Incidental Mutation 'G5030:Twf2'
ID 497
Institutional Source Beutler Lab
Gene Symbol Twf2
Ensembl Gene ENSMUSG00000023277
Gene Name twinfilin actin binding protein 2
Synonyms Ptk9l, Twinfilin-2, A6-related, Twf2
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # G5030 (G3) of strain 560
Quality Score
Status Validated
Chromosome 9
Chromosomal Location 106080307-106092586 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to A at 106084141 bp (GRCm39)
Zygosity Heterozygous
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]
AlphaFold Q9Z0P5
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 Efficiency 35.6%
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: 109,961,165 (GRCm39) I585F probably damaging Het
Adam18 C G 8: 25,141,872 (GRCm39) L232F probably benign Homo
Atp13a4 A G 16: 29,274,306 (GRCm39) I385T probably damaging Homo
Ccdc17 T A 4: 116,455,699 (GRCm39) S277T probably benign Het
Ccng1 A G 11: 40,644,629 (GRCm39) probably benign Het
Ces1f T C 8: 94,000,847 (GRCm39) D99G probably benign Het
Clec16a G A 16: 10,389,425 (GRCm39) R187Q probably damaging Homo
Cryl1 C T 14: 57,579,595 (GRCm39) probably benign Het
Cryzl2 C T 1: 157,292,580 (GRCm39) Q48* probably null Het
Dtx4 A G 19: 12,446,943 (GRCm39) L583P probably benign Het
Ephx4 A T 5: 107,577,693 (GRCm39) D339V probably damaging Het
Eri2 A T 7: 119,385,601 (GRCm39) V300E possibly damaging Het
F3 T A 3: 121,518,648 (GRCm39) N37K probably damaging Homo
Fpr1 A T 17: 18,097,068 (GRCm39) L307H probably damaging Het
Fv1 T A 4: 147,953,618 (GRCm39) N61K possibly damaging Het
Gm5548 T C 3: 112,961,512 (GRCm39) noncoding transcript Homo
Il1r1 A G 1: 40,352,323 (GRCm39) K498E possibly damaging Homo
Myh11 T C 16: 14,068,443 (GRCm39) I192M probably damaging Homo
Nckap5 T C 1: 125,953,591 (GRCm39) K923R probably damaging Het
Nmbr A T 10: 14,642,747 (GRCm39) Y102F possibly damaging Het
Or6c75 A G 10: 129,337,406 (GRCm39) T218A probably benign Homo
Pde1a C T 2: 79,718,180 (GRCm39) probably benign Het
Pex6 T C 17: 47,026,382 (GRCm39) probably benign Het
Rtn2 T C 7: 19,027,099 (GRCm39) S305P probably damaging Homo
Saal1 G A 7: 46,342,207 (GRCm39) T412I probably damaging Homo
Slc46a2 A T 4: 59,913,867 (GRCm39) I352N probably damaging Het
Trim37 A T 11: 87,033,967 (GRCm39) H99L probably damaging Het
Tubgcp4 C T 2: 121,014,815 (GRCm39) R242C probably damaging Het
Usp40 A T 1: 87,921,941 (GRCm39) H307Q probably damaging Het
Zfhx3 T G 8: 109,678,091 (GRCm39) V3047G possibly damaging Het
Other mutations in Twf2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01135:Twf2 APN 9 106,090,027 (GRCm39) missense probably benign 0.01
IGL02616:Twf2 APN 9 106,089,955 (GRCm39) nonsense probably null
R0139:Twf2 UTSW 9 106,090,155 (GRCm39) missense possibly damaging 0.69
R1432:Twf2 UTSW 9 106,092,012 (GRCm39) unclassified probably benign
R4579:Twf2 UTSW 9 106,090,025 (GRCm39) missense probably benign 0.20
R4969:Twf2 UTSW 9 106,089,098 (GRCm39) critical splice donor site probably null
R4975:Twf2 UTSW 9 106,089,539 (GRCm39) missense probably damaging 1.00
R5831:Twf2 UTSW 9 106,091,386 (GRCm39) missense probably benign 0.00
R6368:Twf2 UTSW 9 106,090,032 (GRCm39) missense probably benign 0.33
R7026:Twf2 UTSW 9 106,092,079 (GRCm39) missense probably damaging 1.00
R7338:Twf2 UTSW 9 106,081,138 (GRCm39) intron probably benign
R7439:Twf2 UTSW 9 106,091,597 (GRCm39) missense probably damaging 1.00
R7793:Twf2 UTSW 9 106,089,079 (GRCm39) missense probably damaging 1.00
R8743:Twf2 UTSW 9 106,090,010 (GRCm39) missense possibly damaging 0.77
R9252:Twf2 UTSW 9 106,088,999 (GRCm39) missense probably benign 0.01
R9357:Twf2 UTSW 9 106,092,100 (GRCm39) missense probably benign 0.06
X0024:Twf2 UTSW 9 106,090,168 (GRCm39) missense probably benign
Z1177:Twf2 UTSW 9 106,090,203 (GRCm39) 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 On 2010-10-26