Mutagenetix > Incidental Mutation

Incidental Mutation 'R6046:Actn4'

483289

Institutional Source

Beutler Lab

Gene Symbol

Actn4

Ensembl Gene

ENSMUSG00000054808

Gene Name

actinin alpha 4

Synonyms

MMRRC Submission

044214-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.752) question?

Stock #

R6046 (G1)

Quality Score

170.009

Status

Validated

Chromosome

Chromosomal Location

28592673-28661765 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 28604044 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Valine at position 406 (I406V)

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: I406V

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000066068
Gene: ENSMUSG00000054808
AA Change: I406V

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: I406V

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

SMART Domains

Protein: ENSMUSP00000115436
Gene: ENSMUSG00000054808
AA Change: I406V

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: I406V

PolyPhen 2 Score 0.026 (Sensitivity: 0.95; Specificity: 0.81)

Meta Mutation Damage Score

0.1188

Coding Region Coverage

1x: 99.9%
3x: 99.5%
10x: 97.7%
20x: 92.8%

Validation Efficiency

100% (78/78)

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: 74 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abtb3	T	C	10: 85,223,947 (GRCm39)	V252A	unknown	Het
Acyp2	C	T	11: 30,456,354 (GRCm39)	E98K	possibly damaging	Het
Ank1	T	A	8: 23,606,114 (GRCm39)	F1124I	probably damaging	Het
Arhgap44	CTGCT	CTGCTTGCT	11: 64,922,910 (GRCm39)		probably null	Het
Atp9a	C	A	2: 168,476,790 (GRCm39)	V1000L	probably benign	Het
Bnip3	A	G	7: 138,511,033 (GRCm39)		probably benign	Het
Btnl6	T	A	17: 34,727,371 (GRCm39)	R386S	probably damaging	Het
Calcrl	A	G	2: 84,205,658 (GRCm39)	V11A	probably benign	Het
Cc2d1a	G	T	8: 84,863,571 (GRCm39)	A597D	possibly damaging	Het
Celsr3	A	G	9: 108,714,350 (GRCm39)	T1960A	probably benign	Het
Cfb	T	A	17: 35,081,078 (GRCm39)		probably null	Het
Chd8	A	G	14: 52,458,528 (GRCm39)	I860T	possibly damaging	Het
Col28a1	A	G	6: 8,168,102 (GRCm39)		probably null	Het
Crhr2	T	A	6: 55,068,277 (GRCm39)	T428S	probably damaging	Het
Crybg2	A	T	4: 133,819,388 (GRCm39)	I1753F	probably damaging	Het
Ctsq	A	T	13: 61,186,955 (GRCm39)	V46E	probably benign	Het
Cxcr1	T	C	1: 74,231,440 (GRCm39)	E194G	probably damaging	Het
Dop1a	A	T	9: 86,397,396 (GRCm39)	H900L	probably damaging	Het
Dpyd	T	A	3: 119,225,224 (GRCm39)	M999K	probably benign	Het
Gbp3	A	C	3: 142,273,560 (GRCm39)	D369A	possibly damaging	Het
Glmp	A	G	3: 88,232,495 (GRCm39)	E36G	probably damaging	Het
Gm10113	T	C	13: 46,330,919 (GRCm39)		noncoding transcript	Het
Gm6486	T	A	5: 3,120,846 (GRCm39)		noncoding transcript	Het
Gm973	T	G	1: 59,671,509 (GRCm39)	L891R	unknown	Het
Heatr3	C	T	8: 88,866,582 (GRCm39)	T8M	probably damaging	Het
Herc1	A	G	9: 66,352,831 (GRCm39)	M2106V	probably damaging	Het
Hfm1	A	T	5: 107,046,509 (GRCm39)		probably null	Het
Hspa14	A	G	2: 3,490,801 (GRCm39)	V462A	possibly damaging	Het
Hspa5	C	A	2: 34,665,761 (GRCm39)	T535K	possibly damaging	Het
Ift140	A	G	17: 25,274,563 (GRCm39)	D745G	probably benign	Het
Ift27	A	T	15: 78,057,981 (GRCm39)	C8S	possibly damaging	Het
Irak1bp1	G	A	9: 82,728,616 (GRCm39)	W182*	probably null	Het
Itga3	A	G	11: 94,953,541 (GRCm39)	I236T	probably benign	Het
Kctd15	T	A	7: 34,349,547 (GRCm39)	N26Y	possibly damaging	Het
Kdm1b	T	C	13: 47,232,729 (GRCm39)	V733A	possibly damaging	Het
Lhx8	A	T	3: 154,027,340 (GRCm39)	L234H	probably damaging	Het
Lrp2	T	A	2: 69,337,098 (GRCm39)	T1225S	probably damaging	Het
Lrrn1	G	A	6: 107,545,488 (GRCm39)	D429N	probably benign	Het
Mettl3	A	T	14: 52,536,243 (GRCm39)	N200K	possibly damaging	Het
Mixl1	G	T	1: 180,524,336 (GRCm39)	A81D	possibly damaging	Het
Mroh2b	T	C	15: 4,980,763 (GRCm39)	I1444T	probably benign	Het
Muc15	T	A	2: 110,561,786 (GRCm39)	L74*	probably null	Het
Olfm2	T	A	9: 20,579,824 (GRCm39)	Y317F	probably damaging	Het
Or52a33	C	T	7: 103,288,886 (GRCm39)	V154M	probably benign	Het
Or5b114-ps1	G	A	19: 13,352,698 (GRCm39)	S124N	probably benign	Het
Or5p54	T	A	7: 107,554,001 (GRCm39)	I51N	probably benign	Het
Pclo	A	T	5: 14,763,302 (GRCm39)	Y3925F	unknown	Het
Pik3c2g	A	T	6: 139,599,137 (GRCm39)	R84S	probably damaging	Het
Pik3c2g	A	G	6: 139,842,518 (GRCm39)	Q449R	probably damaging	Het
Psg28	T	C	7: 18,160,305 (GRCm39)	E297G	probably damaging	Het
Qrich2	A	T	11: 116,337,832 (GRCm39)		probably benign	Het
Rgs9	A	G	11: 109,130,386 (GRCm39)	I363T	probably damaging	Het
Rnpepl1	A	G	1: 92,844,543 (GRCm39)	D345G	probably damaging	Het
Rtn4	T	A	11: 29,658,023 (GRCm39)	F726I	probably damaging	Het
Sart3	A	T	5: 113,893,507 (GRCm39)	I330N	probably damaging	Het
Scn5a	T	C	9: 119,391,440 (GRCm39)	D84G	probably damaging	Het
Sema4a	T	C	3: 88,348,008 (GRCm39)	T438A	probably damaging	Het
Sfxn1	A	C	13: 54,242,961 (GRCm39)	Y73S	probably benign	Het
Slc24a2	A	G	4: 86,914,882 (GRCm39)	M585T	probably damaging	Het
Slc26a7	A	G	4: 14,505,471 (GRCm39)	V656A	probably benign	Het
Smok2a	T	G	17: 13,445,021 (GRCm39)	D199E	probably benign	Het
Tbc1d10c	T	C	19: 4,235,030 (GRCm39)	I344V	probably benign	Het
Tll1	A	T	8: 64,506,925 (GRCm39)	Y605*	probably null	Het
Trim75	G	A	8: 65,435,535 (GRCm39)	P305L	probably damaging	Het
Unc13c	T	C	9: 73,838,166 (GRCm39)	N895S	probably benign	Het
Vmn2r25	A	T	6: 123,799,876 (GRCm39)	I822N	probably damaging	Het
Wasf3	T	G	5: 146,407,166 (GRCm39)	D495E	unknown	Het
Wdhd1	T	A	14: 47,510,667 (GRCm39)	K119*	probably null	Het
Wnt2b	T	A	3: 104,858,339 (GRCm39)	D310V	probably damaging	Het
Zfat	G	T	15: 68,052,626 (GRCm39)	D389E	probably damaging	Het
Zfp282	G	A	6: 47,857,102 (GRCm39)	V112M	probably damaging	Het
Zfp617	A	T	8: 72,687,257 (GRCm39)	K529I	probably damaging	Het
Zfp866	A	T	8: 70,218,373 (GRCm39)	C416S	probably damaging	Het
Zfp991	G	A	4: 147,264,222 (GRCm39)	G533D	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
R5818:Actn4	UTSW	7	28,618,444 (GRCm39)	missense	probably damaging	1.00
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'- GCCATCTTAGGTCAGAGCAG -3'
(R):5'- CACTGAGATTCATTCAGTTAGCCC -3'

Sequencing Primer
(F):5'- CAGAGGCGAGAGGGACTGC -3'
(R):5'- CAAAGGATCCGAGTTGAGTCCC -3'

Posted On

2017-07-14