TWF2
protein-codingtwinfilin actin binding protein 2
Gene summary
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]
- PTK9L
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~18.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TWF2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007284.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 38 | 1 | 39 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 43 | 2 | 0 | 45 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_009215.1 | 9 | MANE Select | |
| Ensembl | ENSP00000303908.4 | 9 | MANE Select | |
| Ensembl | ENSP00000426464.1 | 8 | Standard | |
| Ensembl | ENSP00000426464.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of lamellipodium assembly
- positive regulation of lamellipodium assembly
- positive regulation of neuron projection development
- cell projection organization
- actin filament depolymerization
Molecular Function
- RNA binding
- actin monomer binding
- protein kinase C binding
- protein binding
- ATP binding
Cellular Component
- cytoplasm
- actin filament
- myofibril
- lamellipodium
- filopodium
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000305533
- Coding exons
- 9
- Length
- 10651
- Individuals with no LoFs
- 125717
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125720
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.08 | 182 | 228 | 0.799 | 0.0000150 | 2270 |
| Missense (PolyPhen) | 64 | 88.288 | 0.7249 | 930 | ||
| Synonymous | 0.722 | 89 | 98.1 | 0.907 | 0.00000687 | 680 |
| Loss of Function | 3.83 | 2 | 20.9 | 0.0959 | 0.00000116 | 214 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Actin-binding protein involved in motile and morphological processes. Inhibits actin polymerization, likely by sequestering G-actin. By capping the barbed ends of filaments, it also regulates motility. Seems to play an important role in clathrin-mediated endocytosis and distribution of endocytic organelles. May play a role in regulating the mature length of the middle and short rows of stereocilia (By similarity). {ECO:0000250}.;
Intolerance Scores
- LoFtool
- 0.192
- RVIS EVS
- -0.8
- RVIS percentile EVS
- 12.24
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.764
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |