FKBP4

Chr 12

FKBP prolyl isomerase 4

Also known as: FKBP51, FKBP52, FKBP59, HBI, Hsp56, PPIase, p52

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 has high structural and functional similarity to FK506-binding protein 1A (FKBP1A), but unlike FKBP1A, this protein does not have immunosuppressant activity when complexed with FK506. It interacts with interferon regulatory factor-4 and plays an important role in immunoregulatory gene expression in B and T lymphocytes. This encoded protein is known to associate with phytanoyl-CoA alpha-hydroxylase. It can also associate with two heat shock proteins (hsp90 and hsp70) and thus may play a role in the intracellular trafficking of hetero-oligomeric forms of the steroid hormone receptors. This protein correlates strongly with adeno-associated virus type 2 vectors (AAV) resulting in a significant increase in AAV-mediated transgene expression in human cell lines. Thus this encoded protein is thought to have important implications for the optimal use of AAV vectors in human gene therapy. The human genome contains several non-transcribed pseudogenes similar to this gene. [provided by RefSeq, Sep 2008]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
3
Active trials
39
Pubs (1 yr)
P/LP submissions
P/LP missense
0.50
LOEUF
Multiple*
Mechanism· predicted
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.50LOEUF
pLI 0.155
Z-score 3.34
OE 0.26 (0.140.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
1.21Z-score
OE missense 0.79 (0.700.88)
197 obs / 250.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.26 (0.140.50)
00.351.4
Missense OE?0.79 (0.700.88)
00.61.4
Synonymous OE?1.14
01.21.6
LoF obs/exp: 6 / 23.5Missense obs/exp: 197 / 250.8Syn Z: -1.06

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FKBP4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.