Incidental Mutation 'R5818:Actn4'
| ID |
449159 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Actn4
|
| Ensembl Gene |
ENSMUSG00000054808 |
| Gene Name |
actinin alpha 4 |
| Synonyms |
|
| MMRRC Submission |
043398-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.778)
|
| Stock # |
R5818 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
7 |
| Chromosomal Location |
28592673-28661765 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 28618444 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Isoleucine to Threonine
at position 72
(I72T)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000151028
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000068045]
[ENSMUST00000127210]
[ENSMUST00000140622]
[ENSMUST00000148196]
[ENSMUST00000217157]
|
| AlphaFold |
P57780 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000068045
AA Change: I72T
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000066068
Gene: ENSMUSG00000054808
AA Change: I72T
| 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 |
probably damaging
Transcript: ENSMUST00000127210
AA Change: I72T
PolyPhen 2
Score 0.972 (Sensitivity: 0.77; Specificity: 0.96)
|
| SMART Domains |
Protein: ENSMUSP00000115436
Gene: ENSMUSG00000054808
AA Change: I72T
| 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 |
probably benign
Transcript: ENSMUST00000140622
|
| SMART Domains |
Protein: ENSMUSP00000123210
Gene: ENSMUSG00000054808
| Domain | Start | End | E-Value | Type |
|---|
|
CH
|
3 |
68 |
1.09e-1 |
SMART |
|
CH
|
81 |
180 |
3.49e-24 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000148196
|
| SMART Domains |
Protein: ENSMUSP00000122268
Gene: ENSMUSG00000054808
| 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 |
noncoding transcript
Transcript: ENSMUST00000208229
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000217157
AA Change: I72T
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| Meta Mutation Damage Score |
0.9692 |
| Coding Region Coverage |
- 1x: 99.9%
- 3x: 99.6%
- 10x: 98.3%
- 20x: 95.1%
|
| Validation Efficiency |
100% (64/64) |
| 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: 54 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abca6 |
A |
T |
11: 110,110,469 (GRCm39) |
V560D |
probably damaging |
Het |
| Adam33 |
A |
T |
2: 130,896,278 (GRCm39) |
C440S |
possibly damaging |
Het |
| Bace1 |
T |
C |
9: 45,770,347 (GRCm39) |
I361T |
possibly damaging |
Het |
| Bend6 |
T |
C |
1: 33,922,654 (GRCm39) |
|
probably benign |
Het |
| Bpifb9a |
T |
G |
2: 154,104,215 (GRCm39) |
N219K |
probably damaging |
Het |
| Cacna1g |
C |
A |
11: 94,308,946 (GRCm39) |
K1634N |
probably damaging |
Het |
| Cdk18 |
A |
G |
1: 132,046,836 (GRCm39) |
|
probably null |
Het |
| Chrng |
G |
A |
1: 87,137,523 (GRCm39) |
V320I |
probably benign |
Het |
| Corin |
G |
T |
5: 72,592,738 (GRCm39) |
H87N |
probably benign |
Het |
| Cps1 |
A |
T |
1: 67,205,647 (GRCm39) |
I557F |
possibly damaging |
Het |
| Cyp4a29 |
T |
C |
4: 115,104,229 (GRCm39) |
V99A |
possibly damaging |
Het |
| Dach1 |
T |
C |
14: 98,406,120 (GRCm39) |
D209G |
probably damaging |
Het |
| Dgat1 |
G |
A |
15: 76,386,407 (GRCm39) |
|
probably benign |
Het |
| Eif1ad8 |
T |
G |
12: 87,563,830 (GRCm39) |
V55G |
possibly damaging |
Het |
| Fbxw26 |
G |
T |
9: 109,561,634 (GRCm39) |
R187S |
probably benign |
Het |
| Gabrd |
G |
A |
4: 155,472,818 (GRCm39) |
P122S |
probably damaging |
Het |
| Gm11677 |
C |
T |
11: 111,615,537 (GRCm39) |
|
noncoding transcript |
Het |
| Hif1a |
A |
G |
12: 73,986,338 (GRCm39) |
Q343R |
possibly damaging |
Het |
| Hyou1 |
G |
A |
9: 44,300,223 (GRCm39) |
|
probably null |
Het |
| Igfn1 |
A |
T |
1: 135,893,864 (GRCm39) |
I2072K |
possibly damaging |
Het |
| Itprid2 |
T |
A |
2: 79,474,937 (GRCm39) |
S299T |
probably damaging |
Het |
| Kash5 |
C |
T |
7: 44,843,383 (GRCm39) |
|
probably null |
Het |
| Kctd8 |
C |
T |
5: 69,454,054 (GRCm39) |
A328T |
probably benign |
Het |
| Krt10 |
A |
G |
11: 99,279,597 (GRCm39) |
Y188H |
probably damaging |
Het |
| Krtap4-16 |
T |
A |
11: 99,742,349 (GRCm39) |
Q17L |
unknown |
Het |
| Larp4b |
T |
A |
13: 9,208,596 (GRCm39) |
S416R |
probably benign |
Het |
| Lmtk2 |
G |
A |
5: 144,093,718 (GRCm39) |
V232M |
probably benign |
Het |
| Mroh4 |
A |
G |
15: 74,483,831 (GRCm39) |
I571T |
probably damaging |
Het |
| Myo15a |
G |
A |
11: 60,388,777 (GRCm39) |
R2021Q |
probably benign |
Het |
| Npl |
G |
A |
1: 153,411,661 (GRCm39) |
R63C |
probably damaging |
Het |
| Ntn4 |
A |
G |
10: 93,480,626 (GRCm39) |
I80V |
probably benign |
Het |
| Numb |
C |
T |
12: 83,872,028 (GRCm39) |
|
probably null |
Het |
| Nusap1 |
A |
C |
2: 119,465,994 (GRCm39) |
M205L |
possibly damaging |
Het |
| Onecut2 |
T |
A |
18: 64,474,046 (GRCm39) |
M180K |
possibly damaging |
Het |
| Or10d1b |
T |
C |
9: 39,613,661 (GRCm39) |
S135G |
probably benign |
Het |
| Pmfbp1 |
T |
C |
8: 110,265,311 (GRCm39) |
|
probably null |
Het |
| Ppfia1 |
T |
C |
7: 144,074,305 (GRCm39) |
|
probably benign |
Het |
| Ppm1b |
A |
G |
17: 85,301,147 (GRCm39) |
K9R |
probably benign |
Het |
| Rab11fip3 |
T |
C |
17: 26,235,090 (GRCm39) |
S608G |
probably damaging |
Het |
| Smim8 |
TTTAATGAAGAGCT |
TT |
4: 34,771,261 (GRCm39) |
|
probably benign |
Het |
| Sohlh2 |
A |
G |
3: 55,097,922 (GRCm39) |
T125A |
probably damaging |
Het |
| Tet1 |
C |
A |
10: 62,652,187 (GRCm39) |
M1610I |
possibly damaging |
Het |
| Tgfbr3 |
A |
T |
5: 107,280,869 (GRCm39) |
D630E |
probably benign |
Het |
| Thnsl2 |
T |
C |
6: 71,111,127 (GRCm39) |
D247G |
probably benign |
Het |
| Tmem198b |
G |
A |
10: 128,638,057 (GRCm39) |
R169W |
probably benign |
Het |
| Tmem201 |
G |
A |
4: 149,811,849 (GRCm39) |
A332V |
probably benign |
Het |
| Tsku |
T |
C |
7: 98,001,305 (GRCm39) |
D342G |
possibly damaging |
Het |
| Ucn2 |
A |
T |
9: 108,815,565 (GRCm39) |
H109L |
probably benign |
Het |
| Virma |
T |
G |
4: 11,513,319 (GRCm39) |
L391R |
possibly damaging |
Het |
| Vmn1r60 |
T |
A |
7: 5,548,098 (GRCm39) |
M1L |
probably benign |
Het |
| Vmn2r76 |
T |
C |
7: 85,879,142 (GRCm39) |
H386R |
probably benign |
Het |
| Zfp608 |
C |
T |
18: 55,028,468 (GRCm39) |
R1315Q |
probably benign |
Het |
| Zmym2 |
A |
G |
14: 57,183,986 (GRCm39) |
T983A |
probably benign |
Het |
| Zscan26 |
A |
G |
13: 21,629,931 (GRCm39) |
S65P |
probably benign |
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 |
|
R0845:Actn4
|
UTSW |
7 |
28,612,855 (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 |
|
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'- ACACAGGCTGAAACTGTCAAG -3'
(R):5'- TTAACAGCCTGCCTAGATCAC -3'
Sequencing Primer
(F):5'- TGAAACTGTCAAGCTTCCCAGTG -3'
(R):5'- AGCTGAATGTGGTCCCATGC -3'
|
| Posted On |
2016-12-20 |
Incidental Mutation