PFN2
protein-codingprofilin 2, the group of Profilins
Gene summary
The protein encoded by this gene is a ubiquitous actin monomer-binding protein belonging to the profilin family. It is thought to regulate actin polymerization in response to extracellular signals. There are two alternatively spliced transcript variants encoding different isoforms described for this gene. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~85.9 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 PFN2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_053024.4. 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 | ||||
| missense | 8 | 8 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 9 | 1 | 0 | 10 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_444252.1 | 3 | MANE Select | |
| Ensembl | ENSP00000239940.7 | 3 | MANE Select | |
| RefSeq | NP_002619.1 | 3 | Standard | |
| Ensembl | ENSP00000408283.2 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Salmonella infection - Homo sapiens (human)
- Regulation of actin cytoskeleton - Homo sapiens (human)
- Rap1 signaling pathway - Homo sapiens (human)
- Shigellosis - Homo sapiens (human)
- Association Between Physico-Chemical Features and Toxicity Associated Pathways
Biological Process
- negative regulation of epithelial cell migration
- actin cytoskeleton organization
- regulation of actin filament polymerization
- negative regulation of actin filament polymerization
- positive regulation of actin filament polymerization
Molecular Function
- actin binding
- actin monomer binding
- protein binding
- phosphatidylinositol-4,5-bisphosphate binding
- ATPase activity
Cellular Component
- cytoplasm
- cytoskeleton
- extracellular exosome
- Schaffer collateral - CA1 synapse
- presynapse
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000239940
- Coding exons
- 3
- Length
- 85885
- Individuals with no LoFs
- 124689
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 124690
- p
- 0.00000401
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.97 | 26 | 73.5 | 0.354 | 0.00000393 | 916 |
| Missense (PolyPhen) | 6 | 28.802 | 0.20832 | 376 | ||
| Synonymous | 0.0811 | 28 | 28.6 | 0.981 | 0.00000175 | 258 |
| Loss of Function | 1.72 | 1 | 5.26 | 0.190 | 2.21e-7 | 77 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG.;
Recessive Scores
- pRec
- 0.230
Intolerance Scores
- LoFtool
- 0.285
- RVIS EVS
- 0.04
- RVIS percentile EVS
- 56.25
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.642
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |