BGN

Chr XX-linkedXLR

biglycan

Also known as: DSPG1, MRLS, PG-S1, PGI, SEMDX, SLRR1A

NCBI Gene: 633ENSG00000182492UniProt: P21810OMIM: 301870

Biglycan is a small leucine-rich proteoglycan that regulates collagen fibril assembly and plays a role in bone growth and muscle development. X-linked recessive mutations cause Meester-Loeys syndrome and X-linked spondyloepimetaphyseal dysplasia, both skeletal disorders affecting bone and cartilage development. The gene has moderate constraint against loss-of-function variants (LOEUF 0.637), and primarily affects males due to X-linked inheritance.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismX-linked/XLRLOEUF 0.642 OMIM phenotypes
Clinical Summary— BGN
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Gene-Disease Validity (ClinGen)
familial thoracic aortic aneurysm and aortic dissection · ADLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

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Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.20) despite low pLI — interpret in context.
📋
ClinVar Variants
87 unique Pathogenic / Likely Pathogenic· 179 VUS of 400 total submissions
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
0.64LOEUF
pLI 0.452
Z-score 2.32
OE 0.20 (0.08–0.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.71Z-score
OE missense 0.84 (0.74–0.97)
141 obs / 166.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.20 (0.08–0.64)
0≤0.351.4
Missense OE0.84 (0.74–0.97)
0≤0.61.4
Synonymous OE1.12
0≤1.21.6
LoF obs/exp: 2 / 9.9Missense obs/exp: 141 / 166.9Syn Z: -0.83
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongBGN-related severe syndromic form of thoracic aortic aneurysm and dissectionLOFXLR
strongBGN-related spondyloepimetaphyseal dysplasiaOTHERXLR
DN
0.6647th %ile
GOF
0.6345th %ile
LOF
0.4430th %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

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic80
Likely Pathogenic7
VUS179
Likely Benign79
Benign21
Conflicting11
80
Pathogenic
7
Likely Pathogenic
179
VUS
79
Likely Benign
21
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
79
0
80
Likely Pathogenic
5
0
2
0
7
VUS
6
147
23
3
179
Likely Benign
0
6
23
50
79
Benign
0
0
17
4
21
Conflicting
—11
Total1215314457377

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

View in ClinVar →

Protein Context — Lollipop Plot

BGN · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
BGN/MDK Axis in the Melanoma Tumor Microenvironment Strengthens Tumor Malignancy by Modulating Cancer Cells and Cancer-Associated Fibroblasts Crosstalk.
Shi HZ et al.·Adv Sci (Weinh)
2026
Enhancer-mediated NR2F2 recruitment activates BGN to promote tumor growth and shape tumor microenvironment in papillary thyroid cancer.
Tao M et al.·Theranostics
2026Open Access
A Family with Meester-Loeys Syndrome Caused by a Novel Missense Variant in the BGN Gene.
Riancho JA et al.·Int J Mol Sci
2025Open Access
BGN Secreted by Cancer-Associated Fibroblasts Promotes Esophageal Squamous Cell Carcinoma Progression via Activation of TLR4-Mediated Erk and NF-κB Signaling Pathways.
Yokoo H et al.·Int J Mol Sci
2025Open Access
GLIS2 Promotes Epithelial-Mesenchymal Transition and Gastric Cancer Progression by Regulating BGN to Activate the Wnt/β-Catenin Pathway.
Yan J et al.·Kaohsiung J Med Sci
2026Open Access
Top 5 resultsSearch Europe PMC ↗

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