COL6A3

Chr 2ADAR

collagen type VI alpha 3 chain

Also known as: BTHLM1, BTHLM1C, DYT27, UCMD1, UCMD1C

The alpha-3 chain of type VI collagen organizes extracellular matrix components in connective tissues by binding matrix proteins through its von Willebrand Factor type A domains. Mutations cause Bethlem myopathy (autosomal dominant, milder proximal myopathy with early childhood onset), Ullrich congenital muscular dystrophy (autosomal recessive, more severe congenital myopathy), and dystonia 27. The pathogenic mechanism involves gain-of-function effects.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismAD/ARLOEUF 0.563 OMIM phenotypes
Clinical SummaryCOL6A3
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Gene-Disease Validity (ClinGen)
collagen 6-related myopathy · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

3 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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GeneReview available — COL6A3
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.56LOEUF
pLI 0.000
Z-score 5.65
OE 0.45 (0.360.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-0.61Z-score
OE missense 1.04 (1.001.08)
1908 obs / 1835.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.45 (0.360.56)
00.351.4
Missense OE1.04 (1.001.08)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 55 / 122.5Missense obs/exp: 1908 / 1835.0Syn Z: -2.16
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCOL6A3-related Ullrich congenital muscular dystrophyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7326th %ile
GOF
0.74top 25%
LOF
0.3066th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

DNBiosynthetic studies of mutant fibroblasts indicated that the mutant ?3(VI) collagen protein was produced and exerted a dominant-negative effect on collagen VI microfibrillar assembly.PMID:21943391

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

COL6A3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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