FKBP8: FKBP Prolyl Isomerase 8
A mitochondrial chaperone and anti-apoptotic regulator with roles in neurodevelopment and cancer
Gene Information Card
| Symbol | FKBP8 |
|---|---|
| Full Name | FKBP Prolyl Isomerase 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 19p12 |
| NCBI Gene ID | 23770 ncbi.nlm.nih.gov/gene/23770 |
| Ensembl ID | ENSG00000105675 |
| UniProt ID | Q14318 |
| OMIM ID | 604840 |
| HGNC ID | 3724 |
| Aliases | FKBP38, FKBPr38, hFKBP38 |
Description
FKBP8 (FKBP Prolyl Isomerase 8) encodes a member of the FK506-binding protein (FKBP) family. The encoded protein is a mitochondrial chaperone with peptidyl-prolyl cis-trans isomerase (PPIase) activity. It localizes to the outer mitochondrial membrane and functions as an anti-apoptotic factor by binding to Bcl-2 and targeting it to mitochondria. FKBP8 is involved in protein folding, mitochondrial homeostasis, and regulation of cell death. It is essential for normal brain development and has been implicated in cancer and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with microcephaly and spasticity | Loss-of-function mutations in FKBP8 impair mitochondrial function and neuronal survival | ClinVar, OMIM |
| Hepatocellular carcinoma | Overexpression of FKBP8 promotes anti-apoptotic signaling via Bcl-2 stabilization | COSMIC, PubMed |
| Breast cancer | FKBP8 upregulation correlates with poor prognosis and resistance to chemotherapy | COSMIC, PubMed |
| Colorectal cancer | FKBP8 expression is elevated and associated with tumor progression | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 7.9 | Low |
| Testis | 15.2 | Medium |
| Lung | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.8 | Embryonic kidney cells |
| HeLa | 11.2 | Cervical cancer cells |
| HepG2 | 9.5 | Hepatocellular carcinoma cells |
| SH-SY5Y | 16.3 | Neuroblastoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon, likely loss of function |
| c.286C>T (p.Arg96Trp) | Missense | Rare | Impaired Bcl-2 binding, reduced anti-apoptotic activity |
| c.512G>A (p.Arg171Gln) | Missense | Rare | Decreased PPIase activity |
| c.715C>T (p.Arg239Trp) | Missense | Rare | Associated with neurodevelopmental disorder |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt start codon or PPIase domain reduce chaperone activity and anti-apoptotic function, leading to mitochondrial dysfunction.
Gain of Function (GOF)
Not well characterized; overexpression in cancer suggests potential gain-of-function in anti-apoptotic signaling.
Dominant Negative (DN)
No dominant-negative mutations reported in FKBP8.
View complete mutation data：
Gene Ontology (GO)
| • peptidyl-prolyl cis-trans isomerase activity (GO:0003755) | • protein binding (GO:0005515) |
| • mitochondrion (GO:0005739) | • apoptotic process (GO:0006915) |
| • identical protein binding (GO:0042802) | • unfolded protein binding (GO:0051082) |
| • regulation of mitophagy (GO:1901990) |
Pathways
• Apoptosis - modulation by Bcl-2 family
• Protein folding in mitochondria
• PI3K/Akt signaling (via Bcl-2 interaction)
Protein Summary
FKBP8 (also known as FKBP38) is a 38 kDa mitochondrial protein belonging to the FKBP family. It contains an N-terminal mitochondrial targeting sequence, a PPIase domain, and a C-terminal tetratricopeptide repeat (TPR) domain. FKBP8 acts as a chaperone that facilitates protein folding and mitochondrial import. Its anti-apoptotic function is mediated by direct binding to Bcl-2, recruiting it to the mitochondrial outer membrane and preventing cytochrome c release. FKBP8 is highly expressed in brain and testis, and its dysregulation is linked to neurodevelopmental disorders and multiple cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FKBP8 Knockout HEK293 Cell Line | EDJ-KQ8133 | Human | 23770 | Details Get a Quote |
| FKBP8 Knockout A-549 Cell Line | EDJ-KQ34018 | Human | 23770 | Details Get a Quote |
| FKBP8 Knockout HCT 116 Cell Line | EDJ-KQ34019 | Human | 23770 | Details Get a Quote |
| FKBP8 Knockout HeLa Cell Line | EDJ-KQ34020 | Human | 23770 | Details Get a Quote |
