Mutagenetix > Incidental Mutation

Incidental Mutation 'R7423:Actn4'

575824

Institutional Source

Beutler Lab

Gene Symbol

Actn4

Ensembl Gene

ENSMUSG00000054808

Gene Name

actinin alpha 4

Synonyms

MMRRC Submission

045501-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.778) question?

Stock #

R7423 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

28592673-28661765 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 28593680 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Alanine to Threonine at position 905 (A905T)

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: A905T

PolyPhen 2 Score 0.966 (Sensitivity: 0.77; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000066068
Gene: ENSMUSG00000054808
AA Change: A905T

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

probably benign
Transcript: ENSMUST00000216863
AA Change: A315T

PolyPhen 2 Score 0.014 (Sensitivity: 0.96; Specificity: 0.79)

Predicted Effect

probably benign
Transcript: ENSMUST00000217157
AA Change: A925T

PolyPhen 2 Score 0.104 (Sensitivity: 0.93; Specificity: 0.86)

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 98.8%

Validation Efficiency

96% (91/95)

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: 93 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acsbg2	A	T	17: 57,175,257 (GRCm39)	M85K	probably benign	Het
Aff1	T	A	5: 103,994,967 (GRCm39)	V1055D	probably damaging	Het
Aox3	A	G	1: 58,160,228 (GRCm39)	E137G	possibly damaging	Het
Apaf1	A	T	10: 90,895,468 (GRCm39)	D443E	probably damaging	Het
Arl5b	C	A	2: 15,072,983 (GRCm39)	A28E	probably damaging	Het
Atg16l1	T	C	1: 87,714,023 (GRCm39)	V478A	probably damaging	Het
Atp6v1f	G	C	6: 29,468,105 (GRCm39)	E13Q	probably null	Het
Atpaf1	A	T	4: 115,647,827 (GRCm39)	K162M	probably damaging	Het
C3	A	T	17: 57,521,767 (GRCm39)	L1100Q	probably damaging	Het
Ccr1	A	G	9: 123,764,422 (GRCm39)	L36P	probably damaging	Het
Cct3	T	C	3: 88,216,503 (GRCm39)	L153S	probably benign	Het
Chd4	A	G	6: 125,105,822 (GRCm39)	D1813G	possibly damaging	Het
Chrm3	T	C	13: 9,928,845 (GRCm39)	I64V	probably benign	Het
Cnot2	A	T	10: 116,328,303 (GRCm39)	V477E	probably damaging	Het
Csf2rb2	T	A	15: 78,176,760 (GRCm39)	I211F	possibly damaging	Het
Dnah8	T	C	17: 30,923,743 (GRCm39)	L1237P	possibly damaging	Het
Dnttip2	T	C	3: 122,069,175 (GRCm39)	V130A	probably benign	Het
Dock10	G	A	1: 80,501,497 (GRCm39)	A1852V	possibly damaging	Het
Dock3	A	G	9: 106,844,370 (GRCm39)	V910A	probably damaging	Het
Drgx	A	G	14: 32,350,778 (GRCm39)	S205G	probably damaging	Het
Fbrs	G	A	7: 127,088,633 (GRCm39)	W738*	probably null	Het
Fmnl3	T	A	15: 99,227,281 (GRCm39)	D162V	probably damaging	Het
Fosl2	A	G	5: 32,307,807 (GRCm39)	R133G	probably damaging	Het
Frmpd1	A	G	4: 45,256,948 (GRCm39)	Q172R	probably damaging	Het
Fsd1l	A	T	4: 53,686,406 (GRCm39)	D273V	probably damaging	Het
Fstl4	T	A	11: 52,959,382 (GRCm39)	M141K	possibly damaging	Het
Gcfc2	A	G	6: 81,923,541 (GRCm39)	D535G	probably damaging	Het
Gm19410	A	C	8: 36,271,761 (GRCm39)	D1277A	probably benign	Het
Gnmt	T	A	17: 47,037,066 (GRCm39)	N211Y	probably damaging	Het
Hic2	A	G	16: 17,075,993 (GRCm39)	D274G	probably damaging	Het
Hnrnpu	A	G	1: 178,156,849 (GRCm39)		probably benign	Het
Icam5	T	C	9: 20,948,201 (GRCm39)	S670P	probably benign	Het
Ighv5-4	A	T	12: 113,561,120 (GRCm39)	L100Q	probably damaging	Het
Il17rb	A	T	14: 29,719,072 (GRCm39)	S337T	probably damaging	Het
Inf2	G	T	12: 112,576,172 (GRCm39)	R883L	unknown	Het
Inhbc	C	T	10: 127,193,275 (GRCm39)	C247Y	probably damaging	Het
Ints4	A	G	7: 97,156,926 (GRCm39)	K333E	probably damaging	Het
Iyd	A	T	10: 3,497,088 (GRCm39)	I148F	probably damaging	Het
Klk1b26	A	T	7: 43,664,193 (GRCm39)	D16V	probably damaging	Het
Krt15	A	T	11: 100,026,386 (GRCm39)	V100E	possibly damaging	Het
Lama2	A	T	10: 27,088,222 (GRCm39)	S852T	probably benign	Het
Mbtd1	A	G	11: 93,834,622 (GRCm39)	E600G	probably benign	Het
Mfap3	T	G	11: 57,420,329 (GRCm39)	N103K	probably damaging	Het
Mtor	G	A	4: 148,640,801 (GRCm39)	E2536K	possibly damaging	Het
Mug2	G	A	6: 122,056,685 (GRCm39)	S1210N	probably benign	Het
Nat8	G	A	6: 85,807,477 (GRCm39)	L219F	probably benign	Het
Nisch	A	G	14: 30,893,658 (GRCm39)	V1305A	probably benign	Het
Nup153	A	T	13: 46,850,120 (GRCm39)		probably null	Het
Or3a1b	G	A	11: 74,012,811 (GRCm39)	R232H	probably benign	Het
Otud6b	A	T	4: 14,825,858 (GRCm39)		probably null	Het
Pbld2	A	G	10: 62,883,783 (GRCm39)	T83A	probably damaging	Het
Pcx	A	T	19: 4,671,206 (GRCm39)	M1144L	probably benign	Het
Pdpk1	C	A	17: 24,329,874 (GRCm39)	R81L	probably benign	Het
Pik3cd	A	T	4: 149,736,220 (GRCm39)		probably null	Het
Plch2	A	C	4: 155,068,194 (GRCm39)	D1477E	probably damaging	Het
Plek2	A	G	12: 78,946,884 (GRCm39)	I51T	probably damaging	Het
Plekhn1	A	G	4: 156,315,142 (GRCm39)	V505A	probably benign	Het
Pofut2	T	C	10: 77,098,273 (GRCm39)	S129P	possibly damaging	Het
Prdx5	C	A	19: 6,887,370 (GRCm39)		probably benign	Het
Proca1	G	T	11: 78,085,643 (GRCm39)		probably benign	Het
Ptprs	A	C	17: 56,721,793 (GRCm39)	Y1752D	probably damaging	Het
Pum1	G	A	4: 130,501,856 (GRCm39)	V1127M	probably damaging	Het
Ralbp1	T	C	17: 66,165,976 (GRCm39)	R403G	probably damaging	Het
Reps1	A	T	10: 17,969,635 (GRCm39)	H246L	possibly damaging	Het
Rps6kc1	A	C	1: 190,531,293 (GRCm39)	M903R	probably damaging	Het
Rubcnl	A	G	14: 75,287,083 (GRCm39)	T584A	probably benign	Het
Samd9l	A	T	6: 3,374,408 (GRCm39)	V951E	probably damaging	Het
Sbf2	A	G	7: 110,038,055 (GRCm39)	F463L	possibly damaging	Het
Sdr16c6	G	A	4: 4,076,921 (GRCm39)		probably benign	Het
Shoc1	A	T	4: 59,076,264 (GRCm39)	S560T	probably benign	Het
Slc26a8	A	G	17: 28,867,177 (GRCm39)	I548T	probably benign	Het
Slc2a13	T	A	15: 91,456,883 (GRCm39)	I140F	probably damaging	Het
Smtn	A	T	11: 3,481,200 (GRCm39)		probably null	Het
Sobp	G	T	10: 42,898,564 (GRCm39)	C340*	probably null	Het
Sox6	A	T	7: 115,149,258 (GRCm39)	V413E	probably benign	Het
Spin1	T	C	13: 51,277,326 (GRCm39)		probably null	Het
Sra1	T	C	18: 36,800,536 (GRCm39)	T224A	probably benign	Het
Sv2c	A	T	13: 96,185,056 (GRCm39)	F207Y	probably benign	Het
Tcp10c	T	A	17: 13,581,503 (GRCm39)		probably null	Het
Tkt	G	A	14: 30,292,992 (GRCm39)	G490S	possibly damaging	Het
Tpgs1	G	T	10: 79,511,655 (GRCm39)	A266S	probably damaging	Het
Tprg1	T	G	16: 25,241,003 (GRCm39)	S260A	probably damaging	Het
Trdv2-1	T	A	14: 54,183,935 (GRCm39)	W56R	probably damaging	Het
Trgv6	G	T	13: 19,374,814 (GRCm39)	G40W	possibly damaging	Het
Trpc4	T	A	3: 54,225,450 (GRCm39)	V933E	probably benign	Het
Ulk4	A	T	9: 120,932,687 (GRCm39)	M1051K	possibly damaging	Het
Unc119b	A	G	5: 115,272,743 (GRCm39)	L76P	probably damaging	Het
Vmn2r15	G	A	5: 109,445,394 (GRCm39)	S10F	probably benign	Het
Vwce	A	G	19: 10,641,704 (GRCm39)	E810G	probably benign	Het
Wdr7	T	A	18: 63,910,451 (GRCm39)		probably null	Het
Wnk2	T	A	13: 49,191,608 (GRCm39)	E1283V	probably benign	Het
Zfp28	T	C	7: 6,396,956 (GRCm39)	C464R	probably damaging	Het
Zpld1	C	T	16: 55,054,027 (GRCm39)	C255Y	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	28,604,753 (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
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'- AGAAATGCTGATTGCCAAGCC -3'
(R):5'- CTAGGTCAAGTGGGTAAGACAC -3'

Sequencing Primer
(F):5'- TCCCCTACAAGACTGAGAAAGAGAG -3'
(R):5'- TAAGACACAGTGGCTCAGAGTCC -3'

Posted On

2019-10-07