GeneBe

COL6A3

collagen type VI alpha 3 chain, the group of Collagens

Basic information

Region (hg38): 2:237324003-237414328

Links

ENSG00000163359 ∙ NCBI:1293 ∙ OMIM:120250 ∙ HGNC:2213 ∙ Uniprot:P12111 ∙ 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 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
  • Ullrich congenital muscular dystrophy 1C (Definitive), 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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Ullrich congenital muscular dystrophy 1C; Bethlem myopathy 1C; Dystonia 27AD/ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingMusculoskeletal963533; 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_1A (2887 variants)
  • not_provided (1425 variants)
  • Inborn_genetic_diseases (408 variants)
  • Collagen_6-related_myopathy (300 variants)
  • not_specified (260 variants)
  • COL6A3-related_disorder (152 variants)
  • Ullrich_congenital_muscular_dystrophy_1A (83 variants)
  • Dystonia_27 (82 variants)
  • Bethlem_myopathy_1C (28 variants)
  • Ullrich_congenital_muscular_dystrophy_1C (16 variants)
  • Tip-toe_gait (13 variants)
  • See_cases (5 variants)
  • Limb-girdle_muscular_dystrophy (5 variants)
  • Myopathy (3 variants)
  • COL6A3-related_phenotype (2 variants)
  • Abnormality_of_the_musculature (2 variants)
  • Bethlem_myopathy (1 variants)
  • Intellectual_disability (1 variants)
  • Marfanoid_habitus_and_intellectual_disability (1 variants)
  • Primary_dilated_cardiomyopathy (1 variants)
  • Muscle_weakness (1 variants)
  • Multiple_joint_contractures (1 variants)
  • Muscle_tissue_disorder (1 variants)
  • Congenital_myopathy (1 variants)
  • Spinocerebellar_ataxia_type_13 (1 variants)
  • Neuronopathy,_distal_hereditary_motor,_autosomal_recessive (1 variants)
  • Congenital_contracture (1 variants)
  • Muscular_dystrophy (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. These statistics are base on transcript: NM_000004369.4. 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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
1
clinvar
47
clinvar
758
clinvar
30
clinvar
 838
missense
14
clinvar
35
clinvar
1482
clinvar
532
clinvar
33
clinvar
 2096
nonsense
29
clinvar
22
clinvar
2
clinvar
 53
start loss
0
frameshift
33
clinvar
20
clinvar
4
clinvar
 57
splice donor/acceptor (+/-2bp)
17
clinvar
32
clinvar
1
clinvar
 50
Total 95 110 1536 1290 63

Highest pathogenic variant AF is 0.0007174321

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
COL6A3protein_codingprotein_codingENST00000295550 4390373
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.81e-201.0012558201661257480.000660
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.60619081.84e+31.040.00011820598
Missense in Polyphen666646.731.02987475
Synonymous-2.168447681.100.00005616673
Loss of Function5.65551230.4490.000007111445

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001900.00189
Ashkenazi Jewish0.0001980.000198
East Asian0.0004350.000435
Finnish0.0008780.000878
European (Non-Finnish)0.0007090.000695
Middle Eastern0.0004350.000435
South Asian0.0003590.000359
Other0.0004920.000489

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

AllRecessiveDominant
MendelianHighMediumHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

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