Incidental Mutation 'R0689:Actn4'
| ID |
61274 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Actn4
|
| Ensembl Gene |
ENSMUSG00000054808 |
| Gene Name |
actinin alpha 4 |
| Synonyms |
|
| MMRRC Submission |
038874-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.752)
|
| Stock # |
R0689 (G1)
|
| Quality Score |
142 |
|
Status
|
Validated
|
| Chromosome |
7 |
| Chromosomal Location |
28592673-28661765 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
C to A
at 28596474 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Glycine to Tryptophan
at position 674
(G674W)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000066068
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000066880]
[ENSMUST00000068045]
[ENSMUST00000127210]
[ENSMUST00000217157]
|
| AlphaFold |
P57780 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000066880
|
| SMART Domains |
Protein: ENSMUSP00000069055
Gene: ENSMUSG00000054083
| Domain | Start | End | E-Value | Type |
|---|
|
CysPc
|
27 |
349 |
7.8e-139 |
SMART |
|
calpain_III
|
353 |
529 |
7.47e-72 |
SMART |
|
SCOP:d1alva_
|
552 |
720 |
3e-14 |
SMART |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000068045
AA Change: G674W
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000066068
Gene: ENSMUSG00000054808
AA Change: G674W
| 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 benign
Transcript: ENSMUST00000127210
|
| SMART Domains |
Protein: ENSMUSP00000115436
Gene: ENSMUSG00000054808
| 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 |
noncoding transcript
Transcript: ENSMUST00000129338
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000143584
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000144909
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000150493
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000208299
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000207765
|
| Predicted Effect |
unknown
Transcript: ENSMUST00000216863
AA Change: G89W
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000217157
AA Change: G674W
PolyPhen 2
Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
|
| Meta Mutation Damage Score |
0.7279 |
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.5%
- 10x: 96.4%
- 20x: 91.1%
|
| Validation Efficiency |
99% (80/81) |
| 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: 64 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Adcy9 |
A |
G |
16: 4,130,668 (GRCm39) |
|
probably benign |
Het |
| Adgrv1 |
C |
T |
13: 81,623,224 (GRCm39) |
V3800I |
possibly damaging |
Het |
| Agl |
A |
G |
3: 116,587,277 (GRCm39) |
Y93H |
probably damaging |
Het |
| Aldh1a3 |
T |
A |
7: 66,051,753 (GRCm39) |
D400V |
probably benign |
Het |
| Bpifc |
A |
G |
10: 85,796,411 (GRCm39) |
|
probably benign |
Het |
| Cachd1 |
G |
T |
4: 100,832,073 (GRCm39) |
R745L |
probably damaging |
Het |
| Cadm3 |
T |
A |
1: 173,172,019 (GRCm39) |
T185S |
possibly damaging |
Het |
| Cep85l |
G |
T |
10: 53,224,943 (GRCm39) |
D215E |
probably damaging |
Het |
| Ces1g |
A |
G |
8: 94,055,035 (GRCm39) |
S221P |
probably damaging |
Het |
| Cfap206 |
C |
T |
4: 34,722,668 (GRCm39) |
V138M |
probably benign |
Het |
| Csmd3 |
A |
T |
15: 47,619,421 (GRCm39) |
F1714I |
probably benign |
Het |
| Cyp4f18 |
A |
G |
8: 72,749,812 (GRCm39) |
L279P |
probably benign |
Het |
| Dnah7a |
G |
A |
1: 53,659,840 (GRCm39) |
Q723* |
probably null |
Het |
| Dnaja2 |
A |
G |
8: 86,273,347 (GRCm39) |
|
probably benign |
Het |
| Dnajc6 |
T |
C |
4: 101,468,450 (GRCm39) |
V162A |
possibly damaging |
Het |
| Dok4 |
T |
C |
8: 95,597,547 (GRCm39) |
T3A |
probably benign |
Het |
| Efcab7 |
T |
C |
4: 99,761,981 (GRCm39) |
W424R |
probably damaging |
Het |
| Fah |
A |
T |
7: 84,242,392 (GRCm39) |
|
probably null |
Het |
| Fam120a |
T |
C |
13: 49,121,114 (GRCm39) |
D64G |
probably damaging |
Het |
| G3bp1 |
T |
C |
11: 55,389,452 (GRCm39) |
F383L |
probably damaging |
Het |
| Gas8 |
T |
G |
8: 124,250,845 (GRCm39) |
L106R |
probably damaging |
Het |
| Gykl1 |
T |
G |
18: 52,827,123 (GRCm39) |
N110K |
possibly damaging |
Het |
| Hsd3b3 |
G |
T |
3: 98,649,295 (GRCm39) |
L343I |
possibly damaging |
Het |
| Itch |
T |
A |
2: 155,024,098 (GRCm39) |
S234T |
possibly damaging |
Het |
| Itgbl1 |
A |
T |
14: 124,065,259 (GRCm39) |
I61F |
possibly damaging |
Het |
| Klf6 |
T |
A |
13: 5,915,115 (GRCm39) |
S185T |
probably damaging |
Het |
| Klk1b1 |
A |
C |
7: 43,620,143 (GRCm39) |
K202T |
probably benign |
Het |
| Liph |
T |
C |
16: 21,786,818 (GRCm39) |
Y268C |
probably damaging |
Het |
| Mroh2a |
C |
T |
1: 88,158,402 (GRCm39) |
R150* |
probably null |
Het |
| Mroh2a |
A |
G |
1: 88,186,386 (GRCm39) |
S64G |
probably benign |
Het |
| Myo9b |
G |
A |
8: 71,783,400 (GRCm39) |
D574N |
probably damaging |
Het |
| Nfyb |
G |
A |
10: 82,590,836 (GRCm39) |
A65V |
possibly damaging |
Het |
| Nipbl |
A |
G |
15: 8,322,562 (GRCm39) |
|
probably null |
Het |
| Olfm3 |
T |
A |
3: 114,916,194 (GRCm39) |
N355K |
probably benign |
Het |
| Or4k15c |
A |
T |
14: 50,321,689 (GRCm39) |
F150I |
probably benign |
Het |
| Pcdhb21 |
A |
G |
18: 37,648,370 (GRCm39) |
T500A |
probably benign |
Het |
| Pclo |
A |
G |
5: 14,764,033 (GRCm39) |
I4169V |
unknown |
Het |
| Pde4d |
T |
C |
13: 109,877,078 (GRCm39) |
S144P |
possibly damaging |
Het |
| Pgghg |
T |
C |
7: 140,523,191 (GRCm39) |
Y157H |
probably benign |
Het |
| Pkd1l3 |
C |
G |
8: 110,350,281 (GRCm39) |
D375E |
possibly damaging |
Het |
| Pla2g12a |
T |
C |
3: 129,674,947 (GRCm39) |
|
probably null |
Het |
| Ppp1r14d |
T |
C |
2: 119,060,093 (GRCm39) |
D63G |
probably damaging |
Het |
| Sema6a |
G |
A |
18: 47,423,112 (GRCm39) |
|
probably null |
Het |
| Sgip1 |
A |
T |
4: 102,823,449 (GRCm39) |
D690V |
probably damaging |
Het |
| Skp1 |
T |
C |
11: 52,134,592 (GRCm39) |
|
probably benign |
Het |
| Slc25a12 |
T |
C |
2: 71,141,837 (GRCm39) |
Y272C |
possibly damaging |
Het |
| Slc37a2 |
A |
G |
9: 37,146,846 (GRCm39) |
|
probably benign |
Het |
| Snx6 |
A |
T |
12: 54,810,441 (GRCm39) |
S112T |
probably benign |
Het |
| Sox6 |
A |
G |
7: 115,085,786 (GRCm39) |
V685A |
probably damaging |
Het |
| Taf2 |
A |
T |
15: 54,926,461 (GRCm39) |
V163E |
possibly damaging |
Het |
| Tg |
A |
T |
15: 66,711,253 (GRCm39) |
|
probably benign |
Het |
| Tmem30c |
A |
G |
16: 57,090,536 (GRCm39) |
Y224H |
probably damaging |
Het |
| Tmem45b |
T |
C |
9: 31,339,879 (GRCm39) |
N173D |
probably benign |
Het |
| Traf5 |
T |
C |
1: 191,729,837 (GRCm39) |
T405A |
probably benign |
Het |
| Trerf1 |
C |
T |
17: 47,630,300 (GRCm39) |
|
noncoding transcript |
Het |
| Triobp |
A |
T |
15: 78,844,188 (GRCm39) |
K135* |
probably null |
Het |
| Ttll9 |
T |
A |
2: 152,825,047 (GRCm39) |
D75E |
probably benign |
Het |
| Vmn1r63 |
T |
C |
7: 5,806,609 (GRCm39) |
I8V |
probably benign |
Het |
| Vmn2r77 |
A |
T |
7: 86,460,872 (GRCm39) |
I733F |
probably damaging |
Het |
| Vmn2r98 |
T |
C |
17: 19,300,782 (GRCm39) |
S595P |
possibly damaging |
Het |
| Zcchc2 |
C |
T |
1: 105,958,234 (GRCm39) |
Q504* |
probably null |
Het |
| Zfp2 |
T |
C |
11: 50,791,734 (GRCm39) |
D103G |
probably benign |
Het |
| Zfp59 |
A |
G |
7: 27,553,142 (GRCm39) |
K198R |
probably benign |
Het |
| Zfp64 |
C |
A |
2: 168,777,121 (GRCm39) |
|
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 |
|
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 |
|
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'- GGTGCTCACCTCCATTGTGTAGTTG -3'
(R):5'- AGCCATAGTGATTCTACCTGCCCC -3'
Sequencing Primer
(F):5'- ACCTCCATTGTGTAGTTGGTGTG -3'
(R):5'- GTGAAGGCACTTTCCCAAGTC -3'
|
| Posted On |
2013-07-30 |
Incidental Mutation