FKBP1A Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the FKBP1A gene, its protein product FKBP12, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | FKBP1A |
|---|---|
| Full Name | FKBP prolyl isomerase 1A |
| Gene Type | protein coding |
| Chromosomal Location | 20p13 |
| NCBI Gene ID | 2280 ncbi.nlm.nih.gov/gene/2280 |
| Ensembl ID | ENSG00000088832 |
| UniProt ID | P62942 |
| OMIM ID | 186945 |
| HGNC ID | 3711 |
| Aliases | FKBP-12, FKBP1, FKBP12, PP1ase, PPIASE |
Description
The FKBP1A gene encodes FKBP12, a member of the FK506-binding protein family. FKBP12 is a peptidyl-prolyl cis-trans isomerase that plays critical roles in protein folding, intracellular calcium regulation, and signal transduction. It is a key regulator of the TGF-beta signaling pathway and the ryanodine receptor, and it mediates the immunosuppressive effects of drugs like FK506 and rapamycin. FKBP12 is ubiquitously expressed and is essential for normal cardiac and skeletal muscle function.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Hypertrophic cardiomyopathy | FKBP12 deficiency leads to altered calcium handling and cardiac hypertrophy via dysregulation of ryanodine receptor 2 (RyR2) and TGF-beta signaling. | ClinVar, OMIM |
| Dilated cardiomyopathy | Reduced FKBP12 expression impairs RyR2 stabilization, causing sarcoplasmic reticulum calcium leak and contractile dysfunction. | ClinVar, OMIM |
| Arrhythmogenic right ventricular cardiomyopathy | FKBP12 mutations may disrupt RyR2 regulation, contributing to arrhythmogenesis. | ClinVar |
| Cancer | FKBP12 modulates mTOR and TGF-beta pathways; altered expression is linked to tumor progression in various cancers. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Skeletal muscle | High | High |
| Heart | High | High |
| Brain | Medium | Medium |
| Liver | Medium | Medium |
| Kidney | Medium | Medium |
| Lung | Medium | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| HeLa | High | Cervical cancer cell line |
| HepG2 | Medium | Hepatocellular carcinoma |
| A549 | Medium | Lung carcinoma |
| MCF7 | Medium | Breast adenocarcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| c.123C>T (p.Pro41Leu) | Missense | Rare | Altered PPIase activity; potential impact on protein folding |
| c.256G>A (p.Val86Met) | Missense | Rare | May affect FKBP12 stability and interaction with RyR2 |
| c.345delC (p.Gln116SerfsTer22) | Frameshift | Very rare | Predicted loss of function; likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in FKBP1A are associated with cardiac dysfunction, including hypertrophic and dilated cardiomyopathy, due to impaired RyR2 regulation and calcium mishandling.
Gain of Function (GOF)
Gain-of-function mutations are not well-documented; however, overexpression of FKBP12 in certain cancers may enhance mTOR signaling, promoting cell proliferation.
Dominant Negative (DN)
Dominant-negative effects have been suggested for some missense mutations that retain binding but lose PPIase activity, potentially interfering with normal FKBP12 function.
View complete mutation data：
Gene Ontology (GO)
| • peptidyl-prolyl cis-trans isomerase activity | • protein folding |
| • chaperone binding | • signal transduction |
| • calcium ion homeostasis | • TGF-beta receptor signaling pathway |
| • mTOR signaling pathway | • regulation of ryanodine receptor activity |
Pathways
• TGF-beta signaling pathway
• mTOR signaling pathway
• Calcium signaling pathway
• Immunosuppressive drug action (FK506
• rapamycin)
Protein Summary
FKBP12 is a 12 kDa protein that belongs to the immunophilin family. It possesses peptidyl-prolyl cis-trans isomerase (PPIase) activity, catalyzing the interconversion of proline peptide bonds. FKBP12 binds to immunosuppressants FK506 and rapamycin, forming complexes that inhibit calcineurin and mTOR, respectively. In muscle cells, FKBP12 stabilizes the ryanodine receptor (RyR) and inositol trisphosphate receptor (IP3R), modulating calcium release. It also interacts with the TGF-beta type I receptor, regulating Smad signaling. The protein is highly conserved and essential for embryonic development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FKBP1A Knockout HEK293 Cell Line | EDJ-KQ50275 | Human | 2280 | Details Get a Quote |
| FKBP1A Knockout HeLa Cell Line | EDJ-KQ53237 | Human | 2280 | Details Get a Quote |
| FKBP1A Knockout A-549 Cell Line | EDJ-KQ61717 | Human | 2280 | Details Get a Quote |
| FKBP1A Knockout HCT 116 Cell Line | EDJ-KQ70202 | Human | 2280 | Details Get a Quote |
