COL6A5

Chr 3

collagen type VI alpha 5 chain

Also known as: COL29A1, VWA4

NCBI Gene: 256076 ENSG00000172752 UniProt: A8TX70 OMIM: 611916

This gene encodes a member of the collagen superfamily of proteins. The encoded protein contains multiple von Willebrand factor A-like domains and may interact with the alpha 1 and alpha 2 chains of collagen VI to form the complete collagen VI trimer. Polymorphisms in this gene may be linked to dermal phenotypes, such as eczema. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.92

Clinical Summary— COL6A5

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

319 VUS of 403 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.92LOEUF

pLI 0.000

Z-score 2.25

OE 0.77 (0.64–0.92)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.18Z-score

OE missense 0.83 (0.79–0.87)

1093 obs / 1315.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.77 (0.64–0.92)

0≤0.351.4

Missense OE?0.83 (0.79–0.87)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 83 / 108.3Missense obs/exp: 1093 / 1315.7Syn Z: 2.94

This gene — mechanism propensity

0.7034th %ile

GOF

0.7027th %ile

LOF

0.3549th %ile

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

GOFprediction above median

DNprediction 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.

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

ClinVar Variant Classifications

403 submitted variants in ClinVar

ClinVar

Classification Summary

VUS319

Likely Benign54

Benign12

Conflicting6

319

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	2	316	1	0	319
Likely Benign	2	41	4	7	54
Benign	2	6	0	4	12
Conflicting	—				6
Total	6	363	5	11	391

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap COL6A5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →