COL1A2

Summary

COL1A2 (collagen type I alpha 2 chain, HGNC:2198) is a protein-coding gene on chromosome 7q21.3, encoding Collagen alpha-2(I) chain (P08123). Type I collagen is a member of group I collagen (fibrillar forming collagen).

This gene encodes the pro-alpha2 chain of type I collagen whose triple helix comprises two alpha1 chains and one alpha2 chain. Type I is a fibril-forming collagen found in most connective tissues and is abundant in bone, cornea, dermis and tendon. Mutations in this gene are associated with osteogenesis imperfecta types I-IV, Ehlers-Danlos syndrome type VIIB, recessive Ehlers-Danlos syndrome Classical type, idiopathic osteoporosis, and atypical Marfan syndrome. Symptoms associated with mutations in this gene, however, tend to be less severe than mutations in the gene for the alpha1 chain of type I collagen (COL1A1) reflecting the different role of alpha2 chains in matrix integrity. Three transcripts, resulting from the use of alternate polyadenylation signals, have been identified for this gene.

Source: NCBI Gene 1278 — RefSeq curated summary.

At a glance

• Gene–disease (curated): COL1A2-related Ehlers-Danlos syndrome (Definitive, ClinGen) — +13 more curated relationships
• GWAS associations: 11
• Clinical variants (ClinVar): 2,786 total — 416 pathogenic, 232 likely-pathogenic
• Phenotypes (HPO): 132
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000089

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2198
Approved symbol	COL1A2
Name	collagen type I alpha 2 chain
Location	7q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000164692
Ensembl biotype	protein_coding
OMIM	120160
Entrez	1278

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 11 retained_intron, 8 protein_coding

ENST00000297268, ENST00000461525, ENST00000464916, ENST00000467931, ENST00000469732, ENST00000473573, ENST00000478215, ENST00000481570, ENST00000488121, ENST00000488298, ENST00000492110, ENST00000497316, ENST00000959377, ENST00000959378, ENST00000959379, ENST00000959380, ENST00000959381, ENST00000959382, ENST00000959383

RefSeq mRNA: 1 — MANE Select: NM_000089 NM_000089

CCDS: CCDS34682

Canonical transcript exons

ENST00000297268 — 52 exons

Exon	Start	End
ENSE00001086625	94404839	94404892
ENSE00001086630	94405673	94405726
ENSE00001086642	94410889	94410942
ENSE00001086659	94410242	94410295
ENSE00001086665	94413690	94413743
ENSE00001086669	94427627	94427885
ENSE00001086675	94404556	94404600
ENSE00001086677	94410420	94410527
ENSE00001086678	94406250	94406303
ENSE00001086684	94409564	94409608
ENSE00001086687	94408770	94408823
ENSE00001086693	94394895	94395101
ENSE00001086700	94405199	94405252
ENSE00001086701	94412068	94412121
ENSE00001086704	94407847	94407891
ENSE00001086705	94404693	94404746
ENSE00001086711	94411056	94411154
ENSE00001086712	94401567	94401620
ENSE00001086713	94400196	94400288
ENSE00001086716	94409723	94409821
ENSE00001183027	94424336	94424443
ENSE00001183076	94413083	94413136
ENSE00001183078	94412584	94412682
ENSE00001183096	94409322	94409420
ENSE00001274315	94426423	94426530
ENSE00001274395	94427188	94427295
ENSE00001335486	94408336	94408380
ENSE00001335487	94408183	94408236
ENSE00001348023	94430247	94431227
ENSE00001483044	94399049	94399084
ENSE00002449595	94397748	94397758
ENSE00002453864	94398382	94398396
ENSE00003462782	94422957	94423118
ENSE00003478423	94428293	94428477
ENSE00003486360	94425610	94425663
ENSE00003515642	94429188	94429430
ENSE00003529065	94420541	94420648
ENSE00003530646	94425998	94426051
ENSE00003531447	94421899	94421952
ENSE00003546907	94418499	94418552
ENSE00003547422	94421009	94421062
ENSE00003548385	94427008	94427061
ENSE00003564746	94415226	94415270
ENSE00003574448	94416405	94416503
ENSE00003603160	94417724	94417831
ENSE00003608402	94425750	94425857
ENSE00003608938	94414222	94414275
ENSE00003627805	94420391	94420444
ENSE00003630307	94413894	94413947
ENSE00003649692	94425117	94425224
ENSE00003652009	94420233	94420286
ENSE00003686199	94419498	94419551

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 946.7279 / max 21465.0025, expressed in 1168 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79597	932.7213	1166
79647	2.3593	546
79644	1.9506	544
79651	1.5377	498
79630	1.3807	424
79603	1.2626	409
79605	1.0312	421
79631	0.9986	413
79606	0.9942	404
79632	0.8933	401

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
periodontal ligament	UBERON:0008266	99.99	gold quality
stromal cell of endometrium	CL:0002255	99.98	gold quality
skin of hip	UBERON:0001554	99.98	gold quality
tibia	UBERON:0000979	99.96	gold quality
visceral pleura	UBERON:0002401	99.94	gold quality
parietal pleura	UBERON:0002400	99.93	gold quality
pleura	UBERON:0000977	99.92	gold quality
saphenous vein	UBERON:0007318	99.90	gold quality
tendon of biceps brachii	UBERON:0008188	99.90	gold quality
gall bladder	UBERON:0002110	99.87	gold quality
smooth muscle tissue	UBERON:0001135	99.86	gold quality
upper leg skin	UBERON:0004262	99.86	gold quality
cartilage tissue	UBERON:0002418	99.85	gold quality
mammalian vulva	UBERON:0000997	99.81	gold quality
right coronary artery	UBERON:0001625	99.80	gold quality
urethra	UBERON:0000057	99.78	gold quality
synovial joint	UBERON:0002217	99.76	gold quality
pylorus	UBERON:0001166	99.74	gold quality
descending thoracic aorta	UBERON:0002345	99.74	gold quality
mucosa of urinary bladder	UBERON:0001259	99.71	gold quality
vena cava	UBERON:0004087	99.71	gold quality
cardia of stomach	UBERON:0001162	99.69	gold quality
mammary duct	UBERON:0001765	99.69	gold quality
thoracic aorta	UBERON:0001515	99.65	gold quality
decidua	UBERON:0002450	99.65	gold quality
myometrium	UBERON:0001296	99.64	gold quality
ascending aorta	UBERON:0001496	99.64	gold quality
cauda epididymis	UBERON:0004360	99.64	gold quality
nipple	UBERON:0002030	99.62	gold quality
superficial temporal artery	UBERON:0001614	99.61	gold quality

Single-cell (SCXA)

Detected in 70 experiment(s), a significant marker in 67.

Experiment	Marker?	Max mean expression
E-HCAD-23	yes	32546.04
E-CURD-112	yes	30761.07
E-MTAB-10596	yes	27160.67
E-MTAB-8221	yes	18401.03
E-HCAD-24	yes	17852.24
E-MTAB-7407	yes	12734.08
E-MTAB-8410	yes	12466.78
E-MTAB-9906	yes	9443.48
E-ENAD-20	yes	7801.66
E-MTAB-5061	yes	7629.97
E-MTAB-6701	yes	7592.85
E-CURD-79	yes	7427.79
E-CURD-126	yes	7050.72
E-MTAB-10662	yes	6987.49
E-HCAD-15	yes	6979.71

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CEBPB, CEBPZ, CIITA, EGR1, EP300, ETS1, FLI1, FOXN1, GATA4, HDAC1, HDAC2, HES1, HMGA1, ID2, ID3, IRF1, JUN, JUNB, KAT7, KLF11, MYB, NEUROD1, NFIC, NFKB1, NFKB, NFYA, NFYB, NFYC, NOTCH1, RELA, RFX1, RFX5, RUNX2, SCX, SIRT1, SMAD1, SMAD2, SMAD3, SMAD4

miRNA regulators (miRDB)

117 targeting COL1A2, 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-4533	100.00	69.48	2758
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Deletions and duplications of Gly-Xaa-Yaa triplet repeats in the triple helical domains of type I collagen chains disrupt helix formation and result in several types of osteogenesis imperfecta (PMID:11668615)
• A variant of osteogenesis imperfecta type IV with resolution of femoral bowing is caused by a novel COL1A2 mutation. (PMID:11836364)
• interaction of RFX family at start site resulting in transcription repression (PMID:11986307)
• Upstream elements present in the 3’-untranslated region of the gene influence the processing efficiency of overlapping polyadenylation signals. (PMID:12200454)
• Results represent the first demonstration of an alternate usage of distinct signaling pathways by TNF-alpha to inhibit the expression of a given gene, COL1A2, depending on its activation state. (PMID:12393755)
• regulation by c-Myb (PMID:12424255)
• DNA hypermethylation near the transcription start site of collagen alpha2(I) gene occurs in both cancer cell lines and primary colorectal cancers. (PMID:12702564)
• TGF-beta1-stimulated PKCdelta activity positively regulates Smad3 transcriptional activity and is required for COL1A2 gene transcription (PMID:12759229)
• The COL1A2 endodeoxyribonuclease PvuII binding site polymorphism is associated with nonosteoporotic fractures in prepubertal girls independently of bone density. (PMID:12813128)
• transcription repression by interferon gamma is mediated by RFX5 complex (PMID:12968017)
• linkage and/or association of the collagen type I alpha 2 (COL1A2) gene with bone mineral density and bone area in 1280 subjects from 407 Chinese nuclear families (PMID:14555266)
• Significant genotypic association in the dominant model was noted between an exonic single nucleotide polymorphism[SNP] of COL1A2 and familial intracranial aneurysm patients; this SNP induces Ala to Pro substitution at AA 459, on a triple-helical domain (PMID:14739420)
• Rare autosomal recessive cardiac valvular form of Ehlers-Danlos syndrome results from mutations in the COL1A2 gene that activate the nonsense-mediated RNA decay pathway (PMID:15077201)
• unassociated proalpha2(I) chains leave the endoplasmic reticulum, transit the Golgi, and enter lysosomes where they are degraded (PMID:15149860)
• Data show that p53 is a potent and selective endogenous repressor of TGF-beta-regulated collagen 1A2 gene expression in dermal fibroblasts. (PMID:15345715)
• The predicted rates of AA substitutions for glycine were compared with missense mutations that have been observed to cause disease. Any Gly replacement will cause disease & the level of triple-helix destabilization determines clinical outcome. (PMID:15365990)
• Results suggest that the alpha2(I) collagen gene provides the first example of a TGF-beta responsive gene whose cell type specificity is regulated by CpG methylation. (PMID:15389632)
• hnRNPE1, and K are positive effectors of collagen synthesis acting at the post-transcriptional level by interaction with the 3’-untranslated region (3’-UTR) of COL1A2 mRNAs. (PMID:15514164)
• far upstream enhancer and proximal promoter elements regulate the expression of COL1A2 (PMID:15516691)
• This is the first molecular modeling study addressing type I collagen alpha 2 chain carboxyl (C)-telopeptide conformation using all three chains of the heterotrimer before and after it docks to its receptor domain. (PMID:15581348)
• The (GT)n polymorphism and haplotype of the COL1A2 gene, but not the (AAAG)n polymorphism of the PTHR1 gene, are associated with bone mineral density in Chinese (PMID:15599596)
• Protein kinase C-delta is involved in the regulation of the alpha2(I) collagen gene in dermal fibroblasts. (PMID:15741186)
• CIITA induction is required for interferon gamma-mediated repression of COL1A1 and COL1A2 (PMID:15788405)
• FK-506 inhibits alpha2(I) collagen gene expression by reducing the stability of mRNA without exhibiting its activation effect on TGFbeta signaling in scleroderma fibroblasts. (PMID:15818662)
• GATA-4 seems to regulate constitutive COL1A2 gene expression in fibroblasts (PMID:15982862)
• Data show that S-adenosylmethionine blocks collagen I production and liver fibrosis by preventing transforming growth factor-beta induction of the COL1A2 promoter. (PMID:15983038)
• the alpha-2(I) procollagen gene is regulated by proximal promoter elements in a species-specific manner (PMID:16036621)
• there are species-specific differences in the regulatory networks of the mammalian COL1A2, involving the repressor in the first intron (PMID:16091368)
• the Ala549Pro encoding SNP in exon 28 of COL1A2 may not have an effect on the rigidity or the elasticity of the vascular wall, as there is no association with collagen fibril morphology (PMID:16192463)
• findings show the remarkable impact of the C-pro alpha2 chain on the structure of the assembled trimeric C-propeptide (PMID:16285730)
• Colorado Indians of Ecuador (n = 80) were analysed for the three anthropologically informative RFLPs of the COL1A2 gene. (PMID:16316921)
• Adrenaline can increase the production of bFGF and decrease production of TGF-beta1 and I procollagen in human normal dermal and hypertrophic scar fibroblasts cultured in vitro. (PMID:16463783)
• Analysis of the promotor regions responsible for up-regulating the expression of the alpha2(I) collagen gene in scleroderma dermal fibroblasts. (PMID:16564026)
• EGR-1 is induced by transforming growth factor-beta and mediates stimulation of collagen gene expression (PMID:16702209)
• Novel mutations within the COL1A2 gene are associated with osteogenesis imperfecta. (PMID:16705691)
• Heterozygous mutations in the COL1A2 gene encoding the alpha2 chain of type I collagen generally cause either osteogenesis imperfecta or the arthrochalasis form of Ehlers-Danlos syndrome. (PMID:16816023)
• These results suggest that RACK1 modulates transcription of alpha2(I) collagen by TGF-beta1 through interference with Smad3 binding to the gene promoter. (PMID:16849317)
• Chondrogenesis in mesenchymal stem cells on the other hand resulted in up-regulation of collagen types I, IIA, IIB, and X, demonstrating differentiation towards cartilage of a mixed phenotype. (PMID:17072841)
• Data suggest that a repressor in the first intron of the alpha2(I) collagen gene with a binding site for interferon regulatory factors is a novel target of the pathways elicited by interferon-gamma to blunt transcription from the COL1A2 promoter. (PMID:17142024)
• Altered expression of decorin mRNA in the different dermal strata and a decrease in the collagen-to-decorin ratio inflicted by both age and ultraviolet irradiation affect collagen bundle diameter and subsequently the mechanical properties of human skin. (PMID:17146610)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	col1a2	ENSDARG00000020007
mus_musculus	Col1a2	ENSMUSG00000029661
rattus_norvegicus	Col1a2	ENSRNOG00000011292

Paralogs (37): COL9A2 (ENSG00000049089), COL23A1 (ENSG00000050767), COL11A1 (ENSG00000060718), COL17A1 (ENSG00000065618), COL5A3 (ENSG00000080573), COL4A4 (ENSG00000081052), COL16A1 (ENSG00000084636), COL9A3 (ENSG00000092758), COL20A1 (ENSG00000101203), COL1A1 (ENSG00000108821), COL9A1 (ENSG00000112280), COL7A1 (ENSG00000114270), COL21A1 (ENSG00000124749), COL5A1 (ENSG00000130635), COL4A2 (ENSG00000134871), COL2A1 (ENSG00000139219), COL6A1 (ENSG00000142156), COL6A2 (ENSG00000142173), EDA (ENSG00000158813), COL26A1 (ENSG00000160963), COL3A1 (ENSG00000168542), COL4A3 (ENSG00000169031), COL22A1 (ENSG00000169436), COL24A1 (ENSG00000171502), COL18A1 (ENSG00000182871), EMID1 (ENSG00000186998), COL4A1 (ENSG00000187498), COL4A5 (ENSG00000188153), COL25A1 (ENSG00000188517), COL27A1 (ENSG00000196739), COL13A1 (ENSG00000197467), COL4A6 (ENSG00000197565), COL11A2 (ENSG00000204248), COL5A2 (ENSG00000204262), COL15A1 (ENSG00000204291), COLQ (ENSG00000206561), COL28A1 (ENSG00000215018)

Protein

Protein identifiers

Collagen alpha-2(I) chain — P08123 (reviewed: P08123)

Alternative names: Alpha-2 type I collagen

All UniProt accessions (2): A0A0S2Z3H5, P08123

UniProt curated annotations — full annotation on UniProt →

Function. Type I collagen is a member of group I collagen (fibrillar forming collagen).

Subunit / interactions. Trimers of one alpha 2(I) and two alpha 1(I) chains. Interacts (via C-terminus) with TMEM131 (via PapD-L domain); the interaction is direct and is involved in assembly and TRAPPIII ER-to-Golgi transport complex-dependent secretion of collagen.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Forms the fibrils of tendon, ligaments and bones. In bones the fibrils are mineralized with calcium hydroxyapatite.

Post-translational modifications. Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.

Disease relevance. Ehlers-Danlos syndrome, arthrochalasia type, 2 (EDSARTH2) [MIM:617821] A form of Ehlers-Danlos syndrome, a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDSARTH2 is an autosomal dominant condition characterized by frequent congenital hip dislocation and extreme joint laxity with recurrent joint subluxations and minimal skin involvement. The disease is caused by variants affecting the gene represented in this entry. Osteogenesis imperfecta 1 (OI1) [MIM:166200] An autosomal dominant form of osteogenesis imperfecta, a disorder of bone formation characterized by bone low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI1 is a non-deforming form with normal height or mild short stature, and no dentinogenesis imperfecta. The disease is caused by variants affecting the gene represented in this entry. Osteogenesis imperfecta 2 (OI2) [MIM:166210] An autosomal dominant form of osteogenesis imperfecta, a disorder of bone formation characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI2 is characterized by bone fragility, with many perinatal fractures, severe bowing of long bones, undermineralization, and death in the perinatal period due to respiratory insufficiency. The disease is caused by variants affecting the gene represented in this entry. Ehlers-Danlos syndrome, cardiac valvular type (EDSCV) [MIM:225320] A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. EDSCV is an autosomal recessive disease characterized by mitral valve prolapse and insufficiency, mitral regurgitation, and aortic insufficiency, in addition to joint laxity, skin hyperextensibility and friability, and abnormal scar formation. The disease is caused by variants affecting the gene represented in this entry. Osteogenesis imperfecta 3 (OI3) [MIM:259420] An autosomal dominant form of osteogenesis imperfecta, a disorder of bone formation characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI3 is characterized by progressively deforming bones, very short stature, a triangular face, severe scoliosis, grayish sclera and dentinogenesis imperfecta. The disease is caused by variants affecting the gene represented in this entry. Osteogenesis imperfecta 4 (OI4) [MIM:166220] An autosomal dominant form of osteogenesis imperfecta, a disorder of bone formation characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI4 is characterized by moderately short stature, mild to moderate scoliosis, grayish or white sclera and dentinogenesis imperfecta. The disease is caused by variants affecting the gene represented in this entry. Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 (OIEDS2) [MIM:619120] An autosomal dominant connective tissue disorder characterized by osteopenia, bone fragility, long bone fractures, blue sclerae, joint hyperextensibility, soft and hyperextensible skin, abnormal wound healing, easy bruising, and vascular fragility. The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberration involving COL1A2 may be a cause of lipoblastomas, which are benign tumors resulting from transformation of adipocytes, usually diagnosed in children. Translocation t(7;8)(p22;q13) with PLAG1.

Domain organisation. The C-terminal propeptide, also known as COLFI domain, have crucial roles in tissue growth and repair by controlling both the intracellular assembly of procollagen molecules and the extracellular assembly of collagen fibrils. It binds a calcium ion which is essential for its function.

Similarity. Belongs to the fibrillar collagen family.

RefSeq proteins (1): NP_000080* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000885	Fib_collagen_C	Domain
IPR008160	Collagen	Repeat
IPR050149	Collagen_superfamily	Family

Pfam: PF01391, PF01410

UniProt features (181 total): sequence variant 111, compositionally biased region 28, modified residue 15, sequence conflict 11, binding site 5, disulfide bond 3, propeptide 2, glycosylation site 2, signal peptide 1, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
5CTD	X-RAY DIFFRACTION	1.6
8YV3	X-RAY DIFFRACTION	1.68
5CTI	X-RAY DIFFRACTION	1.9
6JEC	X-RAY DIFFRACTION	2.05
5CVA	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08123-F1	55.02	0.16

Functional residue map

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

Ligand- & substrate-binding residues (5): 1181; 1183; 1184; 1186; 1189

Post-translational modifications (15): 23, 47, 50, 62, 65, 68, 71, 80, 84, 102, 108, 177, 420, 441, 444

Disulfide bonds (3): 1163–1195, 1203–1364, 1272–1317

Glycosylation sites (2): 177, 1267

Function

Pathways and Gene Ontology

Reactome pathways

27 pathways

ID	Pathway
R-HSA-114604	GPVI-mediated activation cascade
R-HSA-1442490	Collagen degradation
R-HSA-1566977	Fibronectin matrix formation
R-HSA-1650814	Collagen biosynthesis and modifying enzymes
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-2022090	Assembly of collagen fibrils and other multimeric structures
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-216083	Integrin cell surface interactions
R-HSA-2173796	SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-2214320	Anchoring fibril formation
R-HSA-2243919	Crosslinking of collagen fibrils
R-HSA-3000170	Syndecan interactions
R-HSA-3000171	Non-integrin membrane-ECM interactions
R-HSA-3000178	ECM proteoglycans
R-HSA-3000480	Scavenging by Class A Receptors
R-HSA-430116	GP1b-IX-V activation signalling
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-75892	Platelet Adhesion to exposed collagen
R-HSA-76009	Platelet Aggregation (Plug Formation)
R-HSA-8874081	MET activates PTK2 signaling
R-HSA-8948216	Collagen chain trimerization
R-HSA-9845619	Enhanced cleavage of VWF variant by ADAMTS13
R-HSA-9845620	Enhanced binding of GP1BA variant to VWF multimer:collagen
R-HSA-9845621	Defective VWF cleavage by ADAMTS13 variant
R-HSA-9845622	Defective VWF binding to collagen type I
R-HSA-9846298	Defective binding of VWF variant to GPIb:IX:V
R-HSA-9925563	Developmental Lineage of Pancreatic Ductal Cells

MSigDB gene sets: 710 (showing top): TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, MULLIGHAN_NPM1_SIGNATURE_3_UP, ACTACCT_MIR196A_MIR196B, CHIBA_RESPONSE_TO_TSA_UP, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOBP_CIRCULATORY_SYSTEM_PROCESS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_ACID_CHEMICAL, REACTOME_PLATELET_AGGREGATION_PLUG_FORMATION

GO Biological Process (14): skeletal system development (GO:0001501), blood vessel development (GO:0001568), transforming growth factor beta receptor signaling pathway (GO:0007179), Rho protein signal transduction (GO:0007266), regulation of blood pressure (GO:0008217), collagen fibril organization (GO:0030199), bone mineralization (GO:0030282), collagen metabolic process (GO:0032963), odontogenesis (GO:0042476), skin morphogenesis (GO:0043589), protein heterotrimerization (GO:0070208), cellular response to amino acid stimulus (GO:0071230), extracellular matrix assembly (GO:0085029), animal organ development (GO:0048513)

GO Molecular Function (9): protease binding (GO:0002020), extracellular matrix structural constituent (GO:0005201), extracellular matrix structural constituent conferring tensile strength (GO:0030020), protein-macromolecule adaptor activity (GO:0030674), identical protein binding (GO:0042802), SMAD binding (GO:0046332), metal ion binding (GO:0046872), platelet-derived growth factor binding (GO:0048407), protein binding (GO:0005515)

GO Cellular Component (8): extracellular region (GO:0005576), collagen type I trimer (GO:0005584), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062), collagen trimer (GO:0005581), fibrillar collagen trimer (GO:0005583)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Extracellular matrix organization	4
Platelet activation, signaling and aggregation	3
Collagen formation	2
Hemostasis	2
Assembly of collagen fibrils and other multimeric structures	2
Degradation of the extracellular matrix	1
Adaptive Immune System	1
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1
Non-integrin membrane-ECM interactions	1
Binding and Uptake of Ligands by Scavenger Receptors	1
Signaling by Interleukins	1
MET promotes cell motility	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	3
anatomical structure development	2
extracellular matrix organization	2
animal organ morphogenesis	2
system development	1
vasculature development	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
small GTPase-mediated signal transduction	1
blood circulation	1
regulation of biological quality	1
ossification	1
biomineral tissue development	1
metabolic process	1
skin development	1
protein heterooligomerization	1
protein trimerization	1
response to amino acid	1
cellular response to acid chemical	1
cellular component assembly	1
enzyme binding	1
structural molecule activity	1
extracellular matrix	1
extracellular matrix structural constituent	1
molecular adaptor activity	1
cation binding	1
growth factor binding	1
binding	1
cellular anatomical structure	1
fibrillar collagen trimer	1
endoplasmic reticulum	1
intracellular organelle lumen	1
external encapsulating structure	1
extracellular vesicle	1
protein-containing complex	1
collagen trimer	1
fibrillar collagen complex	1
extracellular protein-containing complex	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

107 interactions, top by confidence:

A	B	Type	Score
COL1A2	SGTA	psi-mi:“MI:0915”(physical association)	0.810
SGTA	COL1A2	psi-mi:“MI:0915”(physical association)	0.810
UBQLN1	COL1A2	psi-mi:“MI:0915”(physical association)	0.720
COL1A2	UBQLN1	psi-mi:“MI:0915”(physical association)	0.720
COL1A2	KCNIP4	psi-mi:“MI:0915”(physical association)	0.720
COL1A1	P4HA2	psi-mi:“MI:0915”(physical association)	0.710
YAF2	E2F6	psi-mi:“MI:0914”(association)	0.640
COL1A1	COL1A2	psi-mi:“MI:0915”(physical association)	0.580
COL1A1	CRTAP	psi-mi:“MI:0915”(physical association)	0.580
COL1A2	SGTB	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (72): SGTA (Two-hybrid), UBQLN1 (Two-hybrid), COL1A2 (Affinity Capture-MS), COL1A2 (Affinity Capture-MS), COL1A2 (Affinity Capture-MS), COL1A2 (Affinity Capture-MS), COL1A2 (Affinity Capture-MS), COL1A2 (Affinity Capture-MS), COL1A2 (Synthetic Lethality), COL1A2 (Two-hybrid), SERPINB5 (Reconstituted Complex), COL1A2 (Affinity Capture-MS), COL1A2 (Affinity Capture-MS), COL1A2 (Affinity Capture-MS), COL1A2 (Affinity Capture-MS)

ESM2 similar proteins: C0HJN3, C0HJN4, C0HJN5, C0HJN7, C0HJN9, C0HJP0, C0HJP1, C0HJP3, C0HJP5, C0HJP6, C0HJP7, C0HJP8, C0HLG7, C0HLG9, C0HLH1, C0HLH3, C0HLH5, C0HLH9, C0HLI1, C0HLI3, C0HLI5, C0HLI7, C0HLI9, C0HLJ1, C0HLJ3, C0HLJ5, C0HLJ7, C0HLJ9, C0HM84, C0HM85, C0HM93, C0HM95, O46392, P02452, P02453, P02454, P02457, P02461, P02465, P02466

Diamond homologs: B8V7R6, O42350, O46392, O88207, O93484, P02452, P02453, P02454, P02457, P02458, P02459, P02460, P02461, P02465, P02466, P02467, P05539, P05997, P08121, P08123, P11087, P12105, P12107, P13941, P13942, P18856, P20908, P20909, P25940, P28481, Q01149, Q28668, Q3U962, Q60467, Q61245, Q64739, Q6P4Z2, Q91717, Q9JI03, Q9XSJ7

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
RUNX2	“up-regulates quantity by expression”	COL1A2	“transcriptional regulation”
FLI1	“down-regulates quantity by repression”	COL1A2	“transcriptional regulation”
COL1A2	“up-regulates activity”	“A1/b1 integrin”	binding
COL1A2	up-regulates	ECM_synthesis
SMOC1	“up-regulates quantity by expression”	COL1A2	“transcriptional regulation”
TGFB1	“up-regulates quantity by expression”	COL1A2	“transcriptional regulation”
COL1A2	“up-regulates activity”	“A11/b1 integrin”	binding
COLGALT1	“up-regulates activity”	COL1A2	glycosylation
COLGALT2	“up-regulates activity”	COL1A2	glycosylation
MMP1	“down-regulates quantity by destabilization”	COL1A2	cleavage

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 74 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.

GO biological processes:

GO term	Partners	Fold	FDR
collagen fibril organization	5	17.3×	8e-03
ERAD pathway	5	13.9×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

2786 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	416
Likely pathogenic	232
Uncertain significance	865
Likely benign	825
Benign	106

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027380	NM_000089.4(COL1A2):c.1352G>A (p.Gly451Asp)	Pathogenic
1066123	NM_000089.4(COL1A2):c.1388G>C (p.Gly463Ala)	Pathogenic
1067157	NM_000089.4(COL1A2):c.2603G>C (p.Gly868Ala)	Pathogenic
1067319	NM_000089.4(COL1A2):c.3170G>A (p.Gly1057Asp)	Pathogenic
1069621	NM_000089.4(COL1A2):c.3238C>T (p.Arg1080Ter)	Pathogenic
1071305	NM_000089.4(COL1A2):c.821G>A (p.Gly274Asp)	Pathogenic
1071307	NM_000089.4(COL1A2):c.1045G>A (p.Gly349Ser)	Pathogenic
1071308	NM_000089.4(COL1A2):c.1981G>T (p.Gly661Cys)	Pathogenic
1075256	NM_000089.4(COL1A2):c.2215G>C (p.Gly739Arg)	Pathogenic
1075257	NM_000089.4(COL1A2):c.2413G>T (p.Gly805Cys)	Pathogenic
1098566	NM_000089.4(COL1A2):c.3233G>A (p.Gly1078Asp)	Pathogenic
1186681	NM_000089.4(COL1A2):c.2144G>A (p.Gly715Asp)	Pathogenic
1200401	NM_000089.4(COL1A2):c.792G>A (p.Lys264=)	Pathogenic
1203633	NM_000089.4(COL1A2):c.1972G>T (p.Gly658Cys)	Pathogenic
1223742	NM_000089.4(COL1A2):c.2206G>T (p.Gly736Cys)	Pathogenic
1224306	NM_000089.4(COL1A2):c.1774G>A (p.Gly592Ser)	Pathogenic
1314966	NM_000089.4(COL1A2):c.2152G>A (p.Gly718Ser)	Pathogenic
1320217	NM_000089.4(COL1A2):c.1163G>T (p.Gly388Val)	Pathogenic
1320259	NM_000089.4(COL1A2):c.1844_1850del (p.Pro615fs)	Pathogenic
1322122	NM_000089.4(COL1A2):c.1832dup (p.Ser612fs)	Pathogenic
1322123	NM_000089.4(COL1A2):c.3527-1G>T	Pathogenic
1322124	NM_000089.4(COL1A2):c.2296-2A>G	Pathogenic
1341500	NM_000089.4(COL1A2):c.231del (p.Phe77fs)	Pathogenic
1349117	NM_000089.4(COL1A2):c.830G>C (p.Gly277Ala)	Pathogenic
1365880	NM_000089.4(COL1A2):c.3276del (p.Gly1093fs)	Pathogenic
1367319	NM_000089.4(COL1A2):c.3359A>G (p.Asp1120Gly)	Pathogenic
1384088	NM_000089.4(COL1A2):c.693+1G>C	Pathogenic
1389787	NM_000089.4(COL1A2):c.1045G>C (p.Gly349Arg)	Pathogenic
1390690	NM_000089.4(COL1A2):c.2323G>C (p.Gly775Arg)	Pathogenic
1404738	NM_000089.4(COL1A2):c.2431G>A (p.Gly811Ser)	Pathogenic

SpliceAI

4446 predictions. Top by Δscore:

Variant	Effect	Δscore
7:94399083:GG:G	donor_gain	1.0000
7:94399084:GG:G	donor_gain	1.0000
7:94400190:T:G	acceptor_gain	1.0000
7:94400191:AACAG:A	acceptor_gain	1.0000
7:94400194:A:T	acceptor_loss	1.0000
7:94400194:AG:A	acceptor_gain	1.0000
7:94400195:GG:G	acceptor_gain	1.0000
7:94400284:GTGGG:G	donor_gain	1.0000
7:94400287:GGGTA:G	donor_loss	1.0000
7:94400288:GGT:G	donor_loss	1.0000
7:94401557:A:AG	acceptor_gain	1.0000
7:94401558:C:G	acceptor_gain	1.0000
7:94401563:CTA:C	acceptor_loss	1.0000
7:94401564:TA:T	acceptor_loss	1.0000
7:94401565:A:AG	acceptor_gain	1.0000
7:94401566:G:GC	acceptor_gain	1.0000
7:94401566:GA:G	acceptor_gain	1.0000
7:94401566:GAA:G	acceptor_gain	1.0000
7:94401566:GAAC:G	acceptor_gain	1.0000
7:94401566:GAACT:G	acceptor_gain	1.0000
7:94401618:ATGGT:A	donor_loss	1.0000
7:94401619:TGGT:T	donor_loss	1.0000
7:94401621:G:GG	donor_gain	1.0000
7:94401621:GTATG:G	donor_loss	1.0000
7:94401622:T:A	donor_loss	1.0000
7:94404553:CAG:C	acceptor_loss	1.0000
7:94404554:A:AG	acceptor_gain	1.0000
7:94404554:AG:A	acceptor_gain	1.0000
7:94404554:AGG:A	acceptor_gain	1.0000
7:94404555:G:GT	acceptor_gain	1.0000

AlphaMissense

8583 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:94427846:T:C	C1163R	1.000
7:94428349:T:A	C1195S	1.000
7:94428350:G:C	C1195S	1.000
7:94428351:T:G	C1195W	1.000
7:94405692:G:A	G169E	0.999
7:94405701:G:A	G172E	0.999
7:94405718:G:C	G178R	0.999
7:94407875:G:A	G208E	0.999
7:94408798:G:A	G256D	0.999
7:94408807:G:A	G259D	0.999
7:94408816:G:A	G262D	0.999
7:94412657:G:A	G493E	0.999
7:94412666:G:A	G496E	0.999
7:94416478:G:A	G613E	0.999
7:94420428:G:A	G724E	0.999
7:94422967:G:A	G805D	0.999
7:94422976:G:A	G808D	0.999
7:94427775:T:C	L1139P	0.999
7:94427784:T:C	L1142P	0.999
7:94427846:T:A	C1163S	0.999
7:94427847:G:A	C1163Y	0.999
7:94427847:G:C	C1163S	0.999
7:94427848:C:G	C1163W	0.999
7:94428308:A:G	D1181G	0.999
7:94428349:T:C	C1195R	0.999
7:94428350:G:A	C1195Y	0.999
7:94428350:G:T	C1195F	0.999
7:94429252:T:C	L1259P	0.999
7:94429273:A:C	Q1266P	0.999
7:94429284:T:G	Y1270D	0.999

dbSNP variants (sampled 300 via entrez): RS1000088461 (7:94401899 C>T), RS1000326442 (7:94427671 C>T), RS1000610910 (7:94407394 T>C), RS1000729299 (7:94426856 A>G), RS1001138014 (7:94413564 C>A,T), RS1001236221 (7:94430098 G>A,C), RS1001460326 (7:94395704 T>C), RS1001541456 (7:94400445 A>G), RS1001643890 (7:94417126 A>T), RS1001746580 (7:94428186 A>G), RS1001963153 (7:94414994 A>G), RS1002167721 (7:94397975 T>C), RS1002321060 (7:94405135 A>G), RS1002379480 (7:94418811 A>G), RS1002449248 (7:94398240 G>C)

Disease associations

OMIM: gene MIM:120160 | disease phenotypes: MIM:166200, MIM:130000, MIM:166210, MIM:617821, MIM:166220, MIM:225320, MIM:259420, MIM:619120, MIM:166710, MIM:259450, MIM:614429

GenCC curated gene-disease

Disease	Classification	Inheritance
Ehlers-Danlos syndrome, cardiac valvular type	Definitive	Autosomal recessive
COL1A2-related Ehlers-Danlos syndrome	Definitive	Autosomal dominant
Ehlers-Danlos syndrome, arthrochalasia type, 2	Definitive	Autosomal dominant
osteogenesis imperfecta type 2	Definitive	Autosomal dominant
osteogenesis imperfecta	Definitive	Autosomal dominant
Ehlers-Danlos syndrome, arthrochalasia type	Strong	Autosomal recessive
osteogenesis imperfecta type 3	Strong	Autosomal dominant
combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2	Moderate	Autosomal dominant
osteogenesis imperfecta type 1	Supportive	Autosomal dominant
osteogenesis imperfecta type 4	Supportive	Autosomal dominant
Ehlers-Danlos/osteogenesis imperfecta syndrome	Supportive	Autosomal dominant
high bone mass osteogenesis imperfecta	Supportive	Autosomal dominant
congenital heart disease	Disputed Evidence	Unknown

ClinGen Gene-Disease Validity (4)

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

Disease	Classification	Inheritance
COL1A2-related Ehlers-Danlos syndrome	Definitive	AD
Ehlers-Danlos syndrome, cardiac valvular type	Definitive	AR
congenital heart disease	Disputed	UD
COL1A2-related osteogenesis imperfecta	Definitive	AD

Mondo (26): osteogenesis imperfecta type 1 (MONDO:0008146), Ehlers-Danlos syndrome, classic type, 1 (MONDO:0019567), osteogenesis imperfecta type 2 (MONDO:0008147), Ehlers-Danlos syndrome, arthrochalasia type, 2 (MONDO:0040501), Ehlers-Danlos syndrome (MONDO:0020066), Ehlers-Danlos syndrome, arthrochalasia type (MONDO:0007525), osteogenesis imperfecta type 4 (MONDO:0008148), Ehlers-Danlos syndrome, cardiac valvular type (MONDO:0009159), osteogenesis imperfecta type 3 (MONDO:0009804), osteogenesis imperfecta (MONDO:0019019), dentinogenesis imperfecta (MONDO:0018849), combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 (MONDO:0030855), COL1A2-related osteogenesis imperfecta (MONDO:0100596), osteoporosis (MONDO:0005298), connective tissue disorder (MONDO:0003900)

Orphanet (19): Osteogenesis imperfecta type 1 (Orphanet:216796), Osteogenesis imperfecta (Orphanet:666), Osteogenesis imperfecta type 2 (Orphanet:216804), Ehlers-Danlos syndrome (Orphanet:98249), Rare disease with thoracic aortic aneurysm and aortic dissection (Orphanet:285014), Arthrochalasia Ehlers-Danlos syndrome (Orphanet:1899), Osteogenesis imperfecta type 3 (Orphanet:216812), Osteogenesis imperfecta type 4 (Orphanet:216820), Cardiac-valvular Ehlers-Danlos syndrome (Orphanet:230851), OBSOLETE: Ehlers-Danlos syndrome type 7A (Orphanet:99875), OBSOLETE: Ehlers-Danlos syndrome type 7B (Orphanet:99876), Dentinogenesis imperfecta (Orphanet:49042), Kuskokwim syndrome (Orphanet:1149), Bruck syndrome (Orphanet:2771), Classical Ehlers-Danlos syndrome (Orphanet:287)

HPO phenotypes

132 total (30 of 132 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000015	Bladder diverticulum
HP:0000023	Inguinal hernia
HP:0000218	High palate
HP:0000239	Large fontanelles
HP:0000260	Wide anterior fontanel
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000325	Triangular face
HP:0000347	Micrognathia
HP:0000362	Otosclerosis
HP:0000365	Hearing impairment
HP:0000414	Bulbous nose
HP:0000444	Convex nasal ridge
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000545	Myopia
HP:0000574	Thick eyebrow
HP:0000592	Blue sclerae
HP:0000678	Dental crowding
HP:0000703	Dentinogenesis imperfecta
HP:0000767	Pectus excavatum
HP:0000883	Thin ribs
HP:0000926	Platyspondyly
HP:0000939	Osteoporosis
HP:0000963	Thin skin
HP:0000974	Hyperextensible skin
HP:0000977	Soft skin

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000099_1	Mean forced vital capacity from 2 exams	2.000000e-06
GCST001428_21	Intelligence	9.000000e-08
GCST001428_3	Intelligence	6.000000e-07
GCST001537_4	Immune reponse to smallpox (secreted IL-12p40)	3.000000e-07
GCST001599_6	Aging	6.000000e-07
GCST002279_28	PR interval in Tripanosoma cruzi seropositivity	7.000000e-09
GCST003105_1	Low bone mineral density (hip)	2.000000e-08
GCST003106_1	Low bone mineral density (spine)	2.000000e-07
GCST003262_627	Post bronchodilator FEV1	3.000000e-06
GCST006979_132	Heel bone mineral density	2.000000e-09
GCST90000025_306	Appendicular lean mass	3.000000e-18

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004312	vital capacity
EFO:0004337	intelligence
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0022597	aging
EFO:0004462	PR interval
EFO:0007702	hip bone mineral density
EFO:0007701	spine bone mineral density
EFO:0004314	forced expiratory volume
EFO:0009270	heel bone mineral density
EFO:0004980	appendicular lean mass

MeSH disease descriptors (17)

Descriptor	Name	Tree numbers
D003240	Connective Tissue Diseases	C17.300
D003811	Dentinogenesis Imperfecta	C07.650.800.270; C07.793.700.270; C16.131.850.800.270
D004535	Ehlers-Danlos Syndrome	C14.907.454.240; C15.378.463.515.240; C16.131.831.428; C16.320.850.260; C17.300.200.310; C17.800.804.428; C17.800.827.260
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D006345	Heart Septal Defects, Ventricular	C14.240.400.560.540; C14.280.400.560.540; C16.131.240.400.560.540
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D010013	Osteogenesis Imperfecta	C05.116.099.708.685; C16.320.737; C17.300.200.540
D010024	Osteoporosis	C05.116.198.579; C18.452.104.579
D015663	Osteoporosis, Postmenopausal	C05.116.198.579.610; C18.452.104.579.610
D013285	Strabismus	C10.292.562.887; C11.590.810
C565061	EDS VIIB (supp.)
C562625	Ehlers-Danlos Syndrome, Type VII, Autosomal Dominant (supp.)
C536194	Ehlers-Danlos syndrome type 1 (supp.)
C536200	Ehlers-Danlos syndrome, cardiac valvular form (supp.)
C565178	OI-EDS Combined Syndrome (supp.)
C536042	Osteogenesis imperfecta, type 2A (supp.)
C536044	Osteogenesis imperfecta, type 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2364188 (PROTEIN COMPLEX GROUP), CHEMBL2685 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs42524	COL1A2		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases expression, affects cotreatment	9
methylmercuric chloride	increases expression, affects cotreatment	4
Progesterone	affects cotreatment, increases expression, decreases expression	4
Particulate Matter	decreases expression, increases abundance, increases expression	4
bisphenol A	increases expression, decreases expression	3
trichostatin A	affects cotreatment, increases expression	3
Y 27632	decreases reaction, increases expression	3
bisphenol S	decreases expression, increases expression	3
Resveratrol	increases expression, affects cotreatment, decreases expression, affects secretion, affects binding (+2 more)	3
Arsenic Trioxide	affects cotreatment, increases expression, decreases expression	3
Doxorubicin	increases response to substance, decreases expression, increases expression	3
Oxygen	increases expression, increases reaction, affects reaction, decreases reaction	3
Tretinoin	increases expression, decreases expression	3
mercuric bromide	increases expression, affects cotreatment	2
exoenzyme C3, Clostridium botulinum	decreases reaction, increases expression	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
bisphenol AF	decreases expression, increases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetaldehyde	decreases reaction, increases expression, increases reaction	2
Copper	affects binding, increases expression, decreases expression	2
Estradiol	affects cotreatment, increases expression	2
Glucose	increases secretion, increases expression, decreases reaction	2
Lipopolysaccharides	increases reaction, affects cotreatment, decreases reaction, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	increases expression, decreases expression	2
Tetradecanoylphorbol Acetate	affects expression, affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression	2
Triclosan	affects expression, decreases expression	2

ChEMBL screening assays

4 unique, capped per target: 4 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL837224	Functional	Inhibitory activity of collagen type I was determined at concentration of 10e-6 M in cell lysates	Synthesis and biological evaluation of novel bisphosphonates with dual activities on bone in vitro. — Bioorg Med Chem Lett

Cellosaurus cell lines

56 cell lines: 29 finite cell line, 24 transformed cell line, 2 induced pluripotent stem cell, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_1J93	GM17505	Finite cell line	Female
CVCL_1J94	GM17506	Transformed cell line	Female
CVCL_1J95	GM17588	Finite cell line	Male
CVCL_1J96	GM17589	Transformed cell line	Male
CVCL_1J97	GM17586	Finite cell line	Male
CVCL_1J98	GM17587	Transformed cell line	Male
CVCL_4D22	GM16853	Transformed cell line	Male
CVCL_4D23	GM16854	Finite cell line	Male
CVCL_4D26	GM16923	Finite cell line	Female
CVCL_4D27	GM16924	Transformed cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT04890431	PHASE4	UNKNOWN	Impact of Oxygen Therapy on Fatigue in Patients With Hypermobile-type Ehlers-Danlos Syndrome
NCT05603741	PHASE4	ACTIVE_NOT_RECRUITING	Local Anesthetic Response in Ehlers-Danlos Syndrome (EDS) and Healthy Volunteers
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
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT05279937	PHASE3	NOT_YET_RECRUITING	The Ultrasound-Guided Dextrose Prolotherapy in Ehlers-Danlos Syndrome Patients
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