BGLAP

Chr 1

bone gamma-carboxyglutamate protein

Also known as: BGP, OC, OCN

NCBI Gene: 632ENSG00000242252UniProt: P02818OMIM: 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]

OMIMResearchGenerating clinical summary…
DNmechanismLOEUF 1.95
Clinical Summary— BGLAP
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 VUS of 21 total submissions
💊
Clinical Trials
11 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

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

This gene — mechanism propensity

DN
0.6551th %ile
GOF
0.5759th %ile
LOF
0.2776th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

21 submitted variants in ClinVar

ClinVar

Classification Summary

VUS19
Likely Benign1
Benign1
19
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
2
17
0
0
19
Likely Benign
0
0
0
1
1
Benign
0
1
0
0
1
Total2180121

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

19 pathogenic / likely-pathogenic (of 28) ClinVar copy-number / structural variants overlap BGLAP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

BGLAP · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Primary Osteoporosis

Vitamin D Status and Multi-Omics Profiles in Primary Osteoporosis

RECRUITING
NCT07296471Dr. Li ChenStarted 2025-11-11
Klinefelter Syndrome

Klinefelter Syndrome and Testosterone Treatment in Puberty

RECRUITING
NCT06294990Phase PHASE4Lise AksglædeStarted 2024-08-15
Testosterone gelPlacebo
OsteoporosisOsteopenia

A Pilot Study of Vitamin K2 (Menaquinone-7, Soloways ™) in Patients With Osteopenia/Osteoporosis Carrying a VDR Gene Variant

RECRUITING
NCT06867952Phase NAS.LAB (SOLOWAYS)Started 2024-05-03
Vitamin K2 plus vitamin D3Vitamin K2 plus vitamin D3
ObesityWeight Loss

The Effect of Different Diets on Arterial Stiffness in Obese Patients on Semaglutide

RECRUITING
NCT04990024Phase NAAmerican University of Beirut Medical CenterStarted 2021-07-01
Dietary Intervention Med DietDietary Intervention HP/LC Diet
Alveolar Bone Loss Associated Chronic Periodontitis

Clinical Efficacy of 1% Metformin and Alendronate Gel in Adjunct to Fibrin in Chronic Periodontitis

ACTIVE NOT RECRUITING
NCT06856369Phase PHASE4Bahria UniversityStarted 2025-01-22
Platelet rich fibrinMetformin hydrochloride powderalendronate sodium powder
RASopathy

Study of the Thyroid Function and Echostructural Morphology in Patients Affected With Rasopathies (ECORAS2023)

RECRUITING
NCT06489067University of Bari Aldo MoroStarted 2024-01-15
Inflammatory Bowel DiseaseCrohn Disease

Skeletal Health and Bone Marrow Composition in Newly Diagnosed Adolescents With Crohn Disease

RECRUITING
NCT04508088Massachusetts General HospitalStarted 2020-09-10
Coronal T1 weighted spin echo imagesSpin-lattice relaxation (T1)Magnetic resonance spectroscopy
Osteoporosis，Neurological Disorders

Beijing Osteoporosis With Neurological Disorders in Epigenetic Changes Study

ACTIVE NOT RECRUITING
NCT03401619Peking University Third HospitalStarted 2017-09-21
Exercise，Nutrition，Bisphosphonates，Statins，Calcitonin,Vitamin D，et al.
Obesity, Morbid

Different Limb Lengths in Gastric Bypass Surgery (SLIM) - Part 3: Metabolism and Inflammation

ACTIVE NOT RECRUITING
NCT05471037Phase NAUniversity Hospital, Basel, SwitzerlandStarted 2022-08-01
Long Biliopancreatic Limb LRYGBShort Biliopancreatic Limb LRYGB
CAH - Congenital Adrenal Hyperplasia

Hydrocortisone Modified-release in Adults: Real-world Monitoring of Longitudinal Outcomes in coNgenital Adrenal hYperplasia

NOT YET RECRUITING
NCT07622030IRCCS San RaffaeleStarted 2026-07-31
Osteoporosis, Postmenopausal

Vascular Function, Sarcopenia and Pain in Postmenopausal Osteoporosis

RECRUITING
NCT05228262Phase NAUniversity Hospital, Clermont-FerrandStarted 2022-02-15
Cohort follow-up

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients