FKBP4 (FKBP Prolyl Isomerase 4): Gene, Protein, and Disease Relevance
A comprehensive biomedical overview of FKBP4, encoding FKBP52, a co-chaperone involved in steroid receptor signaling, neuronal function, and cancer.
Gene Information Card
| Symbol | FKBP4 |
|---|---|
| Full Name | FKBP prolyl isomerase 4 |
| Gene Type | protein coding |
| Chromosomal Location | 12p13.33 |
| NCBI Gene ID | 2288 ncbi.nlm.nih.gov/gene/2288 |
| Ensembl ID | ENSG00000004478 |
| UniProt ID | Q02790 |
| OMIM ID | 600611 |
| HGNC ID | 3720 |
| Aliases | FKBP52, p52, Hsp56, PPIase, FKBP-52 |
Description
FKBP4 encodes FKBP52, a member of the FK506-binding protein family that possesses peptidyl-prolyl cis/trans isomerase (PPIase) activity. FKBP52 functions as a co-chaperone in steroid receptor complexes, modulating hormone signaling, and is involved in microtubule dynamics, neuronal development, and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate Cancer | FKBP4 enhances androgen receptor (AR) signaling; overexpression promotes AR transcriptional activity and tumor growth. | COSMIC; multiple studies (e.g., Cheung-Flynn et al., 2005; Yong et al., 2007) |
| Breast Cancer | FKBP4 modulates estrogen receptor (ER) activity; high expression correlates with poor prognosis in ER-positive tumors. | ClinVar; literature (e.g., Ward et al., 1999) |
| Neurodevelopmental Disorders | FKBP4 knockout mice show defects in neurite outgrowth and behavior; variants may contribute to autism or intellectual disability. | OMIM; animal model studies (e.g., Morice et al., 2007) |
| Glucocorticoid Resistance | Altered FKBP4 expression affects glucocorticoid receptor (GR) sensitivity, implicated in stress-related disorders. | OMIM; functional studies (e.g., Denny et al., 2000) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Heart | 8.5 | Low |
| Liver | 6.2 | Low |
| Kidney | 9.1 | Medium |
| Testis | 15.7 | High |
| Prostate | 11.4 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 18.2 | Cervical cancer; high expression |
| MCF7 | 22.5 | Breast cancer; ER-positive |
| PC3 | 14.3 | Prostate cancer; AR-negative |
| HepG2 | 7.8 | Liver cancer; moderate |
| SH-SY5Y | 16.9 | Neuroblastoma; neuronal |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.100A>G (p.Thr34Ala) | Missense | Rare (MAF <0.01) | May affect PPIase activity; functional impact unclear |
| c.200C>T (p.Pro67Leu) | Missense | Rare | Potential alteration in protein stability |
| c.450_451insA | Frameshift | Not reported in population databases | Predicted loss-of-function; likely pathogenic in neurodevelopmental context |
| c.700G>A (p.Glu234Lys) | Missense | Rare | Located in TPR domain; may disrupt Hsp90 binding |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., frameshift, nonsense) are rare but may lead to reduced FKBP52 protein, impairing steroid receptor signaling and neuronal development.
Gain of Function (GOF)
Gain-of-function mutations are not well-documented; overexpression of wild-type FKBP4 is more common in cancers, enhancing AR/ER signaling.
Dominant Negative (DN)
Dominant-negative effects are possible if a mutant FKBP52 binds Hsp90 but fails to recruit steroid receptors, disrupting chaperone complex function.
View complete mutation data：
Gene Ontology (GO)
| • peptidyl-prolyl cis-trans isomerase activity | • protein folding |
| • chaperone binding | • steroid hormone receptor binding |
| • microtubule binding | • response to stress |
| • regulation of transcription |
Pathways
• Hsp90 chaperone cycle for steroid hormone receptors
• Androgen receptor signaling pathway
• Estrogen receptor signaling pathway
• Glucocorticoid receptor signaling pathway
• Neurotrophin signaling pathway
Protein Summary
FKBP52 (UniProt Q02790) is a 459-amino acid protein with an N-terminal PPIase domain, a tetratricopeptide repeat (TPR) domain, and a calmodulin-binding motif. It associates with Hsp90 via its TPR domain and modulates steroid receptor trafficking and transcriptional activity. FKBP52 also binds microtubules and dynein, influencing neuronal process formation. Its expression is ubiquitous but enriched in hormone-responsive tissues and brain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FKBP4 Knockout HEK293 Cell Line | EDJ-KQ4604 | Human | 2288 | Details Get a Quote |
| FKBP4 Knockout HeLa Cell Line | EDJ-KQ26026 | Human | 2288 | Details Get a Quote |
| FKBP4 Knockout A-549 Cell Line | EDJ-KQ27274 | Human | 2288 | Details Get a Quote |
| FKBP4 Knockout HCT 116 Cell Line | EDJ-KQ27275 | Human | 2288 | Details Get a Quote |
| FKBP4 Overexpression Hep-G2 Stable Cell Line | EDC90758 | Human | 2288 | Details Get a Quote |
| FKBP4（c.269G>A） Point Mutation in Hep-G2 Cell Line | EDC90611 | Human | 2288 | Details Get a Quote |
| FKBP4 Overexpression Huh-7 Stable Cell Line | EDC90753 | Human | 2288 | Details Get a Quote |
| FKBP4 (p.F130Y)Overexpression Hep-G2 Stable Cell Line | EDC90757 | Human | 2288 | Details Get a Quote |
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