POSTN

Chr 13

periostin

Also known as: OSF-2, OSF2, PDLPOSTN, PN

NCBI Gene: 10631 ENSG00000133110 UniProt: Q15063

The protein encoded by this gene is a secreted extracellular matrix protein that binds to integrins to support cell adhesion and migration, and enhances incorporation of proteins involved in connective tissue formation. Mutations cause autosomal recessive osteogenesis imperfecta type XV, characterized by bone fragility, skeletal deformities, and dental abnormalities. This gene shows minimal constraint against loss-of-function variants, consistent with a recessive inheritance pattern where heterozygous carriers are typically unaffected.

ResearchSummary from RefSeq, UniProt

This gene encodes a secreted extracellular matrix protein that functions in tissue development and regeneration, including wound healing, and ventricular remodeling following myocardial infarction. The encoded protein binds to integrins to support adhesion and migration of epithelial cells. This protein plays a role in cancer stem cell maintenance and metastasis. Mice lacking this gene exhibit cardiac valve disease, and skeletal and dental defects. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2015]

ResearchGenerating clinical summary…

Active trials

321

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.72

LOEUF

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?

0.72LOEUF

pLI 0.000

Z-score 3.00

OE 0.51 (0.36–0.72)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.85Z-score

OE missense 0.89 (0.81–0.96)

393 obs / 443.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.51 (0.36–0.72)

0≤0.351.4

Missense OE?0.89 (0.81–0.96)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 22 / 43.3Missense obs/exp: 393 / 443.5Syn Z: -0.62

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 66

1,030 rare PASS variants

Rare truncating (LoF)

1 in 980

153 rare PASS variants

Rare synonymous (reference)

1 in 170

376 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for POSTN. 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 83	1 in 1,200
South Asian	~43k	1 in 72	1 in 710
Remaining (unassigned)	~30k	1 in 44	1 in 580
European (Finnish)	~27k	1 in 270	1 in 390
Admixed American	~22k	1 in 50	1 in 2,000
African / African American	~21k	1 in 67	1 in 760
East Asian	~20k	1 in 67	1 in 720
Ashkenazi Jewish	~13k	1 in 300	1 in 650
Middle Eastern	~2,884	1 in 60	≈ 1 in 2,900

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): 19 of 23 coding exons well covered in gnomAD exomes; exons 3, 20, 22, 23 marginal. Genomes: 22 of 23 (exon 22 below).? see exons ↓