BGLAP
protein-codingbone gamma-carboxyglutamate protein, the group of Gla domain containing
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to BGLAP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_199173.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 1 | 5 | |||
| missense | 14 | 1 | 15 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 19 | 1 | 1 | 21 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_954642.1 | 4 | MANE Select | |
| Ensembl | ENSP00000357255.4 | 4 | MANE Select | |
| Ensembl | ENSP00000809382.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Warfarin Pathway, Pharmacodynamics
- Interleukin-11 Signaling Pathway
- Vitamin D Receptor Pathway
- Osteoblast Signaling
- RUNX2 regulates osteoblast differentiation
Biological Process
- skeletal system development
- ossification
- osteoblast differentiation
- osteoblast development
- endoplasmic reticulum to Golgi vesicle-mediated transport
Molecular Function
- structural molecule activity
- calcium ion binding
- structural constituent of bone
- hydroxyapatite binding
Cellular Component
- extracellular region
- extracellular space
- cytoplasm
- endoplasmic reticulum lumen
- rough endoplasmic reticulum
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368272
- Coding exons
- 4
- Length
- 1360
- Individuals with no LoFs
- 125663
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 74
- Defined
- 125738
- p
- 0.000298
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.334 | 56 | 63.5 | 0.882 | 0.00000408 | 624 |
| Missense (PolyPhen) | 24 | 21.29 | 1.1273 | 194 | ||
| Synonymous | -1.06 | 37 | 29.6 | 1.25 | 0.00000228 | 196 |
| Loss of Function | -1.58 | 9 | 5.13 | 1.75 | 2.17e-7 | 61 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.000032 | 0.000029 | rare |
| Ashkenazi Jewish | 0.0033 | 0.0029 | notable |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00034 | 0.00033 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Constitutes 1-2% of the total bone protein. It binds strongly to apatite and calcium.;
Recessive Scores
- pRec
- 0.262
Intolerance Scores
- LoFtool
- 0.641
- RVIS EVS
- 0.48
- RVIS percentile EVS
- 79.04
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |