COL6A1

collagen type VI alpha 1 chain, the group of Collagens

Basic information

Region (hg38): 21:45981770-46005050

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
Bethlem myopathy 1A (Definitive), 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 1A; Bethlem myopathy 1A	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 1A (70 variants)
not provided (37 variants)
Ullrich congenital muscular dystrophy 1A (7 variants)
Ullrich congenital muscular dystrophy 1A;Bethlem myopathy 1A (2 variants)
Abnormality of the musculature (2 variants)
ULLRICH CONGENITAL MUSCULAR DYSTROPHY 1A, AUTOSOMAL DOMINANT (2 variants)
Collagen 6-related myopathy (2 variants)
not specified (1 variants)
Inborn genetic diseases (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. These statistics are base on transcript: . Only rare variants are included in the table.

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			15 clinvar	198 clinvar	29 clinvar	242
missense	25 clinvar	29 clinvar	312 clinvar	75 clinvar	49 clinvar	490
nonsense	9 clinvar	2 clinvar	2 clinvar			13
start loss			1			1
frameshift	16 clinvar	9 clinvar	7 clinvar			32
splice donor/acceptor (+/-2bp)	35 clinvar	29 clinvar	9 clinvar	1 clinvar		74
Total	85	69	346	274	78

Highest pathogenic variant AF is 0.000013178

Loading clinvar variants...

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