FKBP10

Chr 17AR

FKBP prolyl isomerase 10

Also known as: BRKS, BRKS1, FKBP65, OI11, OI6, PPIASE, TLH1, hFKBP65

NCBI Gene: 60681 ENSG00000141756 UniProt: Q96AY3 OMIM: 607063

This protein is a peptidyl-prolyl cis/trans isomerase that localizes to the endoplasmic reticulum and functions as a molecular chaperone to accelerate protein folding during synthesis. Mutations cause osteogenesis imperfecta and Bruck syndrome, connective tissue disorders characterized by bone fragility, short stature, and in Bruck syndrome, congenital contractures. The gene shows strong evolutionary constraint (pLI near 1.0) and inheritance is autosomal recessive.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene belongs to the FKBP-type peptidyl-prolyl cis/trans isomerase (PPIase) family. This protein localizes to the endoplasmic reticulum and acts as a molecular chaperone. Alternatively spliced variants encoding different isoforms have been reported, but their biological validity has not been determined.[provided by RefSeq, Nov 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Bruck syndrome 1MIM #259450

Osteogenesis imperfecta, type XIMIM #610968

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Bruck syndrome 1; Osteogenesis imperfecta, type XI; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.85

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — FKBP10

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?

0.85LOEUF

pLI 0.000

Z-score 2.13

OE 0.53 (0.35–0.85)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.71Z-score

OE missense 0.89 (0.82–0.98)

322 obs / 360.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.53 (0.35–0.85)

0≤0.351.4

Missense OE?0.89 (0.82–0.98)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 13 / 24.3Missense obs/exp: 322 / 360.1Syn Z: -1.04

Background carrier burden — how many people carry a rare variant somewhere in FKBP10?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 70

870 rare PASS variants

Rare truncating (LoF)

1 in 1,100

133 rare PASS variants

Rare synonymous (reference)

1 in 100

375 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FKBP10. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 93	1 in 1,300
South Asian	~43k	1 in 59	1 in 710
Remaining (unassigned)	~30k	1 in 52	1 in 1,200
European (Finnish)	~27k	1 in 160	1 in 1,100
Admixed American	~22k	1 in 55	1 in 1,300
African / African American	~21k	1 in 59	1 in 430
East Asian	~20k	1 in 90	1 in 470
Ashkenazi Jewish	~13k	1 in 130	1 in 2,200
Middle Eastern	~2,884	1 in 44	≈ 1 in 850

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓