Incidental Mutation 'R0845:Actn4'
ID |
77319 |
Institutional Source |
Beutler Lab
|
Gene Symbol |
Actn4
|
Ensembl Gene |
ENSMUSG00000054808 |
Gene Name |
actinin alpha 4 |
Synonyms |
|
MMRRC Submission |
039024-MU
|
Accession Numbers |
|
Essential gene? |
Probably essential
(E-score: 0.752)
|
Stock # |
R0845 (G1)
|
Quality Score |
225 |
Status
|
Validated
|
Chromosome |
7 |
Chromosomal Location |
28592673-28661765 bp(-) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
G to T
at 28612855 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Alanine to Glutamic Acid
at position 116
(A116E)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000122268
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000068045]
[ENSMUST00000127210]
[ENSMUST00000140622]
[ENSMUST00000148196]
[ENSMUST00000217157]
|
AlphaFold |
P57780 |
Predicted Effect |
probably benign
Transcript: ENSMUST00000068045
AA Change: A201E
PolyPhen 2
Score 0.346 (Sensitivity: 0.90; Specificity: 0.89)
|
SMART Domains |
Protein: ENSMUSP00000066068 Gene: ENSMUSG00000054808 AA Change: A201E
Domain | Start | End | E-Value | Type |
low complexity region
|
14 |
30 |
N/A |
INTRINSIC |
CH
|
53 |
153 |
1.08e-24 |
SMART |
CH
|
166 |
265 |
3.49e-24 |
SMART |
SPEC
|
297 |
403 |
2.83e0 |
SMART |
SPEC
|
417 |
518 |
3.78e-23 |
SMART |
SPEC
|
532 |
639 |
8.64e-9 |
SMART |
SPEC
|
653 |
752 |
3.56e0 |
SMART |
EFh
|
770 |
798 |
1.92e-3 |
SMART |
EFh
|
811 |
839 |
1.56e-3 |
SMART |
efhand_Ca_insen
|
842 |
908 |
1.27e-36 |
SMART |
|
Predicted Effect |
possibly damaging
Transcript: ENSMUST00000127210
AA Change: A201E
PolyPhen 2
Score 0.862 (Sensitivity: 0.83; Specificity: 0.93)
|
SMART Domains |
Protein: ENSMUSP00000115436 Gene: ENSMUSG00000054808 AA Change: A201E
Domain | Start | End | E-Value | Type |
low complexity region
|
14 |
30 |
N/A |
INTRINSIC |
CH
|
53 |
153 |
1.08e-24 |
SMART |
CH
|
166 |
265 |
1.03e-21 |
SMART |
SPEC
|
297 |
403 |
2.83e0 |
SMART |
SPEC
|
417 |
518 |
3.78e-23 |
SMART |
|
Predicted Effect |
possibly damaging
Transcript: ENSMUST00000140622
AA Change: A116E
PolyPhen 2
Score 0.767 (Sensitivity: 0.85; Specificity: 0.92)
|
SMART Domains |
Protein: ENSMUSP00000123210 Gene: ENSMUSG00000054808 AA Change: A116E
Domain | Start | End | E-Value | Type |
CH
|
3 |
68 |
1.09e-1 |
SMART |
CH
|
81 |
180 |
3.49e-24 |
SMART |
|
Predicted Effect |
probably damaging
Transcript: ENSMUST00000148196
AA Change: A116E
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
SMART Domains |
Protein: ENSMUSP00000122268 Gene: ENSMUSG00000054808 AA Change: A116E
Domain | Start | End | E-Value | Type |
CH
|
3 |
68 |
1.09e-1 |
SMART |
Pfam:CH
|
82 |
133 |
4.5e-11 |
PFAM |
Pfam:CAMSAP_CH
|
89 |
133 |
9.1e-9 |
PFAM |
|
Predicted Effect |
possibly damaging
Transcript: ENSMUST00000217157
AA Change: A201E
PolyPhen 2
Score 0.696 (Sensitivity: 0.86; Specificity: 0.92)
|
Meta Mutation Damage Score |
0.6467 |
Coding Region Coverage |
- 1x: 99.3%
- 3x: 98.6%
- 10x: 96.9%
- 20x: 93.2%
|
Validation Efficiency |
96% (45/47) |
MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Alpha actinins belong to the spectrin gene superfamily which represents a diverse group of cytoskeletal proteins, including the alpha and beta spectrins and dystrophins. Alpha actinin is an actin-binding protein with multiple roles in different cell types. In nonmuscle cells, the cytoskeletal isoform is found along microfilament bundles and adherens-type junctions, where it is involved in binding actin to the membrane. In contrast, skeletal, cardiac, and smooth muscle isoforms are localized to the Z-disc and analogous dense bodies, where they help anchor the myofibrillar actin filaments. This gene encodes a nonmuscle, alpha actinin isoform which is concentrated in the cytoplasm, and thought to be involved in metastatic processes. Mutations in this gene have been associated with focal and segmental glomerulosclerosis. [provided by RefSeq, Jul 2008] PHENOTYPE: Mice homozygous for a disruption in this gene die either around birth or within a few months of birth. Those who do survive after birth show poor growth and kidney abnormalities including glomerulosclerosis. This is manifested functionally as proteinuria and abnormal blood urea nitrogen. [provided by MGI curators]
|
Allele List at MGI |
|
Other mutations in this stock |
Total: 44 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
Adamtsl3 |
A |
G |
7: 82,225,204 (GRCm39) |
I338V |
probably damaging |
Het |
Akap13 |
T |
G |
7: 75,375,128 (GRCm39) |
V1920G |
probably damaging |
Het |
Atp6v0d2 |
C |
T |
4: 19,880,055 (GRCm39) |
V281I |
probably benign |
Het |
AW209491 |
T |
G |
13: 14,811,607 (GRCm39) |
S153R |
probably damaging |
Het |
Brd7 |
A |
T |
8: 89,069,395 (GRCm39) |
Y433* |
probably null |
Het |
Bub1b |
A |
G |
2: 118,440,457 (GRCm39) |
H187R |
probably damaging |
Het |
Clstn2 |
T |
A |
9: 97,452,681 (GRCm39) |
Q242L |
probably benign |
Het |
Col1a2 |
G |
A |
6: 4,518,822 (GRCm39) |
|
probably benign |
Het |
Comt |
T |
C |
16: 18,226,711 (GRCm39) |
Y225C |
probably damaging |
Het |
Ctbs |
T |
A |
3: 146,160,862 (GRCm39) |
L143Q |
probably damaging |
Het |
Ctsw |
T |
C |
19: 5,515,489 (GRCm39) |
|
probably benign |
Het |
Dhx16 |
T |
C |
17: 36,194,194 (GRCm39) |
I435T |
probably damaging |
Het |
Dmxl1 |
T |
C |
18: 50,026,469 (GRCm39) |
F1859S |
probably damaging |
Het |
Glud1 |
A |
G |
14: 34,051,351 (GRCm39) |
|
probably benign |
Het |
Gm8220 |
A |
G |
14: 44,524,248 (GRCm39) |
H71R |
probably damaging |
Het |
Gnb1l |
A |
G |
16: 18,371,223 (GRCm39) |
E238G |
probably benign |
Het |
H2-T23 |
T |
C |
17: 36,341,475 (GRCm39) |
H332R |
probably benign |
Het |
Itga5 |
T |
A |
15: 103,259,196 (GRCm39) |
T744S |
probably benign |
Het |
Larp1 |
A |
G |
11: 57,938,576 (GRCm39) |
E453G |
probably benign |
Het |
Lrrk2 |
C |
A |
15: 91,640,165 (GRCm39) |
P1570Q |
probably benign |
Het |
Lrsam1 |
C |
T |
2: 32,843,455 (GRCm39) |
R150Q |
possibly damaging |
Het |
Mroh2a |
A |
G |
1: 88,186,386 (GRCm39) |
S64G |
probably benign |
Het |
Msln |
T |
C |
17: 25,969,770 (GRCm39) |
Y320C |
probably damaging |
Het |
Mtbp |
T |
C |
15: 55,426,486 (GRCm39) |
|
probably null |
Het |
Muc5b |
A |
G |
7: 141,404,183 (GRCm39) |
|
probably null |
Het |
Mup21 |
A |
G |
4: 62,068,547 (GRCm39) |
S40P |
probably damaging |
Het |
Myh8 |
T |
C |
11: 67,177,090 (GRCm39) |
V414A |
probably damaging |
Het |
P2rx5 |
T |
C |
11: 73,056,400 (GRCm39) |
I108T |
probably damaging |
Het |
Paqr9 |
T |
C |
9: 95,442,793 (GRCm39) |
L261P |
probably damaging |
Het |
Pde5a |
A |
G |
3: 122,522,980 (GRCm39) |
D29G |
probably benign |
Het |
Phf11d |
A |
T |
14: 59,590,793 (GRCm39) |
M188K |
possibly damaging |
Het |
Pih1d1 |
A |
G |
7: 44,809,106 (GRCm39) |
D230G |
probably benign |
Het |
Pik3r1 |
G |
T |
13: 101,822,772 (GRCm39) |
D643E |
probably benign |
Het |
Rnf207 |
A |
G |
4: 152,396,521 (GRCm39) |
|
probably benign |
Het |
Septin9 |
T |
C |
11: 117,247,151 (GRCm39) |
|
probably benign |
Het |
Serinc1 |
A |
T |
10: 57,401,479 (GRCm39) |
S105T |
probably benign |
Het |
Slc8a1 |
A |
G |
17: 81,745,177 (GRCm39) |
S676P |
probably benign |
Het |
Srrm4 |
C |
T |
5: 116,582,944 (GRCm39) |
|
probably null |
Het |
Tcn2 |
T |
A |
11: 3,869,349 (GRCm39) |
D391V |
probably benign |
Het |
Tmem131 |
T |
C |
1: 36,855,303 (GRCm39) |
T808A |
probably damaging |
Het |
Ubqln3 |
G |
T |
7: 103,791,275 (GRCm39) |
Q272K |
probably damaging |
Het |
Unc79 |
T |
C |
12: 103,139,703 (GRCm39) |
|
probably benign |
Het |
Xpo6 |
G |
A |
7: 125,728,715 (GRCm39) |
|
probably benign |
Het |
Zfp667 |
A |
T |
7: 6,309,091 (GRCm39) |
K586N |
possibly damaging |
Het |
|
Other mutations in Actn4 |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
IGL01637:Actn4
|
APN |
7 |
28,604,109 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL02127:Actn4
|
APN |
7 |
28,597,305 (GRCm39) |
missense |
probably benign |
|
IGL02192:Actn4
|
APN |
7 |
28,597,825 (GRCm39) |
missense |
possibly damaging |
0.93 |
IGL02862:Actn4
|
APN |
7 |
28,611,659 (GRCm39) |
splice site |
probably benign |
|
IGL03339:Actn4
|
APN |
7 |
28,601,407 (GRCm39) |
missense |
probably damaging |
1.00 |
R0067:Actn4
|
UTSW |
7 |
28,610,995 (GRCm39) |
missense |
possibly damaging |
0.67 |
R0067:Actn4
|
UTSW |
7 |
28,610,995 (GRCm39) |
missense |
possibly damaging |
0.67 |
R0243:Actn4
|
UTSW |
7 |
28,604,823 (GRCm39) |
missense |
probably benign |
0.29 |
R0689:Actn4
|
UTSW |
7 |
28,596,474 (GRCm39) |
missense |
probably damaging |
1.00 |
R1469:Actn4
|
UTSW |
7 |
28,604,753 (GRCm39) |
missense |
probably benign |
0.15 |
R1469:Actn4
|
UTSW |
7 |
28,604,753 (GRCm39) |
missense |
probably benign |
0.15 |
R1469:Actn4
|
UTSW |
7 |
28,597,691 (GRCm39) |
splice site |
probably benign |
|
R1581:Actn4
|
UTSW |
7 |
28,598,071 (GRCm39) |
missense |
probably benign |
0.04 |
R1690:Actn4
|
UTSW |
7 |
28,610,950 (GRCm39) |
missense |
probably damaging |
1.00 |
R1962:Actn4
|
UTSW |
7 |
28,594,047 (GRCm39) |
missense |
probably damaging |
1.00 |
R2113:Actn4
|
UTSW |
7 |
28,597,549 (GRCm39) |
missense |
probably benign |
0.42 |
R2215:Actn4
|
UTSW |
7 |
28,618,178 (GRCm39) |
missense |
possibly damaging |
0.88 |
R2429:Actn4
|
UTSW |
7 |
28,597,496 (GRCm39) |
missense |
probably benign |
0.00 |
R3945:Actn4
|
UTSW |
7 |
28,611,661 (GRCm39) |
splice site |
probably null |
|
R3962:Actn4
|
UTSW |
7 |
28,597,647 (GRCm39) |
splice site |
probably null |
|
R3970:Actn4
|
UTSW |
7 |
28,661,457 (GRCm39) |
missense |
probably benign |
|
R4909:Actn4
|
UTSW |
7 |
28,598,082 (GRCm39) |
missense |
probably damaging |
1.00 |
R4985:Actn4
|
UTSW |
7 |
28,618,411 (GRCm39) |
missense |
probably damaging |
1.00 |
R5155:Actn4
|
UTSW |
7 |
28,661,442 (GRCm39) |
critical splice donor site |
probably null |
|
R5201:Actn4
|
UTSW |
7 |
28,615,680 (GRCm39) |
splice site |
probably null |
|
R5668:Actn4
|
UTSW |
7 |
28,603,975 (GRCm39) |
missense |
probably damaging |
1.00 |
R5818:Actn4
|
UTSW |
7 |
28,618,444 (GRCm39) |
missense |
probably damaging |
1.00 |
R6046:Actn4
|
UTSW |
7 |
28,604,044 (GRCm39) |
missense |
probably benign |
0.03 |
R6155:Actn4
|
UTSW |
7 |
28,595,566 (GRCm39) |
missense |
probably damaging |
1.00 |
R6559:Actn4
|
UTSW |
7 |
28,606,461 (GRCm39) |
missense |
possibly damaging |
0.87 |
R7224:Actn4
|
UTSW |
7 |
28,661,509 (GRCm39) |
missense |
probably benign |
0.08 |
R7225:Actn4
|
UTSW |
7 |
28,598,124 (GRCm39) |
missense |
probably damaging |
1.00 |
R7423:Actn4
|
UTSW |
7 |
28,593,680 (GRCm39) |
missense |
probably damaging |
0.97 |
R7665:Actn4
|
UTSW |
7 |
28,615,632 (GRCm39) |
missense |
probably damaging |
1.00 |
R7704:Actn4
|
UTSW |
7 |
28,596,467 (GRCm39) |
missense |
possibly damaging |
0.76 |
R8096:Actn4
|
UTSW |
7 |
28,601,338 (GRCm39) |
missense |
probably damaging |
1.00 |
R8096:Actn4
|
UTSW |
7 |
28,594,008 (GRCm39) |
missense |
possibly damaging |
0.88 |
R8954:Actn4
|
UTSW |
7 |
28,594,583 (GRCm39) |
missense |
probably damaging |
0.96 |
R8987:Actn4
|
UTSW |
7 |
28,596,398 (GRCm39) |
missense |
probably benign |
0.00 |
R9128:Actn4
|
UTSW |
7 |
28,593,929 (GRCm39) |
missense |
possibly damaging |
0.90 |
R9507:Actn4
|
UTSW |
7 |
28,606,397 (GRCm39) |
missense |
probably benign |
0.00 |
R9574:Actn4
|
UTSW |
7 |
28,594,864 (GRCm39) |
missense |
probably benign |
0.03 |
R9746:Actn4
|
UTSW |
7 |
28,618,431 (GRCm39) |
missense |
probably benign |
|
Z1088:Actn4
|
UTSW |
7 |
28,594,003 (GRCm39) |
missense |
probably damaging |
1.00 |
Z1177:Actn4
|
UTSW |
7 |
28,618,474 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Predicted Primers |
PCR Primer
(F):5'- AGGTGAGCAGATGGACGCTAACTC -3'
(R):5'- GCCTGCTGGACATGGGAATTAAGC -3'
Sequencing Primer
(F):5'- AGCTGTGAAGGTCAGCAATGG -3'
(R):5'- gaaaaactaccaccaaccacc -3'
|
Posted On |
2013-10-16 |