COL5A1

collagen type V alpha 1 chain, the group of Collagens

Basic information

Region (hg38): 9:134641802-134844843

Links

ENSG00000130635 ∙ NCBI:1289 ∙ OMIM:120215 ∙ HGNC:2209 ∙ Uniprot:P20908 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Ehlers-Danlos syndrome, classic type (Strong), mode of inheritance: AD
• Ehlers-Danlos syndrome, classic type (Strong), mode of inheritance: AD
• Ehlers-Danlos syndrome, classic type (Definitive), mode of inheritance: AD
• Ehlers-Danlos syndrome, classic type (Supportive), mode of inheritance: AD
• arterial disorder (Limited), mode of inheritance: AD
• Ehlers-Danlos syndrome, classic type, 1 (Strong), mode of inheritance: AD
• Ehlers-Danlos syndrome, classic type (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ehlers-Danlos syndrome, classic type, 1	AD	Cardiovascular; Obstetric	Individuals with Ehlers-Danlos syndrome may have aortic root dilatation, but the natural history is unclear, and may not typically progress, though yearly surveillance with echocardiogram when aortic dilatation or mitral valve prolapse is peresent has been recommended; Precautions in pregnancy may be beneficial; Individuals with Fibromuscular dysplasia may have vascular complications, including aneurysms, and early diagnosis may provide early management	Audiologic/Otolaryngologic; Cardiovascular; Dermatologic; Musculoskeletal; Obstetric; Ophthalmologic	8541855; 8923000; 9042913; 10602121; 10777716; 11992482; 12180144; 15264295; 15580559; 18972565; 20635400; 20847697; 20301422; 21611149; 22696272; 32938213
Homozygous variants have been reported

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COL5A1 gene.

• Ehlers-Danlos syndrome, classic type, 1 (2050 variants)
• not provided (1221 variants)
• Familial thoracic aortic aneurysm and aortic dissection (554 variants)
• not specified (373 variants)
• Ehlers-Danlos syndrome, classic type (197 variants)
• Fibromuscular dysplasia, multifocal (185 variants)
• Ehlers-Danlos syndrome type 7A (172 variants)
• Ehlers-Danlos syndrome (124 variants)
• Ehlers-Danlos syndrome, classic type, 1;Fibromuscular dysplasia, multifocal (45 variants)
• Connective tissue disorder (37 variants)
• COL5A1-related condition (18 variants)
• Ehlers-Danlos syndrome, classic type, 2 (11 variants)
• Fibromuscular dysplasia, multifocal;Ehlers-Danlos syndrome, classic type, 1 (8 variants)
• Inborn genetic diseases (6 variants)
• See cases (4 variants)
• Ehlers-Danlos syndrome, classic type, 2;Ehlers-Danlos syndrome, classic type, 1 (3 variants)
• Marfan syndrome (2 variants)
• Abnormal bleeding (2 variants)
• 6 conditions (2 variants)
• Ehlers-Danlos syndrome, classic type, 1;Ehlers-Danlos syndrome, classic type (1 variants)
• Familial thoracic aortic aneurysm and aortic dissection;Aortic valve disease 1 (1 variants)
• Ehlers-Danlos syndrome, classic type;Ehlers-Danlos syndrome, classic type, 2 (1 variants)
• Confusion (1 variants)
• Dural ectasia;Venous malformation;Abnormal digit morphology;Hypertelorism (1 variants)
• Abnormal bleeding;Thrombocytopenia (1 variants)
• Stroke disorder (1 variants)
• 10 conditions (1 variants)
• Brugada syndrome (1 variants)
• 13 conditions (1 variants)
• Aortic root aneurysm (1 variants)
• Loeys-Dietz syndrome (1 variants)
• Hyperextensible skin;Cigarette-paper scars;Atrophic scars;Large joint dislocations;Joint hypermobility (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL5A1 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			20	475	24	519
missense	6	20	610	75	66	777
nonsense	44	10				54
start loss	3					3
frameshift	99	19	3			121
inframe indel	3	2	24			29
splice donor/acceptor (+/-2bp)	9	36		1		46
splice region	4	2	86	108	5	205
non coding	1	2	58	535	310	906
Total	165	89	715	1086	400

Highest pathogenic variant AF is 0.00000712

Variants in COL5A1

This is a list of pathogenic ClinVar variants found in the COL5A1 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-134641806-C-G		Ehlers-Danlos syndrome type 7A • Ehlers-Danlos syndrome, classic type • Ehlers-Danlos syndrome, classic type, 1 • Fibromuscular dysplasia, multifocal	Benign/Likely benign (Mar 15, 2022)
9-134641824-G-C		Ehlers-Danlos syndrome type 7A • Ehlers-Danlos syndrome, classic type, 1;Fibromuscular dysplasia, multifocal	Uncertain significance (Feb 18, 2022)
9-134641831-G-T		Ehlers-Danlos syndrome type 7A	Uncertain significance (Jun 14, 2016)
9-134641901-G-C		Ehlers-Danlos syndrome type 7A	Uncertain significance (Jun 14, 2016)
9-134641909-T-TGGA		Ehlers-Danlos syndrome type 7A	Uncertain significance (Jun 14, 2016)
9-134641939-G-A			Likely benign (Sep 20, 2019)
9-134641941-T-G		Ehlers-Danlos syndrome type 7A • Ehlers-Danlos syndrome, classic type, 1 • Fibromuscular dysplasia, multifocal	Benign (Mar 15, 2022)
9-134641989-C-T		Ehlers-Danlos syndrome, classic type	Benign (Jan 13, 2018)
9-134642008-C-A			Likely benign (Jun 26, 2018)
9-134642049-G-T		Ehlers-Danlos syndrome type 7A	Uncertain significance (Jun 14, 2016)
9-134642078-A-G		Ehlers-Danlos syndrome type 7A • Ehlers-Danlos syndrome, classic type • Ehlers-Danlos syndrome, classic type, 1 • Fibromuscular dysplasia, multifocal	Benign/Likely benign (Mar 15, 2022)
9-134642151-G-A		not specified • Ehlers-Danlos syndrome type 7A • Ehlers-Danlos syndrome, classic type • Ehlers-Danlos syndrome, classic type, 1 • Fibromuscular dysplasia, multifocal	Benign/Likely benign (Nov 11, 2023)
9-134642152-AGCGCCCCTGTGCGCCCCGGCCC-A		not specified	Likely benign (Sep 12, 2017)
9-134642155-G-T		not specified	Likely benign (Aug 04, 2016)
9-134642171-G-A		not specified	Likely benign (Feb 09, 2017)
9-134642173-C-A		not specified	Benign (Oct 29, 2023)
9-134642174-C-T		not specified	Likely benign (Aug 01, 2017)
9-134642184-C-G		Ehlers-Danlos syndrome, classic type • Fibromuscular dysplasia, multifocal • Ehlers-Danlos syndrome, classic type, 1 • Familial thoracic aortic aneurysm and aortic dissection	Benign/Likely benign (May 30, 2023)
9-134642187-C-A		Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (Dec 14, 2022)
9-134642188-A-G		Ehlers-Danlos syndrome, classic type, 1	Pathogenic (Oct 14, 2021)
9-134642189-T-G		Ehlers-Danlos syndrome, classic type, 1	Pathogenic (Nov 26, 2022)
9-134642190-G-T		Ehlers-Danlos syndrome, classic type, 1	Pathogenic (May 30, 2023)
9-134642193-C-G			Uncertain significance (Oct 04, 2017)
9-134642194-G-T		Ehlers-Danlos syndrome, classic type, 1	Uncertain significance (Mar 28, 2022)
9-134642196-C-A		not specified	Likely benign (Nov 13, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COL5A1	protein_coding	protein_coding	ENST00000371817	66	203067

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.15e-17	125729	0	3	125732	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.07	937	1.13e+3	0.827	0.0000747	11580
Missense in Polyphen		245	290.03	0.84473		2969
Synonymous	-1.82	526	476	1.11	0.0000387	3909
Loss of Function	9.75	2	115	0.0174	0.00000578	1322

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Type V collagen is a member of group I collagen (fibrillar forming collagen). It is a minor connective tissue component of nearly ubiquitous distribution. Type V collagen binds to DNA, heparan sulfate, thrombospondin, heparin, and insulin.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:10602121, ECO:0000269|PubMed:11992482, ECO:0000269|PubMed:15580559, ECO:0000269|PubMed:18972565, ECO:0000269|PubMed:9042913}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Protein digestion and absorption - Homo sapiens (human);Allograft Rejection;miRNA targets in ECM and membrane receptors;Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;miR-509-3p alteration of YAP1-ECM axis;Collagen chain trimerization;Collagen biosynthesis and modifying enzymes;Collagen formation;Extracellular matrix organization;Integrin;Validated transcriptional targets of deltaNp63 isoforms;Beta1 integrin cell surface interactions;Syndecan-1-mediated signaling events;Integrins in angiogenesis (Consensus)

Intolerance Scores

• loftool: 0.0114
• rvis_EVS: -3.01
• rvis_percentile_EVS: 0.52

Haploinsufficiency Scores

• pHI: 0.693
• hipred: Y
• hipred_score: 0.853
• ghis: 0.595

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.817

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Col5a1
• 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); embryo phenotype; 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); 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); vision/eye phenotype

Gene ontology

• Biological process: blood vessel development;heart morphogenesis;cell adhesion;cell migration;extracellular matrix organization;collagen fibril organization;collagen biosynthetic process;wound healing, spreading of epidermal cells;tendon development;skin development;integrin biosynthetic process;eye morphogenesis;regulation of cellular component organization;supramolecular fiber organization;negative regulation of endodermal cell differentiation
• Cellular component: extracellular region;collagen type V trimer;basement membrane;extracellular space;endoplasmic reticulum lumen;extracellular matrix;collagen-containing extracellular matrix
• Molecular function: integrin binding;extracellular matrix structural constituent;protein binding;heparin binding;extracellular matrix structural constituent conferring tensile strength;proteoglycan binding;metal ion binding;platelet-derived growth factor binding