COL1A2

collagen type I alpha 2 chain, the group of Collagens

Basic information

Region (hg38): 7:94394895-94431227

Previous symbols: [ "OI4" ]

Links

ENSG00000164692 ∙ NCBI:1278 ∙ OMIM:120160 ∙ HGNC:2198 ∙ Uniprot:P08123 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ehlers-danlos syndrome, arthrochalasia type, 2 (Strong), mode of inheritance: AD
• Ehlers-Danlos syndrome, cardiac valvular type (Strong), mode of inheritance: AR
• ehlers-danlos syndrome, arthrochalasia type, 2 (Strong), mode of inheritance: AD
• Ehlers-Danlos syndrome, cardiac valvular type (Strong), mode of inheritance: AR
• Ehlers-Danlos syndrome, arthrochalasia type (Supportive), mode of inheritance: AD
• osteogenesis imperfecta type 1 (Supportive), mode of inheritance: AD
• osteogenesis imperfecta type 2 (Supportive), mode of inheritance: AD
• osteogenesis imperfecta type 3 (Supportive), mode of inheritance: AD
• osteogenesis imperfecta type 4 (Supportive), mode of inheritance: AD
• Ehlers-Danlos syndrome, cardiac valvular type (Supportive), mode of inheritance: AR
• Ehlers-Danlos/osteogenesis imperfecta syndrome (Supportive), mode of inheritance: AD
• high bone mass osteogenesis imperfecta (Supportive), mode of inheritance: AD
• ehlers-danlos syndrome, arthrochalasia type, 2 (Definitive), mode of inheritance: AD
• combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 (Moderate), mode of inheritance: AD
• Ehlers-Danlos syndrome, cardiac valvular type (Definitive), mode of inheritance: AR
• Ehlers-Danlos syndrome, arthrochalasia type (Strong), mode of inheritance: AR
• osteogenesis imperfecta type 3 (Strong), mode of inheritance: AD
• ehlers-danlos syndrome, arthrochalasia type, 2 (Strong), mode of inheritance: AD
• osteogenesis imperfecta type 4 (Definitive), mode of inheritance: AD
• osteogenesis imperfecta type 2 (Definitive), mode of inheritance: AD
• osteogenesis imperfecta type 1 (Definitive), mode of inheritance: AD
• osteogenesis imperfecta type 3 (Definitive), mode of inheritance: AD
• Ehlers-Danlos syndrome, arthrochalasia type (Definitive), mode of inheritance: AD
• Ehlers-Danlos syndrome, cardiac valvular type (Definitive), mode of inheritance: AR
• combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2; Ehlers-Danlos syndrome, cardiac valvular form	AD/AR	Cardiovascular	Ehlers-Danlos syndrome, cardiac valvular form may be difficult to recognize, and cardiac manifestations, which can include arrhythmias may benefit from early (including surgical) interventions; Some individuals may also have arterial/vascular fragility, and awareness may allow appropriate precautions and prompt management of sequelae; In In Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1, cardiovascular manifestations (eg, aortic dilatation, vascular fragility) have been described, and awareness may allow surveillance and management	Audiologic/Otolaryngologic; Cardiovascular; Dermatologic; Musculoskeletal; Ophthalmologic	4742738; 6773953; 3940669; 2952379; 3621666; 3680255; 2454224; 2897363; 2777808; 1712342; 1301191; 1577745; 7916744; 8071956; 8950681; 9386671; 9295084; 9099837; 9753709; 10843163; 11760017; 11970931; 12417561; 12417568; 12629073; 12728084; 15241796; 15077201; 16778601; 16816023; 16434452; 17217883; 18996919; 19208385; 20087402; 21667357; 22206639; 22791419; 22795120; 23118688; 23692737

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COL1A2 gene.

• Osteogenesis imperfecta type I;Ehlers-Danlos syndrome, classic type, 1 (105 variants)
• not provided (88 variants)
• Ehlers-Danlos syndrome, classic type, 1;Osteogenesis imperfecta type I (79 variants)
• Osteogenesis imperfecta, perinatal lethal (16 variants)
• Osteogenesis imperfecta (12 variants)
• Osteogenesis imperfecta with normal sclerae, dominant form (11 variants)
• Osteogenesis imperfecta type I (9 variants)
• Ehlers-danlos syndrome, arthrochalasia type, 2 (6 variants)
• Osteogenesis imperfecta type III (4 variants)
• COL1A2-related disorder (3 variants)
• Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 (3 variants)
• Osteogenesis imperfecta type I;Ehlers-Danlos syndrome, classic type (3 variants)
• 7 conditions (2 variants)
• Inborn genetic diseases (2 variants)
• Dentinogenesis imperfecta (2 variants)
• 6 conditions (2 variants)
• Ehlers-Danlos syndrome, cardiac valvular type (1 variants)
• Postmenopausal osteoporosis (1 variants)
• See cases (1 variants)
• Ehlers-Danlos syndrome, classic type (1 variants)
• Ehlers-Danlos syndrome, classic type;Osteogenesis imperfecta type I (1 variants)
• Ehlers-Danlos syndrome (1 variants)
• Multiple prenatal fractures;Skeletal dysplasia (1 variants)
• Osteogenesis imperfecta, mild (1 variants)
• Increased susceptibility to fractures (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL1A2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			19	293	5	317
missense	203	191	490	15	2	901
nonsense	3	3	3			9
start loss			1			1
frameshift	13	10	3			26
inframe indel	4	11	14			29
splice donor/acceptor (+/-2bp)	29	26				55
splice region	11	3	64	79	7	164
non coding			26	262	88	376
Total	252	241	556	570	95

Highest pathogenic variant AF is 0.0000263

Variants in COL1A2

This is a list of pathogenic ClinVar variants found in the COL1A2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-94394945-C-T		Osteogenesis imperfecta • Ehlers-danlos syndrome, arthrochalasia type, 2	Uncertain significance (Jan 13, 2018)
7-94395027-T-C			Likely benign (Apr 01, 2023)
7-94395032-A-T		Osteogenesis imperfecta type I;Ehlers-Danlos syndrome, classic type, 1	Uncertain significance (Jun 12, 2023)
7-94395053-C-T		Osteogenesis imperfecta type I;Ehlers-Danlos syndrome, classic type, 1	Uncertain significance (Dec 18, 2022)
7-94395060-T-G		Osteogenesis imperfecta type I;Ehlers-Danlos syndrome, classic type, 1	Uncertain significance (Dec 30, 2023)
7-94395063-T-C		Osteogenesis imperfecta type I;Ehlers-Danlos syndrome, classic type, 1	Uncertain significance (Apr 12, 2022)
7-94395067-G-C		Ehlers-Danlos syndrome, classic type, 1;Osteogenesis imperfecta type I	Likely benign (Dec 22, 2018)
7-94395079-C-T		Connective tissue disorder • Ehlers-danlos syndrome, arthrochalasia type, 2 • Osteogenesis imperfecta • Osteogenesis imperfecta type I;Ehlers-Danlos syndrome, classic type, 1 • Cardiovascular phenotype	Benign/Likely benign (Sep 03, 2023)
7-94395083-T-C		6 conditions • Osteogenesis imperfecta type I;Ehlers-Danlos syndrome, classic type, 1	Uncertain significance (Sep 27, 2023)
7-94395083-T-G		Osteogenesis imperfecta type I;Ehlers-Danlos syndrome, classic type, 1 • COL1A2-related disorder	Benign (Feb 23, 2023)
7-94395088-A-G		Cardiovascular phenotype	Likely benign (Apr 26, 2019)
7-94395089-G-A		Osteogenesis imperfecta type I;Ehlers-Danlos syndrome, classic type, 1	Uncertain significance (May 23, 2023)
7-94395091-A-C		Osteogenesis imperfecta type I;Ehlers-Danlos syndrome, classic type, 1 • Cardiovascular phenotype	Likely benign (Nov 01, 2022)
7-94395098-C-T		Osteogenesis imperfecta with normal sclerae, dominant form;Ehlers-danlos syndrome, arthrochalasia type, 2;Osteogenesis imperfecta, perinatal lethal;Ehlers-Danlos syndrome, cardiac valvular type;Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2	not provided (-)
7-94395100-A-G		Ehlers-Danlos syndrome, classic type, 1;Osteogenesis imperfecta type I • Cardiovascular phenotype	Conflicting classifications of pathogenicity (Dec 19, 2023)
7-94395109-C-A		Ehlers-Danlos syndrome, classic type, 1;Osteogenesis imperfecta type I	Likely benign (Oct 15, 2023)
7-94395109-C-T		Osteogenesis imperfecta type I;Ehlers-Danlos syndrome, classic type, 1	Likely benign (Jul 12, 2022)
7-94395110-C-T		not specified	Likely benign (Nov 15, 2023)
7-94395119-G-A		Osteogenesis imperfecta type I;Ehlers-Danlos syndrome, classic type, 1	Likely benign (Aug 28, 2023)
7-94395619-A-G			Benign (Aug 30, 2018)
7-94395760-G-T			Likely benign (Aug 12, 2018)
7-94395775-A-G			Likely benign (Jun 14, 2018)
7-94395818-A-G		Ehlers-Danlos syndrome, cardiac valvular type	Pathogenic (May 01, 2004)
7-94395819-TAA-T			Benign/Likely benign (Jul 21, 2021)
7-94395905-T-C			Likely benign (Jun 14, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COL1A2	protein_coding	protein_coding	ENST00000297268	52	36672

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000124	125700	1	47	125748	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.15	641	813	0.788	0.0000474	8521
Missense in Polyphen		32	62.385	0.51294		621
Synonymous	-1.44	297	267	1.11	0.0000160	3088
Loss of Function	7.22	9	77.6	0.116	0.00000401	939

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000261	0.000261
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000830	0.0000791
Middle Eastern	0.000109	0.000109
South Asian	0.000882	0.000850
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Type I collagen is a member of group I collagen (fibrillar forming collagen).
• Disease: DISEASE: 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. {ECO:0000269|PubMed:1577745, ECO:0000269|PubMed:2394758, ECO:0000269|PubMed:3680255}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Osteogenesis imperfecta 1 (OI1) [MIM:166200]: An autosomal dominant form of osteogenesis imperfecta, a connective tissue disorder 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. OI1 is a non-deforming form with normal height or mild short stature, and no dentinogenesis imperfecta. {ECO:0000269|PubMed:16705691, ECO:0000269|PubMed:16786509, ECO:0000269|PubMed:1990009, ECO:0000269|PubMed:8456807, ECO:0000269|PubMed:8829649}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Osteogenesis imperfecta 2 (OI2) [MIM:166210]: An autosomal dominant form of osteogenesis imperfecta, a connective tissue disorder 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. {ECO:0000269|PubMed:10627137, ECO:0000269|PubMed:1284475, ECO:0000269|PubMed:1339453, ECO:0000269|PubMed:1385413, ECO:0000269|PubMed:16786509, ECO:0000269|PubMed:16879195, ECO:0000269|PubMed:1874719, ECO:0000269|PubMed:18996919, ECO:0000269|PubMed:2777764, ECO:0000269|PubMed:2914942, ECO:0000269|PubMed:7693712, ECO:0000269|PubMed:7891382, ECO:0000269|PubMed:7906591, ECO:0000269|PubMed:7959683, ECO:0000269|PubMed:8182080, ECO:0000269|Ref.34}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:16816023}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Osteogenesis imperfecta 3 (OI3) [MIM:259420]: An autosomal dominant form of osteogenesis imperfecta, a connective tissue disorder 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. {ECO:0000269|PubMed:10408781, ECO:0000269|PubMed:16786509, ECO:0000269|PubMed:16879195, ECO:0000269|PubMed:1990009, ECO:0000269|PubMed:7520724, ECO:0000269|PubMed:7720740, ECO:0000269|PubMed:7749416, ECO:0000269|PubMed:7860070, ECO:0000269|PubMed:7881420, ECO:0000269|PubMed:8081394, ECO:0000269|PubMed:8444468, ECO:0000269|PubMed:8456807, ECO:0000269|PubMed:8723681, ECO:0000269|PubMed:8800927, ECO:0000269|PubMed:8829649}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Osteogenesis imperfecta 4 (OI4) [MIM:166220]: An autosomal dominant form of osteogenesis imperfecta, a connective tissue disorder 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. {ECO:0000269|PubMed:1642148, ECO:0000269|PubMed:16786509, ECO:0000269|PubMed:16879195, ECO:0000269|PubMed:2052622, ECO:0000269|PubMed:2064612, ECO:0000269|PubMed:2897363, ECO:0000269|PubMed:7693712, ECO:0000269|PubMed:8094076, ECO:0000269|PubMed:8401517, ECO:0000269|PubMed:8800927}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=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.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Platelet activation - Homo sapiens (human);ECM-receptor interaction - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Protein digestion and absorption - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Platelet Aggregation Inhibitor Pathway, Pharmacodynamics;miR-targeted genes in muscle cell - TarBase;miRNA targets in ECM and membrane receptors;Focal Adhesion;TGF-beta Signaling Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Protein alkylation leading to liver fibrosis;Interleukin-4 and 13 signaling;PI3K-Akt Signaling Pathway;Inflammatory Response Pathway;Vesicle-mediated transport;Collagen chain trimerization;Collagen biosynthesis and modifying enzymes;Collagen formation;Extracellular matrix organization;Beta3 integrin cell surface interactions;Integrin;VEGFR3 signaling in lymphatic endothelium;C-MYB transcription factor network;Binding and Uptake of Ligands by Scavenger Receptors;Scavenging by Class A Receptors;Validated targets of C-MYC transcriptional repression;Beta1 integrin cell surface interactions;AP-1 transcription factor network;Syndecan-1-mediated signaling events;IL4-mediated signaling events;Validated transcriptional targets of AP1 family members Fra1 and Fra2;Regulation of nuclear SMAD2/3 signaling;Endothelins;Integrins in angiogenesis (Consensus)

Intolerance Scores

• loftool: 0.00710
• rvis_EVS: -1.14
• rvis_percentile_EVS: 6.36

Haploinsufficiency Scores

• pHI: 0.999
• hipred: Y
• hipred_score: 0.822
• ghis: 0.640

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.170

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Col1a2
• Phenotype: homeostasis/metabolism phenotype; muscle phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); skeleton phenotype; limbs/digits/tail phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: col1a2
• Affected structure: vertebra
• Phenotype tag: abnormal
• Phenotype quality: deformed

Gene ontology

• Biological process: skeletal system development;blood vessel development;transforming growth factor beta receptor signaling pathway;Rho protein signal transduction;blood coagulation;regulation of blood pressure;cytokine-mediated signaling pathway;platelet activation;extracellular matrix organization;collagen fibril organization;odontogenesis;skin morphogenesis;regulation of immune response;leukocyte migration;protein heterotrimerization;cellular response to amino acid stimulus
• Cellular component: extracellular region;collagen type I trimer;extracellular space;endoplasmic reticulum;endoplasmic reticulum lumen;extracellular matrix;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: protease binding;extracellular matrix structural constituent;protein binding;extracellular matrix structural constituent conferring tensile strength;protein binding, bridging;identical protein binding;SMAD binding;metal ion binding;platelet-derived growth factor binding