COL3A1
Chr 2ADARcollagen type III alpha 1 chain
Also known as: EDS4A, EDSVASC, PMGEDSV
The encoded protein forms pro-alpha1 chains of type III collagen, which is found in extensible connective tissues including skin, blood vessels, and lung, and serves as a major ligand regulating cortical development and neuronal migration in the developing brain. Mutations cause Ehlers-Danlos syndrome vascular type and polymicrogyria with or without vascular-type EDS, following autosomal dominant or autosomal recessive inheritance patterns. This gene is highly constrained against loss-of-function variants, reflecting the critical importance of proper collagen function for vascular integrity and brain development.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
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.
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
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
Protein Context — Lollipop Plot
COL3A1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Pelvic Organs Prolapse Treatment Using Neodymium Laser
ACTIVE NOT RECRUITINGNon-Ablative Laser to Treat Scarring Alopecia With Hair Follicle Gene Expression Analysis
RECRUITINGSEDVasc (RaDiCo Cohort) (RaDiCo-SEDVasc)
ACTIVE NOT RECRUITINGHeart Coherence Training on Vascular Ehlers-Danlos Syndrome Patients
RECRUITINGMetabolic Phenotyping in vEDS
RECRUITINGExternal Resources
Links to major genomics databases and tools