Incidental Mutation '0152:Fscn3'
ID 7
Institutional Source Beutler Lab
Gene Symbol Fscn3
Ensembl Gene ENSMUSG00000029707
Gene Name fascin actin-bundling protein 3
Synonyms
Accession Numbers
Essential gene? Probably non essential (E-score: 0.163) question?
Stock # 0152 of strain feeble
Quality Score
Status Validated
Chromosome 6
Chromosomal Location 28427888-28438621 bp(+) (GRCm39)
Type of Mutation unclassified
DNA Base Change (assembly) A to G at 28429966 bp (GRCm39)
Zygosity Homozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000127281 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000020717] [ENSMUST00000031719] [ENSMUST00000064377] [ENSMUST00000169841]
AlphaFold Q9QXW4
Predicted Effect probably benign
Transcript: ENSMUST00000020717
SMART Domains Protein: ENSMUSP00000020717
Gene: ENSMUSG00000020440

DomainStartEndE-ValueType
ARF 1 180 5.83e-121 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000031719
SMART Domains Protein: ENSMUSP00000031719
Gene: ENSMUSG00000029707

DomainStartEndE-ValueType
Pfam:Fascin 24 138 1e-29 PFAM
SCOP:d1dfca2 146 260 2e-48 SMART
Pfam:Fascin 271 381 2.1e-26 PFAM
SCOP:d1dfca4 386 498 3e-53 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000064377
SMART Domains Protein: ENSMUSP00000067395
Gene: ENSMUSG00000029708

DomainStartEndE-ValueType
coiled coil region 13 61 N/A INTRINSIC
low complexity region 93 109 N/A INTRINSIC
low complexity region 130 153 N/A INTRINSIC
coiled coil region 156 315 N/A INTRINSIC
low complexity region 408 418 N/A INTRINSIC
low complexity region 432 443 N/A INTRINSIC
low complexity region 479 491 N/A INTRINSIC
Blast:H2B 492 590 3e-8 BLAST
low complexity region 613 631 N/A INTRINSIC
coiled coil region 659 701 N/A INTRINSIC
Grip 719 766 8.28e-20 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000147036
Predicted Effect probably benign
Transcript: ENSMUST00000169841
SMART Domains Protein: ENSMUSP00000127281
Gene: ENSMUSG00000020440

DomainStartEndE-ValueType
ARF 1 180 5.83e-121 SMART
Coding Region Coverage
  • 1x: 77.9%
  • 3x: 41.0%
Validation Efficiency 83% (65/78)
Allele List at MGI
Other mutations in this stock
Total: 6 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adck1 A T 12: 88,397,921 (GRCm39) Q185L probably benign Het
Per1 T G 11: 68,994,848 (GRCm39) probably benign Het
Pkhd1 A C 1: 20,593,118 (GRCm39) I1665S possibly damaging Het
Tnrc6a C A 7: 122,779,877 (GRCm39) P1303T probably damaging Het
Usp47 T C 7: 111,655,784 (GRCm39) Y154H probably damaging Het
Zfp952 T A 17: 33,222,195 (GRCm39) probably null Het
Other mutations in Fscn3
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01290:Fscn3 APN 6 28,430,505 (GRCm39) missense probably benign 0.43
IGL01312:Fscn3 APN 6 28,434,469 (GRCm39) missense probably damaging 0.99
IGL01634:Fscn3 APN 6 28,430,537 (GRCm39) missense probably damaging 1.00
IGL01899:Fscn3 APN 6 28,436,078 (GRCm39) missense probably damaging 1.00
IGL01928:Fscn3 APN 6 28,430,181 (GRCm39) missense possibly damaging 0.65
IGL02334:Fscn3 APN 6 28,428,153 (GRCm39) splice site probably null
IGL02959:Fscn3 APN 6 28,435,997 (GRCm39) missense possibly damaging 0.93
IGL03201:Fscn3 APN 6 28,430,604 (GRCm39) missense probably benign 0.07
IGL03202:Fscn3 APN 6 28,434,451 (GRCm39) missense probably benign 0.10
IGL03227:Fscn3 APN 6 28,434,429 (GRCm39) missense probably benign 0.00
R1478:Fscn3 UTSW 6 28,430,567 (GRCm39) missense probably benign
R1502:Fscn3 UTSW 6 28,435,622 (GRCm39) missense probably benign 0.05
R1955:Fscn3 UTSW 6 28,430,235 (GRCm39) missense possibly damaging 0.82
R2122:Fscn3 UTSW 6 28,430,388 (GRCm39) missense probably benign 0.18
R2135:Fscn3 UTSW 6 28,431,583 (GRCm39) missense probably benign 0.02
R3713:Fscn3 UTSW 6 28,428,091 (GRCm39) missense possibly damaging 0.89
R3715:Fscn3 UTSW 6 28,428,091 (GRCm39) missense possibly damaging 0.89
R3778:Fscn3 UTSW 6 28,430,031 (GRCm39) missense possibly damaging 0.72
R4572:Fscn3 UTSW 6 28,430,634 (GRCm39) splice site probably null
R4745:Fscn3 UTSW 6 28,435,627 (GRCm39) missense probably damaging 0.98
R4764:Fscn3 UTSW 6 28,436,200 (GRCm39) makesense probably null
R4794:Fscn3 UTSW 6 28,430,595 (GRCm39) missense probably damaging 1.00
R5738:Fscn3 UTSW 6 28,430,030 (GRCm39) missense possibly damaging 0.56
R5951:Fscn3 UTSW 6 28,436,173 (GRCm39) missense possibly damaging 0.88
R5994:Fscn3 UTSW 6 28,430,294 (GRCm39) missense probably benign
R6595:Fscn3 UTSW 6 28,430,174 (GRCm39) missense probably damaging 1.00
R7323:Fscn3 UTSW 6 28,431,544 (GRCm39) missense possibly damaging 0.53
R7738:Fscn3 UTSW 6 28,434,445 (GRCm39) missense probably benign 0.01
R7840:Fscn3 UTSW 6 28,430,175 (GRCm39) missense probably damaging 1.00
R8169:Fscn3 UTSW 6 28,430,328 (GRCm39) missense possibly damaging 0.79
R8991:Fscn3 UTSW 6 28,434,472 (GRCm39) missense probably benign
R9111:Fscn3 UTSW 6 28,430,310 (GRCm39) missense probably damaging 0.98
R9350:Fscn3 UTSW 6 28,430,432 (GRCm39) nonsense probably null
R9370:Fscn3 UTSW 6 28,434,535 (GRCm39) missense probably benign
R9410:Fscn3 UTSW 6 28,430,432 (GRCm39) nonsense probably null
Nature of Mutation
DNA sequencing using the SOLiD technique identified an A to G transition at position 2067 in the Genbank genomic region NC_000072 for the Fscn3 gene on chromosome 6 (ACACCTCCAG->GCACCTCCAG). The mutation is located within intron 1, ten nucleotides upstream from the start of exon 2, and may impair the acceptor splice site of intron 1. The mutation may result in skipping of the 697 nucleotide exon 2, removing 232 amino acids, destroying the reading, and resulting in the insertion of 10 aberrant amino acids before a premature stop codon. Fscn3 contains 7 exons (Figure 1).
 
     <--exon 1 <--intron 1 exon 2--> exon 3--> 
251 AGGAGACAG……ACCCTACCAGACCTGGGAG……ATGCTGAGG……AGCGTTTGA 3645
46  -R--R--Q-            -T--W--E-……-C--L--R-……-S--V--*  58      
     correct              deleted         aberrant 
 
The acceptor splice site of intron 1, which may be impaired by the Fscn3 mutation, is indicated in blue lettering; the mutated nucleotide is indicated in red lettering. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 2).
Protein Function and Prediction

Fscn3 encodes a 498 amino acid protein that is expressed specifically in elongating spermatids and localizes to actin filament sites in the dorsal and ventral spermatid head. Fscn3 has homology to the actin-bundling protein fascin 1 (FSCN1), and may have a role in spermatid remodeling (1). Fascins contain four copies of a domain that is necessary for binding to actin filaments. This domain, known as the fascin-like domain, adopts a β-trefoil topology and contains an internal threefold repeat structurally similar to fibroblast growth factor (FGF) (Figure 3; NCBI pfam06268).

References

1. Tubb, B., Mulholland, D. J., Vogl, W., Lan, Z. J., Niederberger, C., Cooney, A., and Bryan, J. (2002) Testis Fascin (FSCN3): A Novel Paralog of the Actin-Bundling Protein Fascin Expressed Specifically in the Elongate Spermatid Head. Exp. Cell Res. 275, 92-109.

Posted On 2009-10-27