FKBP2

Chr 11

FKBP prolyl isomerase 2

Also known as: FKBP-13, FKBP13, PPIase

NCBI Gene: 2286 ENSG00000173486 UniProt: P26885

This protein is a cis-trans prolyl isomerase that accelerates protein folding by catalyzing the isomerization of proline peptide bonds and functions as an endoplasmic reticulum chaperone. Mutations cause autosomal recessive osteogenesis imperfecta characterized by bone fragility, short stature, and connective tissue abnormalities with onset typically in infancy or early childhood. The gene shows relatively low constraint to loss-of-function variants.

ResearchSummary from RefSeq, UniProt

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 the immunosuppressants FK506 and rapamycin. It is thought to function as an ER chaperone and may also act as a component of membrane cytoskeletal scaffolds. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Sep 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.09

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

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.09LOEUF

pLI 0.049

Z-score 1.43

OE 0.42 (0.19–1.09)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.99Z-score

OE missense 0.68 (0.55–0.86)

53 obs / 77.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.42 (0.19–1.09)

0≤0.351.4

Missense OE?0.68 (0.55–0.86)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 3 / 7.1Missense obs/exp: 53 / 77.4Syn Z: 0.35

Background carrier burden — how many people carry a rare variant somewhere in FKBP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

207 rare PASS variants

Rare truncating (LoF)

1 in 2,100

48 rare PASS variants

Rare synonymous (reference)

1 in 2,900

79 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FKBP2. 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 220	1 in 3,000
South Asian	~43k	1 in 170	1 in 7,200
Remaining (unassigned)	~30k	1 in 410	1 in 3,300
European (Finnish)	~27k	1 in 780	≈ 1 in 13,000
Admixed American	~22k	1 in 200	≈ 1 in 22,000
African / African American	~21k	1 in 200	1 in 1,300
East Asian	~20k	1 in 240	1 in 730
Ashkenazi Jewish	~13k	1 in 430	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 320	none seen

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 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓