FKBP1A
protein-codingFKBP prolyl isomerase 1A, the group of 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. The protein is a cis-trans prolyl isomerase that binds the immunosuppressants FK506 and rapamycin. It interacts with several intracellular signal transduction proteins including type I TGF-beta receptor. It also interacts with multiple intracellular calcium release channels, and coordinates multi-protein complex formation of the tetrameric skeletal muscle ryanodine receptor. In mouse, deletion of this homologous gene causes congenital heart disorder known as noncompaction of left ventricular myocardium. Multiple alternatively spliced variants, encoding the same protein, have been identified. The human genome contains five pseudogenes related to this gene, at least one of which is transcribed. [provided by RefSeq, Sep 2008]
- FKBP1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~24.2 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 FKBP1A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000801.5. 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 | 5 | 5 | ||||
| missense | 7 | 7 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 7 | 5 | 0 | 12 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000792.1 | 4 | MANE Select | |
| Ensembl | ENSP00000383003.4 | 4 | MANE Select | |
| RefSeq | NP_001186715.1 | 4 | Standard | |
| RefSeq | NP_463460.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Tacrolimus/Cyclosporine Pathway, Pharmacodynamics
- Target Of Rapamycin (TOR) Signaling
- Spinal Cord Injury
- Calcium Regulation in the Cardiac Cell
- TGF-beta Receptor Signaling
Biological Process
- protein peptidyl-prolyl isomerization
- heart morphogenesis
- protein folding
- 'de novo' protein folding
- SMAD protein complex assembly
Molecular Function
- peptidyl-prolyl cis-trans isomerase activity
- transforming growth factor beta receptor binding
- protein binding
- macrolide binding
- FK506 binding
Cellular Component
- cytoplasm
- cytosol
- terminal cisterna
- membrane
- sarcoplasmic reticulum
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000400137
- Coding exons
- 4
- Length
- 24185
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.66 | 20 | 54.6 | 0.366 | 0.00000266 | 695 |
| Missense (PolyPhen) | 2 | 14.142 | 0.14143 | 176 | ||
| Synonymous | 0.895 | 15 | 20.1 | 0.746 | 0.00000101 | 214 |
| Loss of Function | 2.19 | 0 | 5.57 | 0.00 | 3.22e-7 | 70 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruits SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. {ECO:0000269|PubMed:16720724, ECO:0000269|PubMed:1696686, ECO:0000269|PubMed:1701173, ECO:0000269|PubMed:9233797}.;
Recessive Scores
- pRec
- 0.338
Intolerance Scores
- RVIS EVS
- 0.1
- RVIS percentile EVS
- 60.96
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.977