COL1A1

Summary

COL1A1 (collagen type I alpha 1 chain, HGNC:2197) is a protein-coding gene on chromosome 17q21.33, encoding Collagen alpha-1(I) chain (P02452). Type I collagen is a member of group I collagen (fibrillar forming collagen). It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes the pro-alpha1 chains 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 VIIA, Ehlers-Danlos syndrome Classical type, Caffey Disease and idiopathic osteoporosis. Reciprocal translocations between chromosomes 17 and 22, where this gene and the gene for platelet-derived growth factor beta are located, are associated with a particular type of skin tumor called dermatofibrosarcoma protuberans, resulting from unregulated expression of the growth factor. Two transcripts, resulting from the use of alternate polyadenylation signals, have been identified for this gene.

Source: NCBI Gene 1277 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Caffey disease (Definitive, ClinGen) — +11 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 3,793 total — 1061 pathogenic, 318 likely-pathogenic
• Phenotypes (HPO): 186
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 5 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000088

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2197
Approved symbol	COL1A1
Name	collagen type I alpha 1 chain
Location	17q21.33
Locus type	gene with protein product
Status	Approved
Aliases	OI4
Ensembl gene	ENSG00000108821
Ensembl biotype	protein_coding
OMIM	120150
Entrez	1277

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 16 protein_coding, 11 retained_intron

ENST00000225964, ENST00000463440, ENST00000471344, ENST00000474644, ENST00000476387, ENST00000485870, ENST00000486572, ENST00000494334, ENST00000495677, ENST00000504289, ENST00000507689, ENST00000510710, ENST00000511732, ENST00000861333, ENST00000861334, ENST00000861335, ENST00000861336, ENST00000861337, ENST00000861338, ENST00000861339, ENST00000861340, ENST00000861341, ENST00000861342, ENST00000861343, ENST00000861344, ENST00000919350, ENST00000963828

RefSeq mRNA: 1 — MANE Select: NM_000088 NM_000088

CCDS: CCDS11561

Canonical transcript exons

ENST00000225964 — 51 exons

Exon	Start	End
ENSE00000736713	50198433	50198504
ENSE00000736743	50196484	50196528
ENSE00000736747	50196314	50196367
ENSE00000736751	50196155	50196199
ENSE00000736786	50193943	50194041
ENSE00000736814	50190543	50190596
ENSE00000736819	50190327	50190380
ENSE00000736823	50190001	50190108
ENSE00000736827	50189859	50189912
ENSE00000736830	50189679	50189732
ENSE00000736832	50189377	50189538
ENSE00000736834	50189168	50189275
ENSE00000736836	50188903	50189010
ENSE00000736838	50188742	50188795
ENSE00000736840	50188530	50188637
ENSE00000736842	50188096	50188149
ENSE00000736851	50186640	50186922
ENSE00000736853	50186317	50186507
ENSE00000736855	50185778	50186020
ENSE00000819877	50199226	50199327
ENSE00001132088	50184101	50185648
ENSE00001594859	50187015	50187122
ENSE00002214498	50195923	50195976
ENSE00002511393	50199556	50199590
ENSE00002515122	50199418	50199453
ENSE00003284476	50187876	50187983
ENSE00003432012	50187484	50187537
ENSE00003458516	50196617	50196670
ENSE00003465830	50191980	50192024
ENSE00003468021	50194130	50194183
ENSE00003471690	50194349	50194447
ENSE00003472408	50194721	50194828
ENSE00003497522	50192994	50193047
ENSE00003500023	50201411	50201631
ENSE00003501696	50192640	50192693
ENSE00003502401	50198161	50198205
ENSE00003520533	50197180	50197233
ENSE00003527609	50195567	50195665
ENSE00003528010	50194573	50194626
ENSE00003541153	50197010	50197063
ENSE00003581772	50191788	50191886
ENSE00003586134	50197732	50197785
ENSE00003603314	50195232	50195330
ENSE00003614903	50195047	50195100
ENSE00003621866	50197949	50198002
ENSE00003626685	50192475	50192528
ENSE00003634235	50190817	50190924
ENSE00003639585	50195434	50195478
ENSE00003665182	50191383	50191490
ENSE00003684820	50199753	50199947
ENSE00003685723	50192797	50192850

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 99.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1383.3737 / max 36784.7674, expressed in 1468 samples.

FANTOM5 promoters (54 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166973	1271.3548	1233
208258	16.2230	843
166972	7.5423	1109
166900	6.5092	737
166908	6.3696	721
166906	5.5118	735
166886	5.1671	676
166929	4.8966	691
166924	4.4311	657
166904	3.3619	650

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.99	gold quality
skin of hip	UBERON:0001554	99.96	gold quality
periodontal ligament	UBERON:0008266	99.94	gold quality
gall bladder	UBERON:0002110	99.90	gold quality
tibia	UBERON:0000979	99.86	gold quality
cartilage tissue	UBERON:0002418	99.86	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.86	gold quality
tendon of biceps brachii	UBERON:0008188	99.86	gold quality
upper leg skin	UBERON:0004262	99.85	gold quality
parietal pleura	UBERON:0002400	99.83	gold quality
visceral pleura	UBERON:0002401	99.82	gold quality
upper arm skin	UBERON:0004263	99.79	gold quality
trabecular bone tissue	UBERON:0002483	99.76	gold quality
pylorus	UBERON:0001166	99.75	gold quality
cardia of stomach	UBERON:0001162	99.74	gold quality
saphenous vein	UBERON:0007318	99.73	gold quality
mammalian vulva	UBERON:0000997	99.72	gold quality
myometrium	UBERON:0001296	99.66	gold quality
smooth muscle tissue	UBERON:0001135	99.63	gold quality
cauda epididymis	UBERON:0004360	99.63	gold quality
endocervix	UBERON:0000458	99.62	gold quality
adult organism	UBERON:0007023	99.61	gold quality
urethra	UBERON:0000057	99.59	gold quality
nipple	UBERON:0002030	99.58	gold quality
vena cava	UBERON:0004087	99.55	gold quality
pleura	UBERON:0000977	99.54	gold quality
mammary duct	UBERON:0001765	99.54	gold quality
body of uterus	UBERON:0009853	99.54	gold quality
seminal vesicle	UBERON:0000998	99.53	gold quality
right coronary artery	UBERON:0001625	99.53	gold quality

Single-cell (SCXA)

Detected in 58 experiment(s), a significant marker in 57.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	48432.62
E-MTAB-10596	yes	42250.84
E-MTAB-8221	yes	28494.09
E-HCAD-24	yes	28388.60
E-MTAB-6701	yes	21099.15
E-MTAB-9906	yes	20090.44
E-GEOD-75688	yes	18621.46
E-MTAB-8410	yes	18053.62
E-MTAB-7407	yes	17802.80
E-HCAD-23	yes	17548.49
E-MTAB-5061	yes	13628.07
E-MTAB-10662	yes	11151.95
E-CURD-79	yes	10565.85
E-HCAD-10	yes	10395.39
E-CURD-126	yes	9557.13

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDK9, CEBPB, CEBPD, CIITA, CREB3L1, DLX5, EGR1, ETS1, HES1, HEXIM1, LEF1, MAPK14, MEF2A, MRTFA, MSX2, MYB, MYBL2, NFATC1, NFATC4, NFIC, NFKB1, NOTCH1, NR1H4, NR4A2, RELA, ROCK1, ROCK2, RUNX2, SCX, SMAD3, SMAD4, SMAD7, SMOC1, SP1, SP3, SP7, SPOP, SRSF1, SRSF2, STAT1

miRNA regulators (miRDB)

154 targeting COL1A1, 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-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-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3692-3P	99.98	70.27	2139
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-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• disulfide disruption permits slow assembly and secretion of overmodified, but stable procollagen trimers and results in mild osteogenesis imperfecta (PMID:11432962)
• 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 member of the Y-box protein family interacts with an upstream element in the alpha1(I) collagen gene. (PMID:11731270)
• COLIA1 Sp1 TT genotype is associated with an increased fracture risk in postmenopausal women (PMID:11792589)
• two new SNPs in the COL1A1 promoter, which may affect bone mass determination (PMID:11874231)
• keratinocyte growth factor (KGF), a key stimulator of epithelial cell proliferation during wound healing, preferentially binds to collagens I, III, and VI. (PMID:11973338)
• The collagen type I, alpha 1 polymorphism in the Sp1 binding site is associated with differences in ultrasound transmission velocity in the calcaneus of postmenopausal women. (PMID:12016466)
• Fusion of COL1A1 exon 29 with PDGFB exon 2 in a der(22)t(17;22) in a pediatric giant cell fibroblastoma with a pigmented Bednar tumor component. Evidence for age-related chromosomal pattern in dermatofibrosarcoma protuberans and related tumors. (PMID:12034531)
• A 30-residue peptide model of the alpha 1(I) chain of type I collagen is designed which demonstrates sequence preference of the C-terminal repeating (Gly-Pro-Hyp)4 subdomain for initiation of triple-helix formation–an all-or-none third-order reaction. (PMID:12069607)
• Interaction of human breast fibroblasts with collagen I increases total cathepsin B protein levels (PMID:12072442)
• investigation of the genetic influence of the Sp1 polymorphism on bone density in Irish women (PMID:12073153)
• C-propeptide region of human pro alpha 1 type 1 collagen interacts with thioredoxin (PMID:12099690)
• A fusion of COLIA1 exon 24 in frame with PDGFB exon 2 was found in a complex marker chromosome from dermatofibrosarcoma protuberans with sequences from chromosomes 7,8,17,21, & 22. (PMID:12127408)
• These data indicate that mitoxantrone and WP631 are very potent inhibitors of basal and TGF-beta-stimulated COL1A1 expression. (PMID:12138160)
• in the presence of high molecular weight fragments of type I collagen, type I procollagen synthesis is inhibited. (PMID:12164934)
• Upstream elements present in the 3’-untranslated region of the gene influence the processing efficiency of overlapping polyadenylation signals. (PMID:12200454)
• Allele frequency of the G–>T mutation of this gene is analyzed by an ARMS-PCR in osteoporotic subjects with femoral neck fractures. (PMID:12211646)
• The COLIA1 polymorphism in children and young adults is associated with several bone characteristics. (PMID:12232678)
• This protein is regulated by human basic fibroblast growth factor. (PMID:12393937)
• Analysis of the Collal alleles provides early detection of the individuals with hereditary predisposition to osteoporosis and prophylaxis of the disease at the presymptomatic stage. (PMID:12575457)
• A degradation fragment originating from the helical part of type I collagen consisting of residues 620-633 of the alpha 1 chain sequence is useful clinically as a bone resorption marker in patients with osteoporosis. (PMID:12584032)
• mutational analysis in Lithuanian patients with osteogenesis imperfecta (PMID:12590186)
• in men, the “ss” genotype of COLIA1 polymorphism could be the best osteoporotic fracture risk genetic predictor, independent of bone mass values (PMID:12753258)
• COL7A1 mutation is characteristic in patients with dystrophic epidermolysis bullosa. (PMID:12787275)
• Polymorphism analysis in the COLIA1 gene of patients with thalassemia major and intermedia. (PMID:12803121)
• The Sp1 transcription factor binding site polymorphism of COL1A1 is associated with a modest reduction in bone mineral density and a significant increase in risk of osteoporotic fracture, particularly vertebral fracture. (PMID:12810179)
• estrogen receptor alpha Px haplotype and collagen IA1 s allele may be involved in causing the phenotypic expression of higher circulating levels of parathyroid hormone and higher bone turnover, which may lead to bone loss (PMID:14506618)
• genetic polymorphisms of the vitamin D receptor, estrogen receptor, and collagen Ialpha1 genes were characterized in 72 osteosarcoma and 53 Ewing sarcomas and in a group of 143 healthy matched children. (PMID:14528100)
• The “s” allele of COLIA1 gene in combination with the Px haplotype of the ER alpha gene contributes to reduced BMD in females. (PMID:14562991)
• In a cohort of 75-year-old Swedish women, there was an association among the Sp1 COLIA1 polymorphism, bone mass, and fracture. (PMID:14595528)
• COL1A1 gene expression is downregulated by B-Myb in fibroblasts from patients with systemic sclerosis. (PMID:14613485)
• Although connective tissue growth factor alone had no effect on collagen secretion, combined stimulation with IGF-I enhanced collagen accumulation. (PMID:14633859)
• This study identified a novel COL1A1 breakpoint, namely, exon 42 of the COL1A1 gene. (PMID:14643521)
• COL1A1 gene may have some effects on bone size variation at the wrist, but not at the spine or hip in Caucasian nuclear families. (PMID:14722584)
• The genotype frequency of COLIA1 polymorphism was also not different between PBC patients and controls, however the “s” allele was significantly less frequent in patients with PBC (p = 0.038). (PMID:15049048)
• Osteogenesis imperfecta Type 1: diagnosis could be verified by moleculargenetic analysis, a newly recognized heterozygous point mutation (Arg420Stop) in the COL1A1-gene was found. (PMID:15106082)
• Results characterize promoters from the human alpha1(I) procollagen gene. (PMID:15133851)
• The lower collagen content in the endopelvic fascia and skin of women with SUI is not due to reduced collagen synthesis or selective reduction in synthesis of either collagen I or collagen III. (PMID:15227656)
• This study showed a significant association between otosclerosis and the COL1A1 first intron Sp1 site. The allelic frequency of the Sp1 site is very similar between otosclerosis and osteoporosis. (PMID:15241219)
• Predicted rates of AA substitution for Gly were compared with missense mutations known to cause disease. The most destabilizing residues, Val, Glu, & Asp, & the least destabilizing residue, Ala, were underrepresented. (PMID:15365990)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	col1a1b	ENSDARG00000035809
mus_musculus	Col1a1	ENSMUSG00000001506
rattus_norvegicus	Col1a1	ENSRNOG00000003897

Paralogs (37): COL9A2 (ENSG00000049089), COL23A1 (ENSG00000050767), COL11A1 (ENSG00000060718), COL17A1 (ENSG00000065618), COL5A3 (ENSG00000080573), COL4A4 (ENSG00000081052), COL16A1 (ENSG00000084636), COL9A3 (ENSG00000092758), COL20A1 (ENSG00000101203), COL9A1 (ENSG00000112280), COL7A1 (ENSG00000114270), COL21A1 (ENSG00000124749), COL5A1 (ENSG00000130635), COL4A2 (ENSG00000134871), COL2A1 (ENSG00000139219), COL6A1 (ENSG00000142156), COL6A2 (ENSG00000142173), EDA (ENSG00000158813), COL26A1 (ENSG00000160963), COL1A2 (ENSG00000164692), 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-1(I) chain — P02452 (reviewed: P02452)

Alternative names: Alpha-1 type I collagen

All UniProt accessions (2): P02452, I3L3H7

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 with MRC2. Interacts with TRAM2. Interacts with MFAP4 in a Ca (2+)-dependent manner.

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. Contains mostly 4-hydroxyproline. Proline residues at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains. Contains 3-hydroxyproline at a few sites. This modification occurs on the first proline residue in the sequence motif Gly-Pro-Hyp, where Hyp is 4-hydroxyproline. Lysine residues at the third position of the tripeptide repeating unit (G-X-Y) are 5-hydroxylated in some or all of the chains. O-glycosylated on hydroxylated lysine residues. The O-linked glycan consists of a Glc-Gal disaccharide.

Disease relevance. Caffey disease (CAFYD) [MIM:114000] An autosomal dominant disorder characterized by an infantile episode of massive subperiosteal new bone formation that typically involves the diaphyses of the long bones, mandible, and clavicles. The involved bones may also appear inflamed, with painful swelling and systemic fever often accompanying the illness. The bone changes usually begin before 5 months of age and resolve before 2 years of age. The disease is caused by variants affecting the gene represented in this entry. Ehlers-Danlos syndrome, classic type, 1 (EDSCL1) [MIM:130000] A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. The main features of classic Ehlers-Danlos syndrome are joint hypermobility and dislocation, and fragile, bruisable skin. EDSCL1 inheritance is autosomal dominant. The disease may be caused by variants affecting the gene represented in this entry. Ehlers-Danlos syndrome, arthrochalasia type, 1 (EDSARTH1) [MIM:130060] A form of Ehlers-Danlos syndrome, a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDSARTH1 is an autosomal dominant form 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. 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 1 (OIEDS1) [MIM:619115] 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. Osteoporosis (OSTEOP) [MIM:166710] A systemic skeletal disorder characterized by decreased bone mass and deterioration of bone microarchitecture without alteration in the composition of bone. The result is fragile bones and an increased risk of fractures, even after minimal trauma. Osteoporosis is a chronic condition of multifactorial etiology and is usually clinically silent until a fracture occurs. Disease susceptibility is associated with variants affecting the gene represented in this entry. A chromosomal aberration involving COL1A1 is found in dermatofibrosarcoma protuberans. Translocation t(17;22)(q22;q13) with PDGF.

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_000079* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000885	Fib_collagen_C	Domain
IPR001007	VWF_dom	Domain
IPR008160	Collagen	Repeat
IPR050149	Collagen_superfamily	Family

Pfam: PF00093, PF01391, PF01410

UniProt features (386 total): sequence variant 175, modified residue 125, compositionally biased region 25, strand 14, sequence conflict 11, helix 6, disulfide bond 5, binding site 5, region of interest 4, glycosylation site 3, site 3, propeptide 2, short sequence motif 2, turn 2, domain 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
5CTD	X-RAY DIFFRACTION	1.6
8YV3	X-RAY DIFFRACTION	1.68
1Q7D	X-RAY DIFFRACTION	1.8
5CTI	X-RAY DIFFRACTION	1.9
5CVA	X-RAY DIFFRACTION	2.1
3EJH	X-RAY DIFFRACTION	2.1
5K31	X-RAY DIFFRACTION	2.2
5CVB	X-RAY DIFFRACTION	2.25
5OU8	X-RAY DIFFRACTION	2.5
5OU9	X-RAY DIFFRACTION	2.5
3GXE	X-RAY DIFFRACTION	2.6
7E7B	ELECTRON MICROSCOPY	2.6
7E7D	ELECTRON MICROSCOPY	3.2
2LLP	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02452-F1	54.26	0.18

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 (3): 161–162 (cleavage; by procollagen n-endopeptidase); 953–954 (cleavage; by collagenase); 1218–1219 (cleavage; by procollagen c-endopeptidase)

Ligand- & substrate-binding residues (5): 1277; 1279; 1280; 1282; 1285

Post-translational modifications (125): 622, 640, 646, 652, 658, 664, 670, 682, 691, 703, 715, 718, 724, 730, 739, 751, 757, 772, 778, 787 …

Disulfide bonds (5): 1259–1291, 1265, 1282, 1299–1462, 1370–1415

Glycosylation sites (3): 265, 1108, 1365

Function

Pathways and Gene Ontology

Reactome pathways

26 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-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-75892	Platelet Adhesion to exposed collagen
R-HSA-76009	Platelet Aggregation (Plug Formation)
R-HSA-8874081	MET activates PTK2 signaling
R-HSA-8940973	RUNX2 regulates osteoblast differentiation
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: 895 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, TGGTGCT_MIR29A_MIR29B_MIR29C, AGGAAGC_MIR5163P, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, ACTACCT_MIR196A_MIR196B, GOBP_BODY_MORPHOGENESIS, TAATAAT_MIR126, GOBP_BONE_TRABECULA_MORPHOGENESIS, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, MYOGENIN_Q6, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_CARTILAGE_DEVELOPMENT

GO Biological Process (51): skeletal system development (GO:0001501), blood vessel development (GO:0001568), osteoblast differentiation (GO:0001649), intramembranous ossification (GO:0001957), endochondral ossification (GO:0001958), visual perception (GO:0007601), sensory perception of sound (GO:0007605), response to xenobiotic stimulus (GO:0009410), positive regulation of epithelial to mesenchymal transition (GO:0010718), negative regulation of cell-substrate adhesion (GO:0010812), protein transport (GO:0015031), collagen fibril organization (GO:0030199), positive regulation of cell migration (GO:0030335), response to estradiol (GO:0032355), response to insulin (GO:0032868), collagen biosynthetic process (GO:0032964), protein localization to nucleus (GO:0034504), tooth mineralization (GO:0034505), collagen-activated tyrosine kinase receptor signaling pathway (GO:0038063), response to hydrogen peroxide (GO:0042542), skin morphogenesis (GO:0043589), cellular response to fibroblast growth factor stimulus (GO:0044344), positive regulation of DNA-templated transcription (GO:0045893), response to steroid hormone (GO:0048545), embryonic skeletal system development (GO:0048706), response to cAMP (GO:0051591), response to hyperoxia (GO:0055093), face morphogenesis (GO:0060325), bone trabecula formation (GO:0060346), cartilage development involved in endochondral bone morphogenesis (GO:0060351), cellular response to amino acid stimulus (GO:0071230), cellular response to mechanical stimulus (GO:0071260), cellular response to retinoic acid (GO:0071300), cellular response to vitamin E (GO:0071306), cellular response to glucose stimulus (GO:0071333), cellular response to tumor necrosis factor (GO:0071356), cellular response to epidermal growth factor stimulus (GO:0071364), cellular response to transforming growth factor beta stimulus (GO:0071560), positive regulation of canonical Wnt signaling pathway (GO:0090263), cellular response to fluoride (GO:1902618)

GO Molecular Function (7): protease binding (GO:0002020), extracellular matrix structural constituent conferring tensile strength (GO:0030020), identical protein binding (GO:0042802), metal ion binding (GO:0046872), platelet-derived growth factor binding (GO:0048407), extracellular matrix structural constituent (GO:0005201), protein binding (GO:0005515)

GO Cellular Component (9): extracellular region (GO:0005576), collagen type I trimer (GO:0005584), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), secretory granule (GO:0030141), extracellular matrix (GO:0031012), collagen trimer (GO:0005581), fibrillar collagen trimer (GO:0005583), cytoplasm (GO:0005737)

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
Non-integrin membrane-ECM interactions	1
Binding and Uptake of Ligands by Scavenger Receptors	1
MET promotes cell motility	1
RUNX2 regulates bone development	1
Collagen biosynthesis and modifying enzymes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
system development	1
vasculature development	1
anatomical structure development	1
ossification	1
cell differentiation	1
direct ossification	1
replacement ossification	1
endochondral bone morphogenesis	1
sensory perception of light stimulus	1
sensory perception of mechanical stimulus	1
response to chemical	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
positive regulation of cell differentiation	1
positive regulation of multicellular organismal process	1
negative regulation of cell adhesion	1
regulation of cell-substrate adhesion	1
cell-substrate adhesion	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
extracellular matrix organization	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
response to lipid	1
response to oxygen-containing compound	1
response to peptide hormone	1
biosynthetic process	1
collagen metabolic process	1
protein localization to organelle	1
biomineral tissue development	1
odontogenesis	1
cell surface receptor protein tyrosine kinase signaling pathway	1
collagen-activated signaling pathway	1
response to reactive oxygen species	1
enzyme binding	1
extracellular matrix structural constituent	1
protein binding	1

Protein interactions and networks

STRING

5086 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COL1A1	COL1A2	P02464	981
COL1A1	COL3A1	P02461	965
COL1A1	CRTAP	O75718	925
COL1A1	BGN	P13247	916
COL1A1	FN1	P02751	912
COL1A1	COL5A2	P05997	912
COL1A1	ACTA2	P03996	900
COL1A1	BGLAP	P02818	889
COL1A1	CD44	P16070	882
COL1A1	P3H1	Q32P28	881
COL1A1	COL5A1	P20908	880
COL1A1	SP7	Q8TDD2	879
COL1A1	COL6A3	P12111	875
COL1A1	LUM	P51884	854
COL1A1	FBN1	P35555	852

IntAct

114 interactions, top by confidence:

A	B	Type	Score
FN1	COL1A1	psi-mi:“MI:0407”(direct interaction)	0.710
COL1A1	P4HA2	psi-mi:“MI:0915”(physical association)	0.710
COL1A1	FN1	psi-mi:“MI:0407”(direct interaction)	0.710
PEG10	RTL8C	psi-mi:“MI:0914”(association)	0.670
YAF2	E2F6	psi-mi:“MI:0914”(association)	0.640
COL1A1		psi-mi:“MI:0407”(direct interaction)	0.600
	COL1A1	psi-mi:“MI:0407”(direct interaction)	0.600
COL1A1	COL1A2	psi-mi:“MI:0915”(physical association)	0.580
COL1A1	CRTAP	psi-mi:“MI:0915”(physical association)	0.580
COL1A1	KEAP1	psi-mi:“MI:0915”(physical association)	0.560
COL1A1	PDIA4	psi-mi:“MI:0914”(association)	0.560
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
TIMM44	COL1A1	psi-mi:“MI:0914”(association)	0.530
ERAL1	COL1A1	psi-mi:“MI:0914”(association)	0.530
UBXN11	COL1A1	psi-mi:“MI:0914”(association)	0.530
CAMKMT	COL1A1	psi-mi:“MI:0914”(association)	0.530
COLGALT2	COL1A1	psi-mi:“MI:0914”(association)	0.530
TMTC4	CLGN	psi-mi:“MI:0914”(association)	0.530
LAIR2	LAMA5	psi-mi:“MI:0914”(association)	0.530
COL1A1	GOLIM4	psi-mi:“MI:0914”(association)	0.500

BioGRID (141): COL1A1 (Affinity Capture-MS), COL1A1 (Affinity Capture-MS), COL1A1 (Affinity Capture-MS), COL1A1 (Affinity Capture-MS), COL1A1 (Affinity Capture-MS), COL1A1 (Affinity Capture-MS), COL1A1 (Affinity Capture-MS), COL1A1 (Affinity Capture-MS), COL1A1 (Affinity Capture-MS), COL1A1 (Affinity Capture-MS), COL1A1 (Affinity Capture-MS), COL1A1 (Affinity Capture-MS), COL1A1 (Affinity Capture-MS), COL1A1 (Affinity Capture-MS), COL1A1 (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: A0MSJ1, C7DZK3, O42350, O88207, P02452, P02457, P02458, P02459, P02460, P02461, P02466, P05997, P08121, P12105, P12107, P13941, P13942, P20908, P20909, Q17RW2, Q30D77, Q32S24, Q3U962, Q5QNQ9, Q60467, Q61245, Q64739, Q6P4Z2, Q80ZF0, Q8IZC6, Q91717, Q9JI03, Q9YIB4, B8V7R6, O46392, O93484, P02453, P02454, P02465, P02467

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
RUNX2	“up-regulates quantity by expression”	COL1A1	“transcriptional regulation”
MAPK14	“up-regulates quantity by expression”	COL1A1	“transcriptional regulation”
COL1A1	“up-regulates activity”	“A1/b1 integrin”	binding
COL1A1	up-regulates	ECM_synthesis
SMOC1	“up-regulates quantity by expression”	COL1A1	“transcriptional regulation”
COL1A1	“up-regulates activity”	DDR1	binding
COL1A1	“up-regulates activity”	DDR2	binding
TGFB1	“up-regulates quantity by expression”	COL1A1	“transcriptional regulation”
COL1A1	up-regulates	“A2/b1 integrin”	binding
COL1A1	up-regulates	DDR1	binding
COL1A1	“up-regulates activity”	“A11/b1 integrin”	binding
BMP1	“up-regulates activity”	COL1A1	cleavage
COLGALT1	“up-regulates activity”	COL1A1	glycosylation
COLGALT2	“up-regulates activity”	COL1A1	glycosylation
MMP1	“down-regulates quantity by destabilization”	COL1A1	cleavage
COL1A1	“up-regulates activity”	“A2/b1 integrin”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 114 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
Collagen biosynthesis and modifying enzymes	8	18.4×	5e-06
Developmental Lineage of Pancreatic Ductal Cells	5	15.4×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
collagen fibril organization	7	16.7×	2e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 5 cancer types — ANSC, GBM, MEL, PAAD, PCM.

Clinical variants and AI predictions

ClinVar

3793 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1061
Likely pathogenic	318
Uncertain significance	779
Likely benign	988
Benign	103

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1065492	NM_000088.4(COL1A1):c.4291del (p.Thr1431fs)	Pathogenic
1069647	NM_000088.4(COL1A1):c.2678G>C (p.Gly893Ala)	Pathogenic
1069928	NM_000088.4(COL1A1):c.2235+1G>C	Pathogenic
1069954	NM_000088.4(COL1A1):c.394_395del (p.Asp132fs)	Pathogenic
1070187	NM_000088.4(COL1A1):c.3589_3590del (p.Asp1197fs)	Pathogenic
1070188	NM_000088.4(COL1A1):c.3569G>A (p.Gly1190Asp)	Pathogenic
1070189	NM_000088.4(COL1A1):c.3531+1G>C	Pathogenic
1070241	NM_000088.4(COL1A1):c.3020del (p.Gly1007fs)	Pathogenic
1070818	NM_000088.4(COL1A1):c.3051del (p.Pro1018fs)	Pathogenic
1070914	NM_000088.4(COL1A1):c.2907_2908delinsAT (p.Arg970Ter)	Pathogenic
1071489	NM_000088.4(COL1A1):c.814G>A (p.Gly272Ser)	Pathogenic
1072196	NM_000088.4(COL1A1):c.2585_2586del (p.Lys862fs)	Pathogenic
1072430	NM_000088.4(COL1A1):c.1981C>T (p.Gln661Ter)	Pathogenic
1072431	NM_000088.4(COL1A1):c.1886del (p.Gly629fs)	Pathogenic
1073168	NM_000088.4(COL1A1):c.595C>T (p.Gln199Ter)	Pathogenic
1073803	NM_000088.4(COL1A1):c.3061_3068del (p.Glu1021fs)	Pathogenic
1074006	NM_000088.4(COL1A1):c.3910C>T (p.Gln1304Ter)	Pathogenic
1074007	NM_000088.4(COL1A1):c.3385C>T (p.Gln1129Ter)	Pathogenic
1074064	NM_000088.4(COL1A1):c.1797del (p.Val600fs)	Pathogenic
1074183	NM_000088.4(COL1A1):c.1821del (p.Gly608fs)	Pathogenic
1074312	NM_000088.4(COL1A1):c.1614+1G>A	Pathogenic
1074344	NM_000088.4(COL1A1):c.1804G>T (p.Gly602Ter)	Pathogenic
1074370	NM_000088.4(COL1A1):c.642+2T>A	Pathogenic
1074716	NM_000088.4(COL1A1):c.1451del (p.Pro484fs)	Pathogenic
1074717	NM_000088.4(COL1A1):c.1003G>A (p.Gly335Ser)	Pathogenic
1074867	NM_000088.4(COL1A1):c.3649del (p.Arg1217fs)	Pathogenic
1075011	NM_000088.4(COL1A1):c.2584A>T (p.Lys862Ter)	Pathogenic
1076006	NM_000088.4(COL1A1):c.288del (p.Asp97fs)	Pathogenic
1076168	NM_000088.4(COL1A1):c.3470G>A (p.Gly1157Asp)	Pathogenic
1076244	NM_000088.4(COL1A1):c.3302_3303insTTGTAACTATTATGAGTCCTAGTTGACTTGAAGTGGAGAAGGCTACGATTTTTTTGAAGCCGCCTAGTTTTAAGAGTACTGCGGCAAGTACTATTGACCCAGCGATGGGGGCTTCGACATGGGCTTTAGGGAGTCATAAGTGGAGTCCGTAAGGCGA (p.Glu1101delinsAspCysAsnTyrTyrGluSerTer)	Pathogenic

SpliceAI

4269 predictions. Top by Δscore:

Variant	Effect	Δscore
17:50185647:CT:C	acceptor_gain	1.0000
17:50185770:GCAC:G	donor_loss	1.0000
17:50185771:CACT:C	donor_loss	1.0000
17:50185772:ACTC:A	donor_loss	1.0000
17:50185773:CTCAC:C	donor_loss	1.0000
17:50185774:TCAC:T	donor_loss	1.0000
17:50185775:C:CG	donor_loss	1.0000
17:50185776:A:AC	donor_gain	1.0000
17:50185776:A:AG	donor_loss	1.0000
17:50185777:C:CC	donor_gain	1.0000
17:50185777:CCGTG:C	donor_gain	1.0000
17:50186016:TCGAA:T	acceptor_gain	1.0000
17:50186017:CGAA:C	acceptor_gain	1.0000
17:50186017:CGAAC:C	acceptor_gain	1.0000
17:50186018:GAA:G	acceptor_gain	1.0000
17:50186019:AA:A	acceptor_gain	1.0000
17:50186021:C:CC	acceptor_gain	1.0000
17:50186024:C:CT	acceptor_gain	1.0000
17:50186025:A:T	acceptor_gain	1.0000
17:50186312:CGCA:C	donor_gain	1.0000
17:50186314:CA:C	donor_loss	1.0000
17:50186315:A:AC	donor_gain	1.0000
17:50186315:A:AT	donor_loss	1.0000
17:50186316:C:CC	donor_gain	1.0000
17:50186503:CTCTC:C	acceptor_gain	1.0000
17:50186505:CTC:C	acceptor_gain	1.0000
17:50186506:TC:T	acceptor_gain	1.0000
17:50186506:TCCTG:T	acceptor_loss	1.0000
17:50186507:CC:C	acceptor_gain	1.0000
17:50186507:CCTGT:C	acceptor_loss	1.0000

AlphaMissense

9226 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:50185587:A:G	L1437P	1.000
17:50185782:C:G	C1415S	1.000
17:50185783:A:G	C1415R	1.000
17:50185783:A:T	C1415S	1.000
17:50185916:G:C	C1370W	1.000
17:50185917:C:G	C1370S	1.000
17:50185918:A:G	C1370R	1.000
17:50185918:A:T	C1370S	1.000
17:50185956:A:G	L1357P	1.000
17:50186449:G:C	C1291W	1.000
17:50186450:C:G	C1291S	1.000
17:50186450:C:T	C1291Y	1.000
17:50186451:A:G	C1291R	1.000
17:50186451:A:T	C1291S	1.000
17:50186669:A:G	L1262P	1.000
17:50186677:G:C	C1259W	1.000
17:50186678:C:G	C1259S	1.000
17:50186678:C:T	C1259Y	1.000
17:50186679:A:G	C1259R	1.000
17:50186679:A:T	C1259S	1.000
17:50187058:C:T	G1163E	1.000
17:50193959:C:T	G584E	1.000
17:50193968:C:T	G581E	1.000
17:50193969:C:G	G581R	1.000
17:50193969:C:T	G581R	1.000
17:50199863:C:G	C63S	1.000
17:50199864:A:T	C63S	1.000
17:50199869:C:G	C61S	1.000
17:50199870:A:G	C61R	1.000
17:50199870:A:T	C61S	1.000

dbSNP variants (sampled 300 via entrez): RS1000231009 (17:50184915 A>G), RS1000386116 (17:50189513 G>T), RS1000616928 (17:50193756 C>T), RS1000683455 (17:50195127 T>C,G), RS1000721897 (17:50188125 C>T), RS1001015192 (17:50200461 C>T), RS1001018768 (17:50200705 C>A,T), RS1001533491 (17:50200955 AC>A), RS1001554485 (17:50184485 A>G), RS1001739152 (17:50194704 C>G,T), RS1001925288 (17:50199035 A>G), RS1002020181 (17:50187555 A>G), RS1002076072 (17:50193379 T>A), RS1002741196 (17:50194471 C>G,T), RS1002752803 (17:50203026 T>G)

Disease associations

OMIM: gene MIM:120150 | disease phenotypes: MIM:166200, MIM:130000, MIM:166710, MIM:114000, MIM:166210, MIM:166220, MIM:259420, MIM:619115, MIM:261600, MIM:132400, MIM:608099, MIM:148300, MIM:607086, MIM:604841, MIM:617821, MIM:225320

GenCC curated gene-disease

Disease	Classification	Inheritance
Caffey disease	Definitive	Autosomal dominant
Ehlers-Danlos syndrome, arthrochalasia type	Definitive	Autosomal dominant
osteogenesis imperfecta type 4	Definitive	Autosomal dominant
Ehlers-Danlos syndrome, classic type	Definitive	Autosomal dominant
osteogenesis imperfecta type 3	Strong	Autosomal dominant
combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1	Moderate	Autosomal dominant
osteogenesis imperfecta type 1	Supportive	Autosomal dominant
osteogenesis imperfecta type 2	Supportive	Autosomal dominant
Ehlers-Danlos/osteogenesis imperfecta syndrome	Supportive	Autosomal dominant
high bone mass osteogenesis imperfecta	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (3)

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

Disease	Classification	Inheritance
Caffey disease	Definitive	AD
osteogenesis imperfecta	Definitive	AD
COL1A1-related Ehlers-Danlos syndrome	Definitive	AD

Mondo (31): osteogenesis imperfecta type 1 (MONDO:0008146), Ehlers-Danlos syndrome, classic type, 1 (MONDO:0019567), osteoporosis (MONDO:0005298), Caffey disease (MONDO:0007244), Ehlers-Danlos syndrome, arthrochalasia type (MONDO:0007525), osteogenesis imperfecta type 2 (MONDO:0008147), osteogenesis imperfecta type 4 (MONDO:0008148), osteogenesis imperfecta type 3 (MONDO:0009804), combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 (MONDO:0030854), Ehlers-Danlos syndrome (MONDO:0020066), osteogenesis imperfecta (MONDO:0019019), postmenopausal osteoporosis (MONDO:0008159), congenital heart disease (MONDO:0005453), Ehlers-Danlos syndrome, classic type (MONDO:0007522), phenylketonuria (MONDO:0009861)

Orphanet (27): Osteogenesis imperfecta type 1 (Orphanet:216796), Osteogenesis imperfecta (Orphanet:666), Caffey disease (Orphanet:1310), Arthrochalasia Ehlers-Danlos syndrome (Orphanet:1899), Osteogenesis imperfecta type 2 (Orphanet:216804), Osteogenesis imperfecta type 3 (Orphanet:216812), Osteogenesis imperfecta type 4 (Orphanet:216820), OBSOLETE: Ehlers-Danlos syndrome type 7A (Orphanet:99875), OBSOLETE: Ehlers-Danlos syndrome type 7B (Orphanet:99876), Ehlers-Danlos syndrome (Orphanet:98249), Classical Ehlers-Danlos syndrome (Orphanet:287), Phenylketonuria (Orphanet:716), Multiple epiphyseal dysplasia type 1 (Orphanet:93308), Alpha-sarcoglycan-related limb-girdle muscular dystrophy R3 (Orphanet:62), Familial prostate cancer (Orphanet:1331)

HPO phenotypes

186 total (30 of 186 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000015	Bladder diverticulum
HP:0000023	Inguinal hernia
HP:0000139	Uterine prolapse
HP:0000239	Large fontanelles
HP:0000260	Wide anterior fontanel
HP:0000272	Malar flattening
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000324	Facial asymmetry
HP:0000325	Triangular face
HP:0000347	Micrognathia
HP:0000362	Otosclerosis
HP:0000365	Hearing impairment
HP:0000444	Convex nasal ridge
HP:0000481	Abnormal cornea morphology
HP:0000520	Proptosis
HP:0000592	Blue sclerae
HP:0000703	Dentinogenesis imperfecta
HP:0000708	Atypical behavior
HP:0000883	Thin ribs
HP:0000926	Platyspondyly
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0000963	Thin skin
HP:0000974	Hyperextensible skin
HP:0000978	Bruising susceptibility
HP:0000993	Molluscoid pseudotumors
HP:0001001	Abnormality of subcutaneous fat tissue

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000079_6	Breast cancer	8.000000e-08
GCST001692_9	Response to taxane treatment (docetaxel)	1.000000e-06
GCST006979_501	Heel bone mineral density	7.000000e-24
GCST008338_7	Blood cell traits (multivariate analysis)	1.000000e-08
GCST90013442_31	Keratoconus	3.000000e-09

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0004305	erythrocyte count
EFO:0004309	platelet count
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0005090	basophil count
EFO:0005091	monocyte count

MeSH disease descriptors (21)

Descriptor	Name	Tree numbers
D001238	Asphyxia Neonatorum	C16.614.092
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D003240	Connective Tissue Diseases	C17.300
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
D006958	Hyperostosis, Cortical, Congenital	C05.116.099.708.479; C05.116.540.400; C16.614.465
D007640	Keratoconus	C11.204.627
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
D010661	Phenylketonurias	C10.228.140.163.100.687; C16.320.565.100.766; C16.320.565.189.687; C18.452.132.100.687; C18.452.648.100.766; C18.452.648.189.687
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
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.)
C537493	Stickler syndrome, type 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2364188 (PROTEIN COMPLEX GROUP), CHEMBL3030 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1800012	Dosage	3	somatropin recombinant
rs1800012	Toxicity	3	valproic acid	Epilepsy

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1800012	COL1A1	3	2.00	2	valproic acid;somatropin recombinant

ChEMBL bioactivities

5 potent at pChembl≥5 of 19 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.70	IC50	2000	nM	CHEMBL5415605
5.11	IC50	7830	nM	CHEMBL5194526
5.10	IC50	8010	nM	CHEMBL5398209
5.09	IC50	8190	nM	CHEMBL5415777
5.00	IC50	1e+04	nM	CHEMBL5440427

PubChem BioAssay actives

5 with measured affinity, of 136 total; 5 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
2-[(5R,6R,9S,13S)-6-butyl-1,7-diazatricyclo[7.3.1.05,13]tridecan-7-yl]-N-(3-phenylphenyl)acetamide	1991399: Inhibition of COL1A1 (unknown origin) expressed in human LX2 cells	ic50	2.0000	uM
2,3,10-trimethoxy-9-[(4-propan-2-ylphenyl)methoxy]-5,6-dihydroisoquinolino[2,1-b]isoquinolin-7-ium bromide	2032035: Inhibition of COL1A1 (unknown origin) expressed in human LX2 cells incubated for 48 hrs by Bright-Glo luciferase assay	ic50	7.8300	uM
2-[(5R,6R,9S,13S)-6-butyl-1,7-diazatricyclo[7.3.1.05,13]tridecan-7-yl]-N-(2,4-dichlorophenyl)acetamide	1991399: Inhibition of COL1A1 (unknown origin) expressed in human LX2 cells	ic50	8.0100	uM
2,3,10-trimethoxy-9-[(3-methylphenyl)methoxy]-5,6-dihydroisoquinolino[2,1-b]isoquinolin-7-ium bromide	2032035: Inhibition of COL1A1 (unknown origin) expressed in human LX2 cells incubated for 48 hrs by Bright-Glo luciferase assay	ic50	8.1900	uM
(5R,6R,9S,13S)-6-butyl-N-(4-butylphenyl)-1,7-diazatricyclo[7.3.1.05,13]tridecane-7-carboxamide	1991399: Inhibition of COL1A1 (unknown origin) expressed in human LX2 cells	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Resveratrol	decreases expression, affects secretion, increases reaction, increases oxidation, increases phosphorylation (+5 more)	9
sodium arsenite	decreases reaction, affects reaction, affects methylation, decreases expression, affects cotreatment (+2 more)	8
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	8
Particulate Matter	decreases expression, increases abundance, increases expression	7
Dexamethasone	decreases reaction, increases expression, affects reaction, increases reaction, affects cotreatment	6
methylmercuric chloride	affects cotreatment, increases expression	4
trichostatin A	affects expression, affects cotreatment, increases expression	4
Arsenic Trioxide	decreases expression, decreases reaction, increases expression	4
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	4
Glucose	affects secretion, affects reaction, decreases expression, decreases reaction, increases expression	4
Quercetin	increases expression, increases secretion, decreases secretion, decreases expression, decreases reaction	4
Tretinoin	decreases reaction, increases expression, decreases expression	4
ascorbate-2-phosphate	increases expression, affects cotreatment, decreases reaction	3
beta-glycerophosphoric acid	affects cotreatment, affects reaction, decreases reaction, increases expression	3
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases activity, decreases reaction, increases expression, increases phosphorylation, decreases expression	3
Y 27632	decreases reaction, increases expression	3
Air Pollutants	affects cotreatment, increases abundance, increases expression, decreases expression	3
Ascorbic Acid	increases expression, affects cotreatment, affects reaction, decreases reaction	3
Calcitriol	increases expression, decreases reaction	3
Hydrogen Peroxide	decreases expression, increases expression, decreases reaction	3
Methotrexate	decreases expression, increases expression	3
Oxygen	decreases reaction, increases expression, affects reaction	3
Ozone	affects cotreatment, increases expression, increases abundance	3
Silicon Dioxide	decreases reaction, increases expression, decreases expression, increases response to substance	3
Tetrachlorodibenzodioxin	increases expression, affects expression	3
Tobacco Smoke Pollution	affects expression, decreases expression	3
Asbestos, Crocidolite	increases expression, decreases expression	3
Cadmium Chloride	decreases reaction, increases abundance, increases expression, decreases expression	3
baicalein	affects cotreatment, affects reaction, decreases reaction, increases expression	2
bisphenol A	increases abundance, increases expression, affects cotreatment, affects expression	2

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5338438	Binding	Binding affinity to Col1a1 (unknown origin) at 200 uM preincubated for 2 hrs followed by pronase addition and measured after 30 mins by coomassie blue staining based SDS-PAGE gel analysis	Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans. — J Nat Prod

Cellosaurus cell lines

22 cell lines: 12 cancer cell line, 8 induced pluripotent stem cell, 1 finite cell line, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B7E2	SMBCi014-A	Induced pluripotent stem cell	Female
CVCL_B8DY	Abcam HCT 116 COL1A1 KO	Cancer cell line	Male
CVCL_B8U9	Abcam MCF-7 COL1A1 KO	Cancer cell line	Female
CVCL_B9G6	Abcam A-549 COL1A1 KO	Cancer cell line	Male
CVCL_C0BN	Abcam U2OS COL1A1 KO	Cancer cell line	Female
CVCL_D4A8	MDFSP-S1	Cancer cell line	Female
CVCL_D4ZC	OI-Pt1 iPSC	Induced pluripotent stem cell	Female
CVCL_D4ZD	OI-Pt2 iPSC	Induced pluripotent stem cell	Male
CVCL_D4ZE	OI-Pt1 iPSC corrected	Induced pluripotent stem cell	Female
CVCL_D4ZK	NCC-DFSP5-C1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00006180	PHASE4	COMPLETED	Bone Loss in Premenopausal Women With Depression
NCT00035256	PHASE4	COMPLETED	Sequential Use of Teriparatide and Raloxifene HCl in the Treatment of Postmenopausal Women With Osteoporosis
NCT00035971	PHASE4	COMPLETED	EVA: Evista Alendronate Comparison
NCT00114556	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Density in Liver Transplant Patients
NCT00130403	PHASE4	COMPLETED	OPTAMISE: Clinical Effectiveness of Teriparatide After Alendronate or Risedronate Therapy in Osteoporotic Postmenopausal Women
NCT00148915	PHASE4	COMPLETED	A Study To Assess the Quality and Strength of Bone in Women Participants With Osteoporosis Taking Oral Ibandronate Versus Placebo
NCT00157690	PHASE4	COMPLETED	Study of Alendronate to Prevent and Treat Osteoporosis in Cystic Fibrosis Patients
NCT00159419	PHASE4	COMPLETED	Bisphosphonate Therapy for Osteogenesis Imperfecta
NCT00165607	PHASE4	COMPLETED	Randomized, Open, Parallel, Active Controlled Study on Fracture Prevention in Antiosteoporosis Treatment (OF Study)
NCT00168909	PHASE4	COMPLETED	Influence of Alfacalcidol on Falls in Osteopenic/Osteoporotic Postmenopausal Women (ALFA Study)
NCT00182871	PHASE4	COMPLETED	Testosterone Effects on Bone and Frailty
NCT00191425	PHASE4	COMPLETED	2-Year Therapy With Teriparatide vs 1-yr Therapy Followed by 1-Year of Raloxifene or Calcium/Vit D in Severe Postmenopausal Osteoporosis
NCT00211211	PHASE4	COMPLETED	FREE Study - Fracture Reduction Evaluation
NCT00221299	PHASE4	COMPLETED	Risedronate and Parathyroid Hormone to Reverse Osteoporosis Caused by Chronic Steroid Use
NCT00252408	PHASE4	COMPLETED	Danish Osteoporosis Prevention Study
NCT00259298	PHASE4	COMPLETED	Evaluation of the Effects of Teriparatide on Skeleton Images in Postmenopausal Women With Osteoporosis
NCT00261625	PHASE4	COMPLETED	Can Alendronate Suppress Calcification and Improve Bone Density in Chronic Peritoneal Dialysis Patients?
NCT00271713	PHASE4	COMPLETED	Impact of Oral Ibandronate 150 mg Monthly on Structural Properties of Bone in Postmenopausal Osteoporosis (SPIMOS-3D)
NCT00294463	PHASE4	COMPLETED	Effects of Tibolone Treatment on the Endometrium
NCT00327990	PHASE4	COMPLETED	Evaluation Of Missed Osteoporosis Diagnoses, And Preference Between Once Monthly Ibandronate And Once Weekly Alendronate
NCT00357331	PHASE4	COMPLETED	The Effects of Potassium Citrate on Bone Metabolism
NCT00371956	PHASE4	COMPLETED	Raloxifene for Prevention of Bone Loss in Postmenopausal Patients Receiving Chronic Corticosteroid Therapy
NCT00372372	PHASE4	COMPLETED	The Efficacy of Risedronate in Prevention of Bone Loss in Patients Receiving High Dose Corticosteroid Treatment
NCT00376662	PHASE4	COMPLETED	HRT Versus Etidronate for Osteoporosis and Fractures in Asthmatics Receiving Glucocorticoids.
NCT00402441	PHASE4	COMPLETED	Risedronate in the Prevention of Osteoporosis in Postmenopausal Women
NCT00405392	PHASE4	COMPLETED	Study To Investigate Patient Preference On Dosing In Ibandronate And Risedronate In Korean Women With Postmenopausal Osteoporosis
NCT00431444	PHASE4	COMPLETED	Effects of Zoledronic Acid and Raloxifene on Bone Turnover Markers in Postmenopausal Women With Low Bone Mineral Density
NCT00446589	PHASE4	TERMINATED	The Effects of Ibandronate or Teriparatide Therapy on Bone Histology and Biochemical Indices in Patients on Hemodialysis With Low Bone Mineral Density
NCT00453492	PHASE4	COMPLETED	Risedronate Sodium in Post Menopausal Osteoporosis
NCT00460057	PHASE4	COMPLETED	The Change of Bone Markers After Low Dose Alendronate in Postmenopausal Women With Bone Loss
NCT00479037	PHASE4	COMPLETED	Effect of Full Length Parathyroid Hormone, PTH(1-84) or Strontium Ranelate on Bone Markers in Postmenopausal Women With Primary Osteoporosis (FP-006-IM)
NCT00485953	PHASE4	COMPLETED	Effect of Bisphosphonate on Bone Loss in Postmenopausal Women With Breast Cancer Initiating Aromatase Inhibitor Therapy
NCT00489424	PHASE4	COMPLETED	Acetaminophen or Fluvastatin Compared to Placebo on the Transient Post-Dose Symptoms (PDS) Following an Intravenous (i.v.) Infusion of a Single Dose of Zoledronic Acid 5mg, in Post-menopausal Women With Low Bone Mass
NCT00491920	PHASE4	COMPLETED	High Dosage Vitamin D and Osteoporosis
NCT00504166	PHASE4	COMPLETED	Alendronate Prevents Microarchitectural Deterioration of Trabecular Bone in Early Postmenopausal Women
NCT00544180	PHASE4	TERMINATED	ROSPA - Record on Satisfaction of Patients With Actonel 35 mg Once a Week
NCT00548509	PHASE4	COMPLETED	The Effect of Vitamin K2 on Bone Turnover
NCT00549068	PHASE4	COMPLETED	POWER Point of Care Effect on Satisfaction of Treatment
NCT00549965	PHASE4	COMPLETED	Satisfaction and Compliance of Risedronate in PMO
NCT00557310	PHASE4	COMPLETED	A Study Using Imaging Technology to Measure Changes in Bone Structure After Treatment With Teriparatide