COL6A2

Chr 21ARAD

collagen type VI alpha 2 chain

Also known as: BTHLM1, BTHLM1B, PP3610, UCMD1, UCMD1B

NCBI Gene: 1292ENSG00000142173UniProt: P12110

This gene encodes one of the three alpha chains of type VI collagen, a beaded filament collagen found in most connective tissues. The product of this gene contains several domains similar to von Willebrand Factor type A domains. These domains have been shown to bind extracellular matrix proteins, an interaction that explains the importance of this collagen in organizing matrix components. Mutations in this gene are associated with Bethlem myopathy and Ullrich scleroatonic muscular dystrophy. Three transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Myosclerosis, congenitalMIM #255600
AR
Bethlem myopathy 1BMIM #620725
ADAR
Ullrich congenital muscular dystrophy 1BMIM #620727
ADAR
UniProtMyosclerosis autosomal recessive
2500
ClinVar variants
41
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— COL6A2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
41 Pathogenic / Likely Pathogenic· 204 VUS of 2500 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.58LOEUF
pLI 0.000
Z-score 4.06
OE 0.41 (0.29–0.58)
Moderately constrained

More LoF-intolerant than ~75% 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.
-1.15Z-score
OE missense 1.12 (1.06–1.19)
799 obs / 712.7 exp
Tolerant

Tolerant to missense variation

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.0.41 (0.29–0.58)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.12 (1.06–1.19)
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.1.47
0≤1.21.6
LoF obs/exp: 22 / 54.3Missense obs/exp: 799 / 712.7Syn Z: -6.61

ClinVar Variant Classifications

2500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic17
VUS204
Likely Benign195
Benign8
Conflicting10
24
Pathogenic
17
Likely Pathogenic
204
VUS
195
Likely Benign
8
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
3
8
0
24
Likely Pathogenic
12
1
4
0
17
VUS
5
168
28
3
204
Likely Benign
1
9
94
91
195
Benign
0
2
3
3
8
Conflicting
—10
Total3118313797458

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

View in ClinVar →

Protein Context — Lollipop Plot

COL6A2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

COL6A2-related muscular dystrophy

definitive
ADDominant NegativeAltered Gene Product Structure
Dev. Disorders
G2P ↗

COL6A2-related muscular dystrophy

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Myosclerosis, congenital

MIM #255600

Molecular basis of disorder known

Autosomal recessive

Bethlem myopathy 1B

MIM #620725

Molecular basis of disorder known

Autosomal dominantAutosomal recessive

Ullrich congenital muscular dystrophy 1B

MIM #620727

Molecular basis of disorder known

Autosomal dominantAutosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness.
Töpf A et al.·Genet Med
2020Cohort
Panel-Based Exome Sequencing for Neuromuscular Disorders as a Diagnostic Service.
Westra D et al.·J Neuromuscul Dis
2019
Whole-exome sequencing identifies novel pathogenic mutations and putative phenotype-influencing variants in Polish limb-girdle muscular dystrophy patients.
Fichna JP et al.·Hum Genomics
2018Cohort
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
Rare genetic variation in fibronectin 1 (FN1) protects against APOEε4 in Alzheimer's disease.
Bhattarai P et al.·Acta Neuropathol
2024
COL6A2 in clear cell renal cell carcinoma: a multifaceted driver of tumor progression, immune evasion, and drug sensitivity.
Yang Y et al.·J Transl Med
2025
Collagen type VI myopathies.
Bushby KM et al.·Adv Exp Med Biol
2014Review
Clinical, Pathologic, and Genetic Spectrum of Collagen VI-Related Disorder in China-A Retrospective Observational Multicenter Study.
Hu C et al.·Hum Mutat
2024
Deconstruction of tophi and synovium defines SPP1(+) macrophages involved in extracellular matrix remodelling in gout.
Xu H et al.·Ann Rheum Dis
2025Functional
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
2025Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Keratoconus

The Collagen Factors of Rapid Progression of Keratoconus in Children.

RECRUITING
NCT06722937Zhongshan Ophthalmic Center, Sun Yat-sen UniversityStarted 2023-04-14
Observation
Breast Cancer

Carboplatin and Nab-Paclitaxel With or Without Vorinostat in Treating Women With Newly Diagnosed Operable Breast Cancer

ACTIVE NOT RECRUITING
NCT00616967Phase PHASE2Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsStarted 2008-05
carboplatinpaclitaxel albumin-stabilized nanoparticle formulationvorinostat

External Resources

Links to major genomics databases and tools