BGLAP

Chr 1

bone gamma-carboxyglutamate protein

Also known as: BGP, OC, OCN

NCBI Gene: 632 ENSG00000242252 UniProt: P02818 OMIM: 112260

This gene encodes a highly abundant bone protein secreted by osteoblasts that regulates bone remodeling and energy metabolism. The encoded protein contains a Gla (gamma carboxyglutamate) domain, which functions in binding to calcium and hydroxyapatite, the mineral component of bone. Serum osteocalcin levels may be negatively correlated with metabolic syndrome. Read-through transcription exists between this gene and the neighboring upstream gene, PMF1 (polyamine-modulated factor 1), but the encoded protein only shows sequence identity with the upstream gene product. [provided by RefSeq, Jun 2015]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

134

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.95

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.95LOEUF

pLI 0.000

Z-score -1.58

OE 1.76 (0.96–1.95)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.33Z-score

OE missense 0.88 (0.71–1.10)

56 obs / 63.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.76 (0.96–1.95)

0≤0.351.4

Missense OE?0.88 (0.71–1.10)

0≤0.61.4

Synonymous OE?1.25

0≤1.21.6

LoF obs/exp: 9 / 5.1Missense obs/exp: 56 / 63.5Syn Z: -1.06

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 270

133 rare PASS variants

Rare truncating (LoF)

1 in 1,000

38 rare PASS variants

Rare synonymous (reference)

1 in 420

72 rare PASS variants

Rare missense and truncating variants are carried at similar rates in BGLAP; this gene does not show strong loss-of-function constraint by this measure. 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 670	1 in 1,600
South Asian	~43k	1 in 260	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 210	1 in 500
European (Finnish)	~27k	1 in 3,700	≈ 1 in 26,000
Admixed American	~22k	1 in 220	1 in 2,100
African / African American	~21k	1 in 390	1 in 710
East Asian	~20k	1 in 260	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 1,600	none seen
Middle Eastern	~2,884	1 in 320	≈ 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): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓