FKBP5

Chr 6

FKBP prolyl isomerase 5

Also known as: AIG6, FKBP51, FKBP54, P54, PPIase, Ptg-10

NCBI Gene: 2289 ENSG00000096060 UniProt: Q13451

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]

ClinVar variants

Pathogenic / LP

0.73

pLI score

Active trials

Clinical Summary— FKBP5

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.73) — some intolerance to loss-of-function variants.

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ClinVar Variants

7 Pathogenic / Likely Pathogenic· 43 VUS of 55 total submissions

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Clinical Trials

8 active or recruiting trials — potential therapeutic options may be available

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.42LOEUF

pLI 0.734

Z-score 3.54

OE 0.18 (0.09–0.42)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

1.62Z-score

OE missense 0.71 (0.63–0.81)

179 obs / 251.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.18 (0.09–0.42)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.63–0.81)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	6	0	6
Likely Pathogenic	0	1	0	1
VUS	40	3	0	43
Likely Benign	2	0	0	2
Benign	0	2	1	3
Total	42	12	1	55

FKBP5

Population Genetics & Constraint

ClinVar Variant Classifications

Classification Summary

Curated Variants Distribution

Protein Context — Lollipop Plot

OMIM — Genotype-Phenotype

Gene Overview

ClinGen Curation

Disease Associations

External Resources

Variant Interpretation

Population Databases

Gene Resources