FKBP14

Chr 7

FKBP prolyl isomerase 14

Also known as: EDSKMH, EDSKSCL2, FKBP22, IPBP12

NCBI Gene: 55033ENSG00000106080UniProt: Q9NWM8

The protein encoded by this gene is a member of the FK506-binding protein family of peptidyl-prolyl cis-trans isomerases. The encoded protein is found in the lumen of the endoplasmic reticulum, where it is thought to accelerate protein folding. Defects in this gene are a cause of a type of Ehlers-Danlos syndrome (EDS). Both a protein-coding variant and noncoding variants are transcribed from this gene. [provided by RefSeq, Mar 2012]

Primary Disease Associations & Inheritance

UniProtEhlers-Danlos syndrome, kyphoscoliotic type, 2
306
ClinVar variants
43
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— FKBP14
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
43 Pathogenic / Likely Pathogenic· 140 VUS of 306 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
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?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.
0.09Z-score
OE missense 0.97 (0.83–1.15)
105 obs / 107.7 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.0.98 (0.58–1.66)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.83–1.15)
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.0.84
0≤1.21.6
LoF obs/exp: 9 / 9.2Missense obs/exp: 105 / 107.7Syn Z: 0.78

ClinVar Variant Classifications

306 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic13
VUS140
Likely Benign107
Benign9
Conflicting7
30
Pathogenic
13
Likely Pathogenic
140
VUS
107
Likely Benign
9
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
0
23
0
30
Likely Pathogenic
8
0
5
0
13
VUS
2
125
13
0
140
Likely Benign
0
5
39
63
107
Benign
0
0
8
1
9
Conflicting
—7
Total171308864306

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.

Gene2Phenotype Curations

FKBP14-related Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — FKBP14
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
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
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
A cohort of 17 patients with kyphoscoliotic Ehlers-Danlos syndrome caused by biallelic mutations in FKBP14: expansion of the clinical and mutational spectrum and description of the natural history.
Giunta C et al.·Genet Med
2018Cohort
Mutations in FKBP14 cause a variant of Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss.
Baumann M et al.·Am J Hum Genet
2012
The neuromuscular differential diagnosis of joint hypermobility.
Donkervoort S et al.·Am J Med Genet C Semin Med Genet
2015Review
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
FKBP14 kyphoscoliotic Ehlers-Danlos syndrome misdiagnosed as Larsen syndrome: a case report.
Wiegand A et al.·Cold Spring Harb Mol Case Stud
2023Case report
FKBP14-related Ehlers-Danlos syndrome: expansion of the phenotype to include vascular complications.
Murray ML et al.·Am J Med Genet A
2014Case report
Genotype-based databases for variants causing rare diseases.
Lanthaler B et al.·Gene
2014
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools