Incidental Mutation 'R1690:Actn4'
ID 191712
Institutional Source Beutler Lab
Gene Symbol Actn4
Ensembl Gene ENSMUSG00000054808
Gene Name actinin alpha 4
Synonyms
MMRRC Submission 039723-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.752) question?
Stock # R1690 (G1)
Quality Score 225
Status Not validated
Chromosome 7
Chromosomal Location 28592673-28661765 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 28610950 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Proline at position 263 (S263P)
Ref Sequence ENSEMBL: ENSMUSP00000151028 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000068045] [ENSMUST00000127210] [ENSMUST00000140622] [ENSMUST00000148196] [ENSMUST00000217157]
AlphaFold P57780
Predicted Effect probably damaging
Transcript: ENSMUST00000068045
AA Change: S263P

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000066068
Gene: ENSMUSG00000054808
AA Change: S263P

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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 damaging
Transcript: ENSMUST00000140622
AA Change: S178P

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000123210
Gene: ENSMUSG00000054808
AA Change: S178P

DomainStartEndE-ValueType
CH 3 68 1.09e-1 SMART
CH 81 180 3.49e-24 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000144909
Predicted Effect probably benign
Transcript: ENSMUST00000148196
SMART Domains Protein: ENSMUSP00000122268
Gene: ENSMUSG00000054808

DomainStartEndE-ValueType
CH 3 68 1.09e-1 SMART
Pfam:CH 82 133 4.5e-11 PFAM
Pfam:CAMSAP_CH 89 133 9.1e-9 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000150493
Predicted Effect probably damaging
Transcript: ENSMUST00000217157
AA Change: S263P

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.4%
  • 10x: 96.5%
  • 20x: 93.3%
Validation Efficiency
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: 41 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adcy10 A G 1: 165,347,494 (GRCm39) E403G probably damaging Het
Adgrg7 A T 16: 56,615,993 (GRCm39) V11E probably damaging Het
Arhgap35 A G 7: 16,297,206 (GRCm39) C620R probably damaging Het
Cfap43 A G 19: 47,739,505 (GRCm39) probably null Het
Cfap54 A G 10: 92,871,304 (GRCm39) S639P possibly damaging Het
Csf2rb T C 15: 78,232,844 (GRCm39) V717A probably benign Het
D17H6S53E A G 17: 35,346,188 (GRCm39) D33G possibly damaging Het
Dpf2 C T 19: 5,955,490 (GRCm39) R131Q probably damaging Het
Dtx3l C T 16: 35,753,638 (GRCm39) A323T probably damaging Het
Fabp3 C T 4: 130,206,180 (GRCm39) T57I probably benign Het
Fgf15 A G 7: 144,453,665 (GRCm39) S213G probably damaging Het
Fmn1 T A 2: 113,355,827 (GRCm39) F756Y unknown Het
Hnrnpk T A 13: 58,548,168 (GRCm39) T13S probably benign Het
Htr3b T A 9: 48,848,394 (GRCm39) M284L possibly damaging Het
Itgal T C 7: 126,901,289 (GRCm39) M225T possibly damaging Het
Lipi A G 16: 75,338,013 (GRCm39) Y454H probably damaging Het
Lrit3 T C 3: 129,594,394 (GRCm39) K61R probably damaging Het
Lta4h A G 10: 93,320,554 (GRCm39) D583G probably benign Het
Mettl17 T A 14: 52,128,918 (GRCm39) V396D probably damaging Het
Nlrc4 G A 17: 74,744,518 (GRCm39) R788* probably null Het
Or8k25 T A 2: 86,244,298 (GRCm39) I33F probably benign Het
Pepd G A 7: 34,730,782 (GRCm39) G278D probably damaging Het
Pramel23 T C 4: 143,424,693 (GRCm39) E250G probably benign Het
Prkcsh T A 9: 21,921,871 (GRCm39) D245E probably damaging Het
Prlr A T 15: 10,317,676 (GRCm39) D84V probably damaging Het
Pth2r C T 1: 65,411,462 (GRCm39) T333I probably benign Het
Ptk2 T A 15: 73,134,459 (GRCm39) I547F probably damaging Het
Rab11fip2 A T 19: 59,925,732 (GRCm39) S162T probably damaging Het
Rnf41 C A 10: 128,271,329 (GRCm39) Q80K possibly damaging Het
Scn7a T G 2: 66,506,287 (GRCm39) D1534A probably damaging Het
Septin12 A G 16: 4,806,378 (GRCm39) V261A probably damaging Het
Sh2d4a T C 8: 68,747,101 (GRCm39) S110P probably benign Het
Soat1 A T 1: 156,272,144 (GRCm39) S114T probably benign Het
Taar8a A G 10: 23,952,813 (GRCm39) Y139C probably damaging Het
Tcf12 A G 9: 71,777,354 (GRCm39) probably null Het
Tmem202 T A 9: 59,426,391 (GRCm39) R258S possibly damaging Het
Ttc39b A T 4: 83,145,414 (GRCm39) I604N probably damaging Het
Vit A G 17: 78,932,294 (GRCm39) D467G probably damaging Het
Zc3hc1 A G 6: 30,390,940 (GRCm39) V21A probably damaging Het
Zfp608 T A 18: 55,120,706 (GRCm39) I294F possibly damaging Het
Zfp825 T A 13: 74,628,781 (GRCm39) H227L probably benign Het
Other mutations in Actn4
AlleleSourceChrCoordTypePredicted EffectPPH 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
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'- TAGATAGGCAGCAATGCCCAGGAC -3'
(R):5'- AGAAAGGAAGTGGCTTCCCTCCAG -3'

Sequencing Primer
(F):5'- CAATGCCCAGGACTGAGG -3'
(R):5'- GTGTGACTGAGCACGGC -3'
Posted On 2014-05-14