FKBP15

Chr 9

FKBP prolyl isomerase family member 15

Also known as: FKBP133, KIAA0674, PPP1R76

NCBI Gene: 23307ENSG00000119321UniProt: Q5T1M5

FKBP15 encodes a protein that binds actin and regulates cytoskeletal organization in neuronal growth cones, while also facilitating early endosome transport between microfilament-based and microtubule-based movement systems. Mutations cause neurodevelopmental disorders through a dominant-negative mechanism. The inheritance pattern and specific associated diseases are not established from the available data.

Summary from RefSeq, UniProt, Mechanism
Research Assistant →
0
Active trials
4
Pubs (1 yr)
0
P/LP submissions
—
P/LP missense
0.61
LOEUF
LOF
Mechanism· G2P
Clinical Summary— FKBP15
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
59 VUS of 100 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.61LOEUF
pLI 0.000
Z-score 4.23
OE 0.45 (0.34–0.61)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.58Z-score
OE missense 0.83 (0.77–0.89)
536 obs / 649.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.45 (0.34–0.61)
0≤0.351.4
Missense OE0.83 (0.77–0.89)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 31 / 68.9Missense obs/exp: 536 / 649.3Syn Z: 0.37
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFKBP15-related Wiskott-Aldrich syndromeLOFAD
DN
0.6648th %ile
GOF
0.5660th %ile
LOF
0.3454th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

VUS59
Likely Benign2
59
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
59
0
0
59
Likely Benign
0
1
0
1
2
Benign
0
0
0
0
0
Total0600161

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FKBP15 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
The peptidyl-prolyl isomerases TaFKBP15-5B is essential for starch synthesis affecting grain weight in wheat (Triticum aestivum L.).
Tian Z et al.·Int J Biol Macromol
2026
Molecular Signatures of Nuclear Protein Alterations in Systemic Lupus Erythematosus across Disease Stages.
Zhang Q et al.·J Proteome Res
2025
The blood transcriptome of musk deer under heat stress condition reveals the regulatory mechanism of genes to maintain homeostasis metabolism
Shi X et al.·BMC Genomics
2025Functional
PAX5 Alterations in a Consecutive Childhood B-Cell Acute Lymphoblastic Leukemia Cohort Treated Using the ALL IC-BFM 2009 Protocol
Črepinšek K et al.·Cancers (Basel)
2024Cohort
Identification of stably expressed reference genes for expression studies in Arabidopsis thaliana using mass spectrometry-based label-free quantification
Cheng SS et al.·Front Plant Sci
2022
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
NTRK-fused central nervous system tumours: clinicopathological and genetic insights and response to TRK inhibitors.
Kim EE et al.·Acta Neuropathol Commun
2024
The peptidyl-prolyl isomerases FKBP15-1 and FKBP15-2 negatively affect lateral root development by repressing the vacuolar invertase VIN2 in Arabidopsis.
Wang J et al.·Planta
2020
A Phytophthora capsici RXLR Effector Targets and Inhibits a Plant PPIase to Suppress Endoplasmic Reticulum-Mediated Immunity.
Fan G et al.·Mol Plant
2018
Multi-omics Analysis Reveals Comprehensive Aberrant Protein and Phosphorylation Characteristics in Breast Cancer and Paired Metastatic Lymph Nodes.
Zhai L et al.·Protein Cell
2026
M(6)A Demethylase Inhibits Osteogenesis of Dental Follicle Stem Cells via Regulating miR-7974/FKBP15 Pathway.
Zheng L et al.·Int J Mol Sci
2023
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients