Description: Homo sapiens collagen, type II, alpha 1 (COL2A1), transcript variant 1, mRNA. RefSeq Summary (NM_001844): This gene encodes the alpha-1 chain of type II collagen, a fibrillar collagen found in cartilage and the vitreous humor of the eye. Mutations in this gene are associated with achondrogenesis, chondrodysplasia, early onset familial osteoarthritis, SED congenita, Langer-Saldino achondrogenesis, Kniest dysplasia, Stickler syndrome type I, and spondyloepimetaphyseal dysplasia Strudwick type. In addition, defects in processing chondrocalcin, a calcium binding protein that is the C-propeptide of this collagen molecule, are also associated with chondrodysplasia. There are two transcripts identified for this gene. [provided by RefSeq, Jul 2008]. Transcript (Including UTRs) Position: hg19 chr12:48,366,748-48,398,285 Size: 31,538 Total Exon Count: 54 Strand: - Coding Region Position: hg19 chr12:48,367,190-48,398,104 Size: 30,915 Coding Exon Count: 54
ID:CO2A1_HUMAN DESCRIPTION: RecName: Full=Collagen alpha-1(II) chain; AltName: Full=Alpha-1 type II collagen; Contains: RecName: Full=Collagen alpha-1(II) chain; Contains: RecName: Full=Chondrocalcin; Flags: Precursor; FUNCTION: Type II collagen is specific for cartilaginous tissues. It is essential for the normal embryonic development of the skeleton, for linear growth and for the ability of cartilage to resist compressive forces. SUBUNIT: Homotrimers of alpha 1(II) chains. SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix (By similarity). TISSUE SPECIFICITY: Isoform 2 is highly expressed in juvenile chondrocyte and low in fetal chondrocyte. DOMAIN: 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 (By similarity). PTM: Probably 3-hydroxylated on prolines by LEPREL1 (By similarity). Proline residues at the third position of the tripeptide repeating unit (G-X-P) are hydroxylated in some or all of the chains. Proline residues at the second position of the tripeptide repeating unit (G-P-X) are hydroxylated in some of the chains. PTM: The N-telopeptide is covalently linked to the helical COL2 region of alpha 1(IX), alpha 2(IX) and alpha 3(IX) chain. The C- telopeptide is covalently linked to an another site in the helical region of alpha 3(IX) COL2. DISEASE: Defects in COL2A1 are the cause of spondyloepiphyseal dysplasia congenital type (SEDC) [MIM:183900]. This disorder is characterized by disproportionate short stature and pleiotropic involvement of the skeletal and ocular systems. DISEASE: Defects in COL2A1 are the cause of spondyloepimetaphyseal dysplasia Strudwick type (SEMD-STR) [MIM:184250]. A bone disease characterized by disproportionate short stature from birth, with a very short trunk and shortened limbs, and skeletal abnormalities including lordosis, scoliosis, flattened vertebrae, pectus carinatum, coxa vara, clubfoot, and abnormal epiphyses or metaphyses. A distinctive radiographic feature is irregular sclerotic changes, described as dappled in the metaphyses of the long bones. DISEASE: Defects in COL2A1 are the cause of achondrogenesis type 2 (ACG2) [MIM:200610]; also known as achondrogenesis- hypochondrogenesis type II. ACG2 is a disease characterized by the absence of ossification in the vertebral column, sacrum and pubic bones. DISEASE: Defects in COL2A1 are the cause of Legg-Calve-Perthes disease (LCPD) [MIM:150600]; also known as Legg-Perthes disease or Perthes disease. LCPD is characterized by loss of circulation to the femoral head, resulting in avascular necrosis in a growing child. Clinical pictures of the disease vary, depending on the phase of disease progression through ischemia, revascularization, fracture and collapse, and repair and remodeling of the bone. DISEASE: Defects in COL2A1 are the cause of Kniest dysplasia (KD) [MIM:156550]; also known as Kniest syndrome or metatropic dwarfism type II. KD is a moderately severe chondrodysplasia phenotype that results from mutations in the COL2A1 gene. Characteristics of the disorder include a short trunk and extremities, mid-face hypoplasia, cleft palate, myopia, retinal detachment, and hearing loss. DISEASE: Defects in COL2A1 are a cause of primary avascular necrosis of femoral head (ANFH) [MIM:608805]; also known as ischemic necrosis of the femoral head or osteonecrosis of the femoral head. ANFH causes disability that often requires surgical intervention. Most cases are sporadic, but families in which there is an autosomal dominant inheritance of the disease have been identified. It has been estimated that 300,000 to 600,000 people in the United States have ANFH. Approximately 15,000 new cases of this common and disabling disorder are reported annually. The age at the onset is earlier than that for osteoarthritis. The diagnosis is typically made when patients are between the ages of 30 and 60 years. The clinical manifestations, such as pain on exertion, a limping gait, and a discrepancy in leg length, cause considerable disability. Moreover, nearly 10 percent of the 500,000 total-hip arthroplasties performed each year in the United States involve patients with ANFH. As a result, this disease creates a substantial socioeconomic cost as well as a burden for patients and their families. DISEASE: Defects in COL2A1 are the cause of osteoarthritis with mild chondrodysplasia (OACD) [MIM:604864]. Osteoarthritis is a common disease that produces joint pain and stiffness together with radiologic evidence of progressive degeneration of joint cartilage. Some forms of osteoarthritis are secondary to events such as trauma, infections, metabolic disorders, or congenital or heritable conditions that deform the epiphyses or related structures. In most patients, however, there is no readily identifiable cause of osteoarthritis. Inheritance in a Mendelian dominant manner has been demonstrated in some families with primary generalized osteoarthritis. Reports demonstrate coinheritance of primary generalized osteoarthritis with specific alleles of the gene COL2A1, the precursor of the major protein of cartilage. DISEASE: Defects in COL2A1 are the cause of platyspondylic lethal skeletal dysplasia Torrance type (PLSD-T) [MIM:151210]. Platyspondylic lethal skeletal dysplasias (PLSDs) are a heterogeneous group of chondrodysplasias characterized by severe platyspondyly and limb shortening. PLSD-T is characterized by varying platyspondyly, short ribs with anterior cupping, hypoplasia of the lower ilia with broad ischial and pubic bones, and shortening of the tubular bones with splayed and cupped metaphyses. Histology of the growth plate typically shows focal hypercellularity with slightly enlarged chondrocytes in the resting cartilage and relatively well-preserved columnar formation and ossification at the chondro-osseous junction. PLSD-T is generally a perinatally lethal disease, but a few long-term survivors have been reported. DISEASE: Defects in COL2A1 are the cause of multiple epiphyseal dysplasia with myopia and conductive deafness (EDMMD) [MIM:132450]. Multiple epiphyseal dysplasia is a generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. EDMMD is an autosomal dominant disorder characterized by epiphyseal dysplasia associated with progressive myopia, retinal thinning, crenated cataracts, conductive deafness. DISEASE: Defects in COL2A1 are the cause of spondyloperipheral dysplasia (SPD) [MIM:271700]. SPD patients manifest short stature, midface hypoplasia, sensorineural hearing loss, spondyloepiphyseal dysplasia, platyspondyly and brachydactyly. DISEASE: Defects in COL2A1 are the cause of Stickler syndrome type 1 (STL1) [MIM:108300]; also known as vitreous type 1, or membranous vitreous type. STL1 is an autosomal dominant form of Stickler syndrome, an inherited disorder that associates ocular signs with more or less complete forms of Pierre Robin sequence, bone disorders and sensorineural deafness. Ocular disorders may include juvenile cataract, myopia, strabismus, vitreoretinal or chorioretinal degeneration, retinal detachment, and chronic uveitis. Robin sequence includes an opening in the roof of the mouth (a cleft palate), a large tongue (macroglossia), and a small lower jaw (micrognathia). Bones are affected by slight platyspondylisis and large, often defective epiphyses. Juvenile joint laxity is followed by early signs of arthrosis. The degree of hearing loss varies among affected individuals and may become more severe over time. Syndrome expressivity is variable. DISEASE: Defects in COL2A1 are the cause of Stickler syndrome type 1 non-syndromic ocular (STL1O) [MIM:609508]. STL1O is an autosomal dominant form of Stickler syndrome characterized by the ocular signs typically seen in STL1 such as cataract, myopia, retinal detachment. STL1 systemic features of premature osteoarthritis, cleft palate, hearing impairment, and craniofacial abnormalities are either absent or very mild in STL1O patients. DISEASE: Defects in COL2A1 are a cause of rhegmatogenous retinal detachment autosomal dominant (DRRD) [MIM:609508]. Rhegmatogenous retinal detachment most frequently results from a break or tear in the retina that allows fluid from the vitreous humor to enter the potential space beneath the retina. It is often associated with pathologic myopia and in most cases leads to visual impairment or blindness if untreated. DISEASE: Defects in COL2A1 are the cause of Czech dysplasia (CZECHD) [MIM:609162]. A skeletal dysplasia characterized by early-onset, progressive pseudorheumatoid arthritis, platyspondyly, and short third and fourth toes. SIMILARITY: Belongs to the fibrillar collagen family. SIMILARITY: Contains 1 fibrillar collagen NC1 domain. SIMILARITY: Contains 1 VWFC domain. SEQUENCE CAUTION: Sequence=AAH07252.1; Type=Frameshift; Positions=1198; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/COL2A1";
Familial spondyloepiphyseal dysplasia tarda, brachydactyly, and precocious osteoarthritis Reginato AJ et al. 1994, Familial spondyloepiphyseal dysplasia tarda brachydactyly and precocious osteoarthritis associated with an arginine 75-->cysteine mutation in the procollagen type II gene in a kindred of Chiloe Islanders. I. Clinical radiographic and pathologic findin, Arthritis and rheumatism. 1994 Jul;37(7):1078-86.
[PubMed 8024616]
Osteoarthritis Granchi D 2004, Association of two gene polymorphisms with osteoarthritis secondary to hip dysplasia., Clinical orthopaedics and related research. 2002 Oct;(403):108-17.
[PubMed 12360016]
These results indicate that genetic markers could contribute to the understanding of the natural history of this disease.
osteoarthritis Valdes, A. M. et al. 2006, Sex and ethnic differences in the association of ASPN, CALM1, COL2A1, COMP, and FRZB with genetic susceptibility to osteoarthritis of the knee, Arthritis Rheum 2006 56(1) 137-146.
[PubMed 17195216]
Our results indicate that genetic polymorphisms affecting knee OA vary between populations (Japanese versus Caucasian) and sexes and indicate a role for ASPN, COMP, FRZB, and COL2A1 in Caucasians.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P02458
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0005201 extracellular matrix structural constituent GO:0030020 extracellular matrix structural constituent conferring tensile strength GO:0042289 MHC class II protein binding GO:0042802 identical protein binding GO:0046872 metal ion binding GO:0048407 platelet-derived growth factor binding
Biological Process: GO:0001501 skeletal system development GO:0001502 cartilage condensation GO:0001503 ossification GO:0001894 tissue homeostasis GO:0001958 endochondral ossification GO:0002062 chondrocyte differentiation GO:0003007 heart morphogenesis GO:0006029 proteoglycan metabolic process GO:0007417 central nervous system development GO:0007601 visual perception GO:0007605 sensory perception of sound GO:0010468 regulation of gene expression GO:0030198 extracellular matrix organization GO:0030199 collagen fibril organization GO:0030903 notochord development GO:0035108 limb morphogenesis GO:0042472 inner ear morphogenesis GO:0048705 skeletal system morphogenesis GO:0048839 inner ear development GO:0050776 regulation of immune response GO:0051216 cartilage development GO:0060021 palate development GO:0060174 limb bud formation GO:0060272 embryonic skeletal joint morphogenesis GO:0060348 bone development GO:0060351 cartilage development involved in endochondral bone morphogenesis GO:0071599 otic vesicle development GO:0071773 cellular response to BMP stimulus GO:0097065 anterior head development GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand