FKBP5 Gene: FK506-Binding Protein 5 – Function, Disease Associations, and Expression
A comprehensive biomedical overview of the FKBP5 gene, including genomic context, protein function, disease links, tissue expression, and mutation data.
Gene Information Card
| Symbol | FKBP5 |
|---|---|
| Full Name | FK506 binding protein 5 |
| Gene Type | protein coding |
| Chromosomal Location | 6p21.31 |
| NCBI Gene ID | 2289 ncbi.nlm.nih.gov/gene/2289 |
| Ensembl ID | ENSG00000096060 |
| UniProt ID | Q13451 |
| OMIM ID | 602623 |
| HGNC ID | 3721 |
| Aliases | FKBP51, P54, FKBP54, Ptg-10 |
Description
FKBP5 encodes FK506-binding protein 5, a member of the immunophilin family that functions as a co-chaperone in steroid receptor complexes. It plays a critical role in regulating glucocorticoid receptor (GR) sensitivity and stress response. FKBP5 is involved in protein folding, intracellular trafficking, and modulation of transcriptional activity. Its expression is induced by glucocorticoids, forming a negative feedback loop. Genetic variants in FKBP5 have been associated with stress-related psychiatric disorders, including PTSD and major depression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Post-Traumatic Stress Disorder (PTSD) | FKBP5 variants alter GR sensitivity and stress hormone regulation, affecting fear memory and stress response. | ClinVar, OMIM |
| Major Depressive Disorder | Dysregulation of FKBP5 expression leads to altered HPA axis activity and impaired stress adaptation. | ClinVar, OMIM |
| Anxiety Disorders | FKBP5 polymorphisms influence anxiety-related phenotypes through GR signaling modulation. | ClinVar |
| Bipolar Disorder | FKBP5 expression changes may contribute to mood instability and stress reactivity. | ClinVar |
| Cancer (e.g., breast, prostate) | FKBP5 modulates steroid receptor signaling, potentially affecting tumor growth and therapy response. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebellum) | 10.2 | Medium |
| Brain (cortex) | 8.5 | Medium |
| Adrenal gland | 12.1 | High |
| Lung | 6.3 | Low |
| Liver | 4.8 | Low |
| Kidney | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.3 | High expression |
| A549 | 9.7 | Moderate |
| MCF7 | 12.8 | High (steroid-responsive) |
| HepG2 | 7.1 | Low |
| SH-SY5Y | 11.4 | Moderate |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1360780 | SNP (intronic) | ~30% (C allele) | Associated with altered FKBP5 expression and increased risk for PTSD and depression. |
| rs3800373 | SNP (3' UTR) | ~25% (T allele) | Linked to differential mRNA stability and stress-related phenotypes. |
| rs9470080 | SNP (intronic) | ~20% (A allele) | Associated with GR sensitivity and psychiatric disorders. |
| rs4713916 | SNP (intronic) | ~15% (G allele) | Reported in relation to depression and anxiety. |
Mutation functional classification
Loss of Function (LOF)
Rare loss-of-function variants may impair FKBP5 protein function, leading to altered GR signaling and stress response dysregulation.
Gain of Function (GOF)
Common variants like rs1360780 are associated with increased FKBP5 expression, potentially enhancing GR resistance and stress vulnerability.
Dominant Negative (DN)
No well-characterized dominant-negative mutations have been reported for FKBP5.
View complete mutation data：
Gene Ontology (GO)
| • protein binding | • peptidyl-prolyl cis-trans isomerase activity |
| • heat shock protein binding | • glucocorticoid receptor binding |
| • chaperone binding | • signal transduction |
| • response to stress | • protein folding |
| • intracellular steroid hormone receptor signaling pathway |
Pathways
• Glucocorticoid receptor signaling
• HPA axis regulation
• Stress response pathway
• Immunophilin-mediated protein folding
Protein Summary
FKBP5 is a 51 kDa immunophilin that functions as a co-chaperone with Hsp90. It binds to the glucocorticoid receptor (GR) complex, reducing its hormone-binding affinity and nuclear translocation. Upon hormone binding, FKBP5 is replaced by FKBP4, allowing GR signaling. FKBP5 is itself induced by GR activation, creating a negative feedback loop. It also interacts with other steroid receptors and is involved in neuronal plasticity and stress adaptation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FKBP5 Knockout HEK293 Cell Line | EDJ-KQ4598 | Human | 2289 | Details Get a Quote |
| FKBP5 Knockout A-549 Cell Line | EDJ-KQ26011 | Human | 2289 | Details Get a Quote |
| FKBP5 Knockout HCT 116 Cell Line | EDJ-KQ27264 | Human | 2289 | Details Get a Quote |
| FKBP5 Knockout HeLa Cell Line | EDJ-KQ27265 | Human | 2289 | Details Get a Quote |
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