Incidental Mutation 'G5030:Twf2'
ID497
Institutional Source Beutler Lab
Gene Symbol Twf2
Ensembl Gene ENSMUSG00000023277
Gene Nametwinfilin actin binding protein 2
SynonymsPtk9l, Twinfilin-2, Twf2, A6-related
Accession Numbers

Genbank: NM_011876

Is this an essential gene? Non essential (E-score: 0.000) question?
Stock #G5030 (G3) of strain 560
Quality Score
Status Validated
Chromosome9
Chromosomal Location106203108-106215389 bp(+) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) C to A at 106206942 bp
ZygosityHeterozygous
Amino Acid Change Leucine to Isoleucine at position 27 (L27I)
Ref Sequence ENSEMBL: ENSMUSP00000140617 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000024047] [ENSMUST00000187647] [ENSMUST00000187944] [ENSMUST00000188650] [ENSMUST00000216348]
Predicted Effect probably benign
Transcript: ENSMUST00000024047
AA Change: L27I

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)
SMART Domains Protein: ENSMUSP00000024047
Gene: ENSMUSG00000023277
AA Change: L27I

DomainStartEndE-ValueType
ADF 11 139 4.24e-23 SMART
ADF 184 313 1.51e-19 SMART
low complexity region 325 337 N/A INTRINSIC
Predicted Effect possibly damaging
Transcript: ENSMUST00000187647
AA Change: L27I

PolyPhen 2 Score 0.659 (Sensitivity: 0.86; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000140617
Gene: ENSMUSG00000023277
AA Change: L27I

DomainStartEndE-ValueType
SCOP:d1f7sa_ 5 34 5e-4 SMART
PDB:2VAC|A 6 44 1e-12 PDB
Blast:ADF 11 48 6e-8 BLAST
low complexity region 56 70 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000187944
Predicted Effect probably benign
Transcript: ENSMUST00000188650
AA Change: L25I

PolyPhen 2 Score 0.006 (Sensitivity: 0.97; Specificity: 0.75)
SMART Domains Protein: ENSMUSP00000140339
Gene: ENSMUSG00000023277
AA Change: L25I

DomainStartEndE-ValueType
ADF 9 137 4.24e-23 SMART
ADF 182 311 1.51e-19 SMART
low complexity region 323 335 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000189708
Predicted Effect probably benign
Transcript: ENSMUST00000216348
AA Change: L27I

PolyPhen 2 Score 0.253 (Sensitivity: 0.91; Specificity: 0.88)
Predicted Effect probably benign
Transcript: ENSMUST00000216850
Meta Mutation Damage Score 0.0712 question?
Coding Region Coverage
  • 1x: 81.1%
  • 3x: 60.2%
Het Detection Efficiency35.6%
Validation Efficiency 87% (206/237)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene was identified by its interaction with the catalytic domain of protein kinase C-zeta. The encoded protein contains an actin-binding site and an ATP-binding site. It is most closely related to twinfilin (PTK9), a conserved actin monomer-binding protein. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a targeted allele are viable, fertile, and do not display obvious morphological or behavioral abnormalities. [provided by MGI curators]
Allele List at MGI

All alleles(33) : Gene trapped(33)

Other mutations in this stock
Total: 30 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca8a T A 11: 110,070,339 I585F probably damaging Het
Adam18 C G 8: 24,651,856 L232F probably benign Homo
Atp13a4 A G 16: 29,455,488 I385T probably damaging Homo
Ccdc17 T A 4: 116,598,502 S277T probably benign Het
Ccng1 A G 11: 40,753,802 probably benign Het
Ces1f T C 8: 93,274,219 D99G probably benign Het
Clec16a G A 16: 10,571,561 R187Q probably damaging Homo
Cryl1 C T 14: 57,342,138 probably benign Het
Cryzl2 C T 1: 157,465,010 Q48* probably null Het
Dtx4 A G 19: 12,469,579 L583P probably benign Het
Ephx4 A T 5: 107,429,827 D339V probably damaging Het
Eri2 A T 7: 119,786,378 V300E possibly damaging Het
F3 T A 3: 121,724,999 N37K probably damaging Homo
Fpr1 A T 17: 17,876,806 L307H probably damaging Het
Fv1 T A 4: 147,869,161 N61K possibly damaging Het
Gm5548 T C 3: 113,054,196 noncoding transcript Homo
Il1r1 A G 1: 40,313,163 K498E possibly damaging Homo
Myh11 T C 16: 14,250,579 I192M probably damaging Homo
Nckap5 T C 1: 126,025,854 K923R probably damaging Het
Nmbr A T 10: 14,767,003 Y102F possibly damaging Het
Olfr790 A G 10: 129,501,537 T218A probably benign Homo
Pde1a C T 2: 79,887,836 probably benign Het
Pex6 T C 17: 46,715,456 probably benign Het
Rtn2 T C 7: 19,293,174 S305P probably damaging Homo
Saal1 G A 7: 46,692,783 T412I probably damaging Homo
Slc46a2 A T 4: 59,913,867 I352N probably damaging Het
Trim37 A T 11: 87,143,141 H99L probably damaging Het
Tubgcp4 C T 2: 121,184,334 R242C probably damaging Het
Usp40 A T 1: 87,994,219 H307Q probably damaging Het
Zfhx3 T G 8: 108,951,459 V3047G possibly damaging Het
Other mutations in Twf2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01135:Twf2 APN 9 106212828 missense probably benign 0.01
IGL02616:Twf2 APN 9 106212756 nonsense probably null
R0139:Twf2 UTSW 9 106212956 missense possibly damaging 0.69
R1432:Twf2 UTSW 9 106214813 unclassified probably benign
R4579:Twf2 UTSW 9 106212826 missense probably benign 0.20
R4969:Twf2 UTSW 9 106211899 critical splice donor site probably null
R4975:Twf2 UTSW 9 106212340 missense probably damaging 1.00
R5831:Twf2 UTSW 9 106214187 missense probably benign 0.00
R6368:Twf2 UTSW 9 106212833 missense probably benign 0.33
R7026:Twf2 UTSW 9 106214880 missense probably damaging 1.00
R7338:Twf2 UTSW 9 106203939 intron probably benign
R7439:Twf2 UTSW 9 106214398 missense probably damaging 1.00
R7793:Twf2 UTSW 9 106211880 missense probably damaging 1.00
X0024:Twf2 UTSW 9 106212969 missense probably benign
Z1177:Twf2 UTSW 9 106213004 missense probably benign 0.09
Nature of Mutation
DNA sequencing using the SOLiD technique identified a C to A transition at position 231 of the Twf2 transcript in exon 2 of 9 total exons. The mutated nucleotide causes a leucine to isoleucine substitution at amino acid 27 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction

The Twf2 gene encodes a 349 amino acid actin-binding protein involved in motile and morphological processes. Two isoforms are produced by alternative splicing. TWF2 inhibits actin polymerization, likely by sequestering G-actin. By capping the barbed ends of filaments, it also regulates motility.  The protein plays an important role in clathrin-mediated endocytosis and distribution of endocytic organelles. Two actin-depolymerising factor homology (ADF-H) domains are located at residues 4-139 and 177-313 (Uniprot Q9Z0P5).

The L27I change is located in the first ADF-H domain, and is predicted to be benign by the PolyPhen program (see report).
Posted On2010-10-26