Mutagenetix > Incidental Mutation

Incidental Mutation 'R1469:Actn4'

197816

Institutional Source

Beutler Lab

Gene Symbol

Actn4

Ensembl Gene

ENSMUSG00000054808

Gene Name

actinin alpha 4

Synonyms

MMRRC Submission

039522-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.752) question?

Stock #

R1469 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

28592673-28661765 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 28604753 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 348 (V348A)

Ref Sequence

ENSEMBL: ENSMUSP00000151028 (fasta)

Gene Model

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

AlphaFold

P57780

Predicted Effect

probably benign
Transcript: ENSMUST00000068045
AA Change: V348A

PolyPhen 2 Score 0.060 (Sensitivity: 0.94; Specificity: 0.84)

SMART Domains

Protein: ENSMUSP00000066068
Gene: ENSMUSG00000054808
AA Change: V348A

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: V348A

PolyPhen 2 Score 0.010 (Sensitivity: 0.96; Specificity: 0.77)

SMART Domains

Protein: ENSMUSP00000115436
Gene: ENSMUSG00000054808
AA Change: V348A

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: V348A

PolyPhen 2 Score 0.151 (Sensitivity: 0.92; Specificity: 0.87)

Meta Mutation Damage Score

0.2618

Coding Region Coverage

1x: 97.4%
3x: 96.7%
10x: 94.8%
20x: 90.6%

Validation Efficiency

98% (95/97)

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: 102 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aasdh	A	T	5: 77,039,526 (GRCm39)	V261E	probably damaging	Het
Abca15	A	G	7: 119,981,720 (GRCm39)	E1058G	probably benign	Het
Abcb5	T	G	12: 118,831,681 (GRCm39)	I1224L	possibly damaging	Het
Agtr1b	A	T	3: 20,369,664 (GRCm39)	L314H	probably damaging	Het
Ankrd55	T	C	13: 112,504,460 (GRCm39)	M402T	probably benign	Het
Antxrl	T	C	14: 33,789,388 (GRCm39)		probably benign	Het
Asap2	A	G	12: 21,263,180 (GRCm39)	Q265R	probably benign	Het
Atp2b4	G	A	1: 133,634,677 (GRCm39)	R1124C	probably damaging	Het
Atp2c1	A	T	9: 105,312,351 (GRCm39)	C353*	probably null	Het
Atp8b5	T	A	4: 43,291,733 (GRCm39)		probably null	Het
Baz1b	T	A	5: 135,246,833 (GRCm39)	Y761N	probably damaging	Het
Bend6	A	G	1: 33,903,824 (GRCm39)	V38A	probably benign	Het
Camk1g	T	C	1: 193,044,399 (GRCm39)	E5G	possibly damaging	Het
Ccdc14	T	A	16: 34,527,152 (GRCm39)	H352Q	probably damaging	Het
Cdh2	A	G	18: 16,757,324 (GRCm39)	V641A	possibly damaging	Het
Celsr2	C	A	3: 108,321,424 (GRCm39)	D463Y	probably damaging	Het
Cldn16	C	A	16: 26,292,930 (GRCm39)		probably benign	Het
Clec7a	A	C	6: 129,449,535 (GRCm39)		probably benign	Het
Cnih2	T	C	19: 5,143,730 (GRCm39)	Y142C	probably damaging	Het
Coa5	T	A	1: 37,459,681 (GRCm39)	R71*	probably null	Het
Csmd3	A	T	15: 47,532,598 (GRCm39)	Y2532*	probably null	Het
Cytl1	A	T	5: 37,892,991 (GRCm39)	M34L	probably benign	Het
Dctn1	T	A	6: 83,169,871 (GRCm39)	I590N	probably damaging	Het
Dhx57	T	C	17: 80,561,847 (GRCm39)	H889R	probably damaging	Het
Dock10	A	G	1: 80,490,275 (GRCm39)	I1948T	probably benign	Het
Dock3	A	T	9: 106,832,908 (GRCm39)	N1034K	probably benign	Het
Dzip1l	G	A	9: 99,541,829 (GRCm39)		probably null	Het
Eif4g1	T	A	16: 20,498,758 (GRCm39)	V439E	possibly damaging	Het
Eml5	T	C	12: 98,825,082 (GRCm39)	I712V	probably benign	Het
Entrep1	G	A	19: 23,950,970 (GRCm39)	T537I	probably benign	Het
Epha3	C	T	16: 63,473,857 (GRCm39)	G300D	probably damaging	Het
Erbb4	A	C	1: 68,599,841 (GRCm39)	S79A	probably damaging	Het
Gclc	T	C	9: 77,688,419 (GRCm39)	V205A	probably benign	Het
Gdpd4	A	G	7: 97,623,673 (GRCm39)		probably null	Het
Gm11564	C	T	11: 99,706,058 (GRCm39)	C124Y	unknown	Het
Gm16494	T	C	17: 47,327,770 (GRCm39)	E38G	probably damaging	Het
Gtf2h1	T	C	7: 46,454,549 (GRCm39)		probably null	Het
Gtsf2	G	T	15: 103,349,644 (GRCm39)	R68S	probably benign	Het
Heatr5b	T	C	17: 79,115,813 (GRCm39)	Q881R	probably damaging	Het
Hmox1	C	A	8: 75,825,463 (GRCm39)	L236I	probably benign	Het
Ighv8-12	T	C	12: 115,611,963 (GRCm39)	I7V	probably benign	Het
Itprip	A	G	19: 47,885,314 (GRCm39)	Y434H	probably damaging	Het
Izumo1	T	C	7: 45,272,437 (GRCm39)	S73P	probably damaging	Het
Kifbp	A	T	10: 62,395,229 (GRCm39)	F471Y	probably damaging	Het
Knl1	A	G	2: 118,901,827 (GRCm39)	N1176S	possibly damaging	Het
Limch1	T	C	5: 67,039,323 (GRCm39)		probably benign	Het
Mecom	A	T	3: 30,034,197 (GRCm39)	L493Q	probably damaging	Het
Mprip	T	C	11: 59,650,016 (GRCm39)	V1240A	probably damaging	Het
Mrpl3	T	C	9: 104,954,201 (GRCm39)	S302P	probably damaging	Het
Muc19	T	C	15: 91,758,498 (GRCm39)		noncoding transcript	Het
Mycbp2	T	C	14: 103,425,956 (GRCm39)	T2390A	probably damaging	Het
Myo1c	T	C	11: 75,560,787 (GRCm39)	S766P	probably damaging	Het
Myo9b	A	G	8: 71,743,680 (GRCm39)	Q247R	probably damaging	Het
Nav3	G	A	10: 109,596,369 (GRCm39)	T1423I	probably damaging	Het
Nefh	A	T	11: 4,890,066 (GRCm39)	I851N	probably benign	Het
Nup98	T	C	7: 101,788,008 (GRCm39)	T1004A	probably benign	Het
Or1e17	T	C	11: 73,831,383 (GRCm39)	F104L	probably benign	Het
Or1e22	G	A	11: 73,377,149 (GRCm39)	S167L	possibly damaging	Het
Or5k8	G	A	16: 58,644,973 (GRCm39)	T33I	probably benign	Het
Or5p76	T	C	7: 108,122,411 (GRCm39)	T249A	probably benign	Het
Osgin1	G	T	8: 120,172,124 (GRCm39)	R306L	possibly damaging	Het
Otof	A	G	5: 30,537,571 (GRCm39)	L1246P	probably benign	Het
Pde8a	T	A	7: 80,952,019 (GRCm39)	N273K	probably damaging	Het
Phf14	T	A	6: 11,933,726 (GRCm39)	M196K	possibly damaging	Het
Pkd1l3	T	C	8: 110,373,585 (GRCm39)	S1374P	possibly damaging	Het
Pkhd1l1	T	C	15: 44,400,282 (GRCm39)	V2142A	probably benign	Het
Plb1	A	G	5: 32,512,170 (GRCm39)	E1318G	possibly damaging	Het
Plekhh2	A	G	17: 84,883,199 (GRCm39)	I756V	probably benign	Het
Prag1	A	T	8: 36,613,452 (GRCm39)		probably benign	Het
Primpol	A	G	8: 47,046,672 (GRCm39)	V208A	probably benign	Het
Ptch2	C	A	4: 116,965,662 (GRCm39)	A389E	probably benign	Het
Pzp	A	G	6: 128,489,319 (GRCm39)	Y431H	probably benign	Het
Rnf43	G	A	11: 87,622,233 (GRCm39)	G445R	probably damaging	Het
Scn5a	A	T	9: 119,362,727 (GRCm39)		probably null	Het
Sf3a1	A	T	11: 4,125,380 (GRCm39)		probably benign	Het
Shisa9	T	A	16: 11,802,935 (GRCm39)	M164K	probably damaging	Het
Skint1	A	G	4: 111,882,708 (GRCm39)	I251V	probably benign	Het
Slc16a14	C	T	1: 84,907,182 (GRCm39)	D31N	probably damaging	Het
Slc22a13	T	C	9: 119,022,361 (GRCm39)	S548G	possibly damaging	Het
Slc4a9	T	C	18: 36,664,154 (GRCm39)	F316L	probably benign	Het
Smchd1	C	T	17: 71,656,725 (GRCm39)	R1914H	probably damaging	Het
Snx16	C	T	3: 10,499,431 (GRCm39)	D200N	probably damaging	Het
Spock3	A	G	8: 63,404,934 (GRCm39)	D34G	probably damaging	Het
Sspo	T	C	6: 48,467,916 (GRCm39)	C4154R	probably damaging	Het
Sytl3	C	T	17: 6,954,723 (GRCm39)	A131V	probably benign	Het
Tacc1	T	A	8: 25,672,271 (GRCm39)	D319V	probably benign	Het
Tead1	A	T	7: 112,475,391 (GRCm39)	K234I	probably damaging	Het
Tgfbrap1	C	T	1: 43,114,618 (GRCm39)	V161I	probably benign	Het
Tmem94	T	C	11: 115,685,917 (GRCm39)		probably benign	Het
Tnfaip3	A	G	10: 18,884,017 (GRCm39)	V121A	probably damaging	Het
Tnnt2	A	G	1: 135,779,793 (GRCm39)	T297A	possibly damaging	Het
Trappc11	G	A	8: 47,957,000 (GRCm39)	L809F	probably damaging	Het
Ttn	T	C	2: 76,601,869 (GRCm39)	I18598V	probably benign	Het
Ube2o	A	G	11: 116,436,650 (GRCm39)		probably benign	Het
Unc5a	A	G	13: 55,144,232 (GRCm39)	N186D	probably damaging	Het
Uqcrfs1	C	A	13: 30,724,784 (GRCm39)	G252V	probably damaging	Het
Vmn2r115	T	C	17: 23,564,992 (GRCm39)	I293T	probably damaging	Het
Vmn2r9	T	C	5: 108,991,694 (GRCm39)	T556A	probably benign	Het
Wnk1	G	A	6: 119,927,645 (GRCm39)		probably benign	Het
Ythdc2	T	A	18: 44,997,529 (GRCm39)	Y1029N	probably benign	Het
Zfp451	T	A	1: 33,808,894 (GRCm39)	K989M	possibly damaging	Het
Zfpm1	C	T	8: 123,062,585 (GRCm39)	T548M	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
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	28,597,691 (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'- CTGATTTACAACGATGGCAGC -3'
(R):5'- TAAGCTGAAGAGGCAGTCTTTCC -3'

Posted On

2014-05-23