BGLAP

Summary

BGLAP (bone gamma-carboxyglutamate protein, HGNC:1043) is a protein-coding gene on chromosome 1q22, encoding Osteocalcin (P02818). The carboxylated form is one of the main organic components of the bone matrix, which constitutes 1-2% of the total bone protein.

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.

Source: NCBI Gene 632 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 22 total
• MANE Select transcript: NM_199173

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1043
Approved symbol	BGLAP
Name	bone gamma-carboxyglutamate protein
Location	1q22
Locus type	gene with protein product
Status	Approved
Aliases	OCN, BGP
Ensembl gene	ENSG00000242252
Ensembl biotype	protein_coding
OMIM	112260
Entrez	632

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000368272, ENST00000471413

RefSeq mRNA: 1 — MANE Select: NM_199173 NM_199173

CCDS: CCDS1134

Canonical transcript exons

ENST00000368272 — 4 exons

Exon	Start	End
ENSE00001446742	156242184	156242295
ENSE00003552470	156242762	156242831
ENSE00003590844	156242553	156242591
ENSE00003692422	156243033	156243317

Expression profiles

Bgee: expression breadth ubiquitous, 130 present calls, max score 90.98.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2000 / max 2351.0940, expressed in 183 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5710	2.1631	182
5709	0.0368	17

Top tissues by expression

133 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.98	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.73	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.07	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	81.92	gold quality
cerebellar hemisphere	UBERON:0002245	81.64	gold quality
cerebellum	UBERON:0002037	81.49	gold quality
cerebellar cortex	UBERON:0002129	81.47	gold quality
muscle layer of sigmoid colon	UBERON:0035805	80.83	gold quality
putamen	UBERON:0001874	80.77	gold quality
substantia nigra	UBERON:0002038	80.75	gold quality
caudate nucleus	UBERON:0001873	80.50	gold quality
nucleus accumbens	UBERON:0001882	79.75	gold quality
right uterine tube	UBERON:0001302	79.72	gold quality
amygdala	UBERON:0001876	79.53	gold quality
apex of heart	UBERON:0002098	79.52	gold quality
temporal lobe	UBERON:0001871	79.40	gold quality
lower esophagus mucosa	UBERON:0035834	78.51	gold quality
primary visual cortex	UBERON:0002436	78.19	gold quality
mucosa of transverse colon	UBERON:0004991	77.95	gold quality
granulocyte	CL:0000094	77.75	gold quality
right frontal lobe	UBERON:0002810	77.08	gold quality
brain	UBERON:0000955	76.62	gold quality
hypothalamus	UBERON:0001898	76.27	gold quality
anterior cingulate cortex	UBERON:0009835	76.19	gold quality
right lobe of liver	UBERON:0001114	75.93	gold quality
Ammon’s horn	UBERON:0001954	75.81	gold quality
right ovary	UBERON:0002118	75.63	gold quality
left ovary	UBERON:0002119	75.08	gold quality
spleen	UBERON:0002106	74.71	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	74.61	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.21

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, ATF4, ATF6, BMP2, BMPR1B, CCL3, CCR1, CEBPB, CEBPD, CEBPG, CREBZF, CREM, CTNNB1, CUX1, DDIT3, DLX3, DLX5, DMTF1, EGR2, ESR1, ESRRA, ESRRG, ETS2, FOS, FOSB, FOSL2, FOXC1, FOXO1, FOXQ1, GLI2, GLIS3, GTF2F1, HDAC3, HES1, HIVEP2, HNF4A, HNRNPK, HR, ID1

miRNA regulators (miRDB)

19 targeting BGLAP, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-3127-5P	97.52	65.24	786

Literature-anchored findings (GeneRIF, showing 40)

• Osteocalcin was not localized extracellularly within the collagen-rich dentin matrix (predentin or intertubular dentin), but was found in the mature enamel. (PMID:11856645)
• data support the BGP gene as a quantitative trait locus(QTL)underlying hip bone mineral density variation variation (PMID:11918225)
• exists in osteoblasts and suppresses excess calcification (PMID:11979972)
• Differential regulation of Cbfa1/Runx2 and osteocalcin gene expression by vitamin-D3, dexamethasone, and local growth factors in primary human osteoblasts (PMID:12112004)
• Expression is regulated by a novel Ku antigen transcription factor complex (PMID:12145306)
• TWIST inactivation reduces CBFA1/RUNX2 expression and DNA binding to its promoter in osteoblasts (PMID:12270142)
• This protein is regulated by human basic fibroblast growth factor. (PMID:12393937)
• Telomerase accelerates osteogenesis of bone marrow stromal stem cells by upregulation of CBFA1, osterix, and osteocalcin. (PMID:12674332)
• osteocalcin genes are susceptibility loci for reduced bone mineral density in postmenopausal women (PMID:12843190)
• relationship between increase in undercarboxylated osteocalcin levels and low bone mineral density in elderly women with type II diabetes mellitus (PMID:15108065)
• HindIII RFLP of the BGP gene may be limited as a genetic marker to discern women susceptible to low BMD and thus osteoporosis in Chinese (PMID:15108070)
• Low serum level in osteochondrodysplasia. (PMID:15562030)
• the osteocalcin sequences of Neanderthals, modern human, chimpanzee, and orangutan are unusual among mammals in that the ninth amino acid is proline (Pro-9), whereas most species have hydroxyproline (Hyp-9) (PMID:15753298)
• May be a biological markers of bone disease in multiple myeloma. (PMID:16263577)
• mRNA and protein are expressed in c-KIT positive neoplastic stem cells in hematological malignancies. (PMID:16387359)
• The transcription axis of osteocalcin is crucial in maintaining equilibrium of bone formation and resorption. Heparin affects expression in osteoblast culture. (PMID:17000892)
• Serum osteocalcin showed no significant difference with the control healthy subjects. (PMID:17242729)
• Data show that simvastatin and atorvastatin enhance gene expression of collagen type 1 and osteocalcin in primary human osteoblasts and MG-63 cultures. (PMID:17252541)
• local 1,25D synthesis has paracrine effects in the bone microenvironment implying that vitamin D metabolism in human osteoblasts represents a physiologically important pathway (PMID:17254772)
• Our data do not support the BGP gene having a major effect on BMD variation in pre-menopausal Chinese women. (PMID:17627084)
• Combined use of osteocalcin and beta-CTX could be useful in early detection of bone metastatic breast cancer which might improve the outcome of the disease. (PMID:17889845)
• BGLAP is expressed in pancreatic cancer cells and increases their growth and invasion (PMID:18163903)
• TFIIA gamma together with ATF4 and Runx2 stimulates osteocalcin promoter activity and endogenous mRNA expression. (PMID:18171674)
• In cotransfection experiments with an osteocalcin (OC) promoter construct, we confirmed that only RUNX2wt and RUNX2Delta7 could upregulate the OC promoter activity in the osteosarcoma cell line. (PMID:18321663)
• There is a potential role of osteocalcin in regulating blood glucose levels in postmenopausal women (PMID:18657532)
• Exposure of odontoblast-like cells to LPS decreases osteocalcin gene expression. (PMID:19031822)
• Plasma osteocalcin is inversely related to fat mass and plasma glucose. (PMID:19063687)
• serum osteocalcin concentration was inversely associated with markers of dysmetabolic phenotype & measures of adiposity; results provide support for important role of osteocalcin to regulate glucose tolerance, insulin sensitivity & systemic inflammation (PMID:19088165)
• Protein levels and mRNA expression of osteocalcin were greater in calcified compared to noncalcified plaques. (PMID:19136823)
• strain enhance expression of osteocalcin, type I collagen gene and Cbfa1/Runx2 in human osteoblas (PMID:19595020)
• The OC/BAP ratio could be clinically useful for assessing the risk of vertebral fractures independent of BMD in diabetic men. (PMID:19641839)
• Data suggest taht serial measurements of osteocalcin could be useful in the detection of bone metastases from differentiated thyroid carcinoma. (PMID:19732762)
• Relationship between bone formation markers osteocalcin and bone-specific alkaline phosphatase and age in postmenopausal women. (PMID:19751416)
• Prevalence of osteopenia and relationships between osteocalcin, bone alkaline phosphatase, and bone mineral density in patients with insulin-dependent diabetes mellitus. (PMID:19751417)
• not associated with dental fluorosis (PMID:19767102)
• Data show that the gradual process of osteogenesis can be followed by different proteins being expressed at various time points, comprising early bone-specific alkaline phosphatase (bALP)) and late gene osteocalcin. (PMID:19856264)
• Elevated plasma osteocalcin is associated with improved glucose tolerance. Elevated uncarboxylated osteocalcin is associated with enhanced beta-cell function; elevated carboxylated osteocalcin is associated with improved insulin sensitivity. (PMID:19877133)
• A positive association is found between serum level of osteocalcin and severity of hand osteoarthritis, in a cross-sectional population-based study. (PMID:20157712)
• Polymorphisms in and around the osteocalcin locus are significantly associated with serum-TotalOC and fracture. (PMID:20200947)
• These results indicate that older age, a greater number of prevalent fractures and higher undercarboxylated osteocalcin levels, and lower lumbar bone mineral density are risks for incident fractures despite use of amino-bisphosphonates. (PMID:20221651)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	bglap	ENSDARG00000058414
mus_musculus	Bglap	ENSMUSG00000074483
mus_musculus	Bglap2	ENSMUSG00000074486
mus_musculus	Bglap3	ENSMUSG00000074489
rattus_norvegicus	Bglap	ENSRNOG00000019607

Protein

Protein identifiers

Osteocalcin — P02818 (reviewed: P02818)

Alternative names: Bone Gla protein, Gamma-carboxyglutamic acid-containing protein

All UniProt accessions (1): P02818

UniProt curated annotations — full annotation on UniProt →

Function. The carboxylated form is one of the main organic components of the bone matrix, which constitutes 1-2% of the total bone protein. Acts as a negative regulator of bone formation and is required to limit bone formation without impairing bone resorption or mineralization. Binds strongly to apatite and calcium upon gamma-carboxylation; this modification is essential for bone metabolism. The uncarboxylated form acts as a hormone secreted by osteoblasts, which regulates different cellular processes, such as energy metabolism, male fertility and brain development. Regulates of energy metabolism by acting as a hormone favoring pancreatic beta-cell proliferation, insulin secretion and sensitivity and energy expenditure. Uncarboxylated osteocalcin hormone also promotes testosterone production in the testes: acts as a ligand for G protein-coupled receptor GPRC6A at the surface of Leydig cells, initiating a signaling response that promotes the expression of enzymes required for testosterone synthesis in a CREB-dependent manner. Also acts as a regulator of brain development: osteocalcin hormone crosses the blood-brain barrier and acts as a ligand for GPR158 on neurons, initiating a signaling response that prevents neuronal apoptosis in the hippocampus, favors the synthesis of all monoamine neurotransmitters and inhibits that of gamma-aminobutyric acid (GABA). Osteocalcin also crosses the placenta during pregnancy and maternal osteocalcin is required for fetal brain development.

Subcellular location. Secreted.

Post-translational modifications. Carboxylated by vitamin K-dependent GGCX to form gamma-carboxyglutamate; these residues are essential for the binding of calcium. Decarboxylation promotes the hormone activity.

Similarity. Belongs to the osteocalcin/matrix Gla protein family.

RefSeq proteins (1): NP_954642* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000294	GLA_domain	Domain
IPR002384	Osteocalcin/MGP	Family
IPR035972	GLA-like_dom_SF	Homologous_superfamily
IPR039176	Osteocalcin	Family
IPR058704	BGLAP-like_C	Domain

Pfam: PF25890

UniProt features (18 total): binding site 5, modified residue 3, signal peptide 1, propeptide 1, disulfide bond 1, sequence variant 1, sequence conflict 1, turn 1, helix 1, chain 1, domain 1, site 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
8XS1	X-RAY DIFFRACTION	2.3
9L23	ELECTRON MICROSCOPY	2.62
9WF2	ELECTRON MICROSCOPY	2.94
9BUR	ELECTRON MICROSCOPY	2.95
9BUX	ELECTRON MICROSCOPY	3.06
9MQC	ELECTRON MICROSCOPY	3.13
9MQB	ELECTRON MICROSCOPY	3.37
9MQE	ELECTRON MICROSCOPY	3.56

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02818-F1	76.66	0.39

Antibody-complex structures (SAbDab): 1 — 8XS1

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 60 (not hydroxylated)

Ligand- & substrate-binding residues (5): 68; 72; 75; 75; 81

Post-translational modifications (3): 68, 72, 75

Disulfide bonds (1): 74–80

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-159740	Gamma-carboxylation of protein precursors
R-HSA-159763	Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus
R-HSA-159782	Removal of aminoterminal propeptides from gamma-carboxylated proteins
R-HSA-8940973	RUNX2 regulates osteoblast differentiation

MSigDB gene sets: 209 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, GOBP_COGNITION, GOBP_RESPONSE_TO_ZINC_ION, GOBP_BEHAVIOR, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_RESPONSE_TO_CORTICOSTEROID, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, PID_REG_GR_PATHWAY

GO Biological Process (41): skeletal system development (GO:0001501), osteoblast differentiation (GO:0001649), positive regulation of neurotransmitter secretion (GO:0001956), cell adhesion (GO:0007155), brain development (GO:0007420), learning or memory (GO:0007611), response to xenobiotic stimulus (GO:0009410), response to mechanical stimulus (GO:0009612), response to gravity (GO:0009629), response to zinc ion (GO:0010043), response to activity (GO:0014823), bone mineralization (GO:0030282), regulation of bone mineralization (GO:0030500), response to vitamin K (GO:0032571), cellular response to insulin stimulus (GO:0032869), response to vitamin D (GO:0033280), response to testosterone (GO:0033574), response to hydroxyisoflavone (GO:0033594), cellular response to zinc ion starvation (GO:0034224), response to macrophage colony-stimulating factor (GO:0036005), glucose homeostasis (GO:0042593), response to estrogen (GO:0043627), type B pancreatic cell proliferation (GO:0044342), regulation of bone resorption (GO:0045124), response to ethanol (GO:0045471), regulation of osteoclast differentiation (GO:0045670), stem cell differentiation (GO:0048863), cognition (GO:0050890), response to glucocorticoid (GO:0051384), bone development (GO:0060348), cellular response to vitamin D (GO:0071305), cellular response to growth factor stimulus (GO:0071363), regulation of cellular response to insulin stimulus (GO:1900076), negative regulation of bone development (GO:1903011), regulation of testosterone biosynthetic process (GO:2000224), ossification (GO:0001503), signal transduction (GO:0007165), biomineral tissue development (GO:0031214), response to nutrient levels (GO:0031667), response to insulin (GO:0032868)

GO Molecular Function (7): hormone activity (GO:0005179), structural molecule activity (GO:0005198), calcium ion binding (GO:0005509), structural constituent of bone (GO:0008147), hydroxyapatite binding (GO:0046848), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (9): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), endoplasmic reticulum lumen (GO:0005788), Golgi lumen (GO:0005796), dendrite (GO:0030425), vesicle (GO:0031982), perikaryon (GO:0043204), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Gamma-carboxylation, transport, and amino-terminal cleavage of proteins	3
RUNX2 regulates bone development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
response to ketone	3
ossification	2
response to abiotic stimulus	2
response to vitamin	2
response to lipid	2
intracellular organelle lumen	2
system development	1
cell differentiation	1
neurotransmitter secretion	1
regulation of neurotransmitter secretion	1
positive regulation of synaptic transmission	1
positive regulation of neurotransmitter transport	1
positive regulation of secretion by cell	1
cellular process	1
central nervous system development	1
animal organ development	1
head development	1
behavior	1
cognition	1
response to chemical	1
response to external stimulus	1
response to metal ion	1
response to stimulus	1
biomineral tissue development	1
regulation of ossification	1
bone mineralization	1
regulation of biomineral tissue development	1
response to insulin	1
cellular response to peptide hormone stimulus	1
response to oxygen-containing compound	1
response to phenylpropanoid	1
cellular response to starvation	1
response to zinc ion starvation	1
response to cytokine	1
receptor ligand activity	1
molecular_function	1
metal ion binding	1
structural molecule activity	1
small molecule binding	1

Protein interactions and networks

STRING

1974 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BGLAP	SPP1	P10451	994
BGLAP	SPARC	P09486	991
BGLAP	RUNX2	Q13950	981
BGLAP	GPRC6A	Q5T6X5	974
BGLAP	IBSP	P21815	970
BGLAP	PTH	P01270	942
BGLAP	MGP	P08493	933
BGLAP	BMP2	P12643	932
BGLAP	FN1	P02751	916
BGLAP	TNFSF11	O14788	915
BGLAP	SP7	Q8TDD2	908
BGLAP	ALPL	P05186	901
BGLAP	DLX5	P56178	896
BGLAP	COL1A1	P02452	889
BGLAP	ACP5	P13686	882

IntAct

5 interactions, top by confidence:

A	B	Type	Score
BGLAP	ASPH	psi-mi:“MI:0915”(physical association)	0.560
BGLAP	HSPA5	psi-mi:“MI:0914”(association)	0.350
ASPH	BGLAP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): BGLAP (Two-hybrid), SEH1L (Affinity Capture-MS), GRN (Affinity Capture-MS), P3H2 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), POC1A (Affinity Capture-MS), BGLAP (Co-localization), BGLAP (Positive Genetic), BGLAP (Affinity Capture-MS)

ESM2 similar proteins: A0MLS4, A2BD09, A2D4U1, A2D670, A2T6K4, O14669, P01257, P01286, P02818, P02820, P02822, P27916, P41547, P51693, P63292, P70160, P84348, P84349, P84350, Q03157, Q0VCT2, Q2NL23, Q3KNT9, Q3TYX2, Q5HZE8, Q5T124, Q60549, Q64375, Q6AYE5, Q6BEG6, Q6BEG7, Q71SY6, Q76IQ4, Q7M742, Q7TNI2, Q86UD1, Q8JFY4, Q8K2B0, Q8QZR4, Q8R182

Diamond homologs: A2D4U1, A2D670, A2T6K4, K7NTD0, P02818, P02819, P02820, P02821, P02822, P02823, P04640, P0C225, P0C226, P15504, P39056, P40147, P40148, P54615, P81455, P83005, P83238, P83489, P84348, P84349, P84350, P84351, P86312, P86313, P86314, P86315, P86546, P86547, P86863, P86867, Q1EG28, Q6DJ00, Q800Y1, Q8HYY9, A0A024QYT3, K9J977

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
RUNX2	“up-regulates quantity by expression”	BGLAP	“transcriptional regulation”
TGFB1	“down-regulates quantity by repression”	BGLAP	“transcriptional regulation”
SMOC1	“up-regulates quantity by expression”	BGLAP	“transcriptional regulation”
GGCX	“up-regulates activity”	BGLAP	carboxylation
SP7	“up-regulates quantity by expression”	BGLAP	“transcriptional regulation”
ETS2	“up-regulates quantity by expression”	BGLAP	“transcriptional regulation”
RUNX2/EP300	“up-regulates quantity by expression”	BGLAP	“transcriptional regulation”
CTSB	“down-regulates quantity by destabilization”	BGLAP	cleavage
CTSD	“down-regulates quantity by destabilization”	BGLAP	cleavage
CTSL	“down-regulates quantity by destabilization”	BGLAP	cleavage
CTSS	“down-regulates quantity by destabilization”	BGLAP	cleavage
CTSH	“down-regulates quantity by destabilization”	BGLAP	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

22 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

458 predictions. Top by Δscore:

Variant	Effect	Δscore
1:156242547:TTGCA:T	acceptor_loss	1.0000
1:156242548:TGCA:T	acceptor_loss	1.0000
1:156242549:GCAG:G	acceptor_loss	1.0000
1:156242550:CA:C	acceptor_loss	1.0000
1:156242551:A:AT	acceptor_loss	1.0000
1:156242552:G:A	acceptor_loss	1.0000
1:156242552:G:GT	acceptor_loss	1.0000
1:156242551:A:AG	acceptor_gain	0.9900
1:156242552:G:GG	acceptor_gain	0.9900
1:156242552:GGT:G	acceptor_gain	0.9900
1:156242552:GGTGC:G	acceptor_gain	0.9900
1:156242295:GGTG:G	donor_loss	0.9800
1:156242296:G:A	donor_loss	0.9800
1:156242297:T:A	donor_loss	0.9800
1:156242551:AG:A	acceptor_gain	0.9800
1:156242552:GG:G	acceptor_gain	0.9800
1:156242760:A:AG	acceptor_gain	0.9800
1:156242761:G:GG	acceptor_gain	0.9800
1:156242291:GGCAG:G	donor_gain	0.9700
1:156242292:GCAGG:G	donor_gain	0.9700
1:156242551:AGGT:A	acceptor_gain	0.9700
1:156242552:GGTG:G	acceptor_gain	0.9700
1:156242293:C:T	donor_gain	0.9600
1:156242292:GCAG:G	donor_gain	0.9500
1:156243032:G:C	acceptor_gain	0.9500
1:156243030:CAGAG:C	acceptor_gain	0.9400
1:156242761:GC:G	acceptor_gain	0.9300
1:156242296:G:GG	donor_gain	0.9200
1:156242548:T:TA	acceptor_gain	0.9200
1:156242599:G:GT	donor_gain	0.9100

AlphaMissense

636 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:156243079:T:A	C74S	0.996
1:156243080:G:C	C74S	0.996
1:156243097:T:A	C80S	0.996
1:156243098:G:A	C80Y	0.996
1:156243098:G:C	C80S	0.996
1:156243080:G:A	C74Y	0.995
1:156243098:G:T	C80F	0.995
1:156243099:T:G	C80W	0.994
1:156243079:T:C	C74R	0.992
1:156243080:G:T	C74F	0.991
1:156243081:T:G	C74W	0.991
1:156243097:T:C	C80R	0.991
1:156243109:G:C	A84P	0.988
1:156243125:T:G	F89C	0.988
1:156243121:G:T	G88C	0.984
1:156243122:G:T	G88V	0.977
1:156243136:T:G	Y93D	0.977
1:156243125:T:C	F89S	0.976
1:156243134:C:A	A92D	0.974
1:156243145:T:C	F96L	0.974
1:156243147:C:A	F96L	0.974
1:156243147:C:G	F96L	0.974
1:156243121:G:C	G88R	0.970
1:156243107:T:C	L83S	0.969
1:156243083:A:T	E75V	0.968
1:156243084:G:C	E75D	0.966
1:156243084:G:T	E75D	0.966
1:156243101:A:T	D81V	0.966
1:156243079:T:G	C74G	0.962
1:156243110:C:A	A84D	0.962

dbSNP variants (sampled 300 via entrez): RS1001617365 (1:156242155 G>A,T), RS1002070456 (1:156242923 G>A), RS1002620040 (1:156240925 G>A), RS1003836043 (1:156243788 ACCAGAAACGGAG>A), RS1005720380 (1:156241378 G>A), RS1005751643 (1:156241589 G>A), RS1005871870 (1:156242509 C>G,T), RS1006590164 (1:156241931 G>A,T), RS1008002176 (1:156240714 G>A), RS1008793178 (1:156243516 G>T), RS1010156201 (1:156243586 C>T), RS1010801042 (1:156240938 G>A), RS1013730101 (1:156242602 G>A), RS1014299629 (1:156241331 G>A), RS1014466122 (1:156242179 G>A,C)

Disease associations

OMIM: gene MIM:112260 | disease phenotypes: MIM:167030

GenCC curated gene-disease

Mondo (1): nephrolithiasis, calcium oxalate (MONDO:0957318)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000582_7	Mean corpuscular hemoglobin concentration	3.000000e-09
GCST003013_36	White matter hyperintensity burden	2.000000e-08
GCST007344_48	Estimated glomerular filtration rate	1.000000e-08
GCST009067_23	Mosaic loss of chromosome Y (Y chromosome dosage)	3.000000e-88

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0005665	white matter hyperintensity measurement
EFO:0007783	mosaic loss of chromosome Y measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1800247	BGLAP		0.00	0

CTD chemical–gene interactions

104 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Calcitriol	affects cotreatment, affects binding, decreases reaction, increases expression, increases reaction (+1 more)	8
Dexamethasone	affects cotreatment, decreases reaction, increases expression, decreases secretion, increases secretion	6
beta-glycerophosphoric acid	decreases reaction, increases expression, increases secretion, affects cotreatment	5
Simvastatin	increases expression, increases secretion	5
Resveratrol	decreases reaction, increases expression, affects cotreatment	4
ascorbate-2-phosphate	increases secretion, affects cotreatment, decreases reaction, increases expression	3
Ascorbic Acid	affects cotreatment, increases expression, decreases reaction	3
Beclomethasone	decreases expression	3
Cadmium	decreases secretion, increases expression, decreases reaction, decreases expression	3
Sodium Fluoride	affects reaction, increases expression, decreases expression	3
Valproic Acid	affects expression, affects cotreatment, decreases expression	3
cobaltiprotoporphyrin	increases expression, decreases reaction, decreases secretion, affects cotreatment	2
fucoxanthin	decreases reaction, decreases secretion, increases secretion	2
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression, decreases expression	2
U 0126	decreases expression, decreases reaction	2
dorsomorphin	decreases expression, affects cotreatment, decreases reaction, increases expression	2
neohesperidin	increases expression, decreases reaction	2
CRT 0066101	decreases reaction, increases expression, decreases expression	2
Fulvestrant	decreases reaction, increases expression	2
Cholecalciferol	increases expression, increases secretion, affects cotreatment	2
Estradiol	increases expression, decreases reaction, affects cotreatment	2
Hydrogen Peroxide	decreases reaction, decreases expression, increases expression	2
Lead	decreases reaction, decreases secretion	2
Quercetin	decreases reaction, increases expression, decreases expression	2
Tetrachlorodibenzodioxin	affects expression	2
Vitamin K 2	decreases expression, decreases reaction	2
protosappanin B	increases expression	1
kuntai capsule	affects cotreatment, affects expression	1
daidzein	affects cotreatment, increases expression	1
naringin	increases expression	1

Clinical trials (associated diseases)

5 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02096965	PHASE1	COMPLETED	Use of Tolvaptan to Reduce Urinary Supersaturation: a Pilot Proof of Principle Study
NCT00381849	PHASE1/PHASE2	COMPLETED	Use of an Herbal Preparation to Prevent and Dissolve Kidney Stones
NCT06330246	Not specified	RECRUITING	O. Formigenes Colonization in Calcium Oxalate Kidney Stone Disease
NCT06331546	Not specified	RECRUITING	Gut Oxalate Absorption in Calcium Oxalate Stone Disease
NCT06989320	Not specified	RECRUITING	Endogenous Oxalate Synthesis in Idiopathic Calcium Oxalate Kidney Stone Disease