PLOD2

Summary

PLOD2 (procollagen-lysine,2-oxoglutarate 5-dioxygenase 2, HGNC:9082) is a protein-coding gene on chromosome 3q24, encoding Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (O00469). Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens.

The protein encoded by this gene is a membrane-bound homodimeric enzyme that is localized to the cisternae of the rough endoplasmic reticulum. The enzyme (cofactors iron and ascorbate) catalyzes the hydroxylation of lysyl residues in collagen-like peptides. The resultant hydroxylysyl groups are attachment sites for carbohydrates in collagen and thus are critical for the stability of intermolecular crosslinks. Some patients with Ehlers-Danlos syndrome type VIB have deficiencies in lysyl hydroxylase activity. Mutations in the coding region of this gene are associated with Bruck syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 5352 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Bruck syndrome 2 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 526 total — 18 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 26
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_182943

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9082
Approved symbol	PLOD2
Name	procollagen-lysine,2-oxoglutarate 5-dioxygenase 2
Location	3q24
Locus type	gene with protein product
Status	Approved
Aliases	LH2, TLH
Ensembl gene	ENSG00000152952
Ensembl biotype	protein_coding
OMIM	601865
Entrez	5352

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 22 protein_coding, 12 retained_intron, 4 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000282903, ENST00000360060, ENST00000460520, ENST00000461497, ENST00000469350, ENST00000475505, ENST00000478436, ENST00000480704, ENST00000494950, ENST00000495700, ENST00000703517, ENST00000703518, ENST00000703519, ENST00000703520, ENST00000703521, ENST00000703522, ENST00000703523, ENST00000703524, ENST00000703525, ENST00000703526, ENST00000703527, ENST00000703528, ENST00000703529, ENST00000706626, ENST00000706627, ENST00000706631, ENST00000706632, ENST00000706633, ENST00000706634, ENST00000706635, ENST00000706636, ENST00000902447, ENST00000930098, ENST00000956312, ENST00000956313, ENST00000956314, ENST00000956315, ENST00000956316, ENST00000956317, ENST00000956318, ENST00000956319

RefSeq mRNA: 2 — MANE Select: NM_182943 NM_000935, NM_182943

CCDS: CCDS3131, CCDS3132

Canonical transcript exons

ENST00000282903 — 20 exons

Exon	Start	End
ENSE00001008019	146110285	146110448
ENSE00001008021	146104279	146104342
ENSE00001131687	146106532	146106644
ENSE00001339129	146077862	146077924
ENSE00001891544	146102755	146102852
ENSE00003509154	146121112	146121248
ENSE00003546073	146124138	146124229
ENSE00003989124	146076782	146076895
ENSE00003989126	146088586	146088711
ENSE00003989136	146086787	146086908
ENSE00003989140	146073287	146073352
ENSE00003989143	146081738	146081863
ENSE00003989152	146091800	146091901
ENSE00003989161	146071042	146071167
ENSE00003989168	146085169	146085273
ENSE00003989170	146071277	146071423
ENSE00003989173	146069440	146070872
ENSE00003989179	146072561	146072665
ENSE00003989190	146160881	146161184
ENSE00003989195	146079116	146079257

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 110.6321 / max 2677.0866, expressed in 1547 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44900	101.1661	1530
44898	4.5927	1336
44902	3.3106	1162
44899	0.3486	169
44897	0.3290	168
44892	0.2223	93
44896	0.1943	87
44904	0.1830	58
202957	0.1493	65
44905	0.1166	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.17	gold quality
calcaneal tendon	UBERON:0003701	98.78	gold quality
jejunal mucosa	UBERON:0000399	98.52	gold quality
cartilage tissue	UBERON:0002418	98.42	gold quality
periodontal ligament	UBERON:0008266	97.96	gold quality
islet of Langerhans	UBERON:0000006	97.77	gold quality
pericardium	UBERON:0002407	97.72	gold quality
choroid plexus epithelium	UBERON:0003911	97.69	gold quality
type B pancreatic cell	CL:0000169	96.97	gold quality
smooth muscle tissue	UBERON:0001135	96.45	gold quality
saphenous vein	UBERON:0007318	96.06	gold quality
duodenum	UBERON:0002114	95.79	gold quality
gall bladder	UBERON:0002110	95.21	gold quality
colonic epithelium	UBERON:0000397	95.15	gold quality
mucosa of stomach	UBERON:0001199	95.02	gold quality
thyroid gland	UBERON:0002046	94.90	gold quality
left lobe of thyroid gland	UBERON:0001120	94.80	gold quality
stromal cell of endometrium	CL:0002255	94.79	gold quality
parietal pleura	UBERON:0002400	94.77	gold quality
ventricular zone	UBERON:0003053	94.71	gold quality
ascending aorta	UBERON:0001496	94.44	gold quality
germinal epithelium of ovary	UBERON:0001304	94.30	gold quality
thoracic aorta	UBERON:0001515	94.30	gold quality
adipose tissue	UBERON:0001013	94.23	gold quality
tendon	UBERON:0000043	94.17	gold quality
synovial joint	UBERON:0002217	94.08	gold quality
connective tissue	UBERON:0002384	93.99	gold quality
layer of synovial tissue	UBERON:0007616	93.91	gold quality
right lobe of thyroid gland	UBERON:0001119	93.78	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.73	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-ENAD-21	yes	889.11
E-MTAB-6678	yes	397.54
E-MTAB-6701	yes	59.74
E-HCAD-10	yes	36.47
E-MTAB-8410	yes	33.37
E-CURD-112	yes	18.42
E-ANND-3	yes	11.89

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYB, PITX2

miRNA regulators (miRDB)

101 targeting PLOD2, 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-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-182-5P	99.87	74.03	2589

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Characterization of Plod2 and Plod3 gene structure in mouse and comparison to PLOD1, PLOD2, and PLOD3 gene structure in human. (PMID:11334715)
• Characterization of three fragments that constitute the monomers of the human lysyl hydroxylase isoenzymes 1-3. The 30-kDa N-terminal fragment is not required for lysyl hydroxylase activity (PMID:11956192)
• PLOD2 has a important role in fibrotic processes (PMID:12881513)
• a boy who had congenital contractures with pterygia at birth and severe OI-like osteopenia and multiple fractures and he was shown to be homozygous for a novel mutation leading to an Arg598His substitution in PLOD2 (PMID:15523624)
• 3 patients with mixed phenotypes of Ehlers-Danlos Syndrome with decreased mRNAs for LH2 in skin fibroblasts; mutations not shown that could explain decreased expression; deficiency of LH2 may be caused by changes in other factors required for expression (PMID:15589118)
• alternate transcripts of LH2 may have specificity for hydroxylation of lysines in either telopeptide or helical collagen domains, so their relative expression determines the type of cross-links formed, thereby affecting collagen strength (PMID:15694128)
• Elevated formation of pyridinoline cross-links by profibrotic cytokines is associated with enhanced PLOD2 levels. (PMID:15955452)
• Data show that lysyl hydroxylase 2(long) exerts a bimodal function on collagen alpha(I) synthesis in human dermal fibroblasts. (PMID:16934803)
• TIA1 and TIAL1 regulate the alternate splicing of lysyl hydroxylase 2 (PMID:19110540)
• Missense mutations that cause Bruck syndrome affect enzymatic activity, folding, and oligomerization of LH2. (PMID:19762917)
• Fox-2 plays an integral role in the regulation of LH2 splicing, and decrease in LH2 mRNA in primary scleroderma cells may suggest a novel approach to strategies directed against scleroderma. (PMID:20131247)
• PLOD2 is a potential novel prognostic factor for HCC patients following surgery. (PMID:22098155)
• PLOD2 in addition to causing BS is also associated with AR-OI phenotypes of variable severity (PMID:22689593)
• Infrapatellar fat pad contributeS to the development of synovial fibrosis in the knee joint by increasing collagen production, PLOD2 expression, cell proliferation, and cell migration. (PMID:23666869)
• data indicate that HIF-1alpha controls sarcoma metastasis through PLOD2-dependent collagen modification and organization in primary tumors (PMID:23906982)
• TGFbeta induced PLOD2/LH2 expression in human synovial osteoarthritic fibroblasts through ALK5 signaling. (PMID:24192939)
• LH2 enhances the metastatic properties of tumor cells and functions as a regulatory switch that controls the relative abundance of biochemically distinct types of collagen cross-links in the tumor stroma. (PMID:25664850)
• findings reveal that TGFbeta1 induces a SP1- and SMAD3-dependent recruitment of histone modifying enzymes to the PLOD2 promoter other than the currently known TGFbeta1 downstream co-activators and epigenetic modifications (PMID:26432637)
• Results show that miR-26a and miR-26b were significantly downregulated in renal cell carcinoma clinical specimens and appeared to function as tumor suppressors through regulation of collagen cross-linking enzymes, LOXL2 and PLOD2, both of which function as oncogenes in this disease. (PMID:26983694)
• FKBP65 is linked to pyridinoline cross-linking by specifically mediating the dimerization of LH2. (PMID:27298363)
• PLOD2, which is associated with the stiffness of the extracellular matrix, was directly regulated by miR-26a-5p and miR-26b-5p and may be a good prognostic marker in patients with BC (PMID:27310702)
• Elevated fasting and postprandial C-terminal telopeptide after Roux-en-Y gastric bypass confers an increased risk of bone loss on recipients. (PMID:27555664)
• The finding that LH2 modifies collagen in the extracellular space challenges the current view that LH2 functions solely on the endoplasmic reticulum and could also have important implications for cancer biology. (PMID:27803159)
• This study reports for the first time the expression of PLOD2 in Brain Arteriovenous Malformations and suggests a potential role of PLOD2 in brain Arteriovenous Malformations pathophysiology. (PMID:28279775)
• knockdown of endogenous PLOD2 suppresses glioma cell proliferation, migration and invasion through modulating multiple EMT-associated factors via inactivation of PI3K/AKT signaling. (PMID:28410212)
• Only the mechanisms of PLOD2 regulated by HIF-1alpha, TGF-beta and microRNA-26a/b have been elaborated. (PMID:28415047)
• Hypoxia upregulated PLOD2 protein in U87 and U251 human glioma cell lines. (PMID:28423580)
• Gain- and loss-of-function studies and orthotopic implantation metastasis model pinpointed that PLOD2 promotes NSCLC metastasis directly by enhancing migration and indirectly by inducing collagen reorganization. (PMID:29072684)
• Mutations in PLOD2 cause Bruck Syndrome (PMID:29177700)
• Expanding the Clinical Spectrum of Phenotypes Caused by Pathogenic Variants in PLOD2. (PMID:29178448)
• Findings suggest that Acanthamoeba polyphaga mimivirus L230 co-evolved with human collagen lysyl hydroxylases (LHs). (PMID:29410444)
• High PLOD2 expression is associated with peritoneal dissemination in gastric cancer. (PMID:29603227)
• High PLOD2 expression is associated with Epithelial-Mesenchymal Transition and Chemoresistance in Biliary Tract Cancer. (PMID:30105440)
• High PLOD2 expression is associated with Epithelial-Mesenchymal Transition and Chemoresistance in Biliary Tract Cancer. (PMID:30167909)
• adipocyte-derived IL-6 and leptin promote PLOD2 expression by activating the JAK/STAT3 and PI3K/AKT signaling pathways (PMID:30563531)
• Hypoxia and TGF-beta1 increase PLOD2 expression through HIF and SMAD pathway. (PMID:31391253)
• Procollagen-lysine, 2-oxoglutarate 5-dioxygenases 1, 2, and 3 are potential prognostic indicators in patients with clear cell renal cell carcinoma. (PMID:31446433)
• We found that PLOD2 could serve as a prognostic marker in patients with LSCC and confer drug resistance in LSCC by increasing CSC-like traits; in addition, a Wnt-responsive CSC pathway was identified. (PMID:31455288)
• PLOD2 promotes aerobic glycolysis and cell progression in colorectal cancer by upregulating HK2. (PMID:31742425)
• Hypoxia-induced PLOD2 regulates invasion and epithelial-mesenchymal transition in endometrial carcinoma cells. (PMID:31872384)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	plod2	ENSDARG00000011821
mus_musculus	Plod2	ENSMUSG00000032374
rattus_norvegicus	Plod2	ENSRNOG00000030183
drosophila_melanogaster	Plod	FBGN0036147
caenorhabditis_elegans		WBGENE00002497

Paralogs (5): PLOD1 (ENSG00000083444), PLOD3 (ENSG00000106397), COLGALT1 (ENSG00000130309), CERCAM (ENSG00000167123), COLGALT2 (ENSG00000198756)

Protein

Protein identifiers

Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 — O00469 (reviewed: O00469)

Alternative names: Lysyl hydroxylase 2

All UniProt accessions (9): O00469, A0A994J3M7, A0A994J6E6, A0A994J6S5, A0A9L9PX47, A0A9L9PXC2, C9JXZ0, E7ETU9, F8WEW3

UniProt curated annotations — full annotation on UniProt →

Function. Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens. These hydroxylysines serve as sites of attachment for carbohydrate units and are essential for the stability of the intermolecular collagen cross-links.

Subunit / interactions. Homodimer.

Subcellular location. Rough endoplasmic reticulum membrane. Cytoplasm.

Tissue specificity. Highly expressed in pancreas and muscle. Isoform 1 and isoform 2 are expressed in the majority of the examined cell types. Isoform 2 is specifically expressed in skin, lung, dura and aorta.

Disease relevance. Bruck syndrome 2 (BRKS2) [MIM:609220] An autosomal recessive disease characterized by generalized osteopenia, congenital joint contractures, fragile bones with onset of fractures in infancy or early childhood, short stature, severe limb deformity, progressive scoliosis, and pterygia. It is distinguished from osteogenesis imperfecta by the absence of hearing loss and dentinogenesis imperfecta, and by the presence of clubfoot and congenital joint limitations. The disease is caused by variants affecting the gene represented in this entry. The molecular defect leading to Bruck syndrome is an aberrant cross-linking of bone collagen, due to underhydroxylation of lysine residues within the telopeptides of type I collagen, whereas the lysine residues in the triple helix are normal.

Isoforms (3)

UniProt ID	Names	Canonical?
O00469-1	1, A	yes
O00469-2	2, B
O00469-3	3

RefSeq proteins (2): NP_000926, NP_891988* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001006	Procol_lys_dOase	Conserved_site
IPR005123	Oxoglu/Fe-dep_dioxygenase_dom	Domain
IPR006620	Pro_4_hyd_alph	Domain
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily
IPR044861	IPNS-like_FE2OG_OXY	Domain
IPR050757	Collagen_mod_GT25	Family
IPR057589	GT_PLOD	Domain

Pfam: PF03171, PF25342

Enzyme classification (BRENDA):

• EC 1.14.11.4 — procollagen-lysine 5-dioxygenase (BRENDA: 11 organisms, 68 substrates, 38 inhibitors, 43 Km, 4 kcat entries)
• EC 2.4.1.50 — procollagen galactosyltransferase (BRENDA: 7 organisms, 62 substrates, 25 inhibitors, 19 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

17 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
2-OXOGLUTARATE	0.011–0.25	8
(ILE-LYS-GLY)3	0.31–0.8	6
ASCORBATE	0.05–0.35	5
(IKG)3	0.4–5	3
ALA-ARG-GLY-ILE-LYS-GLY-ILE-ARG-GLY-PHE-SER-GLY	0.4–0.6	3
TYPE I PROCOLLAGEN	0.08–0.23	3
TYPE IV PROCOLLAGEN	0.04–0.3	3
COLLAGEN	0.0008–0.0072	2
UDP-GALACTOSE	0.0188–0.0335	2
UDPGALACTOSE	0.03–0.049	2
(L-ILE-L-LYS-GLY)3	0.43	1
(PRO-PRO-GLY)4-ALA-ARG-GLY-MET-LYS-GLY-HIS-ARG-G	0.2	1
ALA-ARG-GLY-MET-LYS-GLY-HIS-ARG-GLY-(PRO-PRO-GLY	0.2	1
PEPTIDE (IKG)3	0.169	1
PROCOLLAGEN L-LYSINE	0.1	1

Catalyzed reactions (Rhea), 1 shown:

• L-lysyl-[collagen] + 2-oxoglutarate + O2 = (5R)-5-hydroxy-L-lysyl-[collagen] + succinate + CO2 (RHEA:16569)

UniProt features (39 total): sequence variant 18, glycosylation site 7, splice variant 3, binding site 3, modified residue 3, signal peptide 1, chain 1, domain 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00469-F1	92.63	0.88

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): 728

Ligand- & substrate-binding residues (3): 666; 668; 718

Post-translational modifications (3): 320, 323, 704

Glycosylation sites (7): 63, 209, 297, 365, 522, 696, 725

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1650814	Collagen biosynthesis and modifying enzymes

MSigDB gene sets: 407 (showing top): MODULE_52, chr3q24, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, CROONQUIST_NRAS_SIGNALING_DN, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, MENSE_HYPOXIA_UP, MODULE_478, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GNF2_PTX3, GOBP_AMINO_ACID_BIOSYNTHETIC_PROCESS, GOBP_ASPARTATE_FAMILY_AMINO_ACID_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, DOANE_BREAST_CANCER_CLASSES_DN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS

GO Biological Process (6): response to hypoxia (GO:0001666), collagen fibril organization (GO:0030199), collagen biosynthetic process (GO:0032964), obsolete hydroxylysine biosynthetic process (GO:0046947), peptidyl-lysine hydroxylation (GO:0017185), protein modification process (GO:0036211)

GO Molecular Function (7): iron ion binding (GO:0005506), procollagen-lysine 5-dioxygenase activity (GO:0008475), L-ascorbic acid binding (GO:0031418), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (9): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), rough endoplasmic reticulum membrane (GO:0030867), extracellular exosome (GO:0070062), rough endoplasmic reticulum (GO:0005791), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Collagen formation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
oxidoreductase activity	2
cellular anatomical structure	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
response to stress	1
response to decreased oxygen levels	1
extracellular matrix organization	1
biosynthetic process	1
collagen metabolic process	1
protein hydroxylation	1
peptidyl-lysine modification	1
protein metabolic process	1
macromolecule modification	1
transition metal ion binding	1
2-oxoglutarate-dependent dioxygenase activity	1
catalytic activity, acting on a protein	1
vitamin binding	1
carboxylic acid binding	1
monosaccharide binding	1
heterocyclic compound binding	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
endoplasmic reticulum membrane	1
rough endoplasmic reticulum	1
bounding membrane of organelle	1
extracellular vesicle	1
endoplasmic reticulum	1

Protein interactions and networks

STRING

1406 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLOD2	FKBP10	Q96AY3	915
PLOD2	P4HA1	P13674	824
PLOD2	P4HA2	O15460	804
PLOD2	SDSL	Q96GA7	765
PLOD2	CRTAP	O75718	746
PLOD2	P3H1	Q32P28	728
PLOD2	TMEM38B	Q9NVV0	728
PLOD2	SDS	P20132	697
PLOD2	ZNF469	Q96JG9	651
PLOD2	CHST14	Q8NCH0	647
PLOD2	SERPINH1	P29043	632
PLOD2	IFITM5	A6NNB3	630
PLOD2	LOX	P28300	614
PLOD2	COL1A2	P02464	607
PLOD2	SEC24D	O94855	604

IntAct

77 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
HNRNPH2	PLOD2	psi-mi:“MI:0914”(association)	0.530
	PLOD2	psi-mi:“MI:0914”(association)	0.530
PLOD3	PLOD2	psi-mi:“MI:0914”(association)	0.530
COL1A1	GOLIM4	psi-mi:“MI:0914”(association)	0.500
PPIB	PLOD2	psi-mi:“MI:0915”(physical association)	0.400
Fam107b	PLOD2	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
PLOD2		psi-mi:“MI:0915”(physical association)	0.370
Anxa2	PPL	psi-mi:“MI:0914”(association)	0.350
FOXA1	PLOD2	psi-mi:“MI:0914”(association)	0.350
E6	PLOD2	psi-mi:“MI:0914”(association)	0.350
	PGRMC1	psi-mi:“MI:0914”(association)	0.350
	SNAP23	psi-mi:“MI:0914”(association)	0.350
FBXO6	GNS	psi-mi:“MI:0914”(association)	0.350
GCH1	SECTM1	psi-mi:“MI:0914”(association)	0.350
RNF213	GNB1	psi-mi:“MI:0914”(association)	0.350
TNFSF13B	HEATR1	psi-mi:“MI:0914”(association)	0.350
Stard13	PLOD2	psi-mi:“MI:0914”(association)	0.350
	PLOD2	psi-mi:“MI:0914”(association)	0.350
rep	TMEM120B	psi-mi:“MI:0914”(association)	0.350
pipB2	PLOD2	psi-mi:“MI:0914”(association)	0.350
	VPS37C	psi-mi:“MI:0914”(association)	0.350
ATG5	PLOD2	psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350

BioGRID (220): PLOD2 (Co-fractionation), PLOD2 (Proximity Label-MS), PLOD2 (Affinity Capture-MS), PLOD2 (Affinity Capture-MS), PLOD2 (Affinity Capture-MS), PLOD2 (Affinity Capture-MS), PLOD2 (Affinity Capture-MS), PLOD2 (Affinity Capture-MS), PLOD2 (Affinity Capture-MS), PLOD2 (Affinity Capture-MS), PLOD2 (Affinity Capture-RNA), PLOD2 (Affinity Capture-MS), PLOD2 (Affinity Capture-MS), PLOD2 (Affinity Capture-MS), PLOD2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0A1H7M6, A1YGR5, A1YGR6, E9KID2, E9KID3, F4HXW9, G7LG31, O00469, O36022, O43909, O74745, P14769, P23336, P39107, P50127, P53697, P97259, Q00314, Q08834, Q09199, Q09328, Q1L8D2, Q3L7M0, Q3U4G3, Q494Q2, Q5GF25, Q5RD93, Q5SRI9, Q5ZLK4, Q6DE40, Q6NXH2, Q7YQE1, Q805R1, Q80RC7, Q811A3, Q866Z4, Q8H1E6, Q8LPF8, Q8R4G6, Q8W486

Diamond homologs: A5PMF6, O00469, O60568, O77588, P24802, Q02809, Q20679, Q5R6K5, Q5R9N3, Q5U367, Q5U483, Q63321, Q811A3, Q8NBJ5, Q9R0B9, Q9R0E1, Q9R0E2, Q9VTH0, Q5U309, Q8IYK4, A0JPH3, Q5UQC3, Q6NVG7, Q8K297, A5PK45, Q6N063, Q7Q021, A3KGW5, A7MB73, Q17FB8, Q29NU5, Q5T4B2, Q8IPK4, Q03974, Q5UQ62

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Initial triggering of complement	5	50.9×	7e-06
Collagen biosynthesis and modifying enzymes	10	28.9×	5e-10
Collagen chain trimerization	6	26.4×	1e-05
Collagen degradation	5	14.9×	1e-03
Integrin cell surface interactions	6	13.7×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	18
Likely pathogenic	15
Uncertain significance	223
Likely benign	155
Benign	62

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1075750	NM_182943.3(PLOD2):c.1275G>A (p.Trp425Ter)	Pathogenic
1323472	NM_182943.3(PLOD2):c.67del (p.Cys23fs)	Pathogenic
1425319	NM_182943.3(PLOD2):c.1287G>A (p.Trp429Ter)	Pathogenic
1696826	NM_182943.3(PLOD2):c.648C>A (p.Cys216Ter)	Pathogenic
2711440	NM_182943.3(PLOD2):c.1712del (p.Tyr570_Ser571insTer)	Pathogenic
2747849	NM_182943.3(PLOD2):c.818G>A (p.Trp273Ter)	Pathogenic
2781350	NM_182943.3(PLOD2):c.1345del (p.Gln449fs)	Pathogenic
2826246	NM_182943.3(PLOD2):c.893dup (p.Ser299fs)	Pathogenic
3062703	GRCh37/hg19 3q24(chr3:144717495-148147770)x1	Pathogenic
3727774	NM_182943.3(PLOD2):c.58del (p.Trp20fs)	Pathogenic
391827	NM_182943.3(PLOD2):c.1127+2T>C	Pathogenic
41424	NM_182943.3(PLOD2):c.1559dup (p.Val523fs)	Pathogenic
4292588	NM_182943.3(PLOD2):c.1501-2A>G	Pathogenic
4812155	NM_182943.3(PLOD2):c.1207_1208insA (p.Leu403fs)	Pathogenic
632404	NM_182943.3(PLOD2):c.1417C>T (p.Arg473Ter)	Pathogenic
7641	NM_182943.3(PLOD2):c.1886C>T (p.Thr629Ile)	Pathogenic
7642	NM_182943.3(PLOD2):c.1865G>T (p.Gly622Val)	Pathogenic
988376	NM_182943.3(PLOD2):c.1764G>T (p.Trp588Cys)	Pathogenic
2581069	NM_182943.3(PLOD2):c.1872T>G (p.Tyr624Ter)	Likely pathogenic
2840019	NM_182943.3(PLOD2):c.201+1G>T	Likely pathogenic
3065125	NM_182943.3(PLOD2):c.1848+1G>T	Likely pathogenic
3353406	NM_182943.3(PLOD2):c.319del (p.Val107fs)	Likely pathogenic
3363157	NM_182943.3(PLOD2):c.1754A>T (p.Asp585Val)	Likely pathogenic
3588642	NM_182943.3(PLOD2):c.1359-1G>A	Likely pathogenic
3588643	NM_182943.3(PLOD2):c.502G>T (p.Gly168Ter)	Likely pathogenic
3588644	NM_182943.3(PLOD2):c.202-2A>G	Likely pathogenic
3775580	NM_182943.3(PLOD2):c.900dup (p.Gly301fs)	Likely pathogenic
391826	NM_182943.3(PLOD2):c.1949T>C (p.Phe650Ser)	Likely pathogenic
4278143	NM_182943.3(PLOD2):c.1599dup (p.Gly534fs)	Likely pathogenic
4846892	NM_182943.3(PLOD2):c.1682G>A (p.Trp561Ter)	Likely pathogenic

SpliceAI

3703 predictions. Top by Δscore:

Variant	Effect	Δscore
3:146071037:ATTAC:A	donor_loss	1.0000
3:146071038:TTA:T	donor_loss	1.0000
3:146071039:TACC:T	donor_loss	1.0000
3:146071040:A:AC	donor_gain	1.0000
3:146071041:C:CC	donor_gain	1.0000
3:146071041:C:CT	donor_loss	1.0000
3:146071163:AATCC:A	acceptor_gain	1.0000
3:146071164:ATCC:A	acceptor_gain	1.0000
3:146071165:TCC:T	acceptor_gain	1.0000
3:146071165:TCCC:T	acceptor_loss	1.0000
3:146071166:CC:C	acceptor_gain	1.0000
3:146071166:CCC:C	acceptor_gain	1.0000
3:146071167:CC:C	acceptor_gain	1.0000
3:146071168:C:CC	acceptor_gain	1.0000
3:146071168:C:CG	acceptor_loss	1.0000
3:146071273:CTA:C	donor_loss	1.0000
3:146071276:C:T	donor_loss	1.0000
3:146071276:CCTT:C	donor_gain	1.0000
3:146071419:CTATC:C	acceptor_gain	1.0000
3:146071420:TATC:T	acceptor_gain	1.0000
3:146071421:ATC:A	acceptor_gain	1.0000
3:146071422:TC:T	acceptor_gain	1.0000
3:146071423:CC:C	acceptor_gain	1.0000
3:146071424:C:CC	acceptor_gain	1.0000
3:146071424:CT:C	acceptor_loss	1.0000
3:146072559:A:AC	donor_gain	1.0000
3:146072560:C:CC	donor_gain	1.0000
3:146072661:CAGGG:C	acceptor_gain	1.0000
3:146072662:AGGG:A	acceptor_gain	1.0000
3:146072666:C:CC	acceptor_gain	1.0000

AlphaMissense

5043 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:146070729:A:C	F734L	1.000
3:146070729:A:T	F734L	1.000
3:146070731:A:G	F734L	1.000
3:146070734:A:G	S733P	1.000
3:146070779:G:C	H718D	1.000
3:146070790:A:G	L714P	1.000
3:146070797:C:A	G712W	1.000
3:146070810:G:C	S707R	1.000
3:146070810:G:T	S707R	1.000
3:146070812:T:G	S707R	1.000
3:146070856:A:C	F692C	1.000
3:146070856:A:G	F692S	1.000
3:146071091:G:A	S670F	1.000
3:146071097:T:A	D668V	1.000
3:146071097:T:C	D668G	1.000
3:146071097:T:G	D668A	1.000
3:146071098:C:G	D668H	1.000
3:146071104:G:C	H666D	1.000
3:146071147:A:C	F651L	1.000
3:146071147:A:T	F651L	1.000
3:146071149:A:G	F651L	1.000
3:146072579:C:A	W589C	1.000
3:146072579:C:G	W589C	1.000
3:146072581:A:G	W589R	1.000
3:146072581:A:T	W589R	1.000
3:146079250:A:G	W456R	1.000
3:146079250:A:T	W456R	1.000
3:146081809:C:A	W429C	1.000
3:146081809:C:G	W429C	1.000
3:146081811:A:G	W429R	1.000

dbSNP variants (sampled 300 via entrez): RS1000030143 (3:146113131 C>A,T), RS1000041708 (3:146076441 T>G), RS1000049422 (3:146153952 C>T), RS1000099477 (3:146138663 G>A), RS1000182004 (3:146113449 A>G), RS1000202124 (3:146069580 C>A,T), RS1000206333 (3:146091117 A>G), RS1000245410 (3:146147668 G>A), RS1000251624 (3:146082322 A>C), RS1000322203 (3:146147983 T>G), RS1000404454 (3:146147977 T>G), RS1000408208 (3:146099027 G>A,C,T), RS1000427553 (3:146100735 G>A), RS1000515157 (3:146112395 G>A,C,T), RS1000586991 (3:146135365 A>T)

Disease associations

OMIM: gene MIM:601865 | disease phenotypes: MIM:609220, MIM:166200, MIM:119570, MIM:119800

GenCC curated gene-disease

Disease	Classification	Inheritance
Bruck syndrome 2	Definitive	Autosomal recessive
Bruck syndrome	Supportive	Autosomal recessive

Mondo (6): Bruck syndrome 2 (MONDO:0012217), osteogenesis imperfecta (MONDO:0019019), cleft soft palate (MONDO:0007338), clubfoot (MONDO:0007342), femoral agenesis/hypoplasia (MONDO:0016032), Bruck syndrome (MONDO:0017195)

Orphanet (5): Bruck syndrome (Orphanet:2771), Osteogenesis imperfecta (Orphanet:666), Isolated femoral agenesis/hypoplasia (Orphanet:1987), Familial clubfoot with or without associated lower limb anomalies (Orphanet:199315), Cleft velum (Orphanet:99772)

HPO phenotypes

26 total (26 of 26 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000325	Triangular face
HP:0000768	Pectus carinatum
HP:0000926	Platyspondyly
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0001059	Pterygium
HP:0001371	Flexion contracture
HP:0001387	Joint stiffness
HP:0001762	Talipes equinovarus
HP:0002093	Respiratory insufficiency
HP:0002645	Wormian bones
HP:0002650	Scoliosis
HP:0002659	Increased susceptibility to fractures
HP:0002757	Recurrent fractures
HP:0002804	Arthrogryposis multiplex congenita
HP:0002808	Kyphosis
HP:0002980	Femoral bowing
HP:0002987	Elbow flexion contracture
HP:0003080	Hydroxyprolinuria
HP:0004322	Short stature
HP:0006380	Knee flexion contracture
HP:0006487	Bowing of the long bones
HP:6000807	Cervical C6/C7 vertebrae fusion
HP:6001098	Metaphyseal undermodelling

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001762_321	Obesity-related traits	2.000000e-07
GCST002934_10	Zinc levels	4.000000e-06
GCST004750_68	Squamous cell lung carcinoma	5.000000e-06
GCST008839_318	Height	1.000000e-12

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D003025	Clubfoot	C05.330.488.655.063; C05.330.495.681.063; C05.660.585.512.380.813.063; C16.131.621.585.512.500.681.063
D010013	Osteogenesis Imperfecta	C05.116.099.708.685; C16.320.737; C17.300.200.540
C537407	Bruck syndrome 2 (supp.)
C562950	Cleft Soft Palate (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4742261 (PROTEIN-PROTEIN INTERACTION), CHEMBL5465273 (SINGLE PROTEIN)

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

ChEMBL bioactivities

8 potent at pChembl≥5 of 8 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.52	IC50	300	nM	CHEMBL5433830
6.30	IC50	500	nM	CHEMBL5422717
6.00	IC50	1000	nM	CHEMBL1443628
5.82	IC50	1500	nM	CHEMBL5431602
5.72	IC50	1900	nM	CHEMBL5401981
5.47	IC50	3400	nM	CHEMBL1089782
5.30	IC50	5000	nM	CHEMBL1875205
5.12	IC50	7600	nM	CHEMBL5421171

PubChem BioAssay actives

8 with measured affinity, of 19 total; 8 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-(3-morpholin-4-ylphenyl)-3-pyridin-4-ylpropane-1,3-dione	2016721: Inhibition of human recombinant LH2 expressed in CHO cells incubated for 30 mins by luciferase-based Succinate-GloTM JmjC Demethylase/Hydroxylase Assay	ic50	0.3000	uM
1-[3-(4-methylpiperazin-1-yl)phenyl]-3-pyridin-4-ylpropane-1,3-dione	2016721: Inhibition of human recombinant LH2 expressed in CHO cells incubated for 30 mins by luciferase-based Succinate-GloTM JmjC Demethylase/Hydroxylase Assay	ic50	0.5000	uM
1-phenyl-3-pyridin-4-ylpropane-1,3-dione	2016721: Inhibition of human recombinant LH2 expressed in CHO cells incubated for 30 mins by luciferase-based Succinate-GloTM JmjC Demethylase/Hydroxylase Assay	ic50	1.0000	uM
1-(3-morpholin-4-ylphenyl)-3-pyridin-3-ylpropane-1,3-dione	2016721: Inhibition of human recombinant LH2 expressed in CHO cells incubated for 30 mins by luciferase-based Succinate-GloTM JmjC Demethylase/Hydroxylase Assay	ic50	1.5000	uM
4,4,4-trifluoro-1-pyridin-4-ylbutane-1,3-dione	2016721: Inhibition of human recombinant LH2 expressed in CHO cells incubated for 30 mins by luciferase-based Succinate-GloTM JmjC Demethylase/Hydroxylase Assay	ic50	1.9000	uM
4,4,4-trifluoro-1-pyridin-3-ylbutane-1,3-dione	2016721: Inhibition of human recombinant LH2 expressed in CHO cells incubated for 30 mins by luciferase-based Succinate-GloTM JmjC Demethylase/Hydroxylase Assay	ic50	3.4000	uM
1-phenyl-3-pyridin-3-ylpropane-1,3-dione	2016721: Inhibition of human recombinant LH2 expressed in CHO cells incubated for 30 mins by luciferase-based Succinate-GloTM JmjC Demethylase/Hydroxylase Assay	ic50	5.0000	uM
4,4,4-trifluoro-1-(4-fluorophenyl)butane-1,3-dione	2016721: Inhibition of human recombinant LH2 expressed in CHO cells incubated for 30 mins by luciferase-based Succinate-GloTM JmjC Demethylase/Hydroxylase Assay	ic50	7.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	7
bisphenol A	increases expression, affects expression, affects cotreatment, decreases methylation, decreases expression	5
Particulate Matter	affects cotreatment, affects expression, decreases expression, increases abundance	5
Estradiol	affects expression, affects binding, increases expression, affects cotreatment	4
Cyclosporine	affects expression, decreases expression	4
methylmercuric chloride	decreases expression, increases expression, affects cotreatment	3
trichostatin A	increases expression, affects cotreatment	3
Ethanol	decreases expression, increases abundance, affects cotreatment, increases expression	3
Oxygen	increases expression	3
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	3
sodium arsenite	affects cotreatment, decreases expression	2
cobaltous chloride	increases expression	2
cadmium sulfate	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
chloropicrin	affects expression, decreases expression	2
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Copper	affects binding, increases expression	2
Fluorouracil	decreases expression, increases expression, affects response to substance	2
Isoniazid	affects expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	increases expression	2
Aflatoxin B1	decreases methylation, increases expression, increases methylation	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
tungsten carbide	affects binding, increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4713774	Binding	Protac activity at CRBN/PLOD2 in human BxPC-3 cells assessed as PLOD2 degradation incubated for 16 hrs by proteomic analysis	Discovery of a Napabucasin PROTAC as an Effective Degrader of the E3 Ligase ZFP91. — J Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3E3	Abcam HEK293T PLOD2 KO	Transformed cell line	Female
CVCL_TE69	HAP1 PLOD2 (-) 1	Cancer cell line	Male
CVCL_XR64	HAP1 PLOD2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00131469	PHASE4	COMPLETED	Study of Teriparatide (FORTEO) to Treat Adults With Osteogenesis Imperfecta
NCT00159419	PHASE4	COMPLETED	Bisphosphonate Therapy for Osteogenesis Imperfecta
NCT01713231	PHASE4	COMPLETED	Effect of High-Dose Vitamin D on Bone Density in Osteogenesis Imperfecta
NCT02303873	PHASE4	COMPLETED	Efficacy and Safety of Alendronate in Chinese Children or Adolescents With Osteogenesis Imperfecta
NCT03735537	PHASE4	COMPLETED	Treatment of Osteogenesis Imperfecta With Parathyroid Hormone and Zoledronic Acid
NCT04152551	PHASE4	RECRUITING	Effects of Bisphosphonates on OI-Related Hearing Loss
NCT04564430	PHASE4	UNKNOWN	Clonidine for Tourniquet-related Pain in Children
NCT04766684	PHASE4	COMPLETED	Clubfoot Tenotomy Trial
NCT00001305	PHASE3	COMPLETED	Growth Hormone Therapy in Osteogenesis Imperfecta
NCT00005901	PHASE3	COMPLETED	Pamidronate to Treat Osteogenesis Imperfecta in Children
NCT00106028	PHASE3	COMPLETED	Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children
NCT00982124	PHASE3	COMPLETED	An Efficacy and Safety Trial of Intravenous Zoledronic Acid in Infants Less Than One Year of Age, With Severe Osteogenesis Imperfecta
NCT02352753	PHASE3	TERMINATED	Multicenter,Single-arm Study to Evaluate Efficacy, Safety, & Pharmacokinetics of Denosumab in Children w/ OI
NCT03638128	PHASE3	TERMINATED	Open-label Extension of Study 20130173 of Denosumab in Children and Young Adults With Osteogenesis Imperfecta
NCT05768854	PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab vs Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta
NCT05972551	PHASE3	ACTIVE_NOT_RECRUITING	Study to Evaluate Efficacy and Safety of Romosozumab Compared With Bisphosphonates in Children and Adolescents With Osteogenesis Imperfecta
NCT06636071	PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab in Pediatric Japanese Subjects With Osteogenesis Imperfecta
NCT07366086	PHASE3	RECRUITING	Pediatric Safety Follow-up Study of Prior Treatment With Romosozumab for Osteogenesis Imperfecta
NCT00063479	PHASE2	COMPLETED	Bisphosphonate Treatment of Osteogenesis Imperfecta
NCT00131118	PHASE2	COMPLETED	Zoledronic Acid in Children (1 -17 Years) With Severe Osteogenesis Imperfecta
NCT01417091	PHASE2	COMPLETED	Safety, Pharmacokinetics and Pharmacodynamics of BPS804 in Osteogenesis Imperfecta
NCT01679080	PHASE2	TERMINATED	The Effect of Treatment With Teriparatide and Zoledronic Acid in Patients With Osteogenesis Imperfecta
NCT01799798	PHASE2	COMPLETED	Translational Therapy in Patients With Osteogenesis Imperfecta - A Pilot Trial on Treatment With the Rankl-Antibody Denosumab
NCT03208582	PHASE2	COMPLETED	Do Bisphosphonates Alter the Skeletal Response to Mechanical Stimulation in Children With Osteogenesis Imperfecta?
NCT03216486	PHASE2	WITHDRAWN	An Exploratory Study of BPS804 Treatment in Adult Patients With Type I, III or IV Osteogenesis Imperfecta
NCT05312697	PHASE2	TERMINATED	Long-term Extension Study of Setrusumab in Adults With Type I, III, or IV Osteogenesis Imperfecta
NCT07062588	PHASE2	RECRUITING	Osteogenesis Imperfecta Trial of AGA2115 for ADUlts With COL1A1 and/or COL1A2 GeNetic Variations (IDUN)
NCT07557446	PHASE2	NOT_YET_RECRUITING	A Dose REgimen-Finding Study of AGA2115 in Chinese Patients With Osteogenesis ImpeRfecta (EIR)
NCT00705120	PHASE1	COMPLETED	Treatment of Severe Osteogenesis Imperfecta by Allogeneic Bone Marrow Transplantation
NCT02172885	PHASE1	COMPLETED	Mesenchymal Stem Cell Based Therapy for the Treatment of Osteogenesis Imperfecta
NCT03064074	PHASE1	COMPLETED	Safety of Fresolimumab in the Treatment of Osteogenesis Imperfecta
NCT04545554	PHASE1	COMPLETED	Study to Evaluate Romosozumab in Children and Adolescents With Osteogenesis Imperfecta
NCT05231668	PHASE1	TERMINATED	Single Ascending Dose Study of SAR439459 in Adults With Osteogenesis Imperfecta (OI)
NCT06086613	PHASE1	COMPLETED	A First-in-Human Study Evaluating AGA2115 in Adult Healthy Volunteers
NCT05125809	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab vs Placebo for Osteogenesis Imperfecta
NCT03706482	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Boost Brittle Bones Before Birth
NCT04623606	PHASE1/PHASE2	UNKNOWN	Boost to Brittle Bones - Stem Cell Transplantation for Treatment of Brittle Bones
NCT05559801	PHASE1/PHASE2	NOT_YET_RECRUITING	Mesenchymal Cell Therapy in Osteogenesis Imperfecta (OI)
NCT00001594	Not specified	COMPLETED	Evaluation and Intervention for the Effects of Osteogenesis Imperfecta
NCT00076830	Not specified	COMPLETED	Evaluation and Treatment of Patients With Connective Tissue Disease