COL12A1

Chr 6ARAD

collagen type XII alpha 1 chain

Also known as: BA209D8.1, BTHLM2, COL12A1L, DJ234P15.1, EDSMYP, UCMD2

NCBI Gene: 1303ENSG00000111799UniProt: Q99715OMIM: 120320

This gene encodes the alpha chain of type XII collagen, which interacts with type I collagen fibrils and modifies their interactions with the surrounding extracellular matrix. Mutations cause Bethlem myopathy 2 and Ullrich congenital muscular dystrophy 2, both affecting skeletal muscle with either autosomal dominant or autosomal recessive inheritance patterns. The gene is highly constrained against loss-of-function variants (pLI 0.97), indicating intolerance to protein-truncating mutations.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismAR/ADLOEUF 0.282 OMIM phenotypes
Clinical Summary— COL12A1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.28LOEUF
pLI 0.974
Z-score 9.16
OE 0.21 (0.16–0.28)
Highly constrained

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

Missense Constraint
2.11Z-score
OE missense 0.85 (0.82–0.89)
1423 obs / 1664.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.21 (0.16–0.28)
0≤0.351.4
Missense OE0.85 (0.82–0.89)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 33 / 156.7Missense obs/exp: 1423 / 1664.8Syn Z: -0.34
DN
0.4982th %ile
GOF
0.5072th %ile
LOF
0.60top 25%

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

LOFLOEUF 0.28
DN1 literature citation

Literature Evidence

DNWe identified a novel, potentially pathogenic heterozygous missense COL12A1 c.8329G>C (p.Gly2777Arg) variant using a targeted sequencing panel. Patient fibroblast studies confirmed intracellular retention of the COL12A1 protein, consistent with a dominant-negative mutation.PMID:27348394

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

COL12A1 · 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

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients