Gene summary
| Gene name: COL2A1 | ASpdb.0 ID: 1280 | Gene | Gene symbol | COL2A1 | Gene ID | 1280 |
| Gene name | collagen type II alpha 1 chain |
| Synonyms | ANFH|AOM|COL11A3|SEDC|STL1 |
| Cytomap | 12q13.11 |
| Type of gene | protein-coding |
| Description | collagen alpha-1(II) chainalpha-1 type II collagenarthroophthalmopathy, progressive (Stickler syndrome)cartilage collagenchondrocalcincollagen II, alpha-1 polypeptidecollagen, type II, alpha 1 |
| Modification date | 20240310 |
| UniProtAcc | P02458 |
Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | COL2A1 | GO:0005585 | collagen type II trimer | 8660302 |
| Gene | COL2A1 | GO:0043394 | proteoglycan binding | 29030641 |
| Gene | COL2A1 | GO:0048407 | platelet-derived growth factor binding | 8900172 |
Information of the canonical protein with experimentally identified structure from PDB (2023).
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P02458-2 | P02458-2_5nir_A.pdb | 5NIR | X-ray | 1.74 | A | 30 | 98 |
ASpdb's canonical and alternatively spliced isoform information.
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P02458 | COL2A1 | P02458-2 | P02458-3 | 1487 | 268 | 1 | 1219 | Deletion | none | none | 0 | 0 |
Multiple sequence alignment of our canonical and alternatively spliced COL2A1
Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of COL2A1
| UniProt-id | ENSG | ENST | ENSP |
| P02458-2 | ENSG00000139219.19 | ENST00000380518.8 | ENSP00000369889.3 |
| UniProt-id | NM ID | NP ID |
| P02458-2 | NM_001844.4 | NP_001835.3 |
Amino acid sequences of our canonical and alternatively spliced COL2A1
| accession_id | Protein sequence |
| P02458-2 | MIRLGAPQTLVLLTLLVAAVLRCQGQDVQEAGSCVQDGQRYNDKDVWKPEPCRICVCDTGTVLCDDIICEDVKDCLSPEIPFGECCPICP TDLATASGQPGPKGQKGEPGDIKDIVGPKGPPGPQGPAGEQGPRGDRGDKGEKGAPGPRGRDGEPGTPGNPGPPGPPGPPGPPGLGGNFA AQMAGGFDEKAGGAQLGVMQGPMGPMGPRGPPGPAGAPGPQGFQGNPGEPGEPGVSGPMGPRGPPGPPGKPGDDGEAGKPGKAGERGPPG PQGARGFPGTPGLPGVKGHRGYPGLDGAKGEAGAPGVKGESGSPGENGSPGPMGPRGLPGERGRTGPAGAAGARGNDGQPGPAGPPGPVG PAGGPGFPGAPGAKGEAGPTGARGPEGAQGPRGEPGTPGSPGPAGASGNPGTDGIPGAKGSAGAPGIAGAPGFPGPRGPPGPQGATGPLG PKGQTGEPGIAGFKGEQGPKGEPGPAGPQGAPGPAGEEGKRGARGEPGGVGPIGPPGERGAPGNRGFPGQDGLAGPKGAPGERGPSGLAG PKGANGDPGRPGEPGLPGARGLTGRPGDAGPQGKVGPSGAPGEDGRPGPPGPQGARGQPGVMGFPGPKGANGEPGKAGEKGLPGAPGLRG LPGKDGETGAAGPPGPAGPAGERGEQGAPGPSGFQGLPGPPGPPGEGGKPGDQGVPGEAGAPGLVGPRGERGFPGERGSPGAQGLQGPRG LPGTPGTDGPKGASGPAGPPGAQGPPGLQGMPGERGAAGIAGPKGDRGDVGEKGPEGAPGKDGGRGLTGPIGPPGPAGANGEKGEVGPPG PAGSAGARGAPGERGETGPPGPAGFAGPPGADGQPGAKGEQGEAGQKGDAGAPGPQGPSGAPGPQGPTGVTGPKGARGAQGPPGATGFPG AAGRVGPPGSNGNPGPPGPPGPSGKDGPKGARGDSGPPGRAGEPGLQGPAGPPGEKGEPGDDGPSGAEGPPGPQGLAGQRGIVGLPGQRG ERGFPGLPGPSGEPGKQGAPGASGDRGPPGPVGPPGLTGPAGEPGREGSPGADGPPGRDGAAGVKGDRGETGAVGAPGAPGPPGSPGPAG PTGKQGDRGEAGAQGPMGPSGPAGARGIQGPQGPRGDKGEAGEPGERGLKGHRGFTGLQGLPGPPGPSGDQGASGPAGPSGPRGPPGPVG PSGKDGANGIPGPIGPPGPRGRSGETGPAGPPGNPGPPGPPGPPGPGIDMSAFAGLGPREKGPDPLQYMRADQAAGGLRQHDAEVDATLK SLNNQIESIRSPEGSRKNPARTCRDLKLCHPEWKSGDYWIDPNQGCTLDAMKVFCNMETGETCVYPNPANVPKKNWWSSKSKEKKHIWFG ETINGGFHFSYGDDNLAPNTANVQMTFLRLLSTEGSQNITYHCKNSIAYLDEAAGNLKKALLIQGSNDVEIRAEGNSRFTYTALKDGCTK |
| P02458-3 | MSAFAGLGPREKGPDPLQYMRADQAAGGLRQHDAEVDATLKSLNNQIESIRSPEGSRKNPARTCRDLKLCHPEWKSGDYWIDPNQGCTLD AMKVFCNMETGETCVYPNPANVPKKNWWSSKSKEKKHIWFGETINGGFHFSYGDDNLAPNTANVQMTFLRLLSTEGSQNITYHCKNSIAY |
Main function of this protein. (from UniProt)
COL2A1 (go to UniProt):P02458
download pageRetention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at
- Retained protein feature among the 13 regional features.
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P02458 | Domain | 32 | 90 | Note=VWFC;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00220 | Type=Deletion;Start=1;End=1219 |
| P02458 | Region | 97 | 1237 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=1219 |
| P02458 | Region | 201 | 1214 | Note=Triple-helical region | Type=Deletion;Start=1;End=1219 |
| P02458 | Region | 1215 | 1241 | Note=Nonhelical region (C-terminal) | Type=Deletion;Start=1;End=1219 |
| P02458 | Compositional bias | 133 | 149 | Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=1219 |
| P02458 | Compositional bias | 157 | 174 | Note=Pro residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=1219 |
| P02458 | Compositional bias | 237 | 251 | Note=Pro residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=1219 |
| P02458 | Compositional bias | 351 | 365 | Note=Pro residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=1219 |
| P02458 | Compositional bias | 432 | 446 | Note=Pro residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=1219 |
| P02458 | Compositional bias | 910 | 924 | Note=Pro residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=1219 |
| P02458 | Compositional bias | 1200 | 1217 | Note=Pro residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=1219 |
Gene structures of our canonical and alternative spliced genes of COL2A1
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
Expression levels of gene isoforms across GTEx.
Expression levels of gene isoforms across TCGA.
PDB and CIF files of the predicted protein structures
* Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the modelâs prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.
| 3D view using mol* of P02458-2 |
| 3D view using mol* of P02458-3 |
pLDDT score distribution of the predicted protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
| pLDDT distribution across the protein length of P02458-2 |
| pLDDT distribution across the protein length of P02458-3 |
Ramachandran plot of the torsional angles - phi (Ï)and psi (Ï) - of the residues (amino acids) contained in this protein peptide.
| Ramachandran plot of P02458-2 |
| Ramachandran plot of P02458-3 |
The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite.
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P02458-2 | 0.843 | 73 | 0.775 | 160.181 | 0.585 | 0.623 | 0.829 | 0.081 | 1.233 | 0.065 | 1.509 | 1327,1359,1360,1361,1362,1363,1364,1366,1367,1368, 1371,1372,1375,1376,1379,1416,1461,1463 |
| P02458-3 | 0.874 | 83 | 0.873 | 171.157 | 0.612 | 0.607 | 0.805 | 0.183 | 1.064 | 0.171 | 2.114 | 108,139,140,141,142,143,144,145,147,148,149,152,15 3,156,157,160,197,242,244 |
Protein Structure Comparision Using Template Modeling Scores (TM-score).
Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green)
| 3D view using mol* of P02458-2_P02458-2_5nir_A.pdb |
Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green)
| 3D view using mol* of P02458-2_5nir_A_P02458-3.pdb |
Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green)
| 3D view using mol* of P02458-2_P02458-3.pdb |
Protein Feature Comparison of the protein sequendary structures among the protiens.
| ./stats/secondary_structure/figure/P02458-2_vs_P02458-3.png |
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Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens.
| ./stats/relative_asa/P02458-2_vs_P02458-3.png |
| < |
Interactors from UniProt.
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
Interactors from STRING.
| Gene name | Interactors |
Drugs targeting this gene/protein.
(DrugBank)
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P02458 | COL2A1 | DB00048 | Collagenase clostridium histolyticum | approved, investigational | binder |
Previous studies relating to the alternative splicing of COL2A1 and disease information from the MeSH term (PubMed)
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| COL2A1 | 11812423 | A frame shift mutation in a tissue-specific alternatively spliced exon of collagen 2A1 in Wagner's vitreoretinal degeneration. | To describe the genetic basis of an autosomal dominant vitreoretinopathy in a large French-Canadian kindred. | D005128 | Eye Diseases |
| COL2A1 | 11812423 | A frame shift mutation in a tissue-specific alternatively spliced exon of collagen 2A1 in Wagner's vitreoretinal degeneration. | To describe the genetic basis of an autosomal dominant vitreoretinopathy in a large French-Canadian kindred. | D015785 | Eye Diseases, Hereditary |
| COL2A1 | 11812423 | A frame shift mutation in a tissue-specific alternatively spliced exon of collagen 2A1 in Wagner's vitreoretinal degeneration. | To describe the genetic basis of an autosomal dominant vitreoretinopathy in a large French-Canadian kindred. | D012162 | Retinal Degeneration |
| COL2A1 | 11812423 | A frame shift mutation in a tissue-specific alternatively spliced exon of collagen 2A1 in Wagner's vitreoretinal degeneration. | To describe the genetic basis of an autosomal dominant vitreoretinopathy in a large French-Canadian kindred. | D013577 | Syndrome |
| COL2A1 | 12939326 | Autosomal dominant rhegmatogenous retinal detachment associated with an Arg453Ter mutation in the COL2A1 gene. | To investigate the clinical features and molecular causes of autosomal dominant rhegmatogenous retinal detachment (RRD) in two large families. | D003240 | Connective Tissue Diseases |
| COL2A1 | 12939326 | Autosomal dominant rhegmatogenous retinal detachment associated with an Arg453Ter mutation in the COL2A1 gene. | To investigate the clinical features and molecular causes of autosomal dominant rhegmatogenous retinal detachment (RRD) in two large families. | D005128 | Eye Diseases |
| COL2A1 | 12939326 | Autosomal dominant rhegmatogenous retinal detachment associated with an Arg453Ter mutation in the COL2A1 gene. | To investigate the clinical features and molecular causes of autosomal dominant rhegmatogenous retinal detachment (RRD) in two large families. | D012162 | Retinal Degeneration |
| COL2A1 | 12939326 | Autosomal dominant rhegmatogenous retinal detachment associated with an Arg453Ter mutation in the COL2A1 gene. | To investigate the clinical features and molecular causes of autosomal dominant rhegmatogenous retinal detachment (RRD) in two large families. | D012163 | Retinal Detachment |
| COL2A1 | 12939326 | Autosomal dominant rhegmatogenous retinal detachment associated with an Arg453Ter mutation in the COL2A1 gene. | To investigate the clinical features and molecular causes of autosomal dominant rhegmatogenous retinal detachment (RRD) in two large families. | D012167 | Retinal Perforations |
| COL2A1 | 12939326 | Autosomal dominant rhegmatogenous retinal detachment associated with an Arg453Ter mutation in the COL2A1 gene. | To investigate the clinical features and molecular causes of autosomal dominant rhegmatogenous retinal detachment (RRD) in two large families. | D013577 | Syndrome |
| COL2A1 | 17721977 | Missense and nonsense mutations in the alternatively-spliced exon 2 of COL2A1 cause the ocular variant of Stickler syndrome. | Stickler syndrome type I (STL1) is a phenotypically heterogeneous disorder characterized by ocular and extraocular features. It is caused by null-allele mutations in the COL2A1 gene that codes for procollagen II. COL2A1 precursor mRNA undergoes alternative splicing, resulting in two isoforms, a long form including exon 2 (type IIA isoform) and a short form excluding exon 2 (type IIB isoform). The short form is predominantly expressed by differentiated chondrocytes in adult cartilage, and the long form in chondroprogenitor cells during early development and in the vitreous of the eye, which is the only adult tissue containing procollagen IIA. Recent evidence indicates that due to the tissue-specific expression of these two isoforms, premature termination codon mutations in exon 2 cause Stickler syndrome with minimal or no extraocular manifestations. We describe here two mutations in exon 2 of COL2A1 in three patients with predominantly ocular Stickler syndrome: Cys64Stop in two patients, and a novel structural mutation, Cys57Tyr, in one patient. RT-PCR of total lymphoblast RNA from one patient with the Cys64Stop mutation revealed that only the normal allele of the IIA form was present, indicating that the mutation resulted either in complete loss of the allele by nonsense-mediated mRNA decay or by skipping of exon 2 via nonsense-mediated altered splicing, resulting in production of the type IIB isoform. The results of COL2A1 minigene expression studies suggest that both Cys64Stop and Cys57Tyr alter positive cis regulatory elements for splicing, resulting in a lower IIA:IIB ratio. | D003240 | Connective Tissue Diseases |
| COL2A1 | 17721977 | Missense and nonsense mutations in the alternatively-spliced exon 2 of COL2A1 cause the ocular variant of Stickler syndrome. | Stickler syndrome type I (STL1) is a phenotypically heterogeneous disorder characterized by ocular and extraocular features. It is caused by null-allele mutations in the COL2A1 gene that codes for procollagen II. COL2A1 precursor mRNA undergoes alternative splicing, resulting in two isoforms, a long form including exon 2 (type IIA isoform) and a short form excluding exon 2 (type IIB isoform). The short form is predominantly expressed by differentiated chondrocytes in adult cartilage, and the long form in chondroprogenitor cells during early development and in the vitreous of the eye, which is the only adult tissue containing procollagen IIA. Recent evidence indicates that due to the tissue-specific expression of these two isoforms, premature termination codon mutations in exon 2 cause Stickler syndrome with minimal or no extraocular manifestations. We describe here two mutations in exon 2 of COL2A1 in three patients with predominantly ocular Stickler syndrome: Cys64Stop in two patients, and a novel structural mutation, Cys57Tyr, in one patient. RT-PCR of total lymphoblast RNA from one patient with the Cys64Stop mutation revealed that only the normal allele of the IIA form was present, indicating that the mutation resulted either in complete loss of the allele by nonsense-mediated mRNA decay or by skipping of exon 2 via nonsense-mediated altered splicing, resulting in production of the type IIB isoform. The results of COL2A1 minigene expression studies suggest that both Cys64Stop and Cys57Tyr alter positive cis regulatory elements for splicing, resulting in a lower IIA:IIB ratio. | D015785 | Eye Diseases, Hereditary |
| COL2A1 | 17721977 | Missense and nonsense mutations in the alternatively-spliced exon 2 of COL2A1 cause the ocular variant of Stickler syndrome. | Stickler syndrome type I (STL1) is a phenotypically heterogeneous disorder characterized by ocular and extraocular features. It is caused by null-allele mutations in the COL2A1 gene that codes for procollagen II. COL2A1 precursor mRNA undergoes alternative splicing, resulting in two isoforms, a long form including exon 2 (type IIA isoform) and a short form excluding exon 2 (type IIB isoform). The short form is predominantly expressed by differentiated chondrocytes in adult cartilage, and the long form in chondroprogenitor cells during early development and in the vitreous of the eye, which is the only adult tissue containing procollagen IIA. Recent evidence indicates that due to the tissue-specific expression of these two isoforms, premature termination codon mutations in exon 2 cause Stickler syndrome with minimal or no extraocular manifestations. We describe here two mutations in exon 2 of COL2A1 in three patients with predominantly ocular Stickler syndrome: Cys64Stop in two patients, and a novel structural mutation, Cys57Tyr, in one patient. RT-PCR of total lymphoblast RNA from one patient with the Cys64Stop mutation revealed that only the normal allele of the IIA form was present, indicating that the mutation resulted either in complete loss of the allele by nonsense-mediated mRNA decay or by skipping of exon 2 via nonsense-mediated altered splicing, resulting in production of the type IIB isoform. The results of COL2A1 minigene expression studies suggest that both Cys64Stop and Cys57Tyr alter positive cis regulatory elements for splicing, resulting in a lower IIA:IIB ratio. | D013577 | Syndrome |
(ClinVar, 04/20/2024)
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
| P02458 | P02458-2 | COL2A1 | Deletion | p.Gly822Valfs | Pathogenic |
| P02458 | P02458-2 | COL2A1 | Deletion | p.Gly822Valfs | Pathogenic |
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