COL6A1

Chr 21ADAR

collagen type VI alpha 1 chain

NCBI Gene: 1291ENSG00000142156UniProt: P12109

Collagen VI acts as a cell-binding protein

Primary Disease Associations & Inheritance

Bethlem myopathy 1AMIM #158810
AD
Ullrich congenital muscular dystrophy 1AMIM #254090
ADAR
549
ClinVar variants
66
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— COL6A1
🧬
Gene-Disease Validity (ClinGen)
collagen 6-related myopathy · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
66 Pathogenic / Likely Pathogenic· 188 VUS of 549 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.23LOEUF
pLI 1.000
Z-score 6.45
OE 0.13 (0.07–0.23)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.50Z-score
OE missense 0.95 (0.89–1.01)
644 obs / 680.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.13 (0.07–0.23)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.89–1.01)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.10
0≤1.21.6
LoF obs/exp: 8 / 63.5Missense obs/exp: 644 / 680.8Syn Z: -1.42

ClinVar Variant Classifications

549 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic23
VUS188
Likely Benign197
Benign66
Conflicting32
43
Pathogenic
23
Likely Pathogenic
188
VUS
197
Likely Benign
66
Benign
32
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
4
22
0
43
Likely Pathogenic
13
4
6
0
23
VUS
4
127
52
5
188
Likely Benign
0
12
114
71
197
Benign
0
12
46
8
66
Conflicting
—32
Total3415924084549

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

COL6A1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

COL6A1-related myopathy

definitive
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Bethlem myopathy 1A

MIM #158810

Molecular basis of disorder known

Autosomal dominant

Ullrich congenital muscular dystrophy 1A

MIM #254090

Molecular basis of disorder known

Autosomal dominantAutosomal recessive
📖
GeneReview available — COL6A1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Exome sequencing and characterization of 49,960 individuals in the UK Biobank.
Van Hout CV et al.·Nature
2020
Improving genetic diagnosis in Mendelian disease with transcriptome sequencing.
Cummings BB et al.·Sci Transl Med
2017
Panel-Based Exome Sequencing for Neuromuscular Disorders as a Diagnostic Service.
Westra D et al.·J Neuromuscul Dis
2019
H3K27 acetylation activated-COL6A1 promotes osteosarcoma lung metastasis by repressing STAT1 and activating pulmonary cancer-associated fibroblasts.
Zhang Y et al.·Theranostics
2021
Low-Dose Metformin and Profibrotic Signature in Central Centrifugal Cicatricial Alopecia.
Bao A et al.·JAMA Dermatol
2024
Acquired resistance to immunotherapy by physical barriers with cancer cell-expressing collagens in non-small cell lung cancer.
Wang M et al.·Proc Natl Acad Sci U S A
2025
Position of glycine substitutions in the triple helix of COL6A1, COL6A2, and COL6A3 is correlated with severity and mode of inheritance in collagen VI myopathies.
Butterfield RJ et al.·Hum Mutat
2013
Congenital muscular dystrophies in the UK population: Clinical and molecular spectrum of a large cohort diagnosed over a 12-year period.
Sframeli M et al.·Neuromuscul Disord
2017Cohort
Collagen type VI myopathies.
Bushby KM et al.·Adv Exp Med Biol
2014Review
Sustained oral spermidine supplementation rescues functional and structural defects in COL6-deficient myopathic mice.
Gambarotto L et al.·Autophagy
2023Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Col6a1 knock-in mice provide a promising pre-clinical model for collagen VI-related dystrophies.
López-Márquez A et al.·Dis Model Mech
2026🔓 Open AccessFunctional
Synergistic Anticancer Effects of COL6A1 Downregulation and the PD1 Inhibitor Pembrolizumab in Bladder Cancer.
Yuan F et al.·J Biochem Mol Toxicol
2025
Landscape Analysis of COL6A1, COL6A2, and COL6A3 Pathogenic Variants in a Large Italian Cohort Presenting with Collagen VI-Related Myopathies: A Nationwide Report.
Fortunato F et al.·Biomolecules
2025🔓 Open AccessCohort
COL6A1, LAPTM5, and ZFAND2A as Crucial Biomolecules Driving Immunoregulation in Human Nucleus Pulposus Degeneration.
Lu ZY et al.·FASEB J
2025🔓 Open Access
TGF-βI/FERMT2/COL6A1 Reciprocal Loop Drives Tumor-Stroma Crosstalk and Promotes Peritoneal Metastasis in Gastric Cancer.
He C et al.·Int J Biol Sci
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools