COL6A1

collagen type VI alpha 1 chain, the group of Collagens

Basic information

Region (hg38): 21:45981769-46005050

Links

ENSG00000142156 ∙ NCBI:1291 ∙ OMIM:120220 ∙ HGNC:2211 ∙ Uniprot:P12109 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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 (Supportive), mode of inheritance: AD
• Ullrich congenital muscular dystrophy (Supportive), mode of inheritance: AD
• Ullrich congenital muscular dystrophy 1A (Strong), mode of inheritance: AR
• Ullrich congenital muscular dystrophy 1A (Strong), mode of inheritance: AD
• collagen 6-related myopathy (Definitive), mode of inheritance: AD
• collagen 6-related myopathy (Definitive), 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	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; 3632670; 8782832; 11932968; 12840783; 12958705; 16130093; 15689448; 15955946; 17785674; 17886299; 18362356; 18366090; 19564581; 20301676; 20976770

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COL6A1 gene.

• Bethlem myopathy 1 (1209 variants)
• not provided (731 variants)
• Collagen 6-related myopathy (203 variants)
• not specified (201 variants)
• Inborn genetic diseases (67 variants)
• Ullrich congenital muscular dystrophy 1 (38 variants)
• Bethlem myopathy 1;Ullrich congenital muscular dystrophy 1 (19 variants)
• COL6A1-related condition (6 variants)
• Ullrich congenital muscular dystrophy 1;Bethlem myopathy 1 (3 variants)
• Abnormality of the musculature (3 variants)
• Ullrich congenital muscular dystrophy 1, autosomal dominant (2 variants)
• Motor delay;Limb-girdle muscle weakness;EMG abnormality (1 variants)
• COL6A1-related Disorder (1 variants)
• Sensorimotor neuropathy (1 variants)
• Bethlem myopathy 1;Ullrich congenital muscular dystrophy 1;Collagen 6-related myopathy (1 variants)
• Myopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL6A1 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			18	180	24	222
missense	26	24	304	59	41	454
nonsense	8	2	2			12
start loss			1			1
frameshift	15	7	5			27
inframe indel	1	4	10			15
splice donor/acceptor (+/-2bp)	29	26	4			59
splice region	3	1	59	39	4	106
non coding	1	1	47	277	122	448
Total	80	64	391	516	187

Highest pathogenic variant AF is 0.0000131

Variants in COL6A1

This is a list of pathogenic ClinVar variants found in the COL6A1 region.

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

Position	Type	Phenotype	Significance	ClinVar
21-45981775-G-A		Collagen 6-related myopathy	Uncertain significance (Jan 13, 2018)
21-45981786-C-G		Collagen 6-related myopathy	Benign (Jan 12, 2018)
21-45981811-C-T		Collagen 6-related myopathy	Benign (Jan 13, 2018)
21-45981843-C-A		not specified	Likely benign (-)
21-45981846-C-G		not specified • Collagen 6-related myopathy	Benign (Jan 12, 2018)
21-45981850-C-T			Uncertain significance (Jun 18, 2021)
21-45981851-A-T		Bethlem myopathy 1A	Uncertain significance (Jul 19, 2022)
21-45981855-G-A		Bethlem myopathy 1A	Uncertain significance (Feb 08, 2018)
21-45981859-G-A		Bethlem myopathy 1A	Likely benign (Dec 13, 2023)
21-45981859-G-T			Uncertain significance (Jan 15, 2016)
21-45981860-G-A		Bethlem myopathy 1A	Uncertain significance (Jun 05, 2022)
21-45981863-C-T		Bethlem myopathy 1A	Uncertain significance (Jul 05, 2022)
21-45981864-G-A		Bethlem myopathy 1A	Uncertain significance (Jan 30, 2017)
21-45981865-T-A		Bethlem myopathy 1A	Likely benign (May 30, 2021)
21-45981867-C-G		Bethlem myopathy 1A	Uncertain significance (Jul 06, 2022)
21-45981869-C-A		Bethlem myopathy 1A	Uncertain significance (Nov 13, 2023)
21-45981877-C-G		Bethlem myopathy 1A	Benign (Dec 21, 2023)
21-45981886-G-C		Bethlem myopathy 1A	Likely benign (Aug 07, 2021)
21-45981890-G-A		Bethlem myopathy 1A	Uncertain significance (Dec 09, 2021)
21-45981893-T-C			Uncertain significance (May 17, 2022)
21-45981894-G-T		Bethlem myopathy 1A	Uncertain significance (Apr 24, 2022)
21-45981896-T-C		Bethlem myopathy 1A	Uncertain significance (Dec 15, 2023)
21-45981898-GAC-G		Bethlem myopathy 1A	Pathogenic (Aug 17, 2023)
21-45981900-C-CAGCCGCGCAGGATG		Bethlem myopathy 1A	Pathogenic (Apr 12, 2023)
21-45981907-G-A		Bethlem myopathy 1A	Likely benign (Jan 19, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COL6A1	protein_coding	protein_coding	ENST00000361866	35	23314

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000466	125710	0	33	125743	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.501	644	681	0.946	0.0000494	6530
Missense in Polyphen		213	219.05	0.97237		2037
Synonymous	-1.42	343	311	1.10	0.0000276	2074
Loss of Function	6.45	8	63.5	0.126	0.00000346	706

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000360	0.000356
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000147	0.000141
Middle Eastern	0.00	0.00
South Asian	0.000229	0.000229
Other	0.00	0.00

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:11865138, ECO:0000269|PubMed:15689448, ECO:0000269|PubMed:15955946, ECO:0000269|PubMed:8782832}. 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, ECO:0000269|PubMed:16130093, ECO:0000269|PubMed:17785674}. 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;Integrin;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: 0.540

Intolerance Scores

• loftool: 0.0443
• rvis_EVS: -1.49
• rvis_percentile_EVS: 3.62

Haploinsufficiency Scores

• pHI: 0.641
• hipred: Y
• hipred_score: 0.717
• ghis: 0.638

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.676

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Col6a1
• Phenotype: muscle phenotype

Zebrafish Information Network

• Gene name: col6a1
• Affected structure: skeletal muscle cell
• Phenotype tag: abnormal
• Phenotype quality: structure

Gene ontology

• Biological process: osteoblast differentiation;growth plate cartilage chondrocyte morphogenesis;cell adhesion;extracellular matrix organization;endodermal cell differentiation;protein heterotrimerization;cellular response to amino acid stimulus
• Cellular component: extracellular region;collagen type VI trimer;extracellular space;lysosomal membrane;endoplasmic reticulum lumen;membrane;extracellular matrix;protein-containing complex;sarcolemma;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: extracellular matrix structural constituent conferring tensile strength;platelet-derived growth factor binding