COL5A2

Chr 2AD

collagen type V alpha 2 chain

NCBI Gene: 1290ENSG00000204262UniProt: P05997

Type V collagen is a member of group I collagen (fibrillar forming collagen). It is a minor connective tissue component of nearly ubiquitous distribution. Type V collagen binds to DNA, heparan sulfate, thrombospondin, heparin, and insulin. Type V collagen is a key determinant in the assembly of tissue-specific matrices (By similarity)

Primary Disease Associations & Inheritance

Ehlers-Danlos syndrome, classic type, 2MIM #130010
AD
2409
ClinVar variants
13
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— COL5A2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 158 VUS of 2409 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.10LOEUF
pLI 1.000
Z-score 8.63
OE 0.04 (0.02–0.10)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

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.
2.44Z-score
OE missense 0.77 (0.72–0.82)
679 obs / 883.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.04 (0.02–0.10)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.72–0.82)
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.0.99
0≤1.21.6
LoF obs/exp: 4 / 94.5Missense obs/exp: 679 / 883.0Syn Z: 0.16

ClinVar Variant Classifications

2409 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic9
VUS158
Likely Benign276
Benign11
Conflicting6
4
Pathogenic
9
Likely Pathogenic
158
VUS
276
Likely Benign
11
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
2
0
4
Likely Pathogenic
4
4
1
0
9
VUS
3
142
11
2
158
Likely Benign
0
6
170
100
276
Benign
0
1
6
4
11
Conflicting
—6
Total9153190106464

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

View in ClinVar →

Protein Context — Lollipop Plot

COL5A2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

COL5A2-related Ehlers-Danlos syndrome, classic type

definitive
ADDominant NegativeAltered Gene Product Structure
Skin
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Ehlers-Danlos syndrome, classic type, 2

MIM #130010

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
CHSY3 promotes proliferation and migration in gastric cancer and is associated with immune infiltration.
Huang X et al.·J Transl Med
2023
Clinical and genetic aspects of Ehlers-Danlos syndrome, classic type.
Malfait F et al.·Genet Med
2010Review
Specifications and validation of the ACMG/AMP criteria for clinical interpretation of sequence variants in collagen genes associated with joint hypermobility.
Leone MP et al.·Hum Genet
2023
Exosome-Based Regimen Rescues Endometrial Fibrosis in Intrauterine Adhesions Via Targeting Clinical Fibrosis Biomarkers.
Lin Y et al.·Stem Cells Transl Med
2023
Phenotype of COL3A1/COL5A2 deletion patients.
Kempers MJ et al.·Eur J Med Genet
2022Cohort
COL5A2 as a potential clinical biomarker for gastric cancer and renal metastasis.
Ding YL et al.·Medicine (Baltimore)
2021
Genetic Overlap of Thoracic Aortic Aneurysms and Intracranial Aneurysms.
Changez MIK et al.·Genes (Basel)
2025Review
COL5A2-mediated endoplasmic reticulum stress promotes macrophage M2 polarization in lung adenocarcinoma.
Sun G et al.·Cell Stress Chaperones
2025
COL5A2 is a prognostic-related biomarker and correlated with immune infiltrates in gastric cancer based on transcriptomics and single-cell RNA sequencing.
Chen M et al.·BMC Med Genomics
2023
A novel hypoxia- and lactate metabolism-related prognostic signature to characterize the immune landscape and predict immunotherapy response in osteosarcoma.
Wang Y et al.·Front Immunol
2024
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools