FKBP5
protein-codingFKBP prolyl isomerase 5, the group of Tetratricopeptide repeat domain containing|FKBP prolyl isomerases|MicroRNA protein coding host genes
Gene summary
The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds to the immunosuppressants FK506 and rapamycin. It is thought to mediate calcineurin inhibition. It also interacts functionally with mature hetero-oligomeric progesterone receptor complexes along with the 90 kDa heat shock protein and P23 protein. This gene has been found to have multiple polyadenylation sites. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~155.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to FKBP5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004117.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 43 | 2 | 45 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 45 | 2 | 1 | 48 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004108.1 | 10 | MANE Select | |
| Ensembl | ENSP00000349811.3 | 10 | MANE Select | |
| RefSeq | NP_001139247.1 | 10 | Standard | |
| RefSeq | NP_001139248.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Estrogen signaling pathway - Homo sapiens (human)
- Androgen Receptor Network in Prostate Cancer
- Farnesoid X Receptor Pathway
- Nuclear Receptors Meta-Pathway
- MECP2 and Associated Rett Syndrome
Biological Process
- protein peptidyl-prolyl isomerization
- protein folding
- response to bacterium
- chaperone-mediated protein folding
Molecular Function
- peptidyl-prolyl cis-trans isomerase activity
- protein binding
- FK506 binding
- heat shock protein binding
Cellular Component
- nucleoplasm
- cytoplasm
- cytosol
- membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000536438
- Coding exons
- 10
- Length
- 154999
- Individuals with no LoFs
- 125733
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 12
- Defined
- 125745
- p
- 0.0000477
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.62 | 179 | 251 | 0.713 | 0.0000129 | 3020 |
| Missense (PolyPhen) | 35 | 73.116 | 0.47869 | 838 | ||
| Synonymous | 0.705 | 82 | 90.5 | 0.906 | 0.00000511 | 808 |
| Loss of Function | 3.54 | 4 | 21.9 | 0.183 | 9.14e-7 | 314 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Immunophilin protein with PPIase and co-chaperone activities. Component of unligated steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). Plays a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors maintaining the complex into the cytoplasm when unliganded.;
Recessive Scores
- pRec
- 0.0951
Intolerance Scores
- LoFtool
- 0.0822
- RVIS EVS
- -0.03
- RVIS percentile EVS
- 51.92
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.868
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |