COL3A1

collagen type III alpha 1 chain, the group of Collagens|MicroRNA protein coding host genes

Basic information

Region (hg38): 2:188974372-189012746

Previous symbols: [ "EDS4A" ]

Links

ENSG00000168542 ∙ NCBI:1281 ∙ OMIM:120180 ∙ HGNC:2201 ∙ Uniprot:P02461 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant Ehlers-Danlos syndrome, vascular type (Strong), mode of inheritance: AD
• polymicrogyria with or without vascular-type Ehlers-Danlos syndrome (Strong), mode of inheritance: AR
• autosomal dominant Ehlers-Danlos syndrome, vascular type (Strong), mode of inheritance: AD
• Ehlers-Danlos syndrome, vascular type (Supportive), mode of inheritance: AD
• autosomal dominant Ehlers-Danlos syndrome, vascular type (Strong), mode of inheritance: AD
• polymicrogyria with or without vascular-type Ehlers-Danlos syndrome (Strong), mode of inheritance: AR
• autosomal dominant Ehlers-Danlos syndrome, vascular type (Definitive), mode of inheritance: AD
• autosomal dominant Ehlers-Danlos syndrome, vascular type (Definitive), mode of inheritance: AD
• Ehlers-Danlos syndrome, vascular type (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ehlers-Danlos syndrome, vascular type; Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome	AD/AR	Cardiovascular; Obstetric	Individuals are at risk for manifestations such as bowel and arterial ruptures, as well as severe pregnancy-related complications in women, and surveillance (eg, arterial screening by CT or MRI) and early recognition may allow precautionary measures prompt recognition and treatment of manifestions, which may reduce morbidity and mortality	Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Obstetric	7230200; 6129381; 3204406; 3337712; 2321591; 2349939; 2243125; 1496983; 1352273; 1557695; 8317500; 7833919; 8526472; 10051163; 10928897; 10706896; 11577371; 12131463; 12786757; 15007000; 19455184; 20301667; 21637106; 22713205; 23052746; 23688910; 24922459; 25205403; 28258187; 28742248
Homozygous variants have been reported; An individual with EDS type III with a COL3A1 variant has been reported

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COL3A1 gene.

• Ehlers-Danlos syndrome, type 4 (1520 variants)
• Familial thoracic aortic aneurysm and aortic dissection (994 variants)
• not provided (633 variants)
• not specified (192 variants)
• Ehlers-Danlos syndrome (55 variants)
• Ehlers-Danlos syndrome, type 4;Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome (52 variants)
• Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome;Ehlers-Danlos syndrome, type 4 (38 variants)
• COL3A1-related condition (22 variants)
• Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome (22 variants)
• Connective tissue disorder (17 variants)
• Inborn genetic diseases (15 variants)
• Cardiovascular phenotype (14 variants)
• Familial aortopathy (10 variants)
• See cases (4 variants)
• Isolated thoracic aortic aneurysm (4 variants)
• Ehlers-Danlos syndrome, type 4;Ehlers-Danlos syndrome, type 3 (2 variants)
• Loeys-Dietz syndrome (2 variants)
• Hereditary spastic paraplegia 4 (1 variants)
• Abnormality of neuronal migration (1 variants)
• Aortic aneurysm (1 variants)
• Marfan syndrome (1 variants)
• Seizure;Connective tissue nevi (1 variants)
• COLLAGEN TYPE III POLYMORPHISM (1 variants)
• POLYMICROGYRIA WITHOUT VASCULAR-TYPE EHLERS-DANLOS SYNDROME (1 variants)
• Arterial dissection (1 variants)
• Ehlers-Danlos syndrome, type 3;Ehlers-Danlos syndrome, type 4 (1 variants)
• Disproportionate tall stature (1 variants)
• Congenital aneurysm of ascending aorta (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL3A1 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			13	355	6	374
missense	75	231	720	18	3	1047
nonsense	24	9				33
start loss			1			1
frameshift	33	9				42
inframe indel	1	8	6			15
splice donor/acceptor (+/-2bp)	25	42	4	1		72
splice region	5	9	71	106	6	197
non coding			49	278	113	440
Total	158	299	793	652	122

Highest pathogenic variant AF is 0.00000659

Variants in COL3A1

This is a list of pathogenic ClinVar variants found in the COL3A1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-188974389-G-A		Ehlers-Danlos syndrome, type 4	Uncertain significance (Jan 12, 2018)
2-188974410-G-A		Ehlers-Danlos syndrome, type 4	Benign/Likely benign (Aug 13, 2019)
2-188974480-A-G		Familial thoracic aortic aneurysm and aortic dissection • Ehlers-Danlos syndrome, type 4	Uncertain significance (Aug 15, 2023)
2-188974481-T-C		Ehlers-Danlos syndrome, type 4	Uncertain significance (May 04, 2023)
2-188974490-A-T		Ehlers-Danlos syndrome, type 4	Uncertain significance (Feb 15, 2020)
2-188974492-GA-G		Ehlers-Danlos syndrome, type 4	Pathogenic (Jun 23, 2023)
2-188974498-C-A		Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (Feb 02, 2022)
2-188974502-G-A		not specified • Ehlers-Danlos syndrome, type 4 • Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (Dec 13, 2023)
2-188974503-T-A		Ehlers-Danlos syndrome, type 4	Uncertain significance (Oct 11, 2023)
2-188974507-A-C		Ehlers-Danlos syndrome, type 4	Uncertain significance (Sep 20, 2022)
2-188974507-A-G		Ehlers-Danlos syndrome, type 4	Likely benign (Jul 26, 2022)
2-188974511-G-A		Ehlers-Danlos syndrome, type 4	Uncertain significance (Jun 20, 2022)
2-188974512-G-A		Ehlers-Danlos syndrome, type 4	Uncertain significance (Oct 02, 2023)
2-188974513-G-A		Ehlers-Danlos syndrome, type 4	Likely benign (Oct 01, 2023)
2-188974513-G-C		Ehlers-Danlos syndrome, type 4	Uncertain significance (Aug 15, 2023)
2-188974519-G-A		Ehlers-Danlos syndrome, type 4	Pathogenic (-)
2-188974519-G-C		Ehlers-Danlos syndrome, type 4	Uncertain significance (Mar 04, 2023)
2-188974525-T-G		Ehlers-Danlos syndrome, type 4	Likely benign (Apr 16, 2023)
2-188974527-T-C			Uncertain significance (Jun 10, 2019)
2-188974528-C-G		Ehlers-Danlos syndrome, type 4	Likely benign (Jul 22, 2021)
2-188974528-C-T		Familial thoracic aortic aneurysm and aortic dissection • Ehlers-Danlos syndrome, type 4	Likely benign (Dec 12, 2023)
2-188974529-G-A		Familial thoracic aortic aneurysm and aortic dissection • Ehlers-Danlos syndrome, type 4	Uncertain significance (Aug 15, 2023)
2-188974529-G-C		Ehlers-Danlos syndrome, type 4	Uncertain significance (Dec 01, 2023)
2-188974529-G-T		Familial thoracic aortic aneurysm and aortic dissection • Ehlers-Danlos syndrome, type 4	Uncertain significance (Jun 08, 2023)
2-188974530-C-G		Familial thoracic aortic aneurysm and aortic dissection • Ehlers-Danlos syndrome, type 4	Uncertain significance (Nov 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COL3A1	protein_coding	protein_coding	ENST00000304636	51	38427

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	8.00e-13	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.09	516	852	0.606	0.0000457	9134
Missense in Polyphen		43	102.97	0.41761		999
Synonymous	-0.956	300	280	1.07	0.0000158	3254
Loss of Function	8.59	4	93.7	0.0427	0.00000552	1049

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000583	0.0000583
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000328	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Collagen type III occurs in most soft connective tissues along with type I collagen. Involved in regulation of cortical development. Is the major ligand of ADGRG1 in the developing brain and binding to ADGRG1 inhibits neuronal migration and activates the RhoA pathway by coupling ADGRG1 to GNA13 and possibly GNA12.
• Disease: DISEASE: Ehlers-Danlos syndrome, vascular type (EDSVASC) [MIM:130050]: A severe form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. EDSVASC is an autosomal dominant disease characterized by joint and dermal manifestations as in other forms of the syndrome, and by proneness to spontaneous rupture of bowel and large arteries. The vascular complications may affect all anatomical areas. {ECO:0000269|PubMed:10706896, ECO:0000269|PubMed:10923041, ECO:0000269|PubMed:11168790, ECO:0000269|PubMed:12694234, ECO:0000269|PubMed:12786757, ECO:0000269|PubMed:1352273, ECO:0000269|PubMed:1357232, ECO:0000269|PubMed:1370809, ECO:0000269|PubMed:1496983, ECO:0000269|PubMed:1895316, ECO:0000269|PubMed:2243125, ECO:0000269|PubMed:2349939, ECO:0000269|PubMed:2492273, ECO:0000269|PubMed:2808425, ECO:0000269|PubMed:7749417, ECO:0000269|PubMed:7833919, ECO:0000269|PubMed:7912131, ECO:0000269|PubMed:8019562, ECO:0000269|PubMed:8098182, ECO:0000269|PubMed:8411057, ECO:0000269|PubMed:8514866, ECO:0000269|PubMed:8664902, ECO:0000269|PubMed:8680408, ECO:0000269|PubMed:8884076, ECO:0000269|PubMed:8990011, ECO:0000269|PubMed:9036918, ECO:0000269|PubMed:9147870, ECO:0000269|PubMed:9452103, ECO:0000269|Ref.46, ECO:0000269|Ref.51}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Platelet activation - 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);Platelet Aggregation Inhibitor Pathway, Pharmacodynamics;miR-targeted genes in epithelium - TarBase;miR-targeted genes in muscle cell - TarBase;miRNA targets in ECM and membrane receptors;Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;miR-509-3p alteration of YAP1-ECM axis;Protein alkylation leading to liver fibrosis;Inflammatory Response Pathway;Senescence and Autophagy in Cancer;Vesicle-mediated transport;Collagen chain trimerization;Collagen biosynthesis and modifying enzymes;Collagen formation;Extracellular matrix organization;Integrin;Binding and Uptake of Ligands by Scavenger Receptors;Scavenging by Class A Receptors;Beta1 integrin cell surface interactions;Syndecan-1-mediated signaling events;Endothelins;Integrins in angiogenesis (Consensus)

Recessive Scores

• pRec: 0.878

Intolerance Scores

• loftool: 0.0207
• rvis_EVS: -0.23
• rvis_percentile_EVS: 36.34

Haploinsufficiency Scores

• pHI: 0.997
• hipred: Y
• hipred_score: 0.748
• ghis: 0.636

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.841

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Col3a1
• 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); 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); liver/biliary system phenotype; respiratory system phenotype; immune system phenotype; muscle phenotype; digestive/alimentary 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); homeostasis/metabolism phenotype

Gene ontology

• Biological process: skeletal system development;cell-matrix adhesion;transforming growth factor beta receptor signaling pathway;integrin-mediated signaling pathway;heart development;response to radiation;response to mechanical stimulus;peptide cross-linking;cerebral cortex development;platelet activation;extracellular matrix organization;collagen fibril organization;response to cytokine;positive regulation of Rho protein signal transduction;wound healing;skin development;digestive tract development;regulation of immune response;negative regulation of immune response;aorta smooth muscle tissue morphogenesis;cellular response to amino acid stimulus;supramolecular fiber organization;negative regulation of neuron migration
• Cellular component: extracellular region;collagen type III trimer;extracellular space;endoplasmic reticulum lumen;extracellular matrix;collagen-containing extracellular matrix
• Molecular function: protease binding;integrin binding;extracellular matrix structural constituent;protein binding;extracellular matrix structural constituent conferring tensile strength;SMAD binding;metal ion binding;platelet-derived growth factor binding