 |
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 99.9%
- 10x: 99.5%
- 20x: 98.4%
|
| Validation Efficiency |
98% (57/58) |
| MGI Phenotype |
FUNCTION: This gene encodes a protein that is a member of the lamin family. Nuclear lamins, intermediate filament-like proteins, are the major components of the nuclear lamina, a protein meshwork associated with the inner nuclear membrane. This meshwork is thought to maintain the integrity of the nuclear envelope, participate in chromatin organization, and regulate gene transcription. Vertebrate lamins consist of two types, A and B. This protein is an A-type and is proposed to be developmentally regulated. In mouse deficiency of this gene is associated with muscular dystrophy. Mouse lines with different mutations in this gene serve as pathophysiological models for several human laminopathies. In humans, mutations in this gene lead to several diseases: Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease, and Hutchinson-Gilford progeria syndrome. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, May 2013]
PHENOTYPE: Homozygotes for targeted mutations exhibit retarded postnatal growth, muscular dystrophy, reduced fat stores, micrognathy, abnormal dentition, impaired gonadal development, malformed scapulae, hyperkeratosis, and die by 8 weeks of age. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 56 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abat |
C |
T |
16: 8,420,300 (GRCm39) |
|
probably benign |
Het |
| Abcb10 |
G |
A |
8: 124,688,756 (GRCm39) |
R507W |
probably damaging |
Het |
| Actg1 |
T |
C |
11: 120,238,586 (GRCm39) |
D80G |
possibly damaging |
Het |
| Actr5 |
A |
G |
2: 158,477,264 (GRCm39) |
D405G |
possibly damaging |
Het |
| Ahnak |
C |
T |
19: 8,984,512 (GRCm39) |
T1932I |
probably benign |
Het |
| Ankk1 |
T |
A |
9: 49,327,371 (GRCm39) |
T603S |
possibly damaging |
Het |
| Atp13a3 |
A |
T |
16: 30,155,053 (GRCm39) |
F964I |
probably damaging |
Het |
| Atp6v1g3 |
A |
G |
1: 138,215,570 (GRCm39) |
T77A |
probably benign |
Het |
| Bccip |
A |
G |
7: 133,319,503 (GRCm39) |
H198R |
probably damaging |
Het |
| Bsx |
A |
T |
9: 40,785,519 (GRCm39) |
R16W |
probably damaging |
Het |
| Ccdc88b |
C |
T |
19: 6,826,406 (GRCm39) |
R1103Q |
probably damaging |
Het |
| Cd59a |
A |
C |
2: 103,941,103 (GRCm39) |
Y27S |
probably damaging |
Het |
| Cdk20 |
A |
G |
13: 64,584,413 (GRCm39) |
H162R |
probably damaging |
Het |
| Col6a2 |
C |
T |
10: 76,450,212 (GRCm39) |
E240K |
possibly damaging |
Het |
| Ddr2 |
A |
G |
1: 169,814,634 (GRCm39) |
V603A |
possibly damaging |
Het |
| Dgkz |
A |
G |
2: 91,772,980 (GRCm39) |
V359A |
probably benign |
Het |
| Dis3l2 |
T |
A |
1: 86,782,153 (GRCm39) |
S223T |
probably benign |
Het |
| Dpysl4 |
A |
G |
7: 138,679,734 (GRCm39) |
S535G |
probably benign |
Het |
| Dsp |
A |
T |
13: 38,380,982 (GRCm39) |
K1977* |
probably null |
Het |
| Dync2h1 |
A |
T |
9: 7,165,717 (GRCm39) |
S515T |
probably benign |
Het |
| Epg5 |
A |
G |
18: 78,072,179 (GRCm39) |
E2397G |
possibly damaging |
Het |
| Fam83d |
G |
A |
2: 158,627,096 (GRCm39) |
G262S |
probably damaging |
Het |
| Frmd4a |
A |
T |
2: 4,595,509 (GRCm39) |
T477S |
probably damaging |
Het |
| Gbp3 |
A |
G |
3: 142,274,819 (GRCm39) |
E382G |
probably benign |
Het |
| Gltp |
A |
T |
5: 114,808,572 (GRCm39) |
C157S |
possibly damaging |
Het |
| Grb10 |
A |
G |
11: 11,887,905 (GRCm39) |
S378P |
probably damaging |
Het |
| Gulo |
G |
T |
14: 66,240,080 (GRCm39) |
T126K |
probably damaging |
Het |
| H2-M10.6 |
T |
A |
17: 37,124,836 (GRCm39) |
M251K |
probably damaging |
Het |
| Hecw1 |
T |
C |
13: 14,422,205 (GRCm39) |
D967G |
possibly damaging |
Het |
| Htr3b |
A |
T |
9: 48,858,933 (GRCm39) |
D68E |
probably damaging |
Het |
| Igkv5-39 |
G |
T |
6: 69,877,489 (GRCm39) |
S89* |
probably null |
Het |
| Kctd4 |
C |
A |
14: 76,200,037 (GRCm39) |
|
probably benign |
Het |
| Lsmem1 |
A |
G |
12: 40,230,656 (GRCm39) |
I82T |
possibly damaging |
Het |
| Lyg2 |
T |
A |
1: 37,950,194 (GRCm39) |
M45L |
probably benign |
Het |
| Myo5b |
G |
A |
18: 74,750,064 (GRCm39) |
A176T |
probably damaging |
Het |
| Nudt5 |
A |
T |
2: 5,869,248 (GRCm39) |
K158I |
possibly damaging |
Het |
| Nufip1 |
C |
T |
14: 76,348,494 (GRCm39) |
P41L |
possibly damaging |
Het |
| Or4f14b |
A |
T |
2: 111,775,739 (GRCm39) |
W21R |
probably null |
Het |
| Or52z13 |
A |
T |
7: 103,247,073 (GRCm39) |
E183D |
probably damaging |
Het |
| Pcp2 |
T |
C |
8: 3,674,887 (GRCm39) |
D22G |
probably damaging |
Het |
| Pdk2 |
G |
C |
11: 94,930,228 (GRCm39) |
N69K |
possibly damaging |
Het |
| Pdlim7 |
G |
T |
13: 55,655,905 (GRCm39) |
|
probably benign |
Het |
| Ptprc |
C |
A |
1: 138,041,416 (GRCm39) |
E148* |
probably null |
Het |
| Rassf5 |
A |
T |
1: 131,108,405 (GRCm39) |
V225E |
probably damaging |
Het |
| Rbm6 |
A |
T |
9: 107,664,458 (GRCm39) |
M725K |
probably benign |
Het |
| Scn1a |
T |
A |
2: 66,103,660 (GRCm39) |
I1867F |
probably damaging |
Het |
| Sdk2 |
T |
A |
11: 113,684,581 (GRCm39) |
Q1960L |
probably damaging |
Het |
| Setx |
A |
G |
2: 29,064,474 (GRCm39) |
|
probably benign |
Het |
| Sgo2b |
T |
A |
8: 64,381,345 (GRCm39) |
R496* |
probably null |
Het |
| Slco1a1 |
C |
T |
6: 141,878,176 (GRCm39) |
V222I |
probably damaging |
Het |
| Sntg2 |
A |
C |
12: 30,308,013 (GRCm39) |
L224R |
probably damaging |
Het |
| Syt16 |
C |
A |
12: 74,313,467 (GRCm39) |
C464* |
probably null |
Het |
| Tapbpl |
T |
A |
6: 125,201,881 (GRCm39) |
S420C |
probably benign |
Het |
| Tax1bp1 |
A |
G |
6: 52,723,694 (GRCm39) |
E528G |
probably benign |
Het |
| Tmem168 |
T |
C |
6: 13,602,710 (GRCm39) |
T219A |
probably benign |
Het |
| Zfp180 |
T |
C |
7: 23,804,981 (GRCm39) |
F467L |
probably damaging |
Het |
|
| Other mutations in Lmna |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00468:Lmna
|
APN |
3 |
88,391,991 (GRCm39) |
missense |
probably benign |
0.05 |
|
IGL00933:Lmna
|
APN |
3 |
88,389,856 (GRCm39) |
missense |
possibly damaging |
0.73 |
|
IGL01347:Lmna
|
APN |
3 |
88,392,270 (GRCm39) |
missense |
probably benign |
0.42 |
|
IGL02881:Lmna
|
APN |
3 |
88,410,233 (GRCm39) |
missense |
possibly damaging |
0.56 |
|
P0029:Lmna
|
UTSW |
3 |
88,391,224 (GRCm39) |
missense |
possibly damaging |
0.88 |
|
R0606:Lmna
|
UTSW |
3 |
88,389,885 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1547:Lmna
|
UTSW |
3 |
88,389,658 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4751:Lmna
|
UTSW |
3 |
88,393,840 (GRCm39) |
missense |
possibly damaging |
0.87 |
|
R5157:Lmna
|
UTSW |
3 |
88,391,414 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5857:Lmna
|
UTSW |
3 |
88,389,838 (GRCm39) |
unclassified |
probably benign |
|
|
R6112:Lmna
|
UTSW |
3 |
88,393,928 (GRCm39) |
nonsense |
probably null |
|
|
R6263:Lmna
|
UTSW |
3 |
88,410,265 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6604:Lmna
|
UTSW |
3 |
88,395,589 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R7100:Lmna
|
UTSW |
3 |
88,392,297 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R8080:Lmna
|
UTSW |
3 |
88,393,868 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R8841:Lmna
|
UTSW |
3 |
88,391,920 (GRCm39) |
critical splice donor site |
probably null |
|
|
R9347:Lmna
|
UTSW |
3 |
88,393,548 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R9665:Lmna
|
UTSW |
3 |
88,389,793 (GRCm39) |
missense |
probably benign |
0.18 |
|
R9666:Lmna
|
UTSW |
3 |
88,389,857 (GRCm39) |
frame shift |
probably null |
|
|
R9667:Lmna
|
UTSW |
3 |
88,389,857 (GRCm39) |
frame shift |
probably null |
|
|
R9694:Lmna
|
UTSW |
3 |
88,389,857 (GRCm39) |
frame shift |
probably null |
|
|
RF013:Lmna
|
UTSW |
3 |
88,391,361 (GRCm39) |
missense |
probably benign |
0.00 |
|
Z1177:Lmna
|
UTSW |
3 |
88,393,543 (GRCm39) |
missense |
probably benign |
0.17 |
|
| Predicted Primers |
PCR Primer
(F):5'- GAGGTTGCTGTTCCTCTCAG -3'
(R):5'- GCTTCTAAGGAACCATTGCG -3'
Sequencing Primer
(F):5'- AGCAGACTGCCTGGCATTATC -3'
(R):5'- GCTTCTAAGGAACCATTGCGATGTTC -3'
|
| Posted On |
2018-04-02 |
Incidental Mutation