COL6A2

Chr 21ARAD

collagen type VI alpha 2 chain

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

The protein is one of three alpha chains that form type VI collagen, a beaded filament collagen that organizes extracellular matrix components in connective tissues through binding interactions via von Willebrand Factor type A domains. Mutations cause Bethlem myopathy and Ullrich congenital muscular dystrophy through both autosomal dominant and autosomal recessive inheritance patterns. The pathogenic mechanism involves dominant-negative effects that disrupt normal collagen VI assembly and function.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismAR/ADLOEUF 0.583 OMIM phenotypes
Clinical SummaryCOL6A2
🧬
Gene-Disease Validity (ClinGen)
collagen 6-related myopathy · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.58LOEUF
pLI 0.000
Z-score 4.06
OE 0.41 (0.290.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-1.15Z-score
OE missense 1.12 (1.061.19)
799 obs / 712.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.41 (0.290.58)
00.351.4
Missense OE1.12 (1.061.19)
00.61.4
Synonymous OE1.47
01.21.6
LoF obs/exp: 22 / 54.3Missense obs/exp: 799 / 712.7Syn Z: -6.61
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCOL6A2-related muscular dystrophyDNAD
definitiveCOL6A2-related muscular dystrophyLOFAR
DN
0.77top 25%
GOF
0.72top 25%
LOF
0.2873th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median · 1 literature citation
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

DNIndeed, numerous mutations have now been reported in the COL6A1, COL6A2 and COL6A3 genes, a large proportion of which are de novo and exert dominant-negative effects.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

COL6A2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →