Mutagenetix > Incidental Mutation

Incidental Mutation 'R0243:Actn4'

37856

Institutional Source

Beutler Lab

Gene Symbol

Actn4

Ensembl Gene

ENSMUSG00000054808

Gene Name

actinin alpha 4

Synonyms

MMRRC Submission

038481-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.752) question?

Stock #

R0243 (G1)

Quality Score

155

Status

Validated

Chromosome

Chromosomal Location

28592673-28661765 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 28604823 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 325 (T325A)

Ref Sequence

ENSEMBL: ENSMUSP00000066068 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000068045] [ENSMUST00000127210] [ENSMUST00000140622] [ENSMUST00000217157]

AlphaFold

P57780

Predicted Effect

probably benign
Transcript: ENSMUST00000068045
AA Change: T325A

PolyPhen 2 Score 0.291 (Sensitivity: 0.91; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000066068
Gene: ENSMUSG00000054808
AA Change: T325A

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
AA Change: T325A

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000115436
Gene: ENSMUSG00000054808
AA Change: T325A

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

noncoding transcript
Transcript: ENSMUST00000144909

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000150493

Predicted Effect

probably benign
Transcript: ENSMUST00000217157
AA Change: T325A

PolyPhen 2 Score 0.176 (Sensitivity: 0.92; Specificity: 0.87)

Meta Mutation Damage Score

0.8272

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.2%
20x: 92.0%

Validation Efficiency

98% (148/151)

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: 139 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
0610040J01Rik	T	G	5: 64,055,806 (GRCm39)	Y181D	probably benign	Het
1700029H14Rik	A	G	8: 13,604,715 (GRCm39)	V196A	possibly damaging	Het
2410004B18Rik	A	G	3: 145,643,833 (GRCm39)	D7G	probably damaging	Het
Acap1	A	G	11: 69,776,252 (GRCm39)	V249A	probably damaging	Het
Acat2	A	T	17: 13,162,908 (GRCm39)	D313E	probably benign	Het
Adamdec1	C	T	14: 68,819,407 (GRCm39)		probably null	Het
Adat2	A	G	10: 13,429,037 (GRCm39)	T10A	probably benign	Het
Aff4	T	A	11: 53,288,685 (GRCm39)	S400R	possibly damaging	Het
Agbl2	C	T	2: 90,621,825 (GRCm39)	P104L	possibly damaging	Het
Alox12	G	T	11: 70,133,542 (GRCm39)	T594K	possibly damaging	Het
Als2	C	A	1: 59,254,546 (GRCm39)	K270N	probably benign	Het
Ankhd1	T	A	18: 36,767,787 (GRCm39)	C1235S	probably damaging	Het
Ankrd24	T	A	10: 81,470,778 (GRCm39)	I69N	probably damaging	Het
Aox4	G	A	1: 58,252,235 (GRCm39)	V37I	probably benign	Het
Arfgap3	A	G	15: 83,214,714 (GRCm39)		probably benign	Het
Arhgef4	T	A	1: 34,846,080 (GRCm39)		probably null	Het
Asic1	C	T	15: 99,596,498 (GRCm39)		probably benign	Het
Atp8b5	A	G	4: 43,366,057 (GRCm39)	N776S	probably benign	Het
Bbs7	A	G	3: 36,659,883 (GRCm39)	I184T	probably benign	Het
Bbs9	A	T	9: 22,425,297 (GRCm39)	H117L	probably damaging	Het
Bnip2	T	C	9: 69,902,787 (GRCm39)	W10R	probably damaging	Het
Brd4	G	T	17: 32,443,097 (GRCm39)	Q175K	probably benign	Het
Bysl	A	T	17: 47,917,821 (GRCm39)	V124E	possibly damaging	Het
Cadm3	A	G	1: 173,174,140 (GRCm39)		probably benign	Het
Cc2d2a	T	C	5: 43,853,980 (GRCm39)		probably benign	Het
Ccdc134	G	T	15: 82,025,147 (GRCm39)	E215D	probably damaging	Het
Celsr3	G	T	9: 108,720,923 (GRCm39)		probably benign	Het
Cntn5	T	A	9: 9,781,780 (GRCm39)	D428V	probably damaging	Het
Cog1	A	G	11: 113,547,821 (GRCm39)		probably benign	Het
Col11a2	G	T	17: 34,281,520 (GRCm39)		probably benign	Het
Cyp4f13	G	A	17: 33,143,943 (GRCm39)		probably benign	Het
Dffb	T	A	4: 154,049,835 (GRCm39)	K343*	probably null	Het
Dnah9	T	A	11: 65,802,678 (GRCm39)	I224F	possibly damaging	Het
Dolk	A	T	2: 30,176,031 (GRCm39)	C5S	probably benign	Het
Dynlt2b	A	G	16: 32,245,705 (GRCm39)	D118G	probably damaging	Het
Ebf1	A	T	11: 44,759,915 (GRCm39)		probably benign	Het
Elac1	A	G	18: 73,875,434 (GRCm39)	L199P	probably damaging	Het
Elmod1	A	C	9: 53,842,831 (GRCm39)		probably benign	Het
Ep400	A	C	5: 110,872,273 (GRCm39)		probably benign	Het
F10	A	T	8: 13,098,196 (GRCm39)	N133I	probably damaging	Het
Fasn	A	G	11: 120,706,141 (GRCm39)	Y1068H	probably benign	Het
Fbxo24	T	C	5: 137,622,819 (GRCm39)	E12G	probably damaging	Het
Fer	G	T	17: 64,385,941 (GRCm39)	L304F	probably benign	Het
Filip1	A	C	9: 79,726,285 (GRCm39)	L778R	probably damaging	Het
Fli1	A	T	9: 32,335,277 (GRCm39)	I385N	probably benign	Het
Fpgs	A	T	2: 32,582,506 (GRCm39)	L89*	probably null	Het
Gab2	T	G	7: 96,948,448 (GRCm39)	I346R	probably damaging	Het
Gm10764	G	A	10: 87,126,841 (GRCm39)	G83R	unknown	Het
Gpr83	G	T	9: 14,776,138 (GRCm39)	C153F	possibly damaging	Het
Gtf3c3	A	G	1: 54,442,695 (GRCm39)	L783P	possibly damaging	Het
Gys2	A	G	6: 142,418,394 (GRCm39)		probably benign	Het
Heatr9	C	T	11: 83,404,164 (GRCm39)	V378I	possibly damaging	Het
Helz	A	T	11: 107,528,740 (GRCm39)	Y920F	possibly damaging	Het
Inpp5f	A	T	7: 128,296,907 (GRCm39)	Q459L	probably damaging	Het
Ints12	T	C	3: 132,814,806 (GRCm39)	S338P	probably benign	Het
Kif13a	T	C	13: 46,944,827 (GRCm39)	T925A	probably benign	Het
Kif1a	C	T	1: 92,969,815 (GRCm39)	V1051I	probably damaging	Het
Kif7	T	A	7: 79,349,308 (GRCm39)	H1119L	possibly damaging	Het
Kmt2d	C	T	15: 98,748,018 (GRCm39)		probably benign	Het
Krt90	C	T	15: 101,471,110 (GRCm39)	G51S	possibly damaging	Het
Krtap31-2	A	T	11: 99,827,572 (GRCm39)	I135F	possibly damaging	Het
Lrp2	T	C	2: 69,258,974 (GRCm39)	E4572G	probably benign	Het
Mapk8ip1	T	C	2: 92,216,289 (GRCm39)	E493G	probably damaging	Het
Matk	T	G	10: 81,094,326 (GRCm39)	L28V	probably benign	Het
Mcc	T	A	18: 44,892,366 (GRCm39)	T83S	probably benign	Het
Mtch1	A	T	17: 29,559,080 (GRCm39)	M204K	possibly damaging	Het
Muc4	T	G	16: 32,586,120 (GRCm39)	C2622G	possibly damaging	Het
Myo5a	G	A	9: 75,093,405 (GRCm39)		probably null	Het
Myoz3	T	C	18: 60,712,023 (GRCm39)	Y185C	probably damaging	Het
Nnmt	A	G	9: 48,503,438 (GRCm39)	V196A	probably benign	Het
Nr2f2	G	C	7: 70,009,923 (GRCm39)	P52R	probably damaging	Het
Nup214	T	A	2: 31,888,069 (GRCm39)		probably benign	Het
Or2aj4	T	G	16: 19,385,044 (GRCm39)	E196D	probably damaging	Het
Or2y13	T	C	11: 49,414,739 (GRCm39)	L63P	probably damaging	Het
Or4c126	T	A	2: 89,824,150 (GRCm39)	F138I	probably benign	Het
Pank3	T	C	11: 35,672,543 (GRCm39)		probably benign	Het
Parm1	A	T	5: 91,742,153 (GRCm39)	N174Y	possibly damaging	Het
Pcgf2	A	T	11: 97,583,244 (GRCm39)		probably null	Het
Pclo	A	T	5: 14,825,434 (GRCm39)	K4661M	unknown	Het
Pcsk7	A	C	9: 45,827,357 (GRCm39)	S375R	probably damaging	Het
Pdzrn4	G	T	15: 92,668,200 (GRCm39)	S784I	possibly damaging	Het
Pex6	T	A	17: 47,034,663 (GRCm39)		probably null	Het
Pi4ka	C	T	16: 17,115,499 (GRCm39)	V1384M	probably benign	Het
Polr3f	T	A	2: 144,378,195 (GRCm39)		probably benign	Het
Ppp2r3d	A	T	9: 101,089,483 (GRCm39)	V280E	probably damaging	Het
Prdm14	C	T	1: 13,192,672 (GRCm39)	G356R	probably damaging	Het
Prepl	A	G	17: 85,372,466 (GRCm39)		probably null	Het
Primpol	T	C	8: 47,052,849 (GRCm39)	D154G	probably damaging	Het
Ptchd4	A	C	17: 42,814,307 (GRCm39)	H736P	probably damaging	Het
Rab11fip1	A	G	8: 27,642,253 (GRCm39)	S849P	probably damaging	Het
Rap1gap	T	A	4: 137,446,662 (GRCm39)	D405E	probably damaging	Het
Rbm26	T	C	14: 105,369,374 (GRCm39)	T686A	probably benign	Het
Resf1	T	C	6: 149,227,739 (GRCm39)	Y262H	probably damaging	Het
Rint1	A	G	5: 24,021,930 (GRCm39)		probably benign	Het
Rnasek	G	T	11: 70,129,266 (GRCm39)	Y62*	probably null	Het
Rnf17	T	G	14: 56,719,541 (GRCm39)	N930K	possibly damaging	Het
Sap130	A	G	18: 31,813,734 (GRCm39)		probably benign	Het
Sectm1b	T	A	11: 120,946,611 (GRCm39)	I95F	probably damaging	Het
Sema4f	A	T	6: 82,916,447 (GRCm39)	I53N	possibly damaging	Het
Shld1	T	C	2: 132,592,559 (GRCm39)	V202A	probably benign	Het
Siglec1	T	C	2: 130,927,396 (GRCm39)	T137A	probably damaging	Het
Six5	A	C	7: 18,830,947 (GRCm39)		probably null	Het
Slc22a30	A	T	19: 8,322,721 (GRCm39)	I345N	probably benign	Het
Slc25a27	A	T	17: 43,954,518 (GRCm39)	M316K	probably benign	Het
Slc2a8	A	T	2: 32,870,116 (GRCm39)		probably benign	Het
Snx1	G	A	9: 66,008,608 (GRCm39)		probably benign	Het
Spag17	A	G	3: 99,992,684 (GRCm39)	T1727A	probably benign	Het
Spata20	T	C	11: 94,372,472 (GRCm39)	D633G	probably benign	Het
Spock1	C	T	13: 57,583,922 (GRCm39)		probably null	Het
Sra1	A	T	18: 36,808,759 (GRCm39)	Y291*	probably null	Het
Sspo	C	A	6: 48,470,120 (GRCm39)	P4520T	probably damaging	Het
Stat4	A	G	1: 52,051,016 (GRCm39)	N25S	probably benign	Het
Tbx18	A	T	9: 87,597,569 (GRCm39)		probably benign	Het
Tep1	T	A	14: 51,084,444 (GRCm39)	I187F	probably damaging	Het
Tfap2b	A	T	1: 19,304,347 (GRCm39)	I368F	probably damaging	Het
Tmtc1	A	T	6: 148,148,335 (GRCm39)	L711Q	probably damaging	Het
Tmx3	T	A	18: 90,556,613 (GRCm39)		probably benign	Het
Tnc	G	T	4: 63,888,657 (GRCm39)	T1803K	probably damaging	Het
Tnfrsf21	C	T	17: 43,349,104 (GRCm39)	H239Y	probably benign	Het
Tpgs1	C	T	10: 79,511,700 (GRCm39)	P281S	probably benign	Het
Trim45	A	G	3: 100,837,160 (GRCm39)	R499G	probably benign	Het
Tulp3	A	T	6: 128,302,921 (GRCm39)	Y299*	probably null	Het
Ube4a	A	T	9: 44,857,476 (GRCm39)		probably benign	Het
Ubr3	T	G	2: 69,781,749 (GRCm39)	S642R	probably damaging	Het
Vcpip1	A	T	1: 9,817,431 (GRCm39)	Y317*	probably null	Het
Vmn1r115	G	A	7: 20,578,327 (GRCm39)	T195I	probably benign	Het
Vmn1r226	G	A	17: 20,907,839 (GRCm39)	V24I	probably benign	Het
Wdr41	C	T	13: 95,153,914 (GRCm39)	A321V	probably damaging	Het
Wfdc5	T	C	2: 164,020,755 (GRCm39)	N44D	probably benign	Het
Wnt7b	C	A	15: 85,443,103 (GRCm39)		probably null	Het
Zfp108	T	C	7: 23,961,208 (GRCm39)	S600P	possibly damaging	Het
Zfp267	A	G	3: 36,219,303 (GRCm39)	H442R	possibly damaging	Het
Zfp385b	A	G	2: 77,246,072 (GRCm39)		probably null	Het
Zfp395	T	C	14: 65,623,929 (GRCm39)	S133P	probably benign	Het
Zfp407	T	A	18: 84,576,836 (GRCm39)	M1426L	probably damaging	Het
Zfp641	T	G	15: 98,187,008 (GRCm39)	N191T	possibly damaging	Het
Zfp687	T	C	3: 94,918,864 (GRCm39)	S303G	probably damaging	Het
Zfp759	T	A	13: 67,286,877 (GRCm39)	F143I	possibly damaging	Het
Zgrf1	G	C	3: 127,409,095 (GRCm39)	E1690Q	probably 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
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
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'- CCTGCCCCAAAGGCTGATTTACAAC -3'
(R):5'- TCCCACTTCCCGTAAGCTGAAGAG -3'

Sequencing Primer
(F):5'- ATGGCAGCCAAGCTTTATGC -3'
(R):5'- TAAGCTGAAGAGGCAGTCTTTCC -3'

Posted On

2013-05-23