COL6A3

collagen type VI alpha 3 chain, the group of Collagens

Basic information

Region (hg38): 2:237324002-237414328

Links

ENSG00000163359 ∙ NCBI:1293 ∙ OMIM:120250 ∙ HGNC:2213 ∙ Uniprot:P12111 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Ullrich congenital muscular dystrophy 1A (Definitive), mode of inheritance: AR
• Bethlem myopathy 1A (Strong), mode of inheritance: AD
• Ullrich congenital muscular dystrophy 1A (Strong), mode of inheritance: AD
• Bethlem myopathy 1A (Strong), mode of inheritance: AR
• Ullrich congenital muscular dystrophy 1A (Strong), mode of inheritance: AR
• Bethlem myopathy 1A (Definitive), mode of inheritance: Semidominant
• dystonia 27 (Disputed Evidence), mode of inheritance: AR
• Ullrich congenital muscular dystrophy 1A (Strong), mode of inheritance: Semidominant
• Bethlem myopathy (Supportive), mode of inheritance: AD
• Ullrich congenital muscular dystrophy (Supportive), mode of inheritance: AD
• dystonia 27 (Supportive), mode of inheritance: AR
• dystonia 27 (Limited), mode of inheritance: AR
• Ullrich congenital muscular dystrophy 1A (Strong), mode of inheritance: AD
• Ullrich congenital muscular dystrophy 1A (Strong), mode of inheritance: AR
• dystonia 27 (Strong), mode of inheritance: AR
• collagen 6-related myopathy (Definitive), mode of inheritance: AD
• collagen 6-related myopathy (Definitive), mode of inheritance: AR
• dystonia 27 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ullrich congenital muscular dystrophy 1; Bethlem myopathy 1; Dystonia 27	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	963533; 11992252; 15563506; 15689448; 16141002; 17886299; 18362356; 18366090; 19564581; 20301676; 20976770; 21496625; 21943391; 22526018; 26004199
Medical treatment (eg, with Cyclosporin A) may be beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COL6A3 gene.

• Bethlem myopathy 1 (2356 variants)
• not provided (1332 variants)
• Collagen 6-related myopathy (331 variants)
• not specified (261 variants)
• Inborn genetic diseases (143 variants)
• Ullrich congenital muscular dystrophy 1 (47 variants)
• Dystonia 27 (33 variants)
• COL6A3-related condition (31 variants)
• Bethlem myopathy 1;Ullrich congenital muscular dystrophy 1 (16 variants)
• Bethlem myopathy 1;Ullrich congenital muscular dystrophy 1;Dystonia 27 (12 variants)
• Tip-toe gait (11 variants)
• See cases (5 variants)
• Bethlem myopathy 1;Dystonia 27;Ullrich congenital muscular dystrophy 1 (5 variants)
• Myopathy (3 variants)
• Ullrich congenital muscular dystrophy 1;Bethlem myopathy 1;Dystonia 27 (2 variants)
• Abnormality of the musculature (2 variants)
• Ullrich congenital muscular dystrophy 1;Dystonia 27;Bethlem myopathy 1 (2 variants)
• Dystonia 27;Bethlem myopathy 1;Ullrich congenital muscular dystrophy 1 (2 variants)
• 7 conditions (1 variants)
• Bethlem myopathy 1;Dystonia 27 (1 variants)
• Muscular dystrophy (1 variants)
• Neuronopathy, distal hereditary motor, autosomal recessive (1 variants)
• Congenital contracture (1 variants)
• Marfanoid habitus and intellectual disability (1 variants)
• COL6A3-related disorders (1 variants)
• Ullrich congenital muscular dystrophy 1;Collagen 6-related myopathy;Bethlem myopathy 1 (1 variants)
• COL6A3-related phenotype (1 variants)
• Ullrich congenital muscular dystrophy 1;Bethlem myopathy 1 (1 variants)
• Ullrich congenital muscular dystrophy 1, autosomal dominant (1 variants)
• - (1 variants)
• Dystonia 27;Ullrich congenital muscular dystrophy 1;Bethlem myopathy 1 (1 variants)
• Collagen 6-related myopathy;Dystonia 27;Bethlem myopathy 1 (1 variants)
• Ullrich congenital muscular dystrophy 1;Dystonia 27;Collagen 6-related myopathy;Bethlem myopathy 1 (1 variants)
• Muscle weakness (1 variants)
• Multiple joint contractures (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL6A3 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			50	452	44	546
missense	8	21	1094	167	45	1335
nonsense	24	15	1			40
start loss						0
frameshift	25	12	2			39
inframe indel		3	16	2	1	22
splice donor/acceptor (+/-2bp)	14	21	2			37
splice region	2	1	50	41	5	99
non coding	1		21	219	99	340
Total	72	72	1186	840	189

Highest pathogenic variant AF is 0.0000394

Variants in COL6A3

This is a list of pathogenic ClinVar variants found in the COL6A3 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-237324020-A-T		Collagen 6-related myopathy	Uncertain significance (Jan 13, 2018)
2-237324109-C-A		Collagen 6-related myopathy	Benign (Jan 12, 2018)
2-237324111-A-C		Collagen 6-related myopathy	Benign (Jan 12, 2018)
2-237324159-C-T		Collagen 6-related myopathy	Uncertain significance (Jan 12, 2018)
2-237324168-T-A		Collagen 6-related myopathy	Benign (Jan 13, 2018)
2-237324348-C-T		Collagen 6-related myopathy	Likely benign (Jun 14, 2016)
2-237324397-G-A		Collagen 6-related myopathy	Uncertain significance (Jan 12, 2018)
2-237324489-T-C		Collagen 6-related myopathy	Uncertain significance (Jan 13, 2018)
2-237324684-G-A		Collagen 6-related myopathy	Uncertain significance (Jan 13, 2018)
2-237324723-G-C		Collagen 6-related myopathy	Uncertain significance (Apr 27, 2017)
2-237324767-C-A			Uncertain significance (Mar 22, 2018)
2-237324767-C-G		not specified • Collagen 6-related myopathy	Benign (Jan 13, 2018)
2-237324779-T-G		Bethlem myopathy 1A	Uncertain significance (Feb 08, 2022)
2-237324784-A-G		Collagen 6-related myopathy • not specified • Bethlem myopathy 1A • COL6A3-related disorder	Conflicting classifications of pathogenicity (Dec 06, 2023)
2-237324785-T-G		Bethlem myopathy 1A	Likely benign (Aug 16, 2023)
2-237324800-C-T		Bethlem myopathy 1A	Conflicting classifications of pathogenicity (Dec 30, 2023)
2-237324804-T-C		Bethlem myopathy 1A	Likely benign (Jun 30, 2021)
2-237324809-C-T		Bethlem myopathy 1A	Conflicting classifications of pathogenicity (Aug 22, 2022)
2-237324810-G-A		Bethlem myopathy 1A • COL6A3-related disorder	Conflicting classifications of pathogenicity (Jan 19, 2024)
2-237324814-A-C		Bethlem myopathy 1A	Uncertain significance (Apr 12, 2022)
2-237324816-T-C		Bethlem myopathy 1A	Uncertain significance (Sep 22, 2023)
2-237324819-G-A		Bethlem myopathy 1A	Conflicting classifications of pathogenicity (Aug 27, 2023)
2-237324820-C-A		Bethlem myopathy 1A	Likely benign (Jun 16, 2023)
2-237324820-C-T		Myopathy • Bethlem myopathy 1A	Likely benign (Jul 01, 2023)
2-237324821-G-A		not specified • Bethlem myopathy 1A	Likely benign (Jan 24, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COL6A3	protein_coding	protein_coding	ENST00000295550	43	90373

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.81e-20	1.00	125582	0	166	125748	0.000660

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.606	1908	1.84e+3	1.04	0.000118	20598
Missense in Polyphen		666	646.73	1.0298		7475
Synonymous	-2.16	844	768	1.10	0.0000561	6673
Loss of Function	5.65	55	123	0.449	0.00000711	1445

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00190	0.00189
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000435	0.000435
Finnish	0.000878	0.000878
European (Non-Finnish)	0.000709	0.000695
Middle Eastern	0.000435	0.000435
South Asian	0.000359	0.000359
Other	0.000492	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Collagen VI acts as a cell-binding protein.
• Disease: DISEASE: Bethlem myopathy 1 (BTHLM1) [MIM:158810]: A benign proximal myopathy characterized by early childhood onset and joint contractures most frequently affecting the elbows and ankles. {ECO:0000269|PubMed:10399756, ECO:0000269|PubMed:15689448, ECO:0000269|PubMed:17886299, ECO:0000269|PubMed:9536084}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Ullrich congenital muscular dystrophy 1 (UCMD1) [MIM:254090]: A congenital myopathy characterized by muscle weakness and multiple joint contractures, generally noted at birth or early infancy. The clinical course is more severe than in Bethlem myopathy. {ECO:0000269|PubMed:15689448}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Dystonia 27 (DYT27) [MIM:616411]: A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT27 is an autosomal recessive form characterized by segmental isolated dystonia involving the face, neck, bulbar muscles, and upper limbs. {ECO:0000269|PubMed:26004199}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);ECM-receptor interaction - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Protein digestion and absorption - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);miRNA targets in ECM and membrane receptors;PI3K-Akt Signaling Pathway;Developmental Biology;Assembly of collagen fibrils and other multimeric structures;Signal Transduction;Collagen chain trimerization;Collagen biosynthesis and modifying enzymes;Signaling by PDGF;Collagen formation;Extracellular matrix organization;NCAM signaling for neurite out-growth;NCAM1 interactions;Axon guidance;Signaling by Receptor Tyrosine Kinases;Beta1 integrin cell surface interactions;Syndecan-1-mediated signaling events;Integrins in angiogenesis (Consensus)

Recessive Scores

• pRec: 0.404

Intolerance Scores

• loftool: 0.00372
• rvis_EVS: -2.55
• rvis_percentile_EVS: 0.86

Haploinsufficiency Scores

• pHI: 0.936
• hipred: N
• hipred_score: 0.432
• ghis: 0.594

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.242

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Col6a3
• Phenotype: skeleton phenotype; muscle phenotype; cellular phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: col6a3
• Affected structure: muscle cell
• Phenotype tag: abnormal
• Phenotype quality: apoptotic

Gene ontology

• Biological process: growth plate cartilage chondrocyte morphogenesis;cell adhesion;muscle organ development;negative regulation of endopeptidase activity;extracellular matrix organization
• Cellular component: extracellular region;collagen type VI trimer;extracellular space;endoplasmic reticulum lumen;extracellular matrix;sarcolemma;collagen-containing extracellular matrix;extracellular exosome;extracellular vesicle
• Molecular function: serine-type endopeptidase inhibitor activity;extracellular matrix structural constituent conferring tensile strength