FKBP6
protein-codingFKBP prolyl isomerase family member 6 (inactive), the group of FKBP prolyl isomerases
Gene summary
The protein encoded by this gene is a cis-trans peptidyl-prolyl isomerase that may function in immunoregulation and basic cellular processes involving protein folding and trafficking. This gene is located in a chromosomal region that is deleted in Williams-Beuren syndrome. Defects in this gene may cause male infertility. There are multiple pseudogenes for this gene located nearby on chromosome 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~30.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0031083
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0031083
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Genitourinary
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to FKBP6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003602.5. 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 | 1 | 1 | ||||
| missense | 38 | 3 | 1 | 42 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | 2 | |||
| Total | 2 | 3 | 38 | 4 | 1 | 48 |
Highest pathogenic variant AF is 0.00022987793
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003593.3 | 8 | MANE Select | |
| Ensembl | ENSP00000252037.4 | 8 | MANE Select | |
| RefSeq | NP_001128683.1 | 8 | Standard | |
| RefSeq | NP_001268233.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- protein peptidyl-prolyl isomerization
- protein folding
- spermatogenesis
- cell differentiation
- gene silencing by RNA
Molecular Function
- peptidyl-prolyl cis-trans isomerase activity
- protein binding
- FK506 binding
- identical protein binding
- Hsp90 protein binding
Cellular Component
- synaptonemal complex
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000252037
- Coding exons
- 8
- Length
- 30468
- Individuals with no LoFs
- 125675
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 73
- Defined
- 125748
- p
- 0.000290
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.666 | 154 | 179 | 0.860 | 0.0000112 | 2098 |
| Missense (PolyPhen) | 45 | 58.903 | 0.76396 | 707 | ||
| Synonymous | 0.773 | 66 | 74.5 | 0.886 | 0.00000459 | 658 |
| Loss of Function | 1.46 | 12 | 18.9 | 0.636 | 0.00000111 | 213 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00020 | 0.00020 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00039 | 0.00038 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00045 | 0.00045 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Co-chaperone required during spermatogenesis to repress transposable elements and prevent their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. Acts as a co-chaperone via its interaction with HSP90 and is required for the piRNA amplification process, the secondary piRNA biogenesis. May be required together with HSP90 in removal of 16 nucleotide ping-pong by-products from Piwi complexes, possibly facilitating turnover of Piwi complexes (By similarity). {ECO:0000250}.;
- Disease
- DISEASE: Note=Defects in FKBP6 may be a cause of azoospermia. A study based on 323 patients with azoospermia or severe oligozoospermia suggested an association between FKBP6 variants and azoospermia (PubMed:17307919). However, other studies suggest that defects in FKBP6 are not a common cause of non-obstructive azoospermia (PubMed:16227348). {ECO:0000269|PubMed:16227348, ECO:0000269|PubMed:17307919}.;
Recessive Scores
- pRec
- 0.130
Intolerance Scores
- LoFtool
- 0.637
- RVIS EVS
- 0.24
- RVIS percentile EVS
- 69.21
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.531
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |