FKBP14

Chr 7AR

FKBP prolyl isomerase 14

Also known as: EDSKMH, EDSKSCL2, FKBP22, IPBP12

NCBI Gene: 55033ENSG00000106080UniProt: Q9NWM8OMIM: 614505

The protein is a peptidyl-prolyl isomerase located in the endoplasmic reticulum that accelerates protein folding, with particular preference for substrates containing 4-hydroxyproline modifications including type III collagen. Biallelic mutations cause Ehlers-Danlos syndrome, kyphoscoliotic type 2, which is inherited in an autosomal recessive pattern. The gene shows tolerance to loss-of-function variants in the general population (high LOEUF score), consistent with the recessive inheritance pattern where heterozygous carriers are typically unaffected.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.661 OMIM phenotype
Clinical Summary— FKBP14
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 unique Pathogenic / Likely Pathogenic· 48 VUS of 100 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — FKBP14
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.66LOEUF
pLI 0.000
Z-score 0.07
OE 0.98 (0.58–1.66)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.09Z-score
OE missense 0.97 (0.83–1.15)
105 obs / 107.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.98 (0.58–1.66)
0≤0.351.4
Missense OE0.97 (0.83–1.15)
0≤0.61.4
Synonymous OE0.84
0≤1.21.6
LoF obs/exp: 9 / 9.2Missense obs/exp: 105 / 107.7Syn Z: 0.78
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFKBP14-related Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing lossLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6551th %ile
GOF
0.6346th %ile
LOF
0.3355th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic2
VUS48
Likely Benign39
6
Pathogenic
2
Likely Pathogenic
48
VUS
39
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
2
0
6
Likely Pathogenic
2
0
0
0
2
VUS
0
45
3
0
48
Likely Benign
0
4
7
28
39
Benign
0
0
0
0
0
Total649122895

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

View in ClinVar →

Protein Context — Lollipop Plot

FKBP14 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Further delineation of FKBP14-related Ehlers-Danlos syndrome: A patient with early vascular complications and non-progressive kyphoscoliosis, and literature review.
Dordoni C et al.·Am J Med Genet A
2016Review
Ehlers-Danlos syndrome related to FKBP14 mutations: detailed cutaneous phenotype.
Bursztejn AC et al.·Clin Exp Dermatol
2017Review
Transcriptome Profiling of Primary Skin Fibroblasts Reveal Distinct Molecular Features Between PLOD1- and FKBP14-Kyphoscoliotic Ehlers-Danlos Syndrome.
Lim PJ et al.·Genes (Basel)
2019
Primary muscle involvement in a 15-year-old girl with the recurrent homozygous c.362dupC variant in FKBP14.
Castori M et al.·Am J Med Genet A
2019Case report
Ehlers-Danlos syndrome kyphoscoliotic type 2 caused by mutations in the FKBP14 gene: an analysis of five cases.
Semyachkina AN et al.·F1000Res
2021Cohort
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Surgical management of progressive spinal deformities in FKBP14-associated Ehlers-Danlos syndrome: a case report and literature review.
DeMessie B et al.·Childs Nerv Syst
2025Open AccessReview
Perforation of the Sigmoid Colon due to Diverticular Rupture in a Woman With FKBP14-Related Kyphoscoliotic Ehlers-Danlos Syndrome: A Case Report.
Foy M et al.·Clin Case Rep
2025Case report
FKBP14 kyphoscoliotic Ehlers-Danlos syndrome misdiagnosed as Larsen syndrome: a case report.
Wiegand A et al.·Cold Spring Harb Mol Case Stud
2023Open AccessCase report
Kyphoscoliotic Ehlers-Danlos syndrome caused by pathogenic variants in FKBP14: Further insights into the phenotypic spectrum and pathogenic mechanisms.
Colman M et al.·Hum Mutat
2022Functional
Linc00883 affects colorectal cancer through miR-577/FKBP14 axis: a novel mechanism for regulating colorectal cancer cell proliferation, invasion, and migration.
Bai Y et al.·Cell Cycle
2022Functional
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