BGN

Summary

BGN (biglycan, HGNC:1044) is a protein-coding gene on chromosome Xq28, encoding Biglycan (P21810). May be involved in collagen fiber assembly.

This gene encodes a member of the small leucine-rich proteoglycan (SLRP) family of proteins. The encoded preproprotein is proteolytically processed to generate the mature protein, which plays a role in bone growth, muscle development and regeneration, and collagen fibril assembly in multiple tissues. This protein may also regulate inflammation and innate immunity. Additionally, the encoded protein may contribute to atherosclerosis and aortic valve stenosis in human patients. This gene and the related gene decorin are thought to be the result of a gene duplication.

Source: NCBI Gene 633 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Meester-Loeys syndrome (Strong, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 487 total — 3 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 77
• MANE Select transcript: NM_001711

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1044
Approved symbol	BGN
Name	biglycan
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	DSPG1, SLRR1A
Ensembl gene	ENSG00000182492
Ensembl biotype	protein_coding
OMIM	301870
Entrez	633

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 23 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000331595, ENST00000431891, ENST00000472615, ENST00000480756, ENST00000492658, ENST00000859723, ENST00000859724, ENST00000859725, ENST00000859726, ENST00000859727, ENST00000859728, ENST00000859729, ENST00000859730, ENST00000859731, ENST00000859732, ENST00000859733, ENST00000859734, ENST00000859735, ENST00000859736, ENST00000859737, ENST00000859738, ENST00000859739, ENST00000859740, ENST00000859741, ENST00000971803, ENST00000971804

RefSeq mRNA: 1 — MANE Select: NM_001711 NM_001711

CCDS: CCDS14721

Canonical transcript exons

ENST00000331595 — 8 exons

Exon	Start	End
ENSE00001311763	153505238	153505350
ENSE00001947148	153508248	153509546
ENSE00003494157	153506529	153506639
ENSE00003576457	153506830	153506923
ENSE00003602270	153504621	153504869
ENSE00003643760	153505863	153506076
ENSE00003680986	153507047	153507185
ENSE00003995778	153494980	153495113

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 99.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 262.9455 / max 9572.9735, expressed in 1148 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198037	260.4835	1142
198042	0.7419	388
198041	0.3178	169
198038	0.3042	93
198048	0.2677	152
198043	0.2389	127
198065	0.2366	115
198039	0.2024	64
198040	0.0906	37
209871	0.0618	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
descending thoracic aorta	UBERON:0002345	99.93	gold quality
ascending aorta	UBERON:0001496	99.92	gold quality
thoracic aorta	UBERON:0001515	99.92	gold quality
right coronary artery	UBERON:0001625	99.91	gold quality
tendon of biceps brachii	UBERON:0008188	99.86	gold quality
aorta	UBERON:0000947	99.81	gold quality
popliteal artery	UBERON:0002250	99.79	gold quality
tibial artery	UBERON:0007610	99.79	gold quality
left coronary artery	UBERON:0001626	99.76	gold quality
coronary artery	UBERON:0001621	99.70	gold quality
tibia	UBERON:0000979	99.57	gold quality
metanephros cortex	UBERON:0010533	99.54	gold quality
right lung	UBERON:0002167	99.41	gold quality
gall bladder	UBERON:0002110	99.36	gold quality
right atrium auricular region	UBERON:0006631	99.32	gold quality
upper lobe of left lung	UBERON:0008952	99.13	gold quality
apex of heart	UBERON:0002098	99.08	gold quality
blood vessel layer	UBERON:0004797	99.00	gold quality
endocervix	UBERON:0000458	98.94	gold quality
right lobe of thyroid gland	UBERON:0001119	98.88	gold quality
cartilage tissue	UBERON:0002418	98.85	gold quality
upper lobe of lung	UBERON:0008948	98.81	gold quality
cardiac atrium	UBERON:0002081	98.71	gold quality
left lobe of thyroid gland	UBERON:0001120	98.65	gold quality
saphenous vein	UBERON:0007318	98.61	gold quality
right lobe of liver	UBERON:0001114	98.55	gold quality
spleen	UBERON:0002106	98.52	gold quality
left adrenal gland	UBERON:0001234	98.49	gold quality
smooth muscle tissue	UBERON:0001135	98.42	gold quality
right adrenal gland	UBERON:0001233	98.36	gold quality

Single-cell (SCXA)

Detected in 36 experiment(s), a significant marker in 35.

Experiment	Marker?	Max mean expression
E-MTAB-6653	yes	5557.37
E-CURD-112	yes	4097.51
E-MTAB-5061	yes	3586.08
E-HCAD-15	yes	3329.63
E-CURD-126	yes	3081.13
E-HCAD-36	yes	2940.89
E-GEOD-130473	yes	2696.43
E-MTAB-8410	yes	2605.55
E-MTAB-8894	yes	2588.32
E-MTAB-10553	yes	1999.77
E-MTAB-7407	yes	1694.11
E-MTAB-8221	yes	1461.82
E-MTAB-6308	yes	1351.01
E-ENAD-20	yes	1178.82
E-ENAD-27	yes	1030.81

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB1, RELA, SP1, SP3

miRNA regulators (miRDB)

35 targeting BGN, 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-8485	100.00	77.57	4731
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-4640-5P	97.42	66.33	1543
HSA-MIR-4726-5P	97.24	65.67	1299
HSA-MIR-3192-5P	96.98	65.76	1926

Literature-anchored findings (GeneRIF, showing 40)

• Biglycan binds to alpha-dystroglycan and this binding requires the chondroitin sulfate side chains of biglycan. (PMID:10684260)
• has two GAG chains and affinity to collagen (PMID:11979972)
• BGN expression is regulated by TGFbeta1 in pancreatic tumor cells and has a role in controlling cell growth (PMID:12140283)
• isoforms of biglycan have a smaller core protein substituted with smaller glycosaminoglycan chains, are N-glycosylated, which demonstrates that a lack in N-glycosylation is not the reason for a smaller core. (PMID:12153565)
• biglycan showed a unique ability to organize collagen VI into extensive hexagonal-like networks over a time period of only a few minutes (PMID:12354766)
• regulation of gene expression by transforming growth factor-beta requires MKK6-p38 mitogen-activated protein kinase signaling downstream of Smad signaling (PMID:12538652)
• Biglycan may be involved in vascular smooth muscle growth & migration through cdk2- & p27-dependent pathways. Changes in its expression may affect arterial susceptibility to vascular injury, & may play a direct role in pathogenesis of vascular lesions. (PMID:15031262)
• TGF-beta(1) stimulats human biglycan mRNA expression. (PMID:15372625)
• TGF-beta induces biglycan expression through ALK5 and GADD45beta (PMID:15546867)
• Adhesion and Rac1-dependent regulation of Adhesion and Rac1-dependent BGN gene expression by TGF-beta is thought to act through oxidative signaling through NADPH oxidase. (PMID:16051607)
• beta ig-h3 can differentially modulate the aggregation of collagen VI with biglycan and decorin (PMID:16434404)
• Biglycan regulates assembly of intracellular components of the dystrophin-associated protein complex. (PMID:16807372)
• Biglycan binds two integral membrane proteins, alpha- and gamma- sarcoglycan, expressed in skeletal muscle and heart. Genetic studies show that the biglycan regulates expression of these sarcoglycans in juvenile (<P21) mice. (PMID:16883602)
• Biglycan is a ligand for two members of the sarcoglycan complex and regulates their expression at discrete developmental ages. (PMID:16883602)
• Biglycan expression was very low in CLL patients and does not correlate with decorin mRNA transcription, suggesting that a Bcl-2 independent anti-cancer mechanism may occur. (PMID:16938379)
• decorin and biglycan are increased in DMD skeletal muscle and may have a role in muscle response to dystrophic cell damage (PMID:16989735)
• biglycan in the umbilical cord vein wall is elevated in pre-eclampsia in comparison to the corresponding control vessels (PMID:17097211)
• Biglycan is a positive modulator of BMP-2 induced osteoblast differentiation (PMID:17120779)
• Human biglycan in transgenic is a multifunctional extracellular protein that has a pivotal role in pathological remodeling of cardiac tissue and mediates cardioprotection. (PMID:17269742)
• analysis of distribution patterns of decorin and biglycan and their relation with collagen (PMID:17516017)
• mutations in biglycan are not a common cause of neuromuscular disorders in our cohort (PMID:18602826)
• Multiple core-protein species were detected for decorin, biglycan, lumican and keratocan in the degenerate osteoarthritic articular cartilage and menisci. (PMID:18620607)
• Excess decorin, biglycan, and versican may be associated with the remodeling of other matrix components in myxomatous mitral valves. (PMID:18621549)
• Data suggest that the glycosaminoglycan chains of biglycan serve as inhibitors of elastin synthesis and assembly, and that biglycan can act as an important modulator of the composition of the extracellular matrix of blood vessels. (PMID:18988796)
• study shows (1) a detailed description of ectopic ossification (EO) formed by Bgn, Fmod or combined depletion, (2) the role of exercise in modulating EO and (3) that Bgn and Fmod are critical in controlling motor function. (PMID:19422643)
• intrinsic characteristics of the diabetic LDL other than apoCIII are responsible for further increased proteoglycan binding of diabetic LDL with high-endogenous apoCIII (PMID:19502413)
• evidence of an enhanced expression of BGN in essential hypertension (PMID:19523462)
• Growth factor-mediated hyper-elongation of glycosaminoglycan chains on BGN requires transcription and translation. (PMID:19580379)
• Biglycan impinges on the expression of total epidermal growth factor receptor and possibly, on the cell-surface expression of the receptors, playing a critical role in the regulation of chondrocyte and pericellular matrix homeostasis. (PMID:20367117)
• Data show that biglycan (BGN) induces of phospholipid transfer protein (PLTP) in aortic valve interstitial cells via stimulation of Toll-like receptor 2, so increased BGN in stenotic valves contributes to the production of PLTP via TLR 2. (PMID:20382708)
• expressed decreased in fetal growth restriction placentae (PMID:20591478)
• Data revealed a strong induction of several genes encoding components of the extracellular matrix, such as collagens, COMP, IGFBP5 and biglycan. (PMID:21029365)
• Biglycan demonstrated distinctive localization relative to nodules within calcified aortic valves. (PMID:21185747)
• Differential expression of 4 out of 5 genes related to estrogen metabolism and action (ESR1, ESR2, PGR and BGN) was confirmed in endometriosis. (PMID:21397694)
• Biglycan and decorin reduced the proliferation of pre-adipocytes, partly by induction of apoptosis. Furthermore, the anti-proliferative capabilities of decorin and biglycan were nullified with removal of GAG side-chains. (PMID:21702857)
• Up-regulation of biglycan was significantly correlated with poor tumor differentiation, lymph node metastasis, and distant metastasis in colorectal cancer. (PMID:21879307)
• findings demonstrate that Akt is a downstream signalling component of TGF-beta-mediated biglycan core protein synthesis but not glycosaminoglycan chain hyperelongation in vascular smooth muscle (PMID:21913799)
• Immunoprecipitation analysis revealed that biglycan interacts with both the canonical Wnt ligand Wnt3a and the Wnt coreceptor low-density lipoprotein receptor-related protein 6 (LRP6), possibly via the formation of a trimeric complex. (PMID:21969569)
• This study demonstrates that elevated expression of biglycan may play an important role in the development and progression of gastric cancer, and could be further evaluated as a biomarker for predication of a poor clinical outcome. (PMID:21998129)
• Biglycan enhances ovalbumin-specific cross-priming by over 80% to histocompatibility class I-restricted T cells in both a Toll-like receptor (TLR)2- and TLR4-pathway-dependent manner in transgenic mice. (PMID:22095710)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bgnb	ENSDARG00000002945
danio_rerio	bgna	ENSDARG00000017884
mus_musculus	Bgn	ENSMUSG00000031375
rattus_norvegicus	Bgn	ENSRNOG00000055962

Paralogs (22): DCN (ENSG00000011465), RTN4R (ENSG00000040608), ASPN (ENSG00000106819), FLRT3 (ENSG00000125848), FLRT1 (ENSG00000126500), LRRC4 (ENSG00000128594), LRRC4B (ENSG00000131409), PODNL1 (ENSG00000132000), LRTM1 (ENSG00000144771), LRRC4C (ENSG00000148948), LRRTM1 (ENSG00000162951), LRRC15 (ENSG00000172061), PODN (ENSG00000174348), LRRTM4 (ENSG00000176204), LRRC19 (ENSG00000184434), FLRT2 (ENSG00000185070), GP1BA (ENSG00000185245), RTN4RL1 (ENSG00000185924), RTN4RL2 (ENSG00000186907), NYX (ENSG00000188937), LRRC66 (ENSG00000188993), LRRTM3 (ENSG00000198739)

Protein

Protein identifiers

Biglycan — P21810 (reviewed: P21810)

Alternative names: Bone/cartilage proteoglycan I, PG-S1

All UniProt accessions (2): P21810, C9JKG1

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in collagen fiber assembly.

Subunit / interactions. Homodimer. Forms a ternary complex with MFAP2 and ELN.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Detected in placenta (at protein level). Found in several connective tissues, especially in articular cartilages.

Post-translational modifications. The two attached glycosaminoglycan chains can be either chondroitin sulfate or dermatan sulfate.

Disease relevance. Meester-Loeys syndrome (MRLS) [MIM:300989] An X-linked, thoracic aortic aneurysm syndrome characterized by early-onset, severe aortic aneurysm and dissection. Other recurrent findings include hypertelorism, pectus deformity, joint hypermobility, contractures, and mild skeletal dysplasia. The disease is caused by variants affecting the gene represented in this entry. Spondyloepimetaphyseal dysplasia, X-linked (SEMDX) [MIM:300106] An X-linked recessive bone disease characterized by severe short-trunk dwarfism, brachydactyly, metaphyseal flaring of lower extremities, short and broad long bone diaphyses, moderate platyspondyly, normal facies, and normal intelligence. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class I subfamily.

RefSeq proteins (1): NP_001702* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000372	LRRNT	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR016352	SLRP_I_decor/aspor/byglycan	Family
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR050333	SLRP	Family

Pfam: PF01462, PF13855

UniProt features (32 total): repeat 12, glycosylation site 6, sequence variant 6, disulfide bond 3, sequence conflict 2, signal peptide 1, propeptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21810-F1	85.72	0.78

Functional residue map

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

Disulfide bonds (3): 63–69, 67–76, 321–354

Glycosylation sites (6): 42, 47, 180, 198, 270, 311

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-1971475	Glycosaminoglycan-protein linkage region biosynthesis
R-HSA-2022870	CS-GAG biosynthesis
R-HSA-2022923	DS-GAG biosynthesis
R-HSA-2024101	CS/DS degradation
R-HSA-3000178	ECM proteoglycans
R-HSA-3560783	Defective B4GALT7 causes EDS, progeroid type
R-HSA-3560801	Defective B3GAT3 causes JDSSDHD
R-HSA-3595172	Defective CHST3 causes SEDCJD
R-HSA-3595174	Defective CHST14 causes EDS, musculocontractural type
R-HSA-3595177	Defective CHSY1 causes TPBS
R-HSA-4420332	Defective B3GALT6 causes EDSP2 and SEMDJL1

MSigDB gene sets: 419 (showing top): TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, MODULE_255, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MODULE_317, GOCC_CELL_SURFACE, CLASPER_LYMPHATIC_VESSELS_DURING_METASTASIS_DN, KOKKINAKIS_METHIONINE_DEPRIVATION_96HR_UP, GOBP_BONE_DEVELOPMENT, SASAI_RESISTANCE_TO_NEOPLASTIC_TRANSFROMATION

GO Biological Process (3): blood vessel remodeling (GO:0001974), bone development (GO:0060348), articular cartilage development (GO:0061975)

GO Molecular Function (6): extracellular matrix structural constituent (GO:0005201), glycosaminoglycan binding (GO:0005539), cytokine binding (GO:0019955), extracellular matrix structural constituent conferring compression resistance (GO:0030021), extracellular matrix binding (GO:0050840), protein binding (GO:0005515)

GO Cellular Component (9): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), Golgi lumen (GO:0005796), cell surface (GO:0009986), transport vesicle (GO:0030133), extracellular matrix (GO:0031012), sarcolemma (GO:0042383), lysosomal lumen (GO:0043202), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Diseases associated with glycosaminoglycan metabolism	6
Chondroitin sulfate/dermatan sulfate metabolism	3
Glycosaminoglycan metabolism	1
Extracellular matrix organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular anatomical structure	2
tissue remodeling	1
skeletal system development	1
animal organ development	1
cartilage development	1
structural molecule activity	1
extracellular matrix	1
carbohydrate derivative binding	1
protein binding	1
extracellular matrix structural constituent	1
Golgi apparatus	1
intracellular organelle lumen	1
endomembrane system	1
cytoplasmic vesicle	1
external encapsulating structure	1
plasma membrane	1
lysosome	1
vacuolar lumen	1
extracellular vesicle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

38 interactions, top by confidence:

A	B	Type	Score
BGN	LZTS2	psi-mi:“MI:0915”(physical association)	0.610
BGN	PLEKHG4	psi-mi:“MI:0915”(physical association)	0.560
VPS29	BGN	psi-mi:“MI:0915”(physical association)	0.560
	BGN	psi-mi:“MI:0915”(physical association)	0.560
DSN1	BGN	psi-mi:“MI:0915”(physical association)	0.560
BGN	JPH3	psi-mi:“MI:0915”(physical association)	0.560
BGN	PCOLCE	psi-mi:“MI:0407”(direct interaction)	0.440
BGN	TLR2	psi-mi:“MI:0407”(direct interaction)	0.440
BGN	TLR4	psi-mi:“MI:0407”(direct interaction)	0.440
NUDCD2	BGN	psi-mi:“MI:0915”(physical association)	0.400
BGN	Tlr2	psi-mi:“MI:0915”(physical association)	0.400
BGN	Tlr4	psi-mi:“MI:0915”(physical association)	0.400
HSPB2	BGN	psi-mi:“MI:0915”(physical association)	0.370
Ambn	BGN	psi-mi:“MI:0915”(physical association)	0.370
Enam	BGN	psi-mi:“MI:0915”(physical association)	0.370
BGN	Amelx	psi-mi:“MI:0915”(physical association)	0.370
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (26): BGN (Two-hybrid), BGN (Affinity Capture-MS), HDL3 (Reconstituted Complex), JPH3 (Reconstituted Complex), BGN (Reconstituted Complex), BGN (Reconstituted Complex), BGN (Reconstituted Complex), BGN (Reconstituted Complex), BGN (Reconstituted Complex), BGN (Reconstituted Complex), BGN (Affinity Capture-Western), BGN (Reconstituted Complex), COL1A1 (Reconstituted Complex), COL4A1 (Reconstituted Complex), COL6A1 (Reconstituted Complex)

ESM2 similar proteins: O02678, O15335, O35367, O42235, O46390, O46403, O46542, O55226, O60938, O62702, O70210, O75094, O94813, P07585, P19879, P20774, P21793, P21809, P21810, P28653, P28654, P28675, P47853, P51887, P51888, P82963, Q01129, Q27972, Q28888, Q29393, Q3ZBN5, Q5R1V9, Q5RBL2, Q5RI43, Q8MJF1, Q99MQ4, Q9BXN1, Q9DE65, Q9DE66, Q9DE68

Diamond homologs: B1H134, B1H234, D3ZTV3, F1NUK7, O02678, O43155, O46378, O46379, O46390, O46403, P21809, P21810, P22792, P28653, P47853, P50608, P51887, P58682, P79119, Q3MHH9, Q5R6T0, Q6P3Y9, Q6PEZ8, Q6RKD8, Q70AK3, Q8BGT1, Q8BLU0, Q8C031, Q99MQ4, Q9DBB9, Q9HCJ2, Q9NZU0, Q9NZU1, Q9R1B9, Q9TTB4, A6H789, A6NJW4, A8WQH2, C3YZ59, D0PRN3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NfKb-p65/p50	“up-regulates quantity by expression”	BGN	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	13
Uncertain significance	253
Likely benign	144
Benign	22

Top pathogenic / likely-pathogenic (16)

Variant ID	HGVS	Classification
243090	NM_001711.6(BGN):c.439A>G (p.Lys147Glu)	Pathogenic
2847643	NM_001711.6(BGN):c.440dup (p.Asn148fs)	Pathogenic
4808180	NM_001711.6(BGN):c.622del (p.Gly207_Leu208insTer)	Pathogenic
1395584	NM_001711.6(BGN):c.770+1G>A	Likely pathogenic
1478485	NM_001711.6(BGN):c.351+1G>T	Likely pathogenic
1723874	NM_001711.6(BGN):c.441G>C (p.Lys147Asn)	Likely pathogenic
243091	NM_001711.6(BGN):c.776G>T (p.Gly259Val)	Likely pathogenic
2501127	NM_001711.6(BGN):c.75G>A (p.Trp25Ter)	Likely pathogenic
2579108	NM_001711.6(BGN):c.461del (p.Pro154fs)	Likely pathogenic
265794	NM_001711.6(BGN):c.5G>A (p.Trp2Ter)	Likely pathogenic
2663753	NM_001711.6(BGN):c.46del (p.Ala16fs)	Likely pathogenic
2663754	NM_001711.6(BGN):c.910-1G>A	Likely pathogenic
2663758	NM_001711.6(BGN):c.677-2A>G	Likely pathogenic
2663759	NM_001711.6(BGN):c.677-2A>T	Likely pathogenic
636703	NM_001711.6(BGN):c.59_60insAA (p.Gln21fs)	Likely pathogenic
817331	NM_001711.6(BGN):c.41del (p.Ser14fs)	Likely pathogenic

SpliceAI

1564 predictions. Top by Δscore:

Variant	Effect	Δscore
X:153504749:G:GT	donor_gain	1.0000
X:153505321:G:GT	donor_gain	1.0000
X:153505351:G:GG	donor_gain	1.0000
X:153505858:TTCA:T	acceptor_loss	1.0000
X:153505859:TCA:T	acceptor_loss	1.0000
X:153505861:A:AC	acceptor_loss	1.0000
X:153505861:A:AG	acceptor_gain	1.0000
X:153505862:G:GG	acceptor_gain	1.0000
X:153505862:GGC:G	acceptor_gain	1.0000
X:153505862:GGCC:G	acceptor_gain	1.0000
X:153506040:G:GT	donor_gain	1.0000
X:153506077:G:GG	donor_gain	1.0000
X:153506077:GTGA:G	donor_loss	1.0000
X:153506078:T:A	donor_loss	1.0000
X:153506082:C:G	donor_gain	1.0000
X:153506523:CCCTA:C	acceptor_loss	1.0000
X:153506525:CTA:C	acceptor_loss	1.0000
X:153506526:TAGA:T	acceptor_loss	1.0000
X:153506527:A:AG	acceptor_gain	1.0000
X:153506528:G:GG	acceptor_gain	1.0000
X:153506528:GA:G	acceptor_gain	1.0000
X:153506528:GAGAT:G	acceptor_gain	1.0000
X:153506636:AAAGG:A	donor_loss	1.0000
X:153506640:G:GG	donor_gain	1.0000
X:153506811:T:TA	acceptor_gain	1.0000
X:153506824:T:A	acceptor_gain	1.0000
X:153506828:A:AG	acceptor_gain	1.0000
X:153506828:A:T	acceptor_loss	1.0000
X:153506829:G:GA	acceptor_gain	1.0000
X:153506829:GA:G	acceptor_gain	1.0000

AlphaMissense

2429 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:153504830:T:A	C67S	1.000
X:153504830:T:C	C67R	1.000
X:153504831:G:C	C67S	1.000
X:153504857:T:A	C76S	1.000
X:153504857:T:C	C76R	1.000
X:153504858:G:A	C76Y	1.000
X:153504858:G:C	C76S	1.000
X:153504858:G:T	C76F	1.000
X:153504859:C:G	C76W	1.000
X:153505283:T:C	L95P	1.000
X:153505289:T:A	L97Q	1.000
X:153505289:T:C	L97P	1.000
X:153505297:A:T	N100Y	1.000
X:153505298:A:T	N100I	1.000
X:153505299:C:A	N100K	1.000
X:153505299:C:G	N100K	1.000
X:153505867:T:A	L119H	1.000
X:153505867:T:C	L119P	1.000
X:153505873:T:C	L121P	1.000
X:153505881:A:T	N124Y	1.000
X:153505882:A:T	N124I	1.000
X:153505883:C:A	N124K	1.000
X:153505883:C:G	N124K	1.000
X:153505939:T:C	L143P	1.000
X:153505954:A:T	N148I	1.000
X:153505955:C:A	N148K	1.000
X:153505955:C:G	N148K	1.000
X:153506002:T:C	L164P	1.000
X:153506005:G:C	R165P	1.000
X:153506018:C:A	N169K	1.000

dbSNP variants (sampled 300 via entrez): RS1000007504 (X:153500711 G>A), RS1000053233 (X:153500463 G>T), RS1000310656 (X:153493604 G>A), RS1000912767 (X:153495027 G>A,C), RS1001012754 (X:153501788 C>G), RS1001674569 (X:153499160 G>A), RS1001726833 (X:153498895 A>T), RS1002184539 (X:153504980 T>C), RS1003348797 (X:153497456 C>T), RS1003402754 (X:153497203 C>T), RS1003456109 (X:153503825 C>A,G,T), RS1003615062 (X:153509294 C>G), RS1003914872 (X:153503571 C>T), RS1004088860 (X:153497879 G>A), RS1004195795 (X:153503922 A>C)

Disease associations

OMIM: gene MIM:301870 | disease phenotypes: MIM:300106, MIM:300989, MIM:607086

GenCC curated gene-disease

Disease	Classification	Inheritance
X-linked spondyloepimetaphyseal dysplasia	Strong	X-linked
Meester-Loeys syndrome	Strong	X-linked
familial thoracic aortic aneurysm and aortic dissection	Limited	Unknown

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Meester-Loeys syndrome	Strong	XL
familial thoracic aortic aneurysm and aortic dissection	Limited	AD

Mondo (3): X-linked spondyloepimetaphyseal dysplasia (MONDO:0010248), Meester-Loeys syndrome (MONDO:0010515), familial thoracic aortic aneurysm and aortic dissection (MONDO:0019625)

Orphanet (2): X-linked spondyloepimetaphyseal dysplasia (Orphanet:93349), Familial thoracic aortic aneurysm and aortic dissection (Orphanet:91387)

HPO phenotypes

77 total (30 of 77 shown, HPO-id order):

HPO	Term
HP:0000193	Bifid uvula
HP:0000212	Gingival overgrowth
HP:0000218	High palate
HP:0000268	Dolichocephaly
HP:0000272	Malar flattening
HP:0000316	Hypertelorism
HP:0000327	Hypoplasia of the maxilla
HP:0000494	Downslanted palpebral fissures
HP:0000520	Proptosis
HP:0000766	Abnormal sternum morphology
HP:0000768	Pectus carinatum
HP:0000894	Short clavicles
HP:0000922	Posterior rib cupping
HP:0000926	Platyspondyly
HP:0000978	Bruising susceptibility
HP:0000998	Hypertrichosis
HP:0001058	Poor wound healing
HP:0001065	Striae distensae
HP:0001156	Brachydactyly
HP:0001166	Arachnodactyly
HP:0001216	Delayed ossification of carpal bones
HP:0001230	Broad metacarpals
HP:0001249	Intellectual disability
HP:0001373	Joint dislocation
HP:0001377	Limited elbow extension
HP:0001382	Joint hypermobility
HP:0001417	X-linked inheritance
HP:0001419	X-linked recessive inheritance
HP:0001537	Umbilical hernia
HP:0001634	Mitral valve prolapse

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C564714	Spondyloepimetaphyseal Dysplasia, X-Linked (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases expression, increases methylation, affects cotreatment	4
trichostatin A	increases expression, affects cotreatment	3
Estradiol	affects cotreatment, increases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression, affects cotreatment	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Air Pollutants	increases expression, decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Cadmium	decreases expression, increases abundance	2
Doxorubicin	affects expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression, affects expression	2
Cadmium Chloride	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
uranyl acetate	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
cobaltous chloride	decreases secretion	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1
4-hydroxy-2-nonenal	decreases abundance, decreases ubiquitination, increases stability, affects binding	1
aflatoxin B2	increases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
erastin	increases expression, decreases expression, decreases reaction, decreases response to substance	1
ICG 001	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Dasatinib	increases expression	1
Antineoplastic Agents, Immunological	decreases response to substance, increases expression, decreases reaction	1

Cellosaurus cell lines

3 cell lines: 3 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C0C7	BBANTWi009-A	Induced pluripotent stem cell	Male
CVCL_C1SW	CMGANTi003-A	Induced pluripotent stem cell	Male
CVCL_C1SX	CMGANTi004-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03440697	Not specified	ACTIVE_NOT_RECRUITING	Pathogenetic Basis of Aortopathy and Aortic Valve Disease
NCT06783803	Not specified	ACTIVE_NOT_RECRUITING	Application of Linkage Analysis in the Identification of Novel Hereditary Factors in Familial Aneurysms