PFN4
protein-codingprofilin family member 4, the group of Profilins
Gene summary
Predicted to enable actin monomer binding activity. Predicted to be involved in acrosome assembly; manchette assembly; and sperm flagellum assembly. Predicted to be located in cytoplasm. Predicted to be active in cell cortex. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.7 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 PFN4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_199346.3. 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 | 0 | |||||
| missense | 13 | 3 | 16 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 13 | 3 | 0 | 16 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_955378.1 | 4 | MANE Select | |
| Ensembl | ENSP00000322170.4 | 4 | MANE Select | |
| Ensembl | ENSP00000393504.1 | 1 | Standard | |
| Ensembl | ENSP00000567711.1 | 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
- sequestering of actin monomers
Molecular Function
- actin monomer binding
- lipid binding
Cellular Component
- cytoskeleton
- cell cortex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000313213
- Coding exons
- 4
- Length
- 8107
- Individuals with no LoFs
- 125730
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 18
- Defined
- 125748
- p
- 0.0000716
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0188 | 70 | 70.4 | 0.994 | 0.00000365 | 813 |
| Missense (PolyPhen) | 23 | 23.212 | 0.99085 | 268 | ||
| Synonymous | 0.279 | 24 | 25.8 | 0.930 | 0.00000119 | 249 |
| Loss of Function | 0.820 | 5 | 7.41 | 0.675 | 4.81e-7 | 86 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds to phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), phosphatidylinositol 4-phosphate (PtdIns(4)P) and phosphatidic acid (PA). Does not bind to actin (PubMed:19419568), contrary to other family members. {ECO:0000269|PubMed:19419568}.;
Recessive Scores
- pRec
- 0.114
Intolerance Scores
- LoFtool
- 0.455
- RVIS EVS
- 0.04
- RVIS percentile EVS
- 56.64
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.219
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |