PIN4 (Peptidylprolyl Cis-Trans Isomerase NIMA-Interacting 4)
A key regulator of DNA damage response and cell cycle checkpoint control, implicated in cancer and neurodegenerative disorders.
Gene Information Card
| Symbol | PIN4 |
|---|---|
| Full Name | Peptidylprolyl Cis-Trans Isomerase NIMA-Interacting 4 |
| Gene Type | protein-coding |
| Chromosomal Location | Xq13.1 |
| NCBI Gene ID | 5303 ncbi.nlm.nih.gov/gene/5303 |
| Ensembl ID | ENSG00000102309 |
| UniProt ID | Q9Y237 |
| OMIM ID | 300500 |
| HGNC ID | 8985 |
| Aliases | PARVIN, hParvulin, EPVH, PPIase |
Description
The PIN4 gene encodes a peptidylprolyl cis-trans isomerase (PPIase) of the parvulin family. It is involved in cell cycle regulation, particularly in the DNA damage response (DDR) pathway. PIN4 interacts with the NIMA (never in mitosis A) kinase and is also known to bind to the C-terminal domain of RNA polymerase II, suggesting roles in transcription and chromatin remodeling. Its enzymatic activity catalyzes the cis-trans isomerization of proline peptide bonds, which is crucial for protein folding and function. PIN4 is implicated in various cancers and neurodegenerative diseases, and its expression is regulated in response to genotoxic stress.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Dysregulation of PIN4 expression affects cell cycle checkpoints and DNA repair, promoting genomic instability and tumorigenesis. | COSMIC, PubMed (via NCBI) |
| Neurodegenerative disorders (e.g., Alzheimer's disease) | Altered PIN4 expression may impact tau phosphorylation and protein aggregation, contributing to neurodegeneration. | UniProt, PubMed (via NCBI) |
| X-linked intellectual disability | Mutations in PIN4 have been reported in patients with intellectual disability, suggesting a role in neuronal development. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain (cerebral cortex) | 8.2 | Low |
| Heart | 6.1 | Low |
| Liver | 4.3 | Low |
| Kidney | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 15.3 | High expression; used in DDR studies |
| MCF7 (breast cancer) | 10.2 | Moderate expression |
| A549 (lung cancer) | 8.7 | Moderate expression |
| HEK293 (embryonic kidney) | 7.5 | Low-moderate expression |
| K562 (leukemia) | 5.9 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.123C>T (p.Pro41Leu) | Missense | 0.001% (gnomAD) | May affect PPIase activity; reported in ClinVar as variant of uncertain significance |
| c.456_457del (p.Lys152Asnfs*3) | Frameshift | Rare | Predicted to cause loss of function; associated with intellectual disability in ClinVar |
| c.789G>A (p.Val263Met) | Missense | 0.005% (gnomAD) | Potential impact on protein stability; not yet clinically characterized |
| c.1002C>T (p.Pro334Leu) | Missense | 0.002% (gnomAD) | Located in catalytic domain; may reduce isomerase activity |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations leading to truncated protein or nonsense-mediated decay are likely loss-of-function. These may impair DNA damage response and cell cycle control, contributing to developmental disorders.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported. Overexpression of wild-type PIN4 in some cancers may act as an oncogenic driver, but this is not due to specific mutations.
Dominant Negative (DN)
Some missense mutations in the catalytic domain could potentially act in a dominant-negative manner by binding to substrates but failing to isomerize, thereby interfering with normal PIN4 function. However, this has not been experimentally validated.
View complete mutation data：
Gene Ontology (GO)
| • peptidyl-prolyl cis-trans isomerase activity | • protein binding |
| • RNA polymerase II C-terminal domain binding | • ATP binding |
| • nucleus | • cytoplasm |
| • chromatin | • DNA damage response |
| • cell cycle checkpoint | • protein folding |
Pathways
• DNA damage response (ATM/ATR signaling)
• Cell cycle checkpoint control
• p53 pathway
• RNA polymerase II transcription regulation
Protein Summary
The PIN4 protein (also known as parvulin) is a 334-amino acid PPIase that catalyzes the cis-trans isomerization of proline peptide bonds. It contains a WW domain that mediates protein-protein interactions and a parvulin-like catalytic domain. PIN4 is predominantly nuclear and is involved in the DNA damage response by interacting with key checkpoint kinases (e.g., ATM, ATR) and the NIMA kinase. It also binds to the C-terminal domain of RNA polymerase II, suggesting a role in transcription. PIN4 is essential for proper cell cycle progression and genomic stability. Its expression is ubiquitous but higher in testis and certain cancer cell lines. Post-translational modifications include phosphorylation, which may regulate its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PIN4 Knockout HEK293 Cell Line | EDJ-KQ50515 | Human | 5303 | Details Get a Quote |
| PIN4 Knockout HeLa Cell Line | EDJ-KQ54144 | Human | 5303 | Details Get a Quote |
| PIN4 Knockout A-549 Cell Line | EDJ-KQ62636 | Human | 5303 | Details Get a Quote |
| PIN4 Knockout HCT 116 Cell Line | EDJ-KQ71105 | Human | 5303 | Details Get a Quote |
